ID   LRRK2_HUMAN             Reviewed;        2527 AA.
AC   Q5S007; A6NJU2; Q6ZS50; Q8NCX9;
DT   24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   20-APR-2010, sequence version 2.
DT   27-MAR-2024, entry version 192.
DE   RecName: Full=Leucine-rich repeat serine/threonine-protein kinase 2;
DE            EC=2.7.11.1 {ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421};
DE            EC=3.6.5.- {ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29212815};
DE   AltName: Full=Dardarin;
GN   Name=LRRK2; Synonyms=PARK8;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS PARK8
RP   VAL-1122; CYS-1441; CYS-1699 AND THR-2020.
RC   TISSUE=Brain;
RX   PubMed=15541309; DOI=10.1016/j.neuron.2004.11.005;
RA   Zimprich A., Biskup S., Leitner P., Lichtner P., Farrer M., Lincoln S.J.,
RA   Kachergus J.M., Hulihan M.M., Uitti R.J., Calne D.B., Stoessl A.J.,
RA   Pfeiffer R.F., Patenge N., Carballo Carbajal I., Vieregge P., Asmus F.,
RA   Mueller-Myhsok B., Dickson D.W., Meitinger T., Strom T.M., Wszolek Z.K.,
RA   Gasser T.;
RT   "Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic
RT   pathology.";
RL   Neuron 44:601-607(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16541075; DOI=10.1038/nature04569;
RA   Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA   Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA   Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA   Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA   Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA   Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA   Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA   Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA   Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA   Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA   Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA   Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA   Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA   Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA   Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA   Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA   Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA   David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA   D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA   Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA   Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA   Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA   LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA   Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA   Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA   Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA   Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA   Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA   Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA   Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA   Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA   Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA   Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA   Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA   Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA   Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA   Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA   Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA   Gibbs R.A.;
RT   "The finished DNA sequence of human chromosome 12.";
RL   Nature 440:346-351(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2128-2527.
RC   TISSUE=Testis;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [4]
RP   DISEASE.
RX   PubMed=16081470; DOI=10.1093/brain/awh607;
RA   Adams J.R., van Netten H., Schulzer M., Mak E., McKenzie J., Strongosky A.,
RA   Sossi V., Ruth T.J., Lee C.S., Farrer M., Gasser T., Uitti R.J.,
RA   Calne D.B., Wszolek Z.K., Stoessl A.J.;
RT   "PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and
RT   evidence for presymptomatic compensation.";
RL   Brain 128:2777-2785(2005).
RN   [5]
RP   SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT PARK8 THR-2020.
RX   PubMed=16321986; DOI=10.1093/hmg/ddi439;
RA   Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E.,
RA   Meitinger T., Kolch W., Prokisch H., Ueffing M.;
RT   "The Parkinson disease causing LRRK2 mutation I2020T is associated with
RT   increased kinase activity.";
RL   Hum. Mol. Genet. 15:223-232(2006).
RN   [6]
RP   DISEASE.
RX   PubMed=16087219; DOI=10.1016/j.mad.2005.06.010;
RA   Toft M., Sando S.B., Melquist S., Ross O.A., White L.R., Aasly J.O.,
RA   Farrer M.J.;
RT   "LRRK2 mutations are not common in Alzheimer's disease.";
RL   Mech. Ageing Dev. 126:1201-1205(2005).
RN   [7]
RP   SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS PARK8 CYS-1441 AND
RP   SER-2019.
RX   PubMed=16269541; DOI=10.1073/pnas.0507360102;
RA   West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A.,
RA   Dawson V.L., Dawson T.M.;
RT   "Parkinson's disease-associated mutations in leucine-rich repeat kinase 2
RT   augment kinase activity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005).
RN   [8]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH PRKN.
RX   PubMed=16352719; DOI=10.1073/pnas.0508052102;
RA   Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L.,
RA   Dawson T.M., Ross C.A.;
RT   "Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant
RT   LRRK2 induces neuronal degeneration.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005).
RN   [9]
RP   TISSUE SPECIFICITY.
