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UniProtKB - Q5S007 (LRRK2_HUMAN)
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>sp|Q5S007|LRRK2_HUMAN Leucine-rich repeat serine/threonine-protein kinase 2 OS=Homo sapiens OX=9606 GN=LRRK2 PE=1 SV=2 MASGSCQGCEEDEETLKKLIVRLNNVQEGKQIETLVQILEDLLVFTYSERASKLFQGKNI HVPLLIVLDSYMRVASVQQVGWSLLCKLIEVCPGTMQSLMGPQDVGNDWEVLGVHQLILK MLTVHNASVNLSVIGLKTLDLLLTSGKITLLILDEESDIFMLIFDAMHSFPANDEVQKLG CKALHVLFERVSEEQLTEFVENKDYMILLSALTNFKDEEEIVLHVLHCLHSLAIPCNNVE VLMSGNVRCYNIVVEAMKAFPMSERIQEVSCCLLHRLTLGNFFNILVLNEVHEFVVKAVQ QYPENAALQISALSCLALLTETIFLNQDLEEKNENQENDDEGEEDKLFWLEACYKALTWH RKNKHVQEAACWALNNLLMYQNSLHEKIGDEDGHFPAHREVMLSMLMHSSSKEVFQASAN ALSTLLEQNVNFRKILLSKGIHLNVLELMQKHIHSPEVAESGCKMLNHLFEGSNTSLDIM AAVVPKILTVMKRHETSLPVQLEALRAILHFIVPGMPEESREDTEFHHKLNMVKKQCFKN DIHKLVLAALNRFIGNPGIQKCGLKVISSIVHFPDALEMLSLEGAMDSVLHTLQMYPDDQ EIQCLGLSLIGYLITKKNVFIGTGHLLAKILVSSLYRFKDVAEIQTKGFQTILAILKLSA SFSKLLVHHSFDLVIFHQMSSNIMEQKDQQFLNLCCKCFAKVAMDDYLKNVMLERACDQN NSIMVECLLLLGADANQAKEGSSLICQVCEKESSPKLVELLLNSGSREQDVRKALTISIG KGDSQIISLLLRRLALDVANNSICLGGFCIGKVEPSWLGPLFPDKTSNLRKQTNIASTLA RMVIRYQMKSAVEEGTASGSDGNFSEDVLSKFDEWTFIPDSSMDSVFAQSDDLDSEGSEG SFLVKKKSNSISVGEFYRDAVLQRCSPNLQRHSNSLGPIFDHEDLLKRKRKILSSDDSLR SSKLQSHMRHSDSISSLASEREYITSLDLSANELRDIDALSQKCCISVHLEHLEKLELHQ NALTSFPQQLCETLKSLTHLDLHSNKFTSFPSYLLKMSCIANLDVSRNDIGPSVVLDPTV KCPTLKQFNLSYNQLSFVPENLTDVVEKLEQLILEGNKISGICSPLRLKELKILNLSKNH ISSLSENFLEACPKVESFSARMNFLAAMPFLPPSMTILKLSQNKFSCIPEAILNLPHLRS LDMSSNDIQYLPGPAHWKSLNLRELLFSHNQISILDLSEKAYLWSRVEKLHLSHNKLKEI PPEIGCLENLTSLDVSYNLELRSFPNEMGKLSKIWDLPLDELHLNFDFKHIGCKAKDIIR FLQQRLKKAVPYNRMKLMIVGNTGSGKTTLLQQLMKTKKSDLGMQSATVGIDVKDWPIQI RDKRKRDLVLNVWDFAGREEFYSTHPHFMTQRALYLAVYDLSKGQAEVDAMKPWLFNIKA RASSSPVILVGTHLDVSDEKQRKACMSKITKELLNKRGFPAIRDYHFVNATEESDALAKL RKTIINESLNFKIRDQLVVGQLIPDCYVELEKIILSERKNVPIEFPVIDRKRLLQLVREN QLQLDENELPHAVHFLNESGVLLHFQDPALQLSDLYFVEPKWLCKIMAQILTVKVEGCPK HPKGIISRRDVEKFLSKKRKFPKNYMSQYFKLLEKFQIALPIGEEYLLVPSSLSDHRPVI ELPHCENSEIIIRLYEMPYFPMGFWSRLINRLLEISPYMLSGRERALRPNRMYWRQGIYL NWSPEAYCLVGSEVLDNHPESFLKITVPSCRKGCILLGQVVDHIDSLMEEWFPGLLEIDI CGEGETLLKKWALYSFNDGEEHQKILLDDLMKKAEEGDLLVNPDQPRLTIPISQIAPDLI LADLPRNIMLNNDELEFEQAPEFLLGDGSFGSVYRAAYEGEEVAVKIFNKHTSLRLLRQE LVVLCHLHHPSLISLLAAGIRPRMLVMELASKGSLDRLLQQDKASLTRTLQHRIALHVAD GLRYLHSAMIIYRDLKPHNVLLFTLYPNAAIIAKIADYGIAQYCCRMGIKTSEGTPGFRA PEVARGNVIYNQQADVYSFGLLLYDILTTGGRIVEGLKFPNEFDELEIQGKLPDPVKEYG CAPWPMVEKLIKQCLKENPQERPTSAQVFDILNSAELVCLTRRILLPKNVIVECMVATHH NSRNASIWLGCGHTDRGQLSFLDLNTEGYTSEEVADSRILCLALVHLPVEKESWIVSGTQ SGTLLVINTEDGKKRHTLEKMTDSVTCLYCNSFSKQSKQKNFLLVGTADGKLAIFEDKTV KLKGAAPLKILNIGNVSTPLMCLSESTNSTERNVMWGGCGTKIFSFSNDFTIQKLIETRT SQLFSYAAFSDSNIITVVVDTALYIAKQNSPVVEVWDKKTEKLCGLIDCVHFLREVMVKE NKESKHKMSYSGRVKTLCLQKNTALWIGTGGGHILLLDLSTRRLIRVIYNFCNSVRVMMT AQLGSLKNVMLVLGYNRKNTEGTQKQKEIQSCLTVWDINLPHEVQNLEKHIEVRKELAEK MRRTSVECommunity curation ()Add a publicationFeedback
Protein
Leucine-rich repeat serine/threonine-protein kinase 2
Gene
LRRK2
Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:
Annotation score:5 out of 5
<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>Select a section on the left to see content.
<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni
Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, autophagy, and vesicle trafficking (PubMed:20949042, PubMed:22012985, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:30635421, PubMed:21850687, PubMed:23395371, PubMed:17114044, PubMed:24687852, PubMed:26014385, PubMed:25201882).
Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421).
Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421, PubMed:23395371).
Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392).
Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392).
Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148).
Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371).
Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044).
Plays a role in synaptic vesicle trafficking (PubMed:24687852).
Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882).
Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985).
The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985).
Phosphorylates PRDX3 (PubMed:21850687).
By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718).
Independent of its kinase activity, inhibits the proteosomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385).
In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29212815).
16 Publications<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More...</a></p> Manual assertion based on experiment ini
- Ref.11"The familial Parkinsonism gene LRRK2 regulates neurite process morphology."
MacLeod D., Dowman J., Hammond R., Leete T., Inoue K., Abeliovich A.
Neuron 52:587-593(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699; SER-2019 AND THR-2020, VARIANT MET-1906. - Ref.12"Signal transduction protein array analysis links LRRK2 to Ste20 kinases and PKC zeta that modulate neuronal plasticity."
Zach S., Felk S., Gillardon F.
PLoS ONE 5:E13191-E13191(2010) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION. - Ref.13"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death."
Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, CHARACTERIZATION OF VARIANT PARK8 SER-2019. - Ref.14"Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP."
Gomez-Suaga P., Luzon-Toro B., Churamani D., Zhang L., Bloor-Young D., Patel S., Woodman P.G., Churchill G.C., Hilfiker S.
Hum. Mol. Genet. 21:511-525(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH TPCN2. - Ref.16"RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk."
MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D., MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A., Abeliovich A.
Neuron 77:425-439(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN RETROGRADE TRANSPORT, INTERACTION WITH RAB29 AND VPS35, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 SER-2019, CHARACTERIZATION OF VARIANT MET-1906. - Ref.19"Leucine-rich repeat kinase 2 binds to neuronal vesicles through protein interactions mediated by its C-terminal WD40 domain."
Piccoli G., Onofri F., Cirnaru M.D., Kaiser C.J., Jagtap P., Kastenmuller A., Pischedda F., Marte A., von Zweydorf F., Vogt A., Giesert F., Pan L., Antonucci F., Kiel C., Zhang M., Weinkauf S., Sattler M., Sala C. , Matteoli M., Ueffing M., Gloeckner C.J.
Mol. Cell. Biol. 34:2147-2161(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, ELECTRON MICROSCOPY, WD REPEATS, CHARACTERIZATION OF VARIANT ARG-2385. - Ref.20"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases."
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF ASP-1994. - Ref.21"LRRK2 Promotes Tau Accumulation, Aggregation and Release."
Guerreiro P.S., Gerhardt E., Lopes da Fonseca T., Baehr M., Outeiro T.F., Eckermann K.
Mol. Neurobiol. 53:3124-3135(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH MAPT, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PAR8 SER-2019, MUTAGENESIS OF LYS-1906; ASP-1994 AND ASP-2017. - Ref.22"Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis."
Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O., Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R., Mann M.
Elife 6:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699 AND SER-2019, MUTAGENESIS OF ASP-2017. - Ref.23"Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease."
Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z., Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L., Tan E.K.
Sci. Signal. 10:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP, PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441 AND SER-2019, MUTAGENESIS OF ASP-1994. - Ref.24"Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils."
Fan Y., Howden A.J.M., Sarhan A.R., Lis P., Ito G., Martinez T.N., Brockmann K., Gasser T., Alessi D.R., Sammler E.M.
Biochem. J. 475:23-44(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT PARK8 SER-2019, PHOSPHORYLATION AT SER-935. - Ref.25"A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain."
Dhekne H.S., Yanatori I., Gomez R.C., Tonelli F., Diez F., Schuele B., Steger M., Alessi D.R., Pfeffer S.R.
Elife 7:0-0(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, VARIANTS PARK8 GLY-1441 AND SER-2019. - Ref.26"Rab29 activation of the Parkinson's disease-associated LRRK2 kinase."
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348 AND ASP-2017. - Ref.28"Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase."
Deng J., Lewis P.A., Greggio E., Sluch E., Beilina A., Cookson M.R.
Proc. Natl. Acad. Sci. U.S.A. 105:1499-1504(2008) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1333-1516 IN COMPLEX WITH GDP, FUNCTION, GTPASE ACTIVITY, ACTIVITY REGULATION, SUBUNIT, DOMAIN ROC, MUTAGENESIS OF THR-1343 AND ARG-1398. - Ref.30"Crystal structure of the WD40 domain dimer of LRRK2."
Zhang P., Fan Y., Ru H., Wang L., Magupalli V.G., Taylor S.S., Alessi D.R., Wu H.
Proc. Natl. Acad. Sci. U.S.A. 116:1579-1584(2019) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 2142-2527, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, DOMAIN, PHOSPHORYLATION AT SER-935 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; SER-2019; ASP-2175; TYR-2189; ILE-2356; ARG-2385; MET-2390 AND ILE-2439, MUTAGENESIS OF ASP-2017; LEU-2343; PHE-2344; SER-2345; TYR-2346; HIS-2391; ARG-2394; GLU-2395; MET-2408 AND SER-2409. - Ref.64"Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export."
Cho H.J., Yu J., Xie C., Rudrabhatla P., Chen X., Wu J., Parisiadou L., Liu G., Sun L., Ma B., Ding J., Liu Z., Cai H.
EMBO J. 33:2314-2331(2014) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; CYS-1699 AND SER-2019, CHARACTERIZATION OF VARIANT ARG-2385, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SEC16A, MUTAGENESIS OF LYS-1347 AND ASP-1994.
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi
- ATPEC:2.7.11.1
- Search proteins in UniProtKB for this molecule.
- Search chemical reactions in Rhea for this molecule.
- See the description of this molecule in ChEBI.
- Search proteins in UniProtKB for this molecule.
- Search chemical reactions in Rhea for this molecule.
- Search proteins in UniProtKB for this molecule.
- Search chemical reactions in Rhea for this molecule.
- See the description of this molecule in ChEBI.
- Search proteins in UniProtKB for this molecule.
- Search chemical reactions in Rhea for this molecule.
- See the description of this molecule in ChEBI.
- Search proteins in UniProtKB for this molecule.
- Search chemical reactions in Rhea for this molecule.
Manual assertion based on experiment ini
- Ref.20"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases."
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF ASP-1994. - Ref.22"Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis."
Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O., Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R., Mann M.
Elife 6:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699 AND SER-2019, MUTAGENESIS OF ASP-2017. - Ref.23"Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease."
Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z., Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L., Tan E.K.
Sci. Signal. 10:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP, PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441 AND SER-2019, MUTAGENESIS OF ASP-1994. - Ref.24"Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils."
Fan Y., Howden A.J.M., Sarhan A.R., Lis P., Ito G., Martinez T.N., Brockmann K., Gasser T., Alessi D.R., Sammler E.M.
Biochem. J. 475:23-44(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT PARK8 SER-2019, PHOSPHORYLATION AT SER-935. - Ref.25"A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain."
Dhekne H.S., Yanatori I., Gomez R.C., Tonelli F., Diez F., Schuele B., Steger M., Alessi D.R., Pfeffer S.R.
Elife 7:0-0(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, VARIANTS PARK8 GLY-1441 AND SER-2019. - Ref.26"Rab29 activation of the Parkinson's disease-associated LRRK2 kinase."
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348 AND ASP-2017. - Ref.30"Crystal structure of the WD40 domain dimer of LRRK2."
Zhang P., Fan Y., Ru H., Wang L., Magupalli V.G., Taylor S.S., Alessi D.R., Wu H.
Proc. Natl. Acad. Sci. U.S.A. 116:1579-1584(2019) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 2142-2527, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, DOMAIN, PHOSPHORYLATION AT SER-935 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; SER-2019; ASP-2175; TYR-2189; ILE-2356; ARG-2385; MET-2390 AND ILE-2439, MUTAGENESIS OF ASP-2017; LEU-2343; PHE-2344; SER-2345; TYR-2346; HIS-2391; ARG-2394; GLU-2395; MET-2408 AND SER-2409.
- Search proteins in UniProtKB for this EC number.
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Manual assertion based on experiment ini
- Ref.20"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases."
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF ASP-1994. - Ref.22"Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis."
Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O., Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R., Mann M.
Elife 6:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699 AND SER-2019, MUTAGENESIS OF ASP-2017. - Ref.23"Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease."
Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z., Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L., Tan E.K.
Sci. Signal. 10:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP, PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441 AND SER-2019, MUTAGENESIS OF ASP-1994. - Ref.24"Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils."
Fan Y., Howden A.J.M., Sarhan A.R., Lis P., Ito G., Martinez T.N., Brockmann K., Gasser T., Alessi D.R., Sammler E.M.
Biochem. J. 475:23-44(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT PARK8 SER-2019, PHOSPHORYLATION AT SER-935. - Ref.25"A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain."
Dhekne H.S., Yanatori I., Gomez R.C., Tonelli F., Diez F., Schuele B., Steger M., Alessi D.R., Pfeffer S.R.
Elife 7:0-0(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, VARIANTS PARK8 GLY-1441 AND SER-2019. - Ref.26"Rab29 activation of the Parkinson's disease-associated LRRK2 kinase."
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348 AND ASP-2017. - Ref.30"Crystal structure of the WD40 domain dimer of LRRK2."
Zhang P., Fan Y., Ru H., Wang L., Magupalli V.G., Taylor S.S., Alessi D.R., Wu H.
Proc. Natl. Acad. Sci. U.S.A. 116:1579-1584(2019) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 2142-2527, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, DOMAIN, PHOSPHORYLATION AT SER-935 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; SER-2019; ASP-2175; TYR-2189; ILE-2356; ARG-2385; MET-2390 AND ILE-2439, MUTAGENESIS OF ASP-2017; LEU-2343; PHE-2344; SER-2345; TYR-2346; HIS-2391; ARG-2394; GLU-2395; MET-2408 AND SER-2409.
Source: Rhea- Search for this reaction in UniProtKB.
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- ATPEC:2.7.11.1
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Manual assertion based on experiment ini
- Ref.20"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases."
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF ASP-1994. - Ref.22"Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis."
Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O., Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R., Mann M.
Elife 6:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699 AND SER-2019, MUTAGENESIS OF ASP-2017. - Ref.23"Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease."
Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z., Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L., Tan E.K.
Sci. Signal. 10:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP, PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441 AND SER-2019, MUTAGENESIS OF ASP-1994. - Ref.24"Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils."
Fan Y., Howden A.J.M., Sarhan A.R., Lis P., Ito G., Martinez T.N., Brockmann K., Gasser T., Alessi D.R., Sammler E.M.
Biochem. J. 475:23-44(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT PARK8 SER-2019, PHOSPHORYLATION AT SER-935. - Ref.25"A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain."
Dhekne H.S., Yanatori I., Gomez R.C., Tonelli F., Diez F., Schuele B., Steger M., Alessi D.R., Pfeffer S.R.
Elife 7:0-0(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, VARIANTS PARK8 GLY-1441 AND SER-2019. - Ref.26"Rab29 activation of the Parkinson's disease-associated LRRK2 kinase."
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348 AND ASP-2017.
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Manual assertion based on experiment ini
- Ref.20"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases."
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF ASP-1994. - Ref.22"Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis."
Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O., Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R., Mann M.
Elife 6:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699 AND SER-2019, MUTAGENESIS OF ASP-2017. - Ref.23"Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease."
Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z., Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L., Tan E.K.
Sci. Signal. 10:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP, PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441 AND SER-2019, MUTAGENESIS OF ASP-1994. - Ref.24"Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils."
Fan Y., Howden A.J.M., Sarhan A.R., Lis P., Ito G., Martinez T.N., Brockmann K., Gasser T., Alessi D.R., Sammler E.M.
Biochem. J. 475:23-44(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT PARK8 SER-2019, PHOSPHORYLATION AT SER-935. - Ref.25"A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain."
Dhekne H.S., Yanatori I., Gomez R.C., Tonelli F., Diez F., Schuele B., Steger M., Alessi D.R., Pfeffer S.R.
Elife 7:0-0(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, VARIANTS PARK8 GLY-1441 AND SER-2019. - Ref.26"Rab29 activation of the Parkinson's disease-associated LRRK2 kinase."
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348 AND ASP-2017.
Source: Rhea- Search for this reaction in UniProtKB.
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- GTP
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Manual assertion based on experiment ini
- Ref.20"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases."
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF ASP-1994. - Ref.22"Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis."
Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O., Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R., Mann M.
Elife 6:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699 AND SER-2019, MUTAGENESIS OF ASP-2017. - Ref.23"Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease."
Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z., Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L., Tan E.K.
Sci. Signal. 10:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP, PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441 AND SER-2019, MUTAGENESIS OF ASP-1994. - Ref.26"Rab29 activation of the Parkinson's disease-associated LRRK2 kinase."
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348 AND ASP-2017. - Ref.28"Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase."
Deng J., Lewis P.A., Greggio E., Sluch E., Beilina A., Cookson M.R.
Proc. Natl. Acad. Sci. U.S.A. 105:1499-1504(2008) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1333-1516 IN COMPLEX WITH GDP, FUNCTION, GTPASE ACTIVITY, ACTIVITY REGULATION, SUBUNIT, DOMAIN ROC, MUTAGENESIS OF THR-1343 AND ARG-1398.
Source: Rhea- Search for this reaction in UniProtKB.
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+H+- Search proteins in UniProtKB for this molecule.
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+phosphate- Search proteins in UniProtKB for this molecule.
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zoom
<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori
Mg2+
- Search proteins in UniProtKB for this molecule.
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Manual assertion based on experiment ini
- Ref.20"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases."
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF ASP-1994. - Ref.22"Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis."
Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O., Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R., Mann M.
Elife 6:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699 AND SER-2019, MUTAGENESIS OF ASP-2017. - Ref.23"Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease."
Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z., Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L., Tan E.K.
Sci. Signal. 10:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP, PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441 AND SER-2019, MUTAGENESIS OF ASP-1994.
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi
Kinase activity is regulated by the GTPase activity of the ROC domain (PubMed:29212815, PubMed:18230735). GTP-bound LLRK2 kinase activity is stimulated by RAB29 (PubMed:29212815). Inhibited by small molecule inhibitor MLi-2 (PubMed:26824392, PubMed:29127255).4 Publications
Manual assertion based on experiment ini
- Ref.20"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases."
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF ASP-1994. - Ref.24"Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils."
Fan Y., Howden A.J.M., Sarhan A.R., Lis P., Ito G., Martinez T.N., Brockmann K., Gasser T., Alessi D.R., Sammler E.M.
Biochem. J. 475:23-44(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT PARK8 SER-2019, PHOSPHORYLATION AT SER-935. - Ref.26"Rab29 activation of the Parkinson's disease-associated LRRK2 kinase."
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348 AND ASP-2017. - Ref.28"Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase."
Deng J., Lewis P.A., Greggio E., Sluch E., Beilina A., Cookson M.R.
Proc. Natl. Acad. Sci. U.S.A. 105:1499-1504(2008) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1333-1516 IN COMPLEX WITH GDP, FUNCTION, GTPASE ACTIVITY, ACTIVITY REGULATION, SUBUNIT, DOMAIN ROC, MUTAGENESIS OF THR-1343 AND ARG-1398.
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei | 1906 | ATPPROSITE-ProRule annotation <p>Manual validated information which has been generated by the UniProtKB automatic annotation system.</p> <p><a href="/manual/evidences#ECO:0000255">More...</a></p> Manual assertion according to rulesi | 1 | |
| <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei | 1994 | Proton acceptorPROSITE-ProRule annotation Manual assertion according to rulesi | 1 |
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi | 1341 – 1348 | GTPPROSITE-ProRule annotation Manual assertion according to rulesi 1 PublicationManual assertion based on experiment ini
| 8 | |
| Nucleotide bindingi | 1885 – 1893 | ATPPROSITE-ProRule annotation Manual assertion according to rulesi | 9 | |
| Nucleotide bindingi | 2098 – 2121 | GTPPROSITE-ProRule annotation Manual assertion according to rulesi Add BLAST | 24 | |
| Nucleotide bindingi | 2295 – 2298 | GTPPROSITE-ProRule annotation Manual assertion according to rulesi | 4 |
<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni
- actin binding Source: ParkinsonsUK-UCL
<p>Inferred from Physical Interaction</p>
<p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p>
Inferred from physical interactioni
- "LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool."
Piccoli G., Condliffe S.B., Bauer M., Giesert F., Boldt K., De Astis S., Meixner A., Sarioglu H., Vogt-Weisenhorn D.M., Wurst W., Gloeckner C.J., Matteoli M., Sala C., Ueffing M.
J Neurosci 31:2225-2237(2011) [PubMed] [Europe PMC] [Abstract]
- ATP binding Source: UniProtKB-KW
- beta-catenin destruction complex binding Source: ParkinsonsUK-UCL
<p>Non-traceable Author Statement</p>
<p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#nas">GO evidence code guide</a></p>
Non-traceable author statementi
- "The regulation and deregulation of Wnt signaling by PARK genes in health and disease."
Berwick D.C., Harvey K.
J Mol Cell Biol 6:3-12(2014) [PubMed] [Europe PMC] [Abstract]
- clathrin binding Source: ParkinsonsUK-UCLInferred from physical interactioni
- "LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool."
Piccoli G., Condliffe S.B., Bauer M., Giesert F., Boldt K., De Astis S., Meixner A., Sarioglu H., Vogt-Weisenhorn D.M., Wurst W., Gloeckner C.J., Matteoli M., Sala C., Ueffing M.
J Neurosci 31:2225-2237(2011) [PubMed] [Europe PMC] [Abstract]
- co-receptor binding Source: ParkinsonsUK-UCL
<p>Traceable Author Statement</p>
<p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p>
Traceable author statementi
- "The regulation and deregulation of Wnt signaling by PARK genes in health and disease."
Berwick D.C., Harvey K.
J Mol Cell Biol 6:3-12(2014) [PubMed] [Europe PMC] [Abstract]
- GTPase activator activity Source: UniProtKB
<p>Inferred from Direct Assay</p>
<p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p>
Inferred from direct assayi
- "The R1441C mutation of LRRK2 disrupts GTP hydrolysis."
Lewis P.A., Greggio E., Beilina A., Jain S., Baker A., Cookson M.R.
Biochem Biophys Res Commun 357:668-671(2007) [PubMed] [Europe PMC] [Abstract]
- GTPase activity Source: BHF-UCLInferred from direct assayi
- "ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2."
Haebig K., Gloeckner C.J., Miralles M.G., Gillardon F., Schulte C., Riess O., Ueffing M., Biskup S., Bonin M.
PLoS One 5:e13762-e13762(2010) [PubMed] [Europe PMC] [Abstract]
- GTP binding Source: UniProtKBInferred from direct assayi
- "Kinase activity of mutant LRRK2 mediates neuronal toxicity."
Smith W.W., Pei Z., Jiang H., Dawson V.L., Dawson T.M., Ross C.A.
Nat Neurosci 9:1231-1233(2006) [PubMed] [Europe PMC] [Abstract] - "The R1441C mutation of LRRK2 disrupts GTP hydrolysis."
Lewis P.A., Greggio E., Beilina A., Jain S., Baker A., Cookson M.R.
Biochem Biophys Res Commun 357:668-671(2007) [PubMed] [Europe PMC] [Abstract]
- GTP-dependent protein kinase activity Source: BHF-UCLInferred from direct assayi
- "GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease."
Ito G., Okai T., Fujino G., Takeda K., Ichijo H., Katada T., Iwatsubo T.
Biochemistry 46:1380-1388(2007) [PubMed] [Europe PMC] [Abstract]
- identical protein binding Source: IntActInferred from physical interactioni
- Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020. - Ref.28"Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase."
Deng J., Lewis P.A., Greggio E., Sluch E., Beilina A., Cookson M.R.
Proc. Natl. Acad. Sci. U.S.A. 105:1499-1504(2008) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1333-1516 IN COMPLEX WITH GDP, FUNCTION, GTPASE ACTIVITY, ACTIVITY REGULATION, SUBUNIT, DOMAIN ROC, MUTAGENESIS OF THR-1343 AND ARG-1398. - "The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation."
Greggio E., Zambrano I., Kaganovich A., Beilina A., Taymans J.M., Daniels V., Lewis P., Jain S., Ding J., Syed A., Thomas K.J., Baekelandt V., Cookson M.R.
J Biol Chem 283:16906-16914(2008) [PubMed] [Europe PMC] [Abstract] - "Homo- and heterodimerization of ROCO kinases: LRRK2 kinase inhibition by the LRRK2 ROCO fragment."
Klein C.L., Rovelli G., Springer W., Schall C., Gasser T., Kahle P.J.
J Neurochem 111:703-715(2009) [PubMed] [Europe PMC] [Abstract] - "The Parkinson's disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites."
Greggio E., Taymans J.M., Zhen E.Y., Ryder J., Vancraenenbroeck R., Beilina A., Sun P., Deng J., Jaffe H., Baekelandt V., Merchant K., Cookson M.R.
Biochem Biophys Res Commun 389:449-454(2009) [PubMed] [Europe PMC] [Abstract] - "Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation."
Berger Z., Smith K.A., Lavoie M.J.
Biochemistry 49:5511-5523(2010) [PubMed] [Europe PMC] [Abstract] - "Insight into the mode of action of the LRRK2 Y1699C pathogenic mutant."
Daniels V., Vancraenenbroeck R., Law B.M., Greggio E., Lobbestael E., Gao F., De Maeyer M., Cookson M.R., Harvey K., Baekelandt V., Taymans J.M.
J Neurochem 116:304-315(2011) [PubMed] [Europe PMC] [Abstract] - "GTPase activity and neuronal toxicity of Parkinson's disease-associated LRRK2 is regulated by ArfGAP1."
Stafa K., Trancikova A., Webber P.J., Glauser L., West A.B., Moore D.J.
PLoS Genet 8:e1002526-e1002526(2012) [PubMed] [Europe PMC] [Abstract] - Ref.15"Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers."
Civiero L., Vancraenenbroeck R., Belluzzi E., Beilina A., Lobbestael E., Reyniers L., Gao F., Micetic I., De Maeyer M., Bubacco L., Baekelandt V., Cookson M.R., Greggio E., Taymans J.M.
PLoS ONE 7:E43472-E43472(2012) [PubMed] [Europe PMC] [Abstract]Cited for: SUBUNIT, AUTOPHOSPHORYLATION. - "Dominant-negative effects of LRRK2 heterodimers: a possible mechanism of neurodegeneration in Parkinson's disease caused by LRRK2 I2020T mutation."
Ohta E., Kawakami F., Kubo M., Obata F.
Biochem Biophys Res Commun 430:560-566(2013) [PubMed] [Europe PMC] [Abstract] - "GTPase activity regulates kinase activity and cellular phenotypes of Parkinson's disease-associated LRRK2."
Biosa A., Trancikova A., Civiero L., Glauser L., Bubacco L., Greggio E., Moore D.J.
Hum Mol Genet 22:1140-1156(2013) [PubMed] [Europe PMC] [Abstract] - "A direct interaction between leucine-rich repeat kinase 2 and specific beta-tubulin isoforms regulates tubulin acetylation."
Law B.M., Spain V.A., Leinster V.H., Chia R., Beilina A., Cho H.J., Taymans J.M., Urban M.K., Sancho R.M., Blanca Ramirez M., Biskup S., Baekelandt V., Cai H., Cookson M.R., Berwick D.C., Harvey K.
J Biol Chem 289:895-908(2014) [PubMed] [Europe PMC] [Abstract] - "Parkinson disease-associated mutation R1441H in LRRK2 prolongs the "active state" of its GTPase domain."
Liao J., Wu C.X., Burlak C., Zhang S., Sahm H., Wang M., Zhang Z.Y., Vogel K.W., Federici M., Riddle S.M., Nichols R.J., Liu D., Cookson M.R., Stone T.A., Hoang Q.Q.
Proc Natl Acad Sci U S A 111:4055-4060(2014) [PubMed] [Europe PMC] [Abstract] - "LRRK2 kinase activity regulates synaptic vesicle trafficking and neurotransmitter release through modulation of LRRK2 macro-molecular complex."
Cirnaru M.D., Marte A., Belluzzi E., Russo I., Gabrielli M., Longo F., Arcuri L., Murru L., Bubacco L., Matteoli M., Fedele E., Sala C., Passafaro M., Morari M., Greggio E., Onofri F., Piccoli G.
Front Mol Neurosci 7:49-49(2014) [PubMed] [Europe PMC] [Abstract] - Ref.20"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases."
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF ASP-1994. - "Protective LRRK2 R1398H Variant Enhances GTPase and Wnt Signaling Activity."
Nixon-Abell J., Berwick D.C., Granno S., Spain V.A., Blackstone C., Harvey K.
Front Mol Neurosci 9:18-18(2016) [PubMed] [Europe PMC] [Abstract] - "Structural model of the dimeric Parkinson's protein LRRK2 reveals a compact architecture involving distant interdomain contacts."
Guaitoli G., Raimondi F., Gilsbach B.K., Gomez-Llorente Y., Deyaert E., Renzi F., Li X., Schaffner A., Jagtap P.K., Boldt K., von Zweydorf F., Gotthardt K., Lorimer D.D., Yue Z., Burgin A., Janjic N., Sattler M., Versees W. , Ueffing M., Ubarretxena-Belandia I., Kortholt A., Gloeckner C.J.
Proc Natl Acad Sci U S A 113:E4357-66(2016) [PubMed] [Europe PMC] [Abstract]
- JUN kinase kinase kinase activity Source: BHF-UCLInferred from direct assayi
- "The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro."
Gloeckner C.J., Schumacher A., Boldt K., Ueffing M.
J Neurochem 109:959-968(2009) [PubMed] [Europe PMC] [Abstract]
- kinase activity Source: UniProtKBInferred from direct assayi
- Ref.11"The familial Parkinsonism gene LRRK2 regulates neurite process morphology."
MacLeod D., Dowman J., Hammond R., Leete T., Inoue K., Abeliovich A.
Neuron 52:587-593(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699; SER-2019 AND THR-2020, VARIANT MET-1906.
- magnesium ion binding Source: UniProtKB
<p>Inferred from Mutant Phenotype</p>
<p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p>
Inferred from mutant phenotypei
- Ref.23"Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease."
Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z., Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L., Tan E.K.
Sci. Signal. 10:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP, PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441 AND SER-2019, MUTAGENESIS OF ASP-1994.
- MAP kinase kinase kinase activity Source: BHF-UCLInferred from direct assayi
- "The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro."
Gloeckner C.J., Schumacher A., Boldt K., Ueffing M.
J Neurochem 109:959-968(2009) [PubMed] [Europe PMC] [Abstract]
- microtubule binding Source: ParkinsonsUK-UCLTraceable author statementi
- "The regulation and deregulation of Wnt signaling by PARK genes in health and disease."
Berwick D.C., Harvey K.
J Mol Cell Biol 6:3-12(2014) [PubMed] [Europe PMC] [Abstract]
- peroxidase inhibitor activity Source: ParkinsonsUK-UCLInferred from direct assayi
- Ref.13"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death."
Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, CHARACTERIZATION OF VARIANT PARK8 SER-2019.