RX   PubMed=16532471; DOI=10.1002/ana.20808;
RA   Galter D., Westerlund M., Carmine A., Lindqvist E., Sydow O., Olson L.;
RT   "LRRK2 expression linked to dopamine-innervated areas.";
RL   Ann. Neurol. 59:714-719(2006).
RN   [10]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=17120249; DOI=10.1002/ana.21019;
RA   Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A.,
RA   Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C.,
RA   Torp R., Ottersen O.P., Dawson T.M., Dawson V.L.;
RT   "Localization of LRRK2 to membranous and vesicular structures in mammalian
RT   brain.";
RL   Ann. Neurol. 60:557-569(2006).
RN   [11]
RP   FUNCTION, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699; SER-2019
RP   AND THR-2020, AND VARIANT MET-1906.
RX   PubMed=17114044; DOI=10.1016/j.neuron.2006.10.008;
RA   MacLeod D., Dowman J., Hammond R., Leete T., Inoue K., Abeliovich A.;
RT   "The familial Parkinsonism gene LRRK2 regulates neurite process
RT   morphology.";
RL   Neuron 52:587-593(2006).
RN   [12]
RP   FUNCTION.
RX   PubMed=20949042; DOI=10.1371/journal.pone.0013191;
RA   Zach S., Felk S., Gillardon F.;
RT   "Signal transduction protein array analysis links LRRK2 to Ste20 kinases
RT   and PKC zeta that modulate neuronal plasticity.";
RL   PLoS ONE 5:E13191-E13191(2010).
RN   [13]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, AND
RP   CHARACTERIZATION OF VARIANT PARK8 SER-2019.
RX   PubMed=21850687; DOI=10.1002/humu.21582;
RA   Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J.,
RA   Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.;
RT   "Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3
RT   exacerbating oxidative stress-induced neuronal death.";
RL   Hum. Mutat. 32:1390-1397(2011).
RN   [14]
RP   FUNCTION, AND INTERACTION WITH TPCN2.
RX   PubMed=22012985; DOI=10.1093/hmg/ddr481;
RA   Gomez-Suaga P., Luzon-Toro B., Churamani D., Zhang L., Bloor-Young D.,
RA   Patel S., Woodman P.G., Churchill G.C., Hilfiker S.;
RT   "Leucine-rich repeat kinase 2 regulates autophagy through a calcium-
RT   dependent pathway involving NAADP.";
RL   Hum. Mol. Genet. 21:511-525(2012).
RN   [15]
RP   SUBUNIT, AND AUTOPHOSPHORYLATION.
RX   PubMed=22952686; DOI=10.1371/journal.pone.0043472;
RA   Civiero L., Vancraenenbroeck R., Belluzzi E., Beilina A., Lobbestael E.,
RA   Reyniers L., Gao F., Micetic I., De Maeyer M., Bubacco L., Baekelandt V.,
RA   Cookson M.R., Greggio E., Taymans J.M.;
RT   "Biochemical characterization of highly purified leucine-rich repeat
RT   kinases 1 and 2 demonstrates formation of homodimers.";
RL   PLoS ONE 7:E43472-E43472(2012).
RN   [16]
RP   FUNCTION IN RETROGRADE TRANSPORT, INTERACTION WITH RAB29 AND VPS35,
RP   SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 SER-2019, AND
RP   CHARACTERIZATION OF VARIANT MET-1906.
RX   PubMed=23395371; DOI=10.1016/j.neuron.2012.11.033;
RA   MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D.,
RA   MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A.,
RA   Abeliovich A.;
RT   "RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and
RT   Parkinson's disease risk.";
RL   Neuron 77:425-439(2013).
RN   [17]
RP   WD REPEATS.
RX   PubMed=23776530; DOI=10.1371/journal.pone.0065705;
RA   Wang Y., Jiang F., Zhuo Z., Wu X.H., Wu Y.D.;
RT   "A method for WD40 repeat detection and secondary structure prediction.";
RL   PLoS ONE 8:E65705-E65705(2013).