- protein homodimerization activity Source: UniProtKBInferred from physical interactioni
- Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020.
- protein kinase A binding Source: ParkinsonsUK-UCLInferred from physical interactioni
- "LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity."
Parisiadou L., Yu J., Sgobio C., Xie C., Liu G., Sun L., Gu X.L., Lin X., Crowley N.A., Lovinger D.M., Cai H.
Nat Neurosci 17:367-376(2014) [PubMed] [Europe PMC] [Abstract]
- protein kinase activity Source: UniProtKBInferred from direct assayi
- Ref.7"Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity."
West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M.
Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441 AND SER-2019. - Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020. - "The R1441C mutation of LRRK2 disrupts GTP hydrolysis."
Lewis P.A., Greggio E., Beilina A., Jain S., Baker A., Cookson M.R.
Biochem Biophys Res Commun 357:668-671(2007) [PubMed] [Europe PMC] [Abstract] - Ref.13"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death."
Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, CHARACTERIZATION OF VARIANT PARK8 SER-2019.
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKBInferred from direct assayi
- "Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity."
West A.B., Moore D.J., Choi C., Andrabi S.A., Li X., Dikeman D., Biskup S., Zhang Z., Lim K.L., Dawson V.L., Dawson T.M.
Hum Mol Genet 16:223-232(2007) [PubMed] [Europe PMC] [Abstract]
- protein serine/threonine phosphatase activity Source: GO_Central
<p>Inferred from Biological aspect of Ancestor</p>
<p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iba">GO evidence code guide</a></p>
Inferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- protein serine kinase activity Source: RHEA
- signaling receptor complex adaptor activity Source: ParkinsonsUK-UCL
<p>Inferred by Curator</p>
<p>Used for cases where an annotation is not supported by any evidence but can be reasonably inferred by a curator from other GO annotations for which evidence<br />is available.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ic">GO evidence code guide</a></p>
Inferred by curatori
- "LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6."
Berwick D.C., Harvey K.
Hum Mol Genet 21:4966-4979(2012) [PubMed] [Europe PMC] [Abstract]
- small GTPase binding Source: BHF-UCLInferred from physical interactioni
- "ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2."
Haebig K., Gloeckner C.J., Miralles M.G., Gillardon F., Schulte C., Riess O., Ueffing M., Biskup S., Bonin M.
PLoS One 5:e13762-e13762(2010) [PubMed] [Europe PMC] [Abstract]
- SNARE binding Source: ParkinsonsUK-UCLInferred from physical interactioni
- "LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool."
Piccoli G., Condliffe S.B., Bauer M., Giesert F., Boldt K., De Astis S., Meixner A., Sarioglu H., Vogt-Weisenhorn D.M., Wurst W., Gloeckner C.J., Matteoli M., Sala C., Ueffing M.
J Neurosci 31:2225-2237(2011) [PubMed] [Europe PMC] [Abstract]
- syntaxin-1 binding Source: ParkinsonsUK-UCLInferred from physical interactioni
- "LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool."
Piccoli G., Condliffe S.B., Bauer M., Giesert F., Boldt K., De Astis S., Meixner A., Sarioglu H., Vogt-Weisenhorn D.M., Wurst W., Gloeckner C.J., Matteoli M., Sala C., Ueffing M.
J Neurosci 31:2225-2237(2011) [PubMed] [Europe PMC] [Abstract]
- transmembrane transporter binding Source: UniProtKBInferred from physical interactioni
- Ref.14"Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP."
Gomez-Suaga P., Luzon-Toro B., Churamani D., Zhang L., Bloor-Young D., Patel S., Woodman P.G., Churchill G.C., Hilfiker S.
Hum. Mol. Genet. 21:511-525(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH TPCN2.
- tubulin binding Source: BHF-UCLInferred from direct assayi
- "LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction."
Lee S., Liu H.P., Lin W.Y., Guo H., Lu B.
J. Neurosci. 30:16959-16969(2010) [PubMed] [Europe PMC] [Abstract]
GO - Biological processi
- autophagy Source: UniProtKB-KW
- calcium-mediated signaling Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition."
Hockey L.N., Kilpatrick B.S., Eden E.R., Lin-Moshier Y., Brailoiu G.C., Brailoiu E., Futter C.E., Schapira A.H., Marchant J.S., Patel S.
J Cell Sci 128:232-238(2015) [PubMed] [Europe PMC] [Abstract]
- canonical Wnt signaling pathway Source: ParkinsonsUK-UCLTraceable author statementi
- "The regulation and deregulation of Wnt signaling by PARK genes in health and disease."
Berwick D.C., Harvey K.
J Mol Cell Biol 6:3-12(2014) [PubMed] [Europe PMC] [Abstract]
- cellular protein localization Source: ParkinsonsUK-UCL
- cellular response to dopamine Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Down-regulation of LRRK2 in control and DAT transfected HEK cells increases manganese-induced oxidative stress and cell toxicity."
Roth J.A., Eichhorn M.
Neurotoxicology 37:100-107(2013) [PubMed] [Europe PMC] [Abstract]
- cellular response to manganese ion Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Down-regulation of LRRK2 in control and DAT transfected HEK cells increases manganese-induced oxidative stress and cell toxicity."
Roth J.A., Eichhorn M.
Neurotoxicology 37:100-107(2013) [PubMed] [Europe PMC] [Abstract]
- cellular response to organic cyclic compound Source: GO_CentralInferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- cellular response to oxidative stress Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress."
Nguyen H.N., Byers B., Cord B., Shcheglovitov A., Byrne J., Gujar P., Kee K., Schule B., Dolmetsch R.E., Langston W., Palmer T.D., Pera R.R.
Cell Stem Cell 8:267-280(2011) [PubMed] [Europe PMC] [Abstract] - "Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans."
Yuan Y., Cao P., Smith M.A., Kramp K., Huang Y., Hisamoto N., Matsumoto K., Hatzoglou M., Jin H., Feng Z.
PLoS One 6:e22354-e22354(2011) [PubMed] [Europe PMC] [Abstract] - "Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease."
Cooper O., Seo H., Andrabi S., Guardia-Laguarta C., Graziotto J., Sundberg M., McLean J.R., Carrillo-Reid L., Xie Z., Osborn T., Hargus G., Deleidi M., Lawson T., Bogetofte H., Perez-Torres E., Clark L., Moskowitz C., Mazzulli J. , Chen L., Volpicelli-Daley L., Romero N., Jiang H., Uitti R.J., Huang Z., Opala G., Scarffe L.A., Dawson V.L., Klein C., Feng J., Ross O.A., Trojanowski J.Q., Lee V.M., Marder K., Surmeier D.J., Wszolek Z.K., Przedborski S., Krainc D., Dawson T.M., Isacson O.
Sci Transl Med 4:141ra90-141ra90(2012) [PubMed] [Europe PMC] [Abstract]
- cellular response to starvation Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation."
Manzoni C., Mamais A., Dihanich S., McGoldrick P., Devine M.J., Zerle J., Kara E., Taanman J.W., Healy D.G., Marti-Masso J.F., Schapira A.H., Plun-Favreau H., Tooze S., Hardy J., Bandopadhyay R., Lewis P.A.
Biochem Biophys Res Commun 441:862-866(2013) [PubMed] [Europe PMC] [Abstract]
- determination of adult lifespan Source: BHF-UCLInferred from mutant phenotypei
- "Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease."
Venderova K., Kabbach G., Abdel-Messih E., Zhang Y., Parks R.J., Imai Y., Gehrke S., Ngsee J., Lavoie M.J., Slack R.S., Rao Y., Zhang Z., Lu B., Haque M.E., Park D.S.
Hum Mol Genet 18:4390-4404(2009) [PubMed] [Europe PMC] [Abstract]
- endocytosis Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on mitochondrial function and endocytosis in a yeast model."
Pereira C., Miguel Martins L., Saraiva L.
Biochim Biophys Acta 1840:2025-2031(2014) [PubMed] [Europe PMC] [Abstract]
- endoplasmic reticulum organization Source: UniProtKBInferred from mutant phenotypei
- Ref.64"Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export."
Cho H.J., Yu J., Xie C., Rudrabhatla P., Chen X., Wu J., Parisiadou L., Liu G., Sun L., Ma B., Ding J., Liu Z., Cai H.
EMBO J. 33:2314-2331(2014) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; CYS-1699 AND SER-2019, CHARACTERIZATION OF VARIANT ARG-2385, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SEC16A, MUTAGENESIS OF LYS-1347 AND ASP-1994.
- excitatory postsynaptic potential Source: ParkinsonsUK-UCL
- exploration behavior Source: BHF-UCLInferred from mutant phenotypei
- "Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice."
Melrose H.L., Dachsel J.C., Behrouz B., Lincoln S.J., Yue M., Hinkle K.M., Kent C.B., Korvatska E., Taylor J.P., Witten L., Liang Y.Q., Beevers J.E., Boules M., Dugger B.N., Serna V.A., Gaukhman A., Yu X., Castanedes-Casey M. , Braithwaite A.T., Ogholikhan S., Yu N., Bass D., Tyndall G., Schellenberg G.D., Dickson D.W., Janus C., Farrer M.J.
Neurobiol Dis 40:503-517(2010) [PubMed] [Europe PMC] [Abstract]
- Golgi organization Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease."
International Parkinson’s Disease Genomics Consortium
Beilina A., Rudenko I.N., Kaganovich A., Civiero L., Chau H., Kalia S.K., Kalia L.V., Lobbestael E., Chia R., Ndukwe K., Ding J., Nalls M.A., Olszewski M., Hauser D.N., Kumaran R., Lozano A.M., Baekelandt V., Greene L.E. , Taymans J.M., Greggio E., Cookson M.R., Nalls M.A., Plagnol V., Hernandez D.G., Sharma M., Sheerin U.M., Saad M., Simon-Sanchez J., Schulte C., Lesage S., Sveinbjornsdottir S., Arepalli S., Barker R., Ben-Shlomo Y., Berendse H.W., Berg D., Bhatia K., de Bie R.M., Biffi A., Bloem B., Bochdanovits Z., Bonin M., Bras J.M., Brockmann K., Brooks J., Burn D.J., Charlesworth G., Chen H., Chinnery P.F., Chong S., Clarke C.E., Cookson M.R., Cooper J.M., Corvol J.C., Counsell C., Damier P., Dartigues J.F., Deloukas P., Deuschl G., Dexter D.T., van Dijk K.D., Dillman A., Durif F., Durr A., Edkins S., Evans J.R., Foltynie T., Gao J., Gardner M., Gibbs J.R., Goate A., Gray E., Guerreiro R., Gustafsson O., Harris C., van Hilten J.J., Hofman A., Hollenbeck A., Holton J., Hu M., Huang X., Huber H., Hudson G., Hunt S.E., Huttenlocher J., Illig T., Jonsson P.V., Lambert J.C., Langford C., Lees A., Lichtner P., Limousin P., Lopez G., Lorenz D., McNeill A., Moorby C., Moore M., Morris H.R., Morrison K.E., Mudanohwo E., O'Sullivan S.S., Pearson J., Perlmutter J.S., Petursson H., Pollak P., Post B., Potter S., Ravina B., Revesz T., Riess O., Rivadeneira F., Rizzu P., Ryten M., Sawcer S., Schapira A., Scheffer H., Shaw K., Shoulson I., Sidransky E., Smith C., Spencer C.C., Stefansson H., Steinberg S., Stockton J.D., Strange A., Talbot K., Tanner C.M., Tashakkori-Ghanbaria A., Tison F., Trabzuni D., Traynor B.J., Uitterlinden A.G., Velseboer D., Vidailhet M., Walker R., van de Warrenburg B., Wickremaratchi M., Williams N., Williams-Gray C.H., Winder-Rhodes S., Stefansson K., Martinez M., Hardy J., Heutink P., Brice A., Gasser T., Singleton A.B., Wood N.W., Arepalli S., Cookson M.R., Dillman A., Ferrucci L., Gibbs J.R., Hernandez D.G., Johnson R., Longo D.L., Majounie E., Nalls M.A., O'Brien R., Singleton A.B., Traynor B.J., Troncoso J., van der Brug M., Zielke H.R., Zonderman A.B.
Proc Natl Acad Sci U S A 111:2626-2631(2014) [PubMed] [Europe PMC] [Abstract]
- GTP metabolic process Source: BHF-UCLInferred from direct assayi
- "ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2."
Haebig K., Gloeckner C.J., Miralles M.G., Gillardon F., Schulte C., Riess O., Ueffing M., Biskup S., Bonin M.
PLoS One 5:e13762-e13762(2010) [PubMed] [Europe PMC] [Abstract]
- intracellular distribution of mitochondria Source: BHF-UCLInferred from mutant phenotypei
- "LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction."
Lee S., Liu H.P., Lin W.Y., Guo H., Lu B.
J. Neurosci. 30:16959-16969(2010) [PubMed] [Europe PMC] [Abstract]
- intracellular signal transduction Source: ParkinsonsUK-UCL
- JNK cascade Source: BHF-UCLInferred from direct assayi
- "The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro."
Gloeckner C.J., Schumacher A., Boldt K., Ueffing M.
J Neurochem 109:959-968(2009) [PubMed] [Europe PMC] [Abstract]
- locomotory exploration behavior Source: Ensembl
- lysosome organization Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Dysregulation of lysosomal morphology by pathogenic LRRK2 is corrected by TPC2 inhibition."
Hockey L.N., Kilpatrick B.S., Eden E.R., Lin-Moshier Y., Brailoiu G.C., Brailoiu E., Futter C.E., Schapira A.H., Marchant J.S., Patel S.
J Cell Sci 128:232-238(2015) [PubMed] [Europe PMC] [Abstract]
- MAPK cascade Source: UniProtKBInferred from direct assayi
- "Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity."
West A.B., Moore D.J., Choi C., Andrabi S.A., Li X., Dikeman D., Biskup S., Zhang Z., Lim K.L., Dawson V.L., Dawson T.M.
Hum Mol Genet 16:223-232(2007) [PubMed] [Europe PMC] [Abstract]
- mitochondrion localization Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease."
Cooper O., Seo H., Andrabi S., Guardia-Laguarta C., Graziotto J., Sundberg M., McLean J.R., Carrillo-Reid L., Xie Z., Osborn T., Hargus G., Deleidi M., Lawson T., Bogetofte H., Perez-Torres E., Clark L., Moskowitz C., Mazzulli J. , Chen L., Volpicelli-Daley L., Romero N., Jiang H., Uitti R.J., Huang Z., Opala G., Scarffe L.A., Dawson V.L., Klein C., Feng J., Ross O.A., Trojanowski J.Q., Lee V.M., Marder K., Surmeier D.J., Wszolek Z.K., Przedborski S., Krainc D., Dawson T.M., Isacson O.
Sci Transl Med 4:141ra90-141ra90(2012) [PubMed] [Europe PMC] [Abstract]
- mitochondrion organization Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease."
Cooper O., Seo H., Andrabi S., Guardia-Laguarta C., Graziotto J., Sundberg M., McLean J.R., Carrillo-Reid L., Xie Z., Osborn T., Hargus G., Deleidi M., Lawson T., Bogetofte H., Perez-Torres E., Clark L., Moskowitz C., Mazzulli J. , Chen L., Volpicelli-Daley L., Romero N., Jiang H., Uitti R.J., Huang Z., Opala G., Scarffe L.A., Dawson V.L., Klein C., Feng J., Ross O.A., Trojanowski J.Q., Lee V.M., Marder K., Surmeier D.J., Wszolek Z.K., Przedborski S., Krainc D., Dawson T.M., Isacson O.
Sci Transl Med 4:141ra90-141ra90(2012) [PubMed] [Europe PMC] [Abstract]
- negative regulation of autophagosome assembly Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Inhibition of LRRK2 kinase activity stimulates macroautophagy."
Manzoni C., Mamais A., Dihanich S., Abeti R., Soutar M.P., Plun-Favreau H., Giunti P., Tooze S.A., Bandopadhyay R., Lewis P.A.
Biochim. Biophys. Acta 1833:2900-2910(2013) [PubMed] [Europe PMC] [Abstract]
- negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans."
Yuan Y., Cao P., Smith M.A., Kramp K., Huang Y., Hisamoto N., Matsumoto K., Hatzoglou M., Jin H., Feng Z.
PLoS One 6:e22354-e22354(2011) [PubMed] [Europe PMC] [Abstract]
- negative regulation of excitatory postsynaptic potential Source: ParkinsonsUK-UCL
- negative regulation of GTPase activity Source: MGIInferred from direct assayi
- "ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal regulation of ArfGAP1 by LRRK2."
Xiong Y., Yuan C., Chen R., Dawson T.M., Dawson V.L.
J Neurosci 32:3877-3886(2012) [PubMed] [Europe PMC] [Abstract]
- negative regulation of hydrogen peroxide-induced cell death Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on mitochondrial function and endocytosis in a yeast model."
Pereira C., Miguel Martins L., Saraiva L.
Biochim Biophys Acta 1840:2025-2031(2014) [PubMed] [Europe PMC] [Abstract]
- negative regulation of late endosome to lysosome transport Source: ParkinsonsUK-UCLTraceable author statementi
- negative regulation of macroautophagy Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model."
Alegre-Abarrategui J., Christian H., Lufino M.M., Mutihac R., Venda L.L., Ansorge O., Wade-Martins R.
Hum Mol Genet 18:4022-4034(2009) [PubMed] [Europe PMC] [Abstract]
- negative regulation of neuron death Source: ParkinsonsUK-UCL
<p>Inferred from Genetic Interaction</p>
<p>Used to describe "traditional" genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p>
<p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#igi">GO evidence code guide</a></p>
Inferred from genetic interactioni
- "Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans."
Yuan Y., Cao P., Smith M.A., Kramp K., Huang Y., Hisamoto N., Matsumoto K., Hatzoglou M., Jin H., Feng Z.
PLoS One 6:e22354-e22354(2011) [PubMed] [Europe PMC] [Abstract]
- negative regulation of neuron projection development Source: Ensembl
- negative regulation of protein binding Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- negative regulation of protein phosphorylation Source: ParkinsonsUK-UCL
- negative regulation of protein processing Source: ParkinsonsUK-UCLInferred from direct assayi
- "Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system."
Cui J., Yu M., Niu J., Yue Z., Xu Z.
Biosci Rep 31:429-437(2011) [PubMed] [Europe PMC] [Abstract]
- negative regulation of protein processing involved in protein targeting to mitochondrion Source: ParkinsonsUK-UCLInferred by curatori
- "Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system."
Cui J., Yu M., Niu J., Yue Z., Xu Z.
Biosci Rep 31:429-437(2011) [PubMed] [Europe PMC] [Abstract]
- negative regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCLInferred from direct assayi
- "Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system."
Cui J., Yu M., Niu J., Yue Z., Xu Z.
Biosci Rep 31:429-437(2011) [PubMed] [Europe PMC] [Abstract]
- negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation Source: ParkinsonsUK-UCLInferred from direct assayi
- Ref.13"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death."
Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, CHARACTERIZATION OF VARIANT PARK8 SER-2019.
- neuromuscular junction development Source: BHF-UCLInferred from mutant phenotypei
- "LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction."
Lee S., Liu H.P., Lin W.Y., Guo H., Lu B.
J. Neurosci. 30:16959-16969(2010) [PubMed] [Europe PMC] [Abstract]
- neuron death Source: BHF-UCLInferred from mutant phenotypei
- "Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease."
Venderova K., Kabbach G., Abdel-Messih E., Zhang Y., Parks R.J., Imai Y., Gehrke S., Ngsee J., Lavoie M.J., Slack R.S., Rao Y., Zhang Z., Lu B., Haque M.E., Park D.S.
Hum Mol Genet 18:4390-4404(2009) [PubMed] [Europe PMC] [Abstract]
- neuron projection arborization Source: Ensembl
- neuron projection morphogenesis Source: UniProtKBInferred from mutant phenotypei
- Ref.11"The familial Parkinsonism gene LRRK2 regulates neurite process morphology."
MacLeod D., Dowman J., Hammond R., Leete T., Inoue K., Abeliovich A.
Neuron 52:587-593(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699; SER-2019 AND THR-2020, VARIANT MET-1906.
- olfactory bulb development Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice."
Winner B., Melrose H.L., Zhao C., Hinkle K.M., Yue M., Kent C., Braithwaite A.T., Ogholikhan S., Aigner R., Winkler J., Farrer M.J., Gage F.H.
Neurobiol Dis 41:706-716(2011) [PubMed] [Europe PMC] [Abstract]
- peptidyl-serine phosphorylation Source: BHF-UCLInferred from direct assayi
- "Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinson disease implications."
Qing H., Wong W., McGeer E.G., McGeer P.L.
Biochem Biophys Res Commun 387:149-152(2009) [PubMed] [Europe PMC] [Abstract]
- peptidyl-threonine phosphorylation Source: BHF-UCLInferred from direct assayi
- "ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2."
Haebig K., Gloeckner C.J., Miralles M.G., Gillardon F., Schulte C., Riess O., Ueffing M., Biskup S., Bonin M.
PLoS One 5:e13762-e13762(2010) [PubMed] [Europe PMC] [Abstract]
- phosphorylation Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Inhibition of LRRK2 kinase activity stimulates macroautophagy."
Manzoni C., Mamais A., Dihanich S., Abeti R., Soutar M.P., Plun-Favreau H., Giunti P., Tooze S.A., Bandopadhyay R., Lewis P.A.
Biochim. Biophys. Acta 1833:2900-2910(2013) [PubMed] [Europe PMC] [Abstract]
- positive regulation of autophagy Source: UniProtKBInferred from mutant phenotypei
- Ref.14"Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP."
Gomez-Suaga P., Luzon-Toro B., Churamani D., Zhang L., Bloor-Young D., Patel S., Woodman P.G., Churchill G.C., Hilfiker S.
Hum. Mol. Genet. 21:511-525(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH TPCN2.
- positive regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCLInferred from genetic interactioni
- "LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6."
Berwick D.C., Harvey K.
Hum Mol Genet 21:4966-4979(2012) [PubMed] [Europe PMC] [Abstract]
- positive regulation of dopamine receptor signaling pathway Source: BHF-UCLInferred from mutant phenotypei
- "Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice."
Melrose H.L., Dachsel J.C., Behrouz B., Lincoln S.J., Yue M., Hinkle K.M., Kent C.B., Korvatska E., Taylor J.P., Witten L., Liang Y.Q., Beevers J.E., Boules M., Dugger B.N., Serna V.A., Gaukhman A., Yu X., Castanedes-Casey M. , Braithwaite A.T., Ogholikhan S., Yu N., Bass D., Tyndall G., Schellenberg G.D., Dickson D.W., Janus C., Farrer M.J.
Neurobiol Dis 40:503-517(2010) [PubMed] [Europe PMC] [Abstract]
- positive regulation of histone deacetylase activity Source: Ensembl
- positive regulation of MAP kinase activity Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Dysregulated LRRK2 signaling in response to endoplasmic reticulum stress leads to dopaminergic neuron degeneration in C. elegans."
Yuan Y., Cao P., Smith M.A., Kramp K., Huang Y., Hisamoto N., Matsumoto K., Hatzoglou M., Jin H., Feng Z.
PLoS One 6:e22354-e22354(2011) [PubMed] [Europe PMC] [Abstract]
- positive regulation of microglial cell activation Source: Ensembl
- positive regulation of nitric-oxide synthase biosynthetic process Source: Ensembl
- positive regulation of programmed cell death Source: UniProtKBInferred from direct assayi
- "Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity."
West A.B., Moore D.J., Choi C., Andrabi S.A., Li X., Dikeman D., Biskup S., Zhang Z., Lim K.L., Dawson V.L., Dawson T.M.
Hum Mol Genet 16:223-232(2007) [PubMed] [Europe PMC] [Abstract]
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
- positive regulation of protein autoubiquitination Source: ParkinsonsUK-UCLInferred from direct assayi
- Ref.8"Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant LRRK2 induces neuronal degeneration."
Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L., Dawson T.M., Ross C.A.
Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PRKN.
- positive regulation of protein binding Source: ParkinsonsUK-UCLInferred from direct assayi
- "Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system."
Cui J., Yu M., Niu J., Yue Z., Xu Z.
Biosci Rep 31:429-437(2011) [PubMed] [Europe PMC] [Abstract]
- positive regulation of protein kinase activity Source: BHF-UCLInferred from direct assayi
- "The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro."
Gloeckner C.J., Schumacher A., Boldt K., Ueffing M.
J Neurochem 109:959-968(2009) [PubMed] [Europe PMC] [Abstract]
- positive regulation of protein phosphorylation Source: ParkinsonsUK-UCLInferred from direct assayi
- Ref.14"Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP."
Gomez-Suaga P., Luzon-Toro B., Churamani D., Zhang L., Bloor-Young D., Patel S., Woodman P.G., Churchill G.C., Hilfiker S.
Hum. Mol. Genet. 21:511-525(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH TPCN2.
- positive regulation of protein ubiquitination Source: UniProtKBInferred from direct assayi
- Ref.8"Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant LRRK2 induces neuronal degeneration."
Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L., Dawson T.M., Ross C.A.
Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PRKN.
- positive regulation of synaptic vesicle endocytosis Source: Ensembl
- positive regulation of tumor necrosis factor production Source: Ensembl
- protein autophosphorylation Source: UniProtKBInferred from direct assayi
- Ref.7"Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity."
West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M.
Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441 AND SER-2019. - Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020. - "Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity."
West A.B., Moore D.J., Choi C., Andrabi S.A., Li X., Dikeman D., Biskup S., Zhang Z., Lim K.L., Dawson V.L., Dawson T.M.
Hum Mol Genet 16:223-232(2007) [PubMed] [Europe PMC] [Abstract] - "The R1441C mutation of LRRK2 disrupts GTP hydrolysis."
Lewis P.A., Greggio E., Beilina A., Jain S., Baker A., Cookson M.R.
Biochem Biophys Res Commun 357:668-671(2007) [PubMed] [Europe PMC] [Abstract]
- protein import into nucleus Source: Ensembl
- protein localization to endoplasmic reticulum exit site Source: UniProtKBInferred from mutant phenotypei
- Ref.64"Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export."
Cho H.J., Yu J., Xie C., Rudrabhatla P., Chen X., Wu J., Parisiadou L., Liu G., Sun L., Ma B., Ding J., Liu Z., Cai H.
EMBO J. 33:2314-2331(2014) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; CYS-1699 AND SER-2019, CHARACTERIZATION OF VARIANT ARG-2385, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SEC16A, MUTAGENESIS OF LYS-1347 AND ASP-1994.
- protein localization to mitochondrion Source: ParkinsonsUK-UCLTraceable author statementi
- "The role of oxidative stress in Parkinson's disease."
Dias V., Junn E., Mouradian M.M.
J Parkinsons Dis 3:461-491(2013) [PubMed] [Europe PMC] [Abstract]
- protein phosphorylation Source: ParkinsonsUK-UCLInferred from direct assayi
- "Phosphorylation of LRRK2 by casein kinase 1alpha regulates trans-Golgi clustering via differential interaction with ARHGEF7."
Chia R., Haddock S., Beilina A., Rudenko I.N., Mamais A., Kaganovich A., Li Y., Kumaran R., Nalls M.A., Cookson M.R.
Nat Commun 5:5827-5827(2014) [PubMed] [Europe PMC] [Abstract]
- reactive oxygen species metabolic process Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "LRRK2, but not pathogenic mutants, protects against H2O2 stress depending on mitochondrial function and endocytosis in a yeast model."
Pereira C., Miguel Martins L., Saraiva L.
Biochim Biophys Acta 1840:2025-2031(2014) [PubMed] [Europe PMC] [Abstract]
- regulation of autophagy Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation."
Manzoni C., Mamais A., Dihanich S., McGoldrick P., Devine M.J., Zerle J., Kara E., Taanman J.W., Healy D.G., Marti-Masso J.F., Schapira A.H., Plun-Favreau H., Tooze S., Hardy J., Bandopadhyay R., Lewis P.A.
Biochem Biophys Res Commun 441:862-866(2013) [PubMed] [Europe PMC] [Abstract]
- regulation of branching morphogenesis of a nerve Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice."
Winner B., Melrose H.L., Zhao C., Hinkle K.M., Yue M., Kent C., Braithwaite A.T., Ogholikhan S., Aigner R., Winkler J., Farrer M.J., Gage F.H.
Neurobiol Dis 41:706-716(2011) [PubMed] [Europe PMC] [Abstract]
- regulation of CAMKK-AMPK signaling cascade Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- Ref.14"Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP."
Gomez-Suaga P., Luzon-Toro B., Churamani D., Zhang L., Bloor-Young D., Patel S., Woodman P.G., Churchill G.C., Hilfiker S.
Hum. Mol. Genet. 21:511-525(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH TPCN2.
- regulation of canonical Wnt signaling pathway Source: GO_CentralInferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- regulation of dendritic spine morphogenesis Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice."
Winner B., Melrose H.L., Zhao C., Hinkle K.M., Yue M., Kent C., Braithwaite A.T., Ogholikhan S., Aigner R., Winkler J., Farrer M.J., Gage F.H.
Neurobiol Dis 41:706-716(2011) [PubMed] [Europe PMC] [Abstract]
- regulation of dopamine receptor signaling pathway Source: ParkinsonsUK-UCL
- regulation of ER to Golgi vesicle-mediated transport Source: UniProtKB
- regulation of kidney size Source: BHF-UCL
- regulation of locomotion Source: BHF-UCLInferred from mutant phenotypei
- "Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease."
Venderova K., Kabbach G., Abdel-Messih E., Zhang Y., Parks R.J., Imai Y., Gehrke S., Ngsee J., Lavoie M.J., Slack R.S., Rao Y., Zhang Z., Lu B., Haque M.E., Park D.S.
Hum Mol Genet 18:4390-4404(2009) [PubMed] [Europe PMC] [Abstract]
- regulation of lysosomal lumen pH Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- Ref.14"Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP."
Gomez-Suaga P., Luzon-Toro B., Churamani D., Zhang L., Bloor-Young D., Patel S., Woodman P.G., Churchill G.C., Hilfiker S.
Hum. Mol. Genet. 21:511-525(2012) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH TPCN2.
- regulation of membrane potential Source: BHF-UCLInferred from mutant phenotypei
- "LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction."
Lee S., Liu H.P., Lin W.Y., Guo H., Lu B.
J. Neurosci. 30:16959-16969(2010) [PubMed] [Europe PMC] [Abstract]
- regulation of mitochondrial depolarization Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization."
Papkovskaia T.D., Chau K.Y., Inesta-Vaquera F., Papkovsky D.B., Healy D.G., Nishio K., Staddon J., Duchen M.R., Hardy J., Schapira A.H., Cooper J.M.
Hum Mol Genet 21:4201-4213(2012) [PubMed] [Europe PMC] [Abstract]
- regulation of mitochondrial fission Source: ParkinsonsUK-UCLTraceable author statementi
- "The role of oxidative stress in Parkinson's disease."
Dias V., Junn E., Mouradian M.M.
J Parkinsons Dis 3:461-491(2013) [PubMed] [Europe PMC] [Abstract]
- regulation of neuroblast proliferation Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice."
Winner B., Melrose H.L., Zhao C., Hinkle K.M., Yue M., Kent C., Braithwaite A.T., Ogholikhan S., Aigner R., Winkler J., Farrer M.J., Gage F.H.
Neurobiol Dis 41:706-716(2011) [PubMed] [Europe PMC] [Abstract]
- regulation of neuron death Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies."
Skibinski G., Nakamura K., Cookson M.R., Finkbeiner S.
J Neurosci 34:418-433(2014) [PubMed] [Europe PMC] [Abstract]
- regulation of neuron maturation Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice."
Winner B., Melrose H.L., Zhao C., Hinkle K.M., Yue M., Kent C., Braithwaite A.T., Ogholikhan S., Aigner R., Winkler J., Farrer M.J., Gage F.H.
Neurobiol Dis 41:706-716(2011) [PubMed] [Europe PMC] [Abstract]
- regulation of protein kinase A signaling Source: ParkinsonsUK-UCL
- regulation of protein stability Source: UniProtKBInferred from mutant phenotypei
- Ref.21"LRRK2 Promotes Tau Accumulation, Aggregation and Release."
Guerreiro P.S., Gerhardt E., Lopes da Fonseca T., Baehr M., Outeiro T.F., Eckermann K.
Mol. Neurobiol. 53:3124-3135(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH MAPT, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PAR8 SER-2019, MUTAGENESIS OF LYS-1906; ASP-1994 AND ASP-2017.
- regulation of retrograde transport, endosome to Golgi Source: ParkinsonsUK-UCLInferred from genetic interactioni
- Ref.16"RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk."
MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D., MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A., Abeliovich A.
Neuron 77:425-439(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN RETROGRADE TRANSPORT, INTERACTION WITH RAB29 AND VPS35, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 SER-2019, CHARACTERIZATION OF VARIANT MET-1906.
- regulation of synaptic transmission, glutamatergic Source: ParkinsonsUK-UCL
- regulation of synaptic vesicle exocytosis Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- regulation of synaptic vesicle transport Source: ParkinsonsUK-UCL
- response to oxidative stress Source: BHF-UCLInferred from mutant phenotypei
- "Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease."
Venderova K., Kabbach G., Abdel-Messih E., Zhang Y., Parks R.J., Imai Y., Gehrke S., Ngsee J., Lavoie M.J., Slack R.S., Rao Y., Zhang Z., Lu B., Haque M.E., Park D.S.