RN   [18]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [19]
RP   FUNCTION, SUBCELLULAR LOCATION, ELECTRON MICROSCOPY, WD REPEATS, AND
RP   CHARACTERIZATION OF VARIANT ARG-2385.
RX   PubMed=24687852; DOI=10.1128/mcb.00914-13;
RA   Piccoli G., Onofri F., Cirnaru M.D., Kaiser C.J., Jagtap P.,
RA   Kastenmuller A., Pischedda F., Marte A., von Zweydorf F., Vogt A.,
RA   Giesert F., Pan L., Antonucci F., Kiel C., Zhang M., Weinkauf S.,
RA   Sattler M., Sala C., Matteoli M., Ueffing M., Gloeckner C.J.;
RT   "Leucine-rich repeat kinase 2 binds to neuronal vesicles through protein
RT   interactions mediated by its C-terminal WD40 domain.";
RL   Mol. Cell. Biol. 34:2147-2161(2014).
RN   [20]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION
RP   WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441;
RP   CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND
RP   ARG-2385, AND MUTAGENESIS OF ASP-1994.
RX   PubMed=26824392; DOI=10.7554/elife.12813;
RA   Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S.,
RA   Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J.,
RA   Morrow J.A., Reith A.D., Alessi D.R., Mann M.;
RT   "Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates
RT   a subset of Rab GTPases.";
RL   Elife 5:0-0(2016).
RN   [21]
RP   FUNCTION, INTERACTION WITH MAPT, SUBCELLULAR LOCATION, CHARACTERIZATION OF
RP   VARIANT PAR8 SER-2019, AND MUTAGENESIS OF LYS-1906; ASP-1994 AND ASP-2017.
RX   PubMed=26014385; DOI=10.1007/s12035-015-9209-z;
RA   Guerreiro P.S., Gerhardt E., Lopes da Fonseca T., Baehr M., Outeiro T.F.,
RA   Eckermann K.;
RT   "LRRK2 Promotes Tau Accumulation, Aggregation and Release.";
RL   Mol. Neurobiol. 53:3124-3135(2016).
RN   [22]
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-1906.
RX   PubMed=27830463; DOI=10.1007/s13238-016-0326-x;
RA   Yan R., Liu Z.;
RT   "LRRK2 enhances Nod1/2-mediated inflammatory cytokine production by
RT   promoting Rip2 phosphorylation.";
RL   Protein Cell 8:55-66(2017).
RN   [23]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION OF VARIANTS PARK8
RP   GLY-1441; CYS-1699 AND SER-2019, AND MUTAGENESIS OF ASP-2017.
RX   PubMed=29125462; DOI=10.7554/elife.31012;
RA   Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O.,
RA   Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R.,
RA   Mann M.;
RT   "Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation
RT   establishes a connection to ciliogenesis.";
RL   Elife 6:0-0(2017).
RN   [24]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP,
RP   PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8
RP   GLY-1441 AND SER-2019, AND MUTAGENESIS OF ASP-1994.
RX   PubMed=28720718; DOI=10.1126/scisignal.aam6790;
RA   Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z.,
RA   Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L.,
RA   Tan E.K.;
RT   "Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD
RT   activity and neurotoxicity in Parkinson's disease.";
RL   Sci. Signal. 10:0-0(2017).
RN   [25]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY,
RP   CHARACTERIZATION OF VARIANT PARK8 SER-2019, AND PHOSPHORYLATION AT SER-935.
RX   PubMed=29127255; DOI=10.1042/bcj20170803;
RA   Fan Y., Howden A.J.M., Sarhan A.R., Lis P., Ito G., Martinez T.N.,
RA   Brockmann K., Gasser T., Alessi D.R., Sammler E.M.;
RT   "Interrogating Parkinson's disease LRRK2 kinase pathway activity by
RT   assessing Rab10 phosphorylation in human neutrophils.";
RL   Biochem. J. 475:23-44(2018).