Hum Mol Genet 18:4390-4404(2009) [PubMed] [Europe PMC] [Abstract]
- signal transduction Source: GO_CentralInferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- spermatogenesis Source: Ensembl
- striatum development Source: Ensembl
- tangential migration from the subventricular zone to the olfactory bulb Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Adult neurogenesis and neurite outgrowth are impaired in LRRK2 G2019S mice."
Winner B., Melrose H.L., Zhao C., Hinkle K.M., Yue M., Kent C., Braithwaite A.T., Ogholikhan S., Aigner R., Winkler J., Farrer M.J., Gage F.H.
Neurobiol Dis 41:706-716(2011) [PubMed] [Europe PMC] [Abstract]
- Wnt signalosome assembly Source: ParkinsonsUK-UCLInferred from physical interactioni
- "LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6."
Berwick D.C., Harvey K.
Hum Mol Genet 21:4966-4979(2012) [PubMed] [Europe PMC] [Abstract]
<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi
| Molecular function | GTPase activation, Hydrolase, Kinase, Serine/threonine-protein kinase, Transferase |
| Biological process | Autophagy, Differentiation |
| Ligand | ATP-binding, GTP-binding, Nucleotide-binding |
Enzyme and pathway databases
Pathway Commons web resource for biological pathway data More...PathwayCommonsi | Q5S007 |
Reactome - a knowledgebase of biological pathways and processes More...Reactomei | R-HSA-8857538, PTK6 promotes HIF1A stabilization |
SignaLink: a signaling pathway resource with multi-layered regulatory networks More...SignaLinki | Q5S007 |
SIGNOR Signaling Network Open Resource More...SIGNORi | Q5S007 |
<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi | Recommended name: Leucine-rich repeat serine/threonine-protein kinase 2 (EC:2.7.11.1
Manual assertion based on experiment ini
Manual assertion based on experiment ini
Alternative name(s): Dardarin |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi | Name:LRRK2 Synonyms:PARK8 |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>Organismi | Homo sapiens (Human) |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri | 9606 [NCBI] |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineagei | cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi |
|
Organism-specific databases
Human Gene Nomenclature Database More...HGNCi | HGNC:18618, LRRK2 |
Online Mendelian Inheritance in Man (OMIM) More...MIMi | 609007, gene |
neXtProt; the human protein knowledge platform More...neXtProti | NX_Q5S007 |
Eukaryotic Pathogen, Vector and Host Database Resources More...VEuPathDBi | HostDB:ENSG00000188906 |
<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi
Lysosome
- Lysosome 1 Publication
Manual assertion based on experiment ini
- Ref.10"Localization of LRRK2 to membranous and vesicular structures in mammalian brain."
Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A., Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C., Torp R., Ottersen O.P., Dawson T.M., Dawson V.L.
Ann. Neurol. 60:557-569(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
- Lysosome 1 Publication
Endoplasmic reticulum
- Endoplasmic reticulum membrane 2 Publications
Manual assertion based on experiment ini
- Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020. - Ref.64"Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export."
Cho H.J., Yu J., Xie C., Rudrabhatla P., Chen X., Wu J., Parisiadou L., Liu G., Sun L., Ma B., Ding J., Liu Z., Cai H.
EMBO J. 33:2314-2331(2014) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; CYS-1699 AND SER-2019, CHARACTERIZATION OF VARIANT ARG-2385, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SEC16A, MUTAGENESIS OF LYS-1347 AND ASP-1994.
Manual assertion based on experiment ini
- Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020.
- Endoplasmic reticulum membrane 2 Publications
Mitochondrion
- Mitochondrion outer membrane 4 Publications
Manual assertion based on experiment ini
- Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020. - Ref.7"Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity."
West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M.
Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441 AND SER-2019. - Ref.10"Localization of LRRK2 to membranous and vesicular structures in mammalian brain."
Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A., Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C., Torp R., Ottersen O.P., Dawson T.M., Dawson V.L.
Ann. Neurol. 60:557-569(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY. - Ref.26"Rab29 activation of the Parkinson's disease-associated LRRK2 kinase."
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348 AND ASP-2017.
Manual assertion based on experiment ini
- Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020. - Ref.7"Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity."
West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M.
Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441 AND SER-2019. - Ref.10"Localization of LRRK2 to membranous and vesicular structures in mammalian brain."
Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A., Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C., Torp R., Ottersen O.P., Dawson T.M., Dawson V.L.
Ann. Neurol. 60:557-569(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY. - Ref.26"Rab29 activation of the Parkinson's disease-associated LRRK2 kinase."
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348 AND ASP-2017.
- Mitochondrion outer membrane 4 Publications
Endosome
- Endosome By similarity
<p>Manually curated information which has been propagated from a related experimentally characterized protein.</p> <p><a href="/manual/evidences#ECO:0000250">More...</a></p> Manual assertion inferred from sequence similarity toi
- Endosome By similarity
Golgi apparatus
- Golgi apparatus membrane 2 Publications
Manual assertion based on experiment ini
- Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020. - Ref.16"RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk."
MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D., MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A., Abeliovich A.
Neuron 77:425-439(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN RETROGRADE TRANSPORT, INTERACTION WITH RAB29 AND VPS35, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 SER-2019, CHARACTERIZATION OF VARIANT MET-1906.
Manual assertion based on experiment ini
- Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020.
- Golgi apparatus membrane 2 Publications
Other locations
- Cytoplasmic vesicle 3 Publications
Manual assertion based on experiment ini
- Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020. - Ref.8"Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant LRRK2 induces neuronal degeneration."
Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L., Dawson T.M., Ross C.A.
Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PRKN. - Ref.21"LRRK2 Promotes Tau Accumulation, Aggregation and Release."
Guerreiro P.S., Gerhardt E., Lopes da Fonseca T., Baehr M., Outeiro T.F., Eckermann K.
Mol. Neurobiol. 53:3124-3135(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH MAPT, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PAR8 SER-2019, MUTAGENESIS OF LYS-1906; ASP-1994 AND ASP-2017.
- Perikaryon 1 Publication
Manual assertion based on experiment ini
- Ref.10"Localization of LRRK2 to membranous and vesicular structures in mammalian brain."
Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A., Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C., Torp R., Ottersen O.P., Dawson T.M., Dawson V.L.
Ann. Neurol. 60:557-569(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
- axon 1 Publication
Manual assertion based on experiment ini
- Ref.10"Localization of LRRK2 to membranous and vesicular structures in mammalian brain."
Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A., Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C., Torp R., Ottersen O.P., Dawson T.M., Dawson V.L.
Ann. Neurol. 60:557-569(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
- dendrite 2 Publications
Manual assertion based on experiment ini
- Ref.10"Localization of LRRK2 to membranous and vesicular structures in mammalian brain."
Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A., Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C., Torp R., Ottersen O.P., Dawson T.M., Dawson V.L.
Ann. Neurol. 60:557-569(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY. - Ref.13"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death."
Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, CHARACTERIZATION OF VARIANT PARK8 SER-2019.
- synaptic vesicle membrane 1 Publication
Manual assertion based on experiment ini
- Ref.19"Leucine-rich repeat kinase 2 binds to neuronal vesicles through protein interactions mediated by its C-terminal WD40 domain."
Piccoli G., Onofri F., Cirnaru M.D., Kaiser C.J., Jagtap P., Kastenmuller A., Pischedda F., Marte A., von Zweydorf F., Vogt A., Giesert F., Pan L., Antonucci F., Kiel C., Zhang M., Weinkauf S., Sattler M., Sala C. , Matteoli M., Ueffing M., Gloeckner C.J.
Mol. Cell. Biol. 34:2147-2161(2014) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, ELECTRON MICROSCOPY, WD REPEATS, CHARACTERIZATION OF VARIANT ARG-2385.
Note: Colocalized with RAB29 along tubular structures emerging from Golgi apparatus (PubMed:23395371). Localizes to endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER) (PubMed:25201882).2 Publications- Cytoplasmic vesicle 3 Publications
- Ref.16"RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk."
MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D., MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A., Abeliovich A.
Neuron 77:425-439(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN RETROGRADE TRANSPORT, INTERACTION WITH RAB29 AND VPS35, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 SER-2019, CHARACTERIZATION OF VARIANT MET-1906. - Ref.64"Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export."
Cho H.J., Yu J., Xie C., Rudrabhatla P., Chen X., Wu J., Parisiadou L., Liu G., Sun L., Ma B., Ding J., Liu Z., Cai H.
EMBO J. 33:2314-2331(2014) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; CYS-1699 AND SER-2019, CHARACTERIZATION OF VARIANT ARG-2385, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SEC16A, MUTAGENESIS OF LYS-1347 AND ASP-1994.
Manual assertion based on experiment ini
Cytosol
- cytosol Source: ParkinsonsUK-UCLInferred from direct assayi
- Ref.13"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death."
Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, CHARACTERIZATION OF VARIANT PARK8 SER-2019. - "G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization."
Papkovskaia T.D., Chau K.Y., Inesta-Vaquera F., Papkovsky D.B., Healy D.G., Nishio K., Staddon J., Duchen M.R., Hardy J., Schapira A.H., Cooper J.M.
Hum Mol Genet 21:4201-4213(2012) [PubMed] [Europe PMC] [Abstract] - "LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6."
Berwick D.C., Harvey K.
Hum Mol Genet 21:4966-4979(2012) [PubMed] [Europe PMC] [Abstract] - "Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies."
Skibinski G., Nakamura K., Cookson M.R., Finkbeiner S.
J Neurosci 34:418-433(2014) [PubMed] [Europe PMC] [Abstract]
- presynaptic cytosol Source: Ensembl
- cytosol Source: ParkinsonsUK-UCLInferred from direct assayi
Endoplasmic reticulum
- endoplasmic reticulum Source: ParkinsonsUK-UCLInferred from direct assayi
- "LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model."
Alegre-Abarrategui J., Christian H., Lufino M.M., Mutihac R., Venda L.L., Ansorge O., Wade-Martins R.
Hum Mol Genet 18:4022-4034(2009) [PubMed] [Europe PMC] [Abstract]
- endoplasmic reticulum exit site Source: UniProtKBInferred from direct assayi
- Ref.64"Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export."
Cho H.J., Yu J., Xie C., Rudrabhatla P., Chen X., Wu J., Parisiadou L., Liu G., Sun L., Ma B., Ding J., Liu Z., Cai H.
EMBO J. 33:2314-2331(2014) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; CYS-1699 AND SER-2019, CHARACTERIZATION OF VARIANT ARG-2385, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SEC16A, MUTAGENESIS OF LYS-1347 AND ASP-1994.
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
- endoplasmic reticulum Source: ParkinsonsUK-UCLInferred from direct assayi
Endosome
- endosome Source: UniProtKB
- multivesicular body, internal vesicle Source: ParkinsonsUK-UCLInferred from direct assayi
- "LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model."
Alegre-Abarrategui J., Christian H., Lufino M.M., Mutihac R., Venda L.L., Ansorge O., Wade-Martins R.
Hum Mol Genet 18:4022-4034(2009) [PubMed] [Europe PMC] [Abstract]
Extracellular region or secreted
- extracellular exosome Source: UniProtKBInferred from high throughput direct assayi
- "Large-scale proteomics and phosphoproteomics of urinary exosomes."
Gonzales P.A., Pisitkun T., Hoffert J.D., Tchapyjnikov D., Star R.A., Kleta R., Wang N.S., Knepper M.A.
J Am Soc Nephrol 20:363-379(2009) [PubMed] [Europe PMC] [Abstract]
- extracellular space Source: UniProtKBInferred from high throughput direct assayi
- "Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach."
Bohm D., Keller K., Pieter J., Boehm N., Wolters D., Siggelkow W., Lebrecht A., Schmidt M., Kolbl H., Pfeiffer N., Grus F.H.
Oncol Rep 28:429-438(2012) [PubMed] [Europe PMC] [Abstract]
- extracellular exosome Source: UniProtKBInferred from high throughput direct assayi
Golgi apparatus
- Golgi apparatus Source: ParkinsonsUK-UCLInferred from direct assayi
- Ref.16"RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk."
MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D., MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A., Abeliovich A.
Neuron 77:425-439(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN RETROGRADE TRANSPORT, INTERACTION WITH RAB29 AND VPS35, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 SER-2019, CHARACTERIZATION OF VARIANT MET-1906.
- Golgi membrane Source: UniProtKB-SubCell
- trans-Golgi network Source: Ensembl
- Golgi apparatus Source: ParkinsonsUK-UCLInferred from direct assayi
Lysosome
- autolysosome Source: ParkinsonsUK-UCLInferred from direct assayi
- "LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model."
Alegre-Abarrategui J., Christian H., Lufino M.M., Mutihac R., Venda L.L., Ansorge O., Wade-Martins R.
Hum Mol Genet 18:4022-4034(2009) [PubMed] [Europe PMC] [Abstract]
- lysosome Source: UniProtKB
- autolysosome Source: ParkinsonsUK-UCLInferred from direct assayi
Mitochondrion
- cytoplasmic side of mitochondrial outer membrane Source: UniProtKBInferred from direct assayi
- Ref.7"Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity."
West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M.
Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441 AND SER-2019.
- mitochondrial inner membrane Source: UniProtKB
- mitochondrial matrix Source: UniProtKB
- mitochondrial membrane Source: ParkinsonsUK-UCLInferred from direct assayi
- "G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization."
Papkovskaia T.D., Chau K.Y., Inesta-Vaquera F., Papkovsky D.B., Healy D.G., Nishio K., Staddon J., Duchen M.R., Hardy J., Schapira A.H., Cooper J.M.
Hum Mol Genet 21:4201-4213(2012) [PubMed] [Europe PMC] [Abstract]
- mitochondrial outer membrane Source: UniProtKB
- mitochondrion Source: UniProtKBInferred from direct assayi
- Ref.13"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death."
Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, CHARACTERIZATION OF VARIANT PARK8 SER-2019.
- cytoplasmic side of mitochondrial outer membrane Source: UniProtKBInferred from direct assayi
Plasma Membrane
- caveola neck Source: ParkinsonsUK-UCLInferred from direct assayi
- "LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model."
Alegre-Abarrategui J., Christian H., Lufino M.M., Mutihac R., Venda L.L., Ansorge O., Wade-Martins R.
Hum Mol Genet 18:4022-4034(2009) [PubMed] [Europe PMC] [Abstract]
- plasma membrane Source: ParkinsonsUK-UCLInferred from direct assayi
- "LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6."
Berwick D.C., Harvey K.
Hum Mol Genet 21:4966-4979(2012) [PubMed] [Europe PMC] [Abstract]
- caveola neck Source: ParkinsonsUK-UCLInferred from direct assayi
Other locations
- amphisome Source: ParkinsonsUK-UCLInferred from direct assayi
- "LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model."
Alegre-Abarrategui J., Christian H., Lufino M.M., Mutihac R., Venda L.L., Ansorge O., Wade-Martins R.
Hum Mol Genet 18:4022-4034(2009) [PubMed] [Europe PMC] [Abstract]
- axon Source: UniProtKBInferred from direct assayi
- Ref.10"Localization of LRRK2 to membranous and vesicular structures in mammalian brain."
Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A., Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C., Torp R., Ottersen O.P., Dawson T.M., Dawson V.L.
Ann. Neurol. 60:557-569(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
- cytoplasm Source: UniProtKBInferred from direct assayi
- Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020. - Ref.8"Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant LRRK2 induces neuronal degeneration."
Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L., Dawson T.M., Ross C.A.
Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PRKN.
- cytoplasmic vesicle Source: UniProtKB
- dendrite Source: UniProtKBInferred from direct assayi
- Ref.10"Localization of LRRK2 to membranous and vesicular structures in mammalian brain."
Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A., Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C., Torp R., Ottersen O.P., Dawson T.M., Dawson V.L.
Ann. Neurol. 60:557-569(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
- dendrite cytoplasm Source: BHF-UCLInferred from direct assayi
- "LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study."
Sharma S., Bandopadhyay R., Lashley T., Renton A.E., Kingsbury A.E., Kumaran R., Kallis C., Vilarino-Guell C., O'Sullivan S.S., Lees A.J., Revesz T., Wood N.W., Holton J.L.
Neuropathol Appl Neurobiol 37:777-790(2011) [PubMed] [Europe PMC] [Abstract]
- glutamatergic synapse Source: Ensembl
- Golgi-associated vesicle Source: ParkinsonsUK-UCLInferred from direct assayi
- "Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease."
International Parkinson’s Disease Genomics Consortium
Beilina A., Rudenko I.N., Kaganovich A., Civiero L., Chau H., Kalia S.K., Kalia L.V., Lobbestael E., Chia R., Ndukwe K., Ding J., Nalls M.A., Olszewski M., Hauser D.N., Kumaran R., Lozano A.M., Baekelandt V., Greene L.E. , Taymans J.M., Greggio E., Cookson M.R., Nalls M.A., Plagnol V., Hernandez D.G., Sharma M., Sheerin U.M., Saad M., Simon-Sanchez J., Schulte C., Lesage S., Sveinbjornsdottir S., Arepalli S., Barker R., Ben-Shlomo Y., Berendse H.W., Berg D., Bhatia K., de Bie R.M., Biffi A., Bloem B., Bochdanovits Z., Bonin M., Bras J.M., Brockmann K., Brooks J., Burn D.J., Charlesworth G., Chen H., Chinnery P.F., Chong S., Clarke C.E., Cookson M.R., Cooper J.M., Corvol J.C., Counsell C., Damier P., Dartigues J.F., Deloukas P., Deuschl G., Dexter D.T., van Dijk K.D., Dillman A., Durif F., Durr A., Edkins S., Evans J.R., Foltynie T., Gao J., Gardner M., Gibbs J.R., Goate A., Gray E., Guerreiro R., Gustafsson O., Harris C., van Hilten J.J., Hofman A., Hollenbeck A., Holton J., Hu M., Huang X., Huber H., Hudson G., Hunt S.E., Huttenlocher J., Illig T., Jonsson P.V., Lambert J.C., Langford C., Lees A., Lichtner P., Limousin P., Lopez G., Lorenz D., McNeill A., Moorby C., Moore M., Morris H.R., Morrison K.E., Mudanohwo E., O'Sullivan S.S., Pearson J., Perlmutter J.S., Petursson H., Pollak P., Post B., Potter S., Ravina B., Revesz T., Riess O., Rivadeneira F., Rizzu P., Ryten M., Sawcer S., Schapira A., Scheffer H., Shaw K., Shoulson I., Sidransky E., Smith C., Spencer C.C., Stefansson H., Steinberg S., Stockton J.D., Strange A., Talbot K., Tanner C.M., Tashakkori-Ghanbaria A., Tison F., Trabzuni D., Traynor B.J., Uitterlinden A.G., Velseboer D., Vidailhet M., Walker R., van de Warrenburg B., Wickremaratchi M., Williams N., Williams-Gray C.H., Winder-Rhodes S., Stefansson K., Martinez M., Hardy J., Heutink P., Brice A., Gasser T., Singleton A.B., Wood N.W., Arepalli S., Cookson M.R., Dillman A., Ferrucci L., Gibbs J.R., Hernandez D.G., Johnson R., Longo D.L., Majounie E., Nalls M.A., O'Brien R., Singleton A.B., Traynor B.J., Troncoso J., van der Brug M., Zielke H.R., Zonderman A.B.
Proc Natl Acad Sci U S A 111:2626-2631(2014) [PubMed] [Europe PMC] [Abstract]
- growth cone Source: ParkinsonsUK-UCLInferred from direct assayi
- "Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways."
Sancho R.M., Law B.M., Harvey K.
Hum Mol Genet 18:3955-3968(2009) [PubMed] [Europe PMC] [Abstract]
- inclusion body Source: ParkinsonsUK-UCLInferred from mutant phenotypei
- "Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies."
Skibinski G., Nakamura K., Cookson M.R., Finkbeiner S.
J Neurosci 34:418-433(2014) [PubMed] [Europe PMC] [Abstract]
- intracellular membrane-bounded organelle Source: HPA
- membrane raft Source: GO_CentralInferred from biological aspect of ancestori
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
- microvillus Source: ParkinsonsUK-UCLInferred from direct assayi
- "LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model."
Alegre-Abarrategui J., Christian H., Lufino M.M., Mutihac R., Venda L.L., Ansorge O., Wade-Martins R.
Hum Mol Genet 18:4022-4034(2009) [PubMed] [Europe PMC] [Abstract]
- neuron projection Source: ParkinsonsUK-UCLInferred from direct assayi
- "Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways."
Sancho R.M., Law B.M., Harvey K.
Hum Mol Genet 18:3955-3968(2009) [PubMed] [Europe PMC] [Abstract]
- neuronal cell body Source: BHF-UCLInferred from direct assayi
- "ARHGEF7 (Beta-PIX) acts as guanine nucleotide exchange factor for leucine-rich repeat kinase 2."
Haebig K., Gloeckner C.J., Miralles M.G., Gillardon F., Schulte C., Riess O., Ueffing M., Biskup S., Bonin M.
PLoS One 5:e13762-e13762(2010) [PubMed] [Europe PMC] [Abstract] - "LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study."
Sharma S., Bandopadhyay R., Lashley T., Renton A.E., Kingsbury A.E., Kumaran R., Kallis C., Vilarino-Guell C., O'Sullivan S.S., Lees A.J., Revesz T., Wood N.W., Holton J.L.
Neuropathol Appl Neurobiol 37:777-790(2011) [PubMed] [Europe PMC] [Abstract]
- perikaryon Source: UniProtKBInferred from direct assayi
- Ref.10"Localization of LRRK2 to membranous and vesicular structures in mammalian brain."
Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A., Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C., Torp R., Ottersen O.P., Dawson T.M., Dawson V.L.
Ann. Neurol. 60:557-569(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
- postsynapse Source: GOC
- ribonucleoprotein complex Source: Ensembl
- synaptic vesicle membrane Source: UniProtKB-SubCell
- terminal bouton Source: ParkinsonsUK-UCLTraceable author statementi
- "Synaptic vesicle trafficking and Parkinson's disease."
Esposito G., Ana Clara F., Verstreken P.
Dev Neurobiol 72:134-144(2012) [PubMed] [Europe PMC] [Abstract]
- Wnt signalosome Source: ParkinsonsUK-UCLInferred from direct assayi
- "LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6."
Berwick D.C., Harvey K.
Hum Mol Genet 21:4966-4979(2012) [PubMed] [Europe PMC] [Abstract]
- amphisome Source: ParkinsonsUK-UCLInferred from direct assayi
Keywords - Cellular componenti
Cell junction, Cell projection, Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Membrane, Mitochondrion, Mitochondrion outer membrane, Synapse<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi
<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei
Parkinson disease 8 (PARK8)42 PublicationsManual assertion based on experiment ini
- Ref.1"Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology."
Zimprich A., Biskup S., Leitner P., Lichtner P., Farrer M., Lincoln S.J., Kachergus J.M., Hulihan M.M., Uitti R.J., Calne D.B., Stoessl A.J., Pfeiffer R.F., Patenge N., Carballo Carbajal I., Vieregge P., Asmus F., Mueller-Myhsok B., Dickson D.W. , Meitinger T., Strom T.M., Wszolek Z.K., Gasser T.
Neuron 44:601-607(2004) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANTS PARK8 VAL-1122; CYS-1441; CYS-1699 AND THR-2020. - Ref.5"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020. - Ref.7"Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity."
West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M.
Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005) [PubMed] [Europe PMC] [Abstract]Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441 AND SER-2019. - Ref.11"The familial Parkinsonism gene LRRK2 regulates neurite process morphology."
MacLeod D., Dowman J., Hammond R., Leete T., Inoue K., Abeliovich A.
Neuron 52:587-593(2006) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699; SER-2019 AND THR-2020, VARIANT MET-1906. - Ref.13"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death."
Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, CHARACTERIZATION OF VARIANT PARK8 SER-2019. - Ref.16"RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk."
MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D., MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A., Abeliovich A.
Neuron 77:425-439(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION IN RETROGRADE TRANSPORT, INTERACTION WITH RAB29 AND VPS35, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 SER-2019, CHARACTERIZATION OF VARIANT MET-1906. - Ref.20"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases."
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF ASP-1994. - Ref.22"Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis."
Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O., Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R., Mann M.
Elife 6:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699 AND SER-2019, MUTAGENESIS OF ASP-2017. - Ref.23"Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease."
Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z., Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L., Tan E.K.
Sci. Signal. 10:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP, PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441 AND SER-2019, MUTAGENESIS OF ASP-1994. - Ref.24"Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils."
Fan Y., Howden A.J.M., Sarhan A.R., Lis P., Ito G., Martinez T.N., Brockmann K., Gasser T., Alessi D.R., Sammler E.M.
Biochem. J. 475:23-44(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT PARK8 SER-2019, PHOSPHORYLATION AT SER-935. - Ref.25"A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain."
Dhekne H.S., Yanatori I., Gomez R.C., Tonelli F., Diez F., Schuele B., Steger M., Alessi D.R., Pfeffer S.R.
Elife 7:0-0(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, VARIANTS PARK8 GLY-1441 AND SER-2019. - Ref.26"Rab29 activation of the Parkinson's disease-associated LRRK2 kinase."
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348 AND ASP-2017. - Ref.29"Structural interface between LRRK2 and 14-3-3 protein."
Stevers L.M., de Vries R.M., Doveston R.G., Milroy L.G., Brunsveld L., Ottmann C.
Biochem. J. 474:1273-1287(2017) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (1.33 ANGSTROMS) OF 929-941 IN COMPLEX WITH SFN, INTERACTION WITH YWHAG, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1444, CHARACTERIZATION OF VARIANT PARK8 CYS-1441. - Ref.30"Crystal structure of the WD40 domain dimer of LRRK2."
Zhang P., Fan Y., Ru H., Wang L., Magupalli V.G., Taylor S.S., Alessi D.R., Wu H.
Proc. Natl. Acad. Sci. U.S.A. 116:1579-1584(2019) [PubMed] [Europe PMC] [Abstract]Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 2142-2527, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, DOMAIN, PHOSPHORYLATION AT SER-935 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; SER-2019; ASP-2175; TYR-2189; ILE-2356; ARG-2385; MET-2390 AND ILE-2439, MUTAGENESIS OF ASP-2017; LEU-2343; PHE-2344; SER-2345; TYR-2346; HIS-2391; ARG-2394; GLU-2395; MET-2408 AND SER-2409. - Ref.31"Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease."
Paisan-Ruiz C., Jain S., Evans E.W., Gilks W.P., Simon J., van der Brug M., Lopez de Munain A., Aparicio S., Gil A.M., Khan N.L., Johnson J., Martinez J.R., Nicholl D., Carrera I.M., Pena A.S., de Silva R., Lees A.J., Marti-Masso J.F. , Perez-Tur J., Wood N.W., Singleton A.B.
Neuron 44:595-600(2004) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PARK8 GLY-1441 AND CYS-1699, TISSUE SPECIFICITY. - Ref.32"Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations."
Kachergus J.M., Mata I.F., Hulihan M., Taylor J.P., Lincoln S., Aasly J.O., Gibson J.M., Ross O.A., Lynch T., Wiley J., Payami H., Nutt J., Maraganore D.M., Czyzewski K., Styczynska M., Wszolek Z.K., Farrer M.J., Toft M.
Am. J. Hum. Genet. 76:672-680(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.33"Clinical and positron emission tomography of Parkinson's disease caused by LRRK2."
Hernandez D.G., Paisan-Ruiz C., McInerney-Leo A., Jain S., Meyer-Lindenberg A., Evans E.W., Berman K.F., Johnson J., Auburger G., Schaeffer A.A., Lopez G.J., Nussbaum R.L., Singleton A.B.
Ann. Neurol. 57:453-456(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.34"Clinical features of LRRK2-associated Parkinson's disease in central Norway."
Aasly J.O., Toft M., Fernandez-Mata I., Kachergus J.M., Hulihan M., White L.R., Farrer M.J.
Ann. Neurol. 57:762-765(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8/PD SER-2019. - Ref.35"G2019S LRRK2 mutation in French and North African families with Parkinson's disease."
French Parkinson's disease genetics study group
Lesage S., Ibanez P., Lohmann E., Pollak P., Tison F., Tazir M., Leutenegger A.-L., Guimaraes J., Bonnet A.-M., Agid Y., Duerr A., Brice A.
Ann. Neurol. 58:784-787(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.36"An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family."
Funayama M., Hasegawa K., Ohta E., Kawashima N., Komiyama M., Kowa H., Tsuji S., Obata F.
Ann. Neurol. 57:918-921(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 THR-2020. - Ref.37"Genetic and clinical identification of Parkinson's disease patients with LRRK2 G2019S mutation."
Deng H., Le W., Guo Y., Hunter C.B., Xie W., Jankovic J.
Ann. Neurol. 57:933-934(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.38"Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease."
Berg D., Schweitzer K., Leitner P., Zimprich A., Lichtner P., Belcredi P., Bruessel T., Schulte C., Maass S., Naegele T.
Brain 128:3000-3011(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PARK8 MET-793; ARG-930; CYS-1096 THR-1228; SER-2019 AND THR-2020, VARIANT LYS-551. - Ref.39"Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data."
Khan N.L., Jain S., Lynch J.M., Pavese N., Abou-Sleiman P.M., Holton J.L., Healy D.G., Gilks W.P., Sweeney M.G., Ganguly M., Gibbons V., Gandhi S., Vaughan J., Eunson L.H., Katzenschlager R., Gayton J., Lennox G., Revesz T. , Nicholl D., Bhatia K.P., Quinn N., Brooks D., Lees A.J., Davis M.B., Piccini P., Singleton A.B., Wood N.W.
Brain 128:2786-2796(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PARK8 CYS-1699; HIS-1941; SER-2019 AND ILE-2356. - Ref.40"Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease."
Di Fonzo A., Tassorelli C., De Mari M., Chien H.F., Ferreira J., Rohe C.F., Riboldazzi G., Antonini A., Albani G., Mauro A., Marconi R., Abbruzzese G., Lopiano L., Fincati E., Guidi M., Marini P., Stocchi F., Onofrj M. , Toni V., Tinazzi M., Fabbrini G., Lamberti P., Vanacore N., Meco G., Leitner P., Uitti R.J., Wszolek Z.K., Gasser T., Simons E.J., Breedveld G.J., Goldwurm S., Pezzoli G., Sampaio C., Barbosa E., Martignoni E., Oostra B.A., Bonifati V.
Eur. J. Hum. Genet. 14:322-331(2006) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PARK8 VAL-1371; CYS-1441 AND SER-2019. - Ref.41"The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor."
Goldwurm S., Di Fonzo A., Simons E.J., Rohe C.F., Zini M., Canesi M., Tesei S., Zecchinelli A., Antonini A., Mariani C., Meucci N., Sacilotto G., Sironi F., Salani G., Ferreira J., Chien H.F., Fabrizio E., Vanacore N. , Dalla Libera A., Stocchi F., Diroma C., Lamberti P., Sampaio C., Meco G., Barbosa E., Bertoli-Avella A.M., Breedveld G.J., Oostra B.A., Pezzoli G., Bonifati V.
J. Med. Genet. 42:E65-E65(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.42"Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease."
The Parkinson study group-PROGENI investigators
Nichols W.C., Pankratz N., Hernandez D., Paisan-Ruiz C., Jain S., Halter C.A., Michaels V.E., Reed T., Rudolph A., Shults C.W., Singleton A., Foroud T.
Lancet 365:410-412(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.43"A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease."
The Italian Parkinson genetics network
Di Fonzo A., Rohe C.F., Ferreira J., Chien H.F., Vacca L., Stocchi F., Guedes L., Fabrizio E., Manfredi M., Vanacore N., Goldwurm S., Breedveld G.J., Sampaio C., Meco G., Barbosa E., Oostra B.A., Bonifati V.
Lancet 365:412-415(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.44"A common LRRK2 mutation in idiopathic Parkinson's disease."
Gilks W.P., Abou-Sleiman P.M., Gandhi S., Jain S., Singleton A., Lees A.J., Shaw K., Bhatia K.P., Bonifati V., Quinn N.P., Lynch J.M., Healy D.G., Holton J.L., Revesz T., Wood N.W.
Lancet 365:415-416(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.45"LRRK2 mutations and Parkinsonism."
Toft M., Mata I.F., Kachergus J.M., Ross O.A., Farrer M.J.
Lancet 365:1229-1230(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.47"Parkinson's disease and LRRK2: frequency of a common mutation in U.S. movement disorder clinics."
Kay D.M., Zabetian C.P., Factor S.A., Nutt J.G., Samii A., Griffith A., Bird T.D., Kramer P., Higgins D.S., Payami H.
Mov. Disord. 21:519-523(2006) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.48"Lrrk2 pathogenic substitutions in Parkinson's disease."
Mata I.F., Kachergus J.M., Taylor J.P., Lincoln S., Aasly J., Lynch T., Hulihan M.M., Cobb S.A., Wu R.-M., Lu C.-S., Lahoz C., Wszolek Z.K., Farrer M.J.
Neurogenetics 6:171-177(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; GLN-1514; SER-1542; GLU-1598; CYS-1699; THR-1869; THR-2012; SER-2019; THR-2020 AND ARG-2385, VARIANTS PRO-119; LYS-551; VAL-723; MET-793; VAL-1122; ALA-1262; HIS-1398; PRO-1628; THR-1646; THR-1647; ASP-2081; LEU-2119; ILE-2261 AND THR-2397. - Ref.49"LRRK2 gene in Parkinson disease: mutation analysis and case control association study."
Paisan-Ruiz C., Lang A.E., Kawarai T., Sato C., Salehi-Rad S., Fisman G.K., Al-Khairallah T., St George-Hyslop P.H., Singleton A., Rogaeva E.
Neurology 65:696-700(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PARK8 VAL-1371 AND SER-2019, VARIANTS HIS-1398 AND THR-2397. - Ref.50"Analysis of LRRK2 functional domains in nondominant Parkinson disease."
Skipper L., Shen H., Chua E., Bonnard C., Kolatkar P., Tan L.C.S., Jamora R.D., Puvan K., Puong K.Y., Zhao Y., Pavanni R., Wong M.C., Yuen Y., Farrer M., Liu J.J., Tan E.K.
Neurology 65:1319-1321(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 GLN-1067. - Ref.51"LRRK2 mutations in Parkinson disease."
Farrer M., Stone J., Mata I.F., Lincoln S., Kachergus J., Hulihan M., Strain K.J., Maraganore D.M.
Neurology 65:738-740(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PARK8 MET-793; THR-1869 AND SER-2019. - Ref.52"A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations."
Zabetian C.P., Samii A., Mosley A.D., Roberts J.W., Leis B.C., Yearout D., Raskind W.H., Griffith A.
Neurology 65:741-744(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PARK8 CYS-1441; HIS-1441 AND SER-2019. - Ref.53"LRRK2 R1441G in Spanish patients with Parkinson's disease."
Mata I.F., Taylor J.P., Kachergus J., Hulihan M., Huerta C., Lahoz C., Blazquez M., Guisasola L.M., Salvador C., Ribacoba R., Martinez C., Farrer M., Alvarez V.
Neurosci. Lett. 382:309-311(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 GLY-1441. - Ref.54"LRRK2 G2019S is a common mutation in Spanish patients with late-onset Parkinson's disease."
Infante J., Rodriguez E., Combarros O., Mateo I., Fontalba A., Pascual J., Oterino A., Polo J.M., Leno C., Berciano J.
Neurosci. Lett. 395:224-226(2006) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.55"Clinical traits of LRRK2-associated Parkinson's disease in Ireland: a link between familial and idiopathic PD."
Gosal D., Ross O.A., Wiley J., Irvine G.B., Johnston J.A., Toft M., Mata I.F., Kachergus J., Hulihan M., Taylor J.P., Lincoln S.J., Farrer M.J., Lynch T., Mark Gibson J.
Parkinsonism Relat. Disord. 11:349-352(2005) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.56"LRRK2 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance."
Gaig C., Ezquerra M., Marti M.J., Munoz E., Valldeoriola F., Tolosa E.
Arch. Neurol. 63:377-382(2006) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PARK8 CYS-1441; GLY-1441 AND SER-2019. - Ref.59"Comprehensive analysis of LRRK2 in publicly available Parkinson's disease cases and neurologically normal controls."
Paisan-Ruiz C., Nath P., Washecka N., Gibbs J.R., Singleton A.B.
Hum. Mutat. 29:485-490(2008) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PARK8 VAL-712; LEU-1728; HIS-1728; SER-2019; MET-2141; HIS-2143 AND HIS-2466, VARIANTS SER-228; VAL-716; GLU-871; PHE-1870 AND LYS-2395. - Ref.63"Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease."
Kilarski L.L., Pearson J.P., Newsway V., Majounie E., Knipe M.D., Misbahuddin A., Chinnery P.F., Burn D.J., Clarke C.E., Marion M.H., Lewthwaite A.J., Nicholl D.J., Wood N.W., Morrison K.E., Williams-Gray C.H., Evans J.R., Sawcer S.J., Barker R.A. , Wickremaratchi M.M., Ben-Shlomo Y., Williams N.M., Morris H.R.
Mov. Disord. 27:1522-1529(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PARK8 SER-2019. - Ref.64"Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export."
Cho H.J., Yu J., Xie C., Rudrabhatla P., Chen X., Wu J., Parisiadou L., Liu G., Sun L., Ma B., Ding J., Liu Z., Cai H.
EMBO J. 33:2314-2331(2014) [PubMed] [Europe PMC] [Abstract]Cited for: CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; CYS-1699 AND SER-2019, CHARACTERIZATION OF VARIANT ARG-2385, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SEC16A, MUTAGENESIS OF LYS-1347 AND ASP-1994.
Ref.1
"Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology."
Zimprich A., Biskup S., Leitner P., Lichtner P., Farrer M., Lincoln S.J., Kachergus J.M., Hulihan M.M., Uitti R.J., Calne D.B., Stoessl A.J., Pfeiffer R.F., Patenge N., Carballo Carbajal I., Vieregge P., Asmus F., Mueller-Myhsok B., Dickson D.W. , Meitinger T., Strom T.M., Wszolek Z.K., Gasser T.
Neuron 44:601-607(2004) [PubMed] [Europe PMC] [Abstract]
Zimprich A., Biskup S., Leitner P., Lichtner P., Farrer M., Lincoln S.J., Kachergus J.M., Hulihan M.M., Uitti R.J., Calne D.B., Stoessl A.J., Pfeiffer R.F., Patenge N., Carballo Carbajal I., Vieregge P., Asmus F., Mueller-Myhsok B., Dickson D.W. , Meitinger T., Strom T.M., Wszolek Z.K., Gasser T.
Neuron 44:601-607(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANTS PARK8 VAL-1122; CYS-1441; CYS-1699 AND THR-2020.
Ref.5
"The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]
Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020.
Ref.7
"Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity."
West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M.
Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005) [PubMed] [Europe PMC] [Abstract]
West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M.
Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441 AND SER-2019.
Ref.11
"The familial Parkinsonism gene LRRK2 regulates neurite process morphology."
MacLeod D., Dowman J., Hammond R., Leete T., Inoue K., Abeliovich A.
Neuron 52:587-593(2006) [PubMed] [Europe PMC] [Abstract]
MacLeod D., Dowman J., Hammond R., Leete T., Inoue K., Abeliovich A.
Neuron 52:587-593(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699; SER-2019 AND THR-2020, VARIANT MET-1906.
Ref.13
"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death."
Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]
Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, CHARACTERIZATION OF VARIANT PARK8 SER-2019.
Ref.16
"RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk."
MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D., MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A., Abeliovich A.
Neuron 77:425-439(2013) [PubMed] [Europe PMC] [Abstract]
MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D., MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A., Abeliovich A.
Neuron 77:425-439(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RETROGRADE TRANSPORT, INTERACTION WITH RAB29 AND VPS35, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 SER-2019, CHARACTERIZATION OF VARIANT MET-1906.
Ref.20
"Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases."
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]
Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J., Morrow J.A., Reith A.D., Alessi D.R., Mann M.
Elife 5:0-0(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441; CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF ASP-1994.
Ref.22
"Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis."
Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O., Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R., Mann M.
Elife 6:0-0(2017) [PubMed] [Europe PMC] [Abstract]
Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O., Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R., Mann M.
Elife 6:0-0(2017) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699 AND SER-2019, MUTAGENESIS OF ASP-2017.
Ref.23
"Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson's disease."
Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z., Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L., Tan E.K.
Sci. Signal. 10:0-0(2017) [PubMed] [Europe PMC] [Abstract]
Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z., Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L., Tan E.K.
Sci. Signal. 10:0-0(2017) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP, PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441 AND SER-2019, MUTAGENESIS OF ASP-1994.
Ref.24
"Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils."
Fan Y., Howden A.J.M., Sarhan A.R., Lis P., Ito G., Martinez T.N., Brockmann K., Gasser T., Alessi D.R., Sammler E.M.
Biochem. J. 475:23-44(2018) [PubMed] [Europe PMC] [Abstract]
Fan Y., Howden A.J.M., Sarhan A.R., Lis P., Ito G., Martinez T.N., Brockmann K., Gasser T., Alessi D.R., Sammler E.M.
Biochem. J. 475:23-44(2018) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT PARK8 SER-2019, PHOSPHORYLATION AT SER-935.
Ref.25
"A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain."
Dhekne H.S., Yanatori I., Gomez R.C., Tonelli F., Diez F., Schuele B., Steger M., Alessi D.R., Pfeffer S.R.
Elife 7:0-0(2018) [PubMed] [Europe PMC] [Abstract]
Dhekne H.S., Yanatori I., Gomez R.C., Tonelli F., Diez F., Schuele B., Steger M., Alessi D.R., Pfeffer S.R.
Elife 7:0-0(2018) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, VARIANTS PARK8 GLY-1441 AND SER-2019.
Ref.26
"Rab29 activation of the Parkinson's disease-associated LRRK2 kinase."
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]
Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M., Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.
EMBO J. 37:1-18(2018) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, MUTAGENESIS OF CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790; LEU-791; THR-1348 AND ASP-2017.
Ref.29
"Structural interface between LRRK2 and 14-3-3 protein."
Stevers L.M., de Vries R.M., Doveston R.G., Milroy L.G., Brunsveld L., Ottmann C.
Biochem. J. 474:1273-1287(2017) [PubMed] [Europe PMC] [Abstract]
Stevers L.M., de Vries R.M., Doveston R.G., Milroy L.G., Brunsveld L., Ottmann C.
Biochem. J. 474:1273-1287(2017) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.33 ANGSTROMS) OF 929-941 IN COMPLEX WITH SFN, INTERACTION WITH YWHAG, PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1444, CHARACTERIZATION OF VARIANT PARK8 CYS-1441.
Ref.30
"Crystal structure of the WD40 domain dimer of LRRK2."
Zhang P., Fan Y., Ru H., Wang L., Magupalli V.G., Taylor S.S., Alessi D.R., Wu H.
Proc. Natl. Acad. Sci. U.S.A. 116:1579-1584(2019) [PubMed] [Europe PMC] [Abstract]
Zhang P., Fan Y., Ru H., Wang L., Magupalli V.G., Taylor S.S., Alessi D.R., Wu H.
Proc. Natl. Acad. Sci. U.S.A. 116:1579-1584(2019) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 2142-2527, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, DOMAIN, PHOSPHORYLATION AT SER-935 AND SER-1292, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; SER-2019; ASP-2175; TYR-2189; ILE-2356; ARG-2385; MET-2390 AND ILE-2439, MUTAGENESIS OF ASP-2017; LEU-2343; PHE-2344; SER-2345; TYR-2346; HIS-2391; ARG-2394; GLU-2395; MET-2408 AND SER-2409.
Ref.31
"Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease."
Paisan-Ruiz C., Jain S., Evans E.W., Gilks W.P., Simon J., van der Brug M., Lopez de Munain A., Aparicio S., Gil A.M., Khan N.L., Johnson J., Martinez J.R., Nicholl D., Carrera I.M., Pena A.S., de Silva R., Lees A.J., Marti-Masso J.F. , Perez-Tur J., Wood N.W., Singleton A.B.
Neuron 44:595-600(2004) [PubMed] [Europe PMC] [Abstract]
Paisan-Ruiz C., Jain S., Evans E.W., Gilks W.P., Simon J., van der Brug M., Lopez de Munain A., Aparicio S., Gil A.M., Khan N.L., Johnson J., Martinez J.R., Nicholl D., Carrera I.M., Pena A.S., de Silva R., Lees A.J., Marti-Masso J.F. , Perez-Tur J., Wood N.W., Singleton A.B.
Neuron 44:595-600(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 GLY-1441 AND CYS-1699, TISSUE SPECIFICITY.
Ref.32
"Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations."
Kachergus J.M., Mata I.F., Hulihan M., Taylor J.P., Lincoln S., Aasly J.O., Gibson J.M., Ross O.A., Lynch T., Wiley J., Payami H., Nutt J., Maraganore D.M., Czyzewski K., Styczynska M., Wszolek Z.K., Farrer M.J., Toft M.
Am. J. Hum. Genet. 76:672-680(2005) [PubMed] [Europe PMC] [Abstract]
Kachergus J.M., Mata I.F., Hulihan M., Taylor J.P., Lincoln S., Aasly J.O., Gibson J.M., Ross O.A., Lynch T., Wiley J., Payami H., Nutt J., Maraganore D.M., Czyzewski K., Styczynska M., Wszolek Z.K., Farrer M.J., Toft M.
Am. J. Hum. Genet. 76:672-680(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.33
"Clinical and positron emission tomography of Parkinson's disease caused by LRRK2."
Hernandez D.G., Paisan-Ruiz C., McInerney-Leo A., Jain S., Meyer-Lindenberg A., Evans E.W., Berman K.F., Johnson J., Auburger G., Schaeffer A.A., Lopez G.J., Nussbaum R.L., Singleton A.B.
Ann. Neurol. 57:453-456(2005) [PubMed] [Europe PMC] [Abstract]
Hernandez D.G., Paisan-Ruiz C., McInerney-Leo A., Jain S., Meyer-Lindenberg A., Evans E.W., Berman K.F., Johnson J., Auburger G., Schaeffer A.A., Lopez G.J., Nussbaum R.L., Singleton A.B.
Ann. Neurol. 57:453-456(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.34
"Clinical features of LRRK2-associated Parkinson's disease in central Norway."
Aasly J.O., Toft M., Fernandez-Mata I., Kachergus J.M., Hulihan M., White L.R., Farrer M.J.
Ann. Neurol. 57:762-765(2005) [PubMed] [Europe PMC] [Abstract]
Aasly J.O., Toft M., Fernandez-Mata I., Kachergus J.M., Hulihan M., White L.R., Farrer M.J.
Ann. Neurol. 57:762-765(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8/PD SER-2019.
Ref.35
"G2019S LRRK2 mutation in French and North African families with Parkinson's disease."
French Parkinson's disease genetics study group
Lesage S., Ibanez P., Lohmann E., Pollak P., Tison F., Tazir M., Leutenegger A.-L., Guimaraes J., Bonnet A.-M., Agid Y., Duerr A., Brice A.
Ann. Neurol. 58:784-787(2005) [PubMed] [Europe PMC] [Abstract]
French Parkinson's disease genetics study group
Lesage S., Ibanez P., Lohmann E., Pollak P., Tison F., Tazir M., Leutenegger A.-L., Guimaraes J., Bonnet A.-M., Agid Y., Duerr A., Brice A.
Ann. Neurol. 58:784-787(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.36
"An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family."
Funayama M., Hasegawa K., Ohta E., Kawashima N., Komiyama M., Kowa H., Tsuji S., Obata F.
Ann. Neurol. 57:918-921(2005) [PubMed] [Europe PMC] [Abstract]
Funayama M., Hasegawa K., Ohta E., Kawashima N., Komiyama M., Kowa H., Tsuji S., Obata F.
Ann. Neurol. 57:918-921(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 THR-2020.
Ref.37
"Genetic and clinical identification of Parkinson's disease patients with LRRK2 G2019S mutation."
Deng H., Le W., Guo Y., Hunter C.B., Xie W., Jankovic J.
Ann. Neurol. 57:933-934(2005) [PubMed] [Europe PMC] [Abstract]
Deng H., Le W., Guo Y., Hunter C.B., Xie W., Jankovic J.
Ann. Neurol. 57:933-934(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.38
"Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease."
Berg D., Schweitzer K., Leitner P., Zimprich A., Lichtner P., Belcredi P., Bruessel T., Schulte C., Maass S., Naegele T.
Brain 128:3000-3011(2005) [PubMed] [Europe PMC] [Abstract]
Berg D., Schweitzer K., Leitner P., Zimprich A., Lichtner P., Belcredi P., Bruessel T., Schulte C., Maass S., Naegele T.
Brain 128:3000-3011(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 MET-793; ARG-930; CYS-1096 THR-1228; SER-2019 AND THR-2020, VARIANT LYS-551.
Ref.39
"Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data."
Khan N.L., Jain S., Lynch J.M., Pavese N., Abou-Sleiman P.M., Holton J.L., Healy D.G., Gilks W.P., Sweeney M.G., Ganguly M., Gibbons V., Gandhi S., Vaughan J., Eunson L.H., Katzenschlager R., Gayton J., Lennox G., Revesz T. , Nicholl D., Bhatia K.P., Quinn N., Brooks D., Lees A.J., Davis M.B., Piccini P., Singleton A.B., Wood N.W.
Brain 128:2786-2796(2005) [PubMed] [Europe PMC] [Abstract]
Khan N.L., Jain S., Lynch J.M., Pavese N., Abou-Sleiman P.M., Holton J.L., Healy D.G., Gilks W.P., Sweeney M.G., Ganguly M., Gibbons V., Gandhi S., Vaughan J., Eunson L.H., Katzenschlager R., Gayton J., Lennox G., Revesz T. , Nicholl D., Bhatia K.P., Quinn N., Brooks D., Lees A.J., Davis M.B., Piccini P., Singleton A.B., Wood N.W.
Brain 128:2786-2796(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 CYS-1699; HIS-1941; SER-2019 AND ILE-2356.
Ref.40
"Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease."
Di Fonzo A., Tassorelli C., De Mari M., Chien H.F., Ferreira J., Rohe C.F., Riboldazzi G., Antonini A., Albani G., Mauro A., Marconi R., Abbruzzese G., Lopiano L., Fincati E., Guidi M., Marini P., Stocchi F., Onofrj M. , Toni V., Tinazzi M., Fabbrini G., Lamberti P., Vanacore N., Meco G., Leitner P., Uitti R.J., Wszolek Z.K., Gasser T., Simons E.J., Breedveld G.J., Goldwurm S., Pezzoli G., Sampaio C., Barbosa E., Martignoni E., Oostra B.A., Bonifati V.
Eur. J. Hum. Genet. 14:322-331(2006) [PubMed] [Europe PMC] [Abstract]
Di Fonzo A., Tassorelli C., De Mari M., Chien H.F., Ferreira J., Rohe C.F., Riboldazzi G., Antonini A., Albani G., Mauro A., Marconi R., Abbruzzese G., Lopiano L., Fincati E., Guidi M., Marini P., Stocchi F., Onofrj M. , Toni V., Tinazzi M., Fabbrini G., Lamberti P., Vanacore N., Meco G., Leitner P., Uitti R.J., Wszolek Z.K., Gasser T., Simons E.J., Breedveld G.J., Goldwurm S., Pezzoli G., Sampaio C., Barbosa E., Martignoni E., Oostra B.A., Bonifati V.
Eur. J. Hum. Genet. 14:322-331(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 VAL-1371; CYS-1441 AND SER-2019.
Ref.41
"The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor."
Goldwurm S., Di Fonzo A., Simons E.J., Rohe C.F., Zini M., Canesi M., Tesei S., Zecchinelli A., Antonini A., Mariani C., Meucci N., Sacilotto G., Sironi F., Salani G., Ferreira J., Chien H.F., Fabrizio E., Vanacore N. , Dalla Libera A., Stocchi F., Diroma C., Lamberti P., Sampaio C., Meco G., Barbosa E., Bertoli-Avella A.M., Breedveld G.J., Oostra B.A., Pezzoli G., Bonifati V.
J. Med. Genet. 42:E65-E65(2005) [PubMed] [Europe PMC] [Abstract]
Goldwurm S., Di Fonzo A., Simons E.J., Rohe C.F., Zini M., Canesi M., Tesei S., Zecchinelli A., Antonini A., Mariani C., Meucci N., Sacilotto G., Sironi F., Salani G., Ferreira J., Chien H.F., Fabrizio E., Vanacore N. , Dalla Libera A., Stocchi F., Diroma C., Lamberti P., Sampaio C., Meco G., Barbosa E., Bertoli-Avella A.M., Breedveld G.J., Oostra B.A., Pezzoli G., Bonifati V.
J. Med. Genet. 42:E65-E65(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.42
"Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease."
The Parkinson study group-PROGENI investigators
Nichols W.C., Pankratz N., Hernandez D., Paisan-Ruiz C., Jain S., Halter C.A., Michaels V.E., Reed T., Rudolph A., Shults C.W., Singleton A., Foroud T.
Lancet 365:410-412(2005) [PubMed] [Europe PMC] [Abstract]
The Parkinson study group-PROGENI investigators
Nichols W.C., Pankratz N., Hernandez D., Paisan-Ruiz C., Jain S., Halter C.A., Michaels V.E., Reed T., Rudolph A., Shults C.W., Singleton A., Foroud T.
Lancet 365:410-412(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.43
"A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease."
The Italian Parkinson genetics network
Di Fonzo A., Rohe C.F., Ferreira J., Chien H.F., Vacca L., Stocchi F., Guedes L., Fabrizio E., Manfredi M., Vanacore N., Goldwurm S., Breedveld G.J., Sampaio C., Meco G., Barbosa E., Oostra B.A., Bonifati V.
Lancet 365:412-415(2005) [PubMed] [Europe PMC] [Abstract]
The Italian Parkinson genetics network
Di Fonzo A., Rohe C.F., Ferreira J., Chien H.F., Vacca L., Stocchi F., Guedes L., Fabrizio E., Manfredi M., Vanacore N., Goldwurm S., Breedveld G.J., Sampaio C., Meco G., Barbosa E., Oostra B.A., Bonifati V.
Lancet 365:412-415(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.44
"A common LRRK2 mutation in idiopathic Parkinson's disease."
Gilks W.P., Abou-Sleiman P.M., Gandhi S., Jain S., Singleton A., Lees A.J., Shaw K., Bhatia K.P., Bonifati V., Quinn N.P., Lynch J.M., Healy D.G., Holton J.L., Revesz T., Wood N.W.
Lancet 365:415-416(2005) [PubMed] [Europe PMC] [Abstract]
Gilks W.P., Abou-Sleiman P.M., Gandhi S., Jain S., Singleton A., Lees A.J., Shaw K., Bhatia K.P., Bonifati V., Quinn N.P., Lynch J.M., Healy D.G., Holton J.L., Revesz T., Wood N.W.
Lancet 365:415-416(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.45
"LRRK2 mutations and Parkinsonism."
Toft M., Mata I.F., Kachergus J.M., Ross O.A., Farrer M.J.
Lancet 365:1229-1230(2005) [PubMed] [Europe PMC] [Abstract]
Toft M., Mata I.F., Kachergus J.M., Ross O.A., Farrer M.J.
Lancet 365:1229-1230(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.47
"Parkinson's disease and LRRK2: frequency of a common mutation in U.S. movement disorder clinics."
Kay D.M., Zabetian C.P., Factor S.A., Nutt J.G., Samii A., Griffith A., Bird T.D., Kramer P., Higgins D.S., Payami H.
Mov. Disord. 21:519-523(2006) [PubMed] [Europe PMC] [Abstract]
Kay D.M., Zabetian C.P., Factor S.A., Nutt J.G., Samii A., Griffith A., Bird T.D., Kramer P., Higgins D.S., Payami H.
Mov. Disord. 21:519-523(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.48
"Lrrk2 pathogenic substitutions in Parkinson's disease."
Mata I.F., Kachergus J.M., Taylor J.P., Lincoln S., Aasly J., Lynch T., Hulihan M.M., Cobb S.A., Wu R.-M., Lu C.-S., Lahoz C., Wszolek Z.K., Farrer M.J.
Neurogenetics 6:171-177(2005) [PubMed] [Europe PMC] [Abstract]
Mata I.F., Kachergus J.M., Taylor J.P., Lincoln S., Aasly J., Lynch T., Hulihan M.M., Cobb S.A., Wu R.-M., Lu C.-S., Lahoz C., Wszolek Z.K., Farrer M.J.
Neurogenetics 6:171-177(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; GLN-1514; SER-1542; GLU-1598; CYS-1699; THR-1869; THR-2012; SER-2019; THR-2020 AND ARG-2385, VARIANTS PRO-119; LYS-551; VAL-723; MET-793; VAL-1122; ALA-1262; HIS-1398; PRO-1628; THR-1646; THR-1647; ASP-2081; LEU-2119; ILE-2261 AND THR-2397.
Ref.49
"LRRK2 gene in Parkinson disease: mutation analysis and case control association study."
Paisan-Ruiz C., Lang A.E., Kawarai T., Sato C., Salehi-Rad S., Fisman G.K., Al-Khairallah T., St George-Hyslop P.H., Singleton A., Rogaeva E.
Neurology 65:696-700(2005) [PubMed] [Europe PMC] [Abstract]
Paisan-Ruiz C., Lang A.E., Kawarai T., Sato C., Salehi-Rad S., Fisman G.K., Al-Khairallah T., St George-Hyslop P.H., Singleton A., Rogaeva E.
Neurology 65:696-700(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 VAL-1371 AND SER-2019, VARIANTS HIS-1398 AND THR-2397.
Ref.50
"Analysis of LRRK2 functional domains in nondominant Parkinson disease."
Skipper L., Shen H., Chua E., Bonnard C., Kolatkar P., Tan L.C.S., Jamora R.D., Puvan K., Puong K.Y., Zhao Y., Pavanni R., Wong M.C., Yuen Y., Farrer M., Liu J.J., Tan E.K.
Neurology 65:1319-1321(2005) [PubMed] [Europe PMC] [Abstract]
Skipper L., Shen H., Chua E., Bonnard C., Kolatkar P., Tan L.C.S., Jamora R.D., Puvan K., Puong K.Y., Zhao Y., Pavanni R., Wong M.C., Yuen Y., Farrer M., Liu J.J., Tan E.K.
Neurology 65:1319-1321(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 GLN-1067.
Ref.51
"LRRK2 mutations in Parkinson disease."
Farrer M., Stone J., Mata I.F., Lincoln S., Kachergus J., Hulihan M., Strain K.J., Maraganore D.M.
Neurology 65:738-740(2005) [PubMed] [Europe PMC] [Abstract]
Farrer M., Stone J., Mata I.F., Lincoln S., Kachergus J., Hulihan M., Strain K.J., Maraganore D.M.
Neurology 65:738-740(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 MET-793; THR-1869 AND SER-2019.
Ref.52
"A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations."
Zabetian C.P., Samii A., Mosley A.D., Roberts J.W., Leis B.C., Yearout D., Raskind W.H., Griffith A.
Neurology 65:741-744(2005) [PubMed] [Europe PMC] [Abstract]
Zabetian C.P., Samii A., Mosley A.D., Roberts J.W., Leis B.C., Yearout D., Raskind W.H., Griffith A.
Neurology 65:741-744(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 CYS-1441; HIS-1441 AND SER-2019.
Ref.53
"LRRK2 R1441G in Spanish patients with Parkinson's disease."
Mata I.F., Taylor J.P., Kachergus J., Hulihan M., Huerta C., Lahoz C., Blazquez M., Guisasola L.M., Salvador C., Ribacoba R., Martinez C., Farrer M., Alvarez V.
Neurosci. Lett. 382:309-311(2005) [PubMed] [Europe PMC] [Abstract]
Mata I.F., Taylor J.P., Kachergus J., Hulihan M., Huerta C., Lahoz C., Blazquez M., Guisasola L.M., Salvador C., Ribacoba R., Martinez C., Farrer M., Alvarez V.
Neurosci. Lett. 382:309-311(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 GLY-1441.
Ref.54
"LRRK2 G2019S is a common mutation in Spanish patients with late-onset Parkinson's disease."
Infante J., Rodriguez E., Combarros O., Mateo I., Fontalba A., Pascual J., Oterino A., Polo J.M., Leno C., Berciano J.
Neurosci. Lett. 395:224-226(2006) [PubMed] [Europe PMC] [Abstract]
Infante J., Rodriguez E., Combarros O., Mateo I., Fontalba A., Pascual J., Oterino A., Polo J.M., Leno C., Berciano J.
Neurosci. Lett. 395:224-226(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.55
"Clinical traits of LRRK2-associated Parkinson's disease in Ireland: a link between familial and idiopathic PD."
Gosal D., Ross O.A., Wiley J., Irvine G.B., Johnston J.A., Toft M., Mata I.F., Kachergus J., Hulihan M., Taylor J.P., Lincoln S.J., Farrer M.J., Lynch T., Mark Gibson J.
Parkinsonism Relat. Disord. 11:349-352(2005) [PubMed] [Europe PMC] [Abstract]
Gosal D., Ross O.A., Wiley J., Irvine G.B., Johnston J.A., Toft M., Mata I.F., Kachergus J., Hulihan M., Taylor J.P., Lincoln S.J., Farrer M.J., Lynch T., Mark Gibson J.
Parkinsonism Relat. Disord. 11:349-352(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.56
"LRRK2 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance."
Gaig C., Ezquerra M., Marti M.J., Munoz E., Valldeoriola F., Tolosa E.
Arch. Neurol. 63:377-382(2006) [PubMed] [Europe PMC] [Abstract]
Gaig C., Ezquerra M., Marti M.J., Munoz E., Valldeoriola F., Tolosa E.
Arch. Neurol. 63:377-382(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 CYS-1441; GLY-1441 AND SER-2019.
Ref.59
"Comprehensive analysis of LRRK2 in publicly available Parkinson's disease cases and neurologically normal controls."
Paisan-Ruiz C., Nath P., Washecka N., Gibbs J.R., Singleton A.B.
Hum. Mutat. 29:485-490(2008) [PubMed] [Europe PMC] [Abstract]
Paisan-Ruiz C., Nath P., Washecka N., Gibbs J.R., Singleton A.B.
Hum. Mutat. 29:485-490(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK8 VAL-712; LEU-1728; HIS-1728; SER-2019; MET-2141; HIS-2143 AND HIS-2466, VARIANTS SER-228; VAL-716; GLU-871; PHE-1870 AND LYS-2395.
Ref.63
"Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease."
Kilarski L.L., Pearson J.P., Newsway V., Majounie E., Knipe M.D., Misbahuddin A., Chinnery P.F., Burn D.J., Clarke C.E., Marion M.H., Lewthwaite A.J., Nicholl D.J., Wood N.W., Morrison K.E., Williams-Gray C.H., Evans J.R., Sawcer S.J., Barker R.A. , Wickremaratchi M.M., Ben-Shlomo Y., Williams N.M., Morris H.R.
Mov. Disord. 27:1522-1529(2012) [PubMed] [Europe PMC] [Abstract]
Kilarski L.L., Pearson J.P., Newsway V., Majounie E., Knipe M.D., Misbahuddin A., Chinnery P.F., Burn D.J., Clarke C.E., Marion M.H., Lewthwaite A.J., Nicholl D.J., Wood N.W., Morrison K.E., Williams-Gray C.H., Evans J.R., Sawcer S.J., Barker R.A. , Wickremaratchi M.M., Ben-Shlomo Y., Williams N.M., Morris H.R.
Mov. Disord. 27:1522-1529(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK8 SER-2019.
Ref.64
"Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export."
Cho H.J., Yu J., Xie C., Rudrabhatla P., Chen X., Wu J., Parisiadou L., Liu G., Sun L., Ma B., Ding J., Liu Z., Cai H.
EMBO J. 33:2314-2331(2014) [PubMed] [Europe PMC] [Abstract]
Cho H.J., Yu J., Xie C., Rudrabhatla P., Chen X., Wu J., Parisiadou L., Liu G., Sun L., Ma B., Ding J., Liu Z., Cai H.
EMBO J. 33:2314-2331(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; CYS-1699 AND SER-2019, CHARACTERIZATION OF VARIANT ARG-2385, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SEC16A, MUTAGENESIS OF LYS-1347 AND ASP-1994.
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_054741 | 712 | M → V in PARK8. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024935 | 793 | R → M in PARK8; unknown pathological significance. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024936 | 930 | Q → R in PARK8; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024938 | 1067 | R → Q in PARK8. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024939 | 1096 | S → C in PARK8; unknown pathological significance. Corresponds to variant dbSNP:rs76535406EnsemblClinVar. | 1 | |
| Natural variantiVAR_024940 | 1122 | I → V in PARK8. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024941 | 1228 | S → T in PARK8. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024943 | 1371 | I → V in PARK8; unknown pathological significance. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024945 | 1441 | R → C in PARK8; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate; loss of interaction with SEC16A; shows an increase in activity in phosphorylation of RAB10; decreases phosphorylation-dependent binding to YWHAG. 10 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024946 | 1441 | R → G in PARK8; shows a progressive reduction in neurite length and branching; shows an increase in activity in phosphorylation of RAB8A and RAB10; decreases phosphorylation-dependent binding to YWHAG. 11 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024947 | 1441 | R → H in PARK8; shows an increase in activity in phosphorylation of RAB8A and RAB10; decreases phosphorylation-dependent binding to YWHAG. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024948 | 1514 | R → Q in PARK8; unknown pathological significance. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024949 | 1542 | P → S in PARK8; unknown pathological significance. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024950 | 1598 | V → E in PARK8; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024954 | 1699 | Y → C in PARK8; shows no progressive reduction in neurite length and branching; no loss of interaction with SEC16A; shows an increase in activity in phosphorylation of RAB8A and RAB10. 9 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_054744 | 1728 | R → H in PARK8; shows an increase in activity in phosphorylation of RAB8A and RAB10. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_054745 | 1728 | R → L in PARK8. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024955 | 1869 | M → T in PARK8; unknown pathological significance. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024956 | 1941 | R → H in PARK8. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024957 | 2012 | I → T in PARK8; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_024958 | 2019 | G → S in PARK8; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate; results in increased PRDX3 phosphorylation promoting dysregulation of mitochondrial function and oxidative damage; results in increased APP phosphorylation on 'T-743' promoting neurotoxicity in dopaminergic neurons; shows increased kinase activity in the phosphorylation of RAB10; does not inhibit interaction with RAB29; shows a progressive reduction in neurite length and branching; shows distinctive spheroid-like inclusions within both neuronal processes and at intracellular membranous structures; shows lysosomal swelling and reduced retrograde transport of selective cargo between lysosomes and the Golgi apparatus; shows apoptotic mechanism of cell death; no loss of interaction with SEC16A. 36 Publications Manual assertion based on experiment ini
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