RN   [26]
RP   FUNCTION, CATALYTIC ACTIVITY, AND VARIANTS PARK8 GLY-1441 AND SER-2019.
RX   PubMed=30398148; DOI=10.7554/elife.40202;
RA   Dhekne H.S., Yanatori I., Gomez R.C., Tonelli F., Diez F., Schuele B.,
RA   Steger M., Alessi D.R., Pfeffer S.R.;
RT   "A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and
RT   Sonic hedgehog signaling in the brain.";
RL   Elife 7:0-0(2018).
RN   [27]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP   PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292,
RP   CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699;
RP   HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, AND MUTAGENESIS OF
RP   CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790;
RP   LEU-791; THR-1348; ARG-1441; TYR-1699; ASP-2017 AND GLY-2019.
RX   PubMed=29212815; DOI=10.15252/embj.201798099;
RA   Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M.,
RA   Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.;
RT   "Rab29 activation of the Parkinson's disease-associated LRRK2 kinase.";
RL   EMBO J. 37:1-18(2018).
RN   [28]
RP   ERRATUM OF PUBMED:29212815.
RX   PubMed=30647193; DOI=10.15252/embj.2018101237;
RA   Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M.,
RA   Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.;
RL   EMBO J. 38:0-0(2019).
RN   [29]
RP   SUBCELLULAR LOCATION, AND UBIQUITINATION BY TRIM1.
RX   PubMed=35266954; DOI=10.1083/jcb.202010065;
RA   Stormo A.E.D., Shavarebi F., FitzGibbon M., Earley E.M., Ahrendt H.,
RA   Lum L.S., Verschueren E., Swaney D.L., Skibinski G., Ravisankar A.,
RA   van Haren J., Davis E.J., Johnson J.R., Von Dollen J., Balen C., Porath J.,
RA   Crosio C., Mirescu C., Iaccarino C., Dauer W.T., Nichols R.J., Wittmann T.,
RA   Cox T.C., Finkbeiner S., Krogan N.J., Oakes S.A., Hiniker A.;
RT   "The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization,
RT   degradation, and toxicity.";
RL   J. Cell Biol. 221:0-0(2022).
RN   [30]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1333-1516 IN COMPLEX WITH GDP,
RP   FUNCTION, GTPASE ACTIVITY, ACTIVITY REGULATION, SUBUNIT, DOMAIN ROC, AND
RP   MUTAGENESIS OF THR-1343 AND ARG-1398.
RX   PubMed=18230735; DOI=10.1073/pnas.0709098105;
RA   Deng J., Lewis P.A., Greggio E., Sluch E., Beilina A., Cookson M.R.;
RT   "Structure of the ROC domain from the Parkinson's disease-associated
RT   leucine-rich repeat kinase 2 reveals a dimeric GTPase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:1499-1504(2008).
RN   [31] {ECO:0007744|PDB:5MY9, ECO:0007744|PDB:5MYC}
RP   X-RAY CRYSTALLOGRAPHY (1.33 ANGSTROMS) OF 929-941 IN COMPLEX WITH SFN,
RP   INTERACTION WITH YWHAG, PHOSPHORYLATION AT SER-910; SER-935; SER-955;
RP   SER-973 AND SER-1444, AND CHARACTERIZATION OF VARIANT PARK8 CYS-1441.
RX   PubMed=28202711; DOI=10.1042/bcj20161078;
RA   Stevers L.M., de Vries R.M., Doveston R.G., Milroy L.G., Brunsveld L.,
RA   Ottmann C.;
RT   "Structural interface between LRRK2 and 14-3-3 protein.";
RL   Biochem. J. 474:1273-1287(2017).
RN   [32] {ECO:0007744|PDB:6DLO, ECO:0007744|PDB:6DLP}
RP   X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 2142-2527, FUNCTION, CATALYTIC
RP   ACTIVITY, SUBUNIT, DOMAIN, PHOSPHORYLATION AT SER-935 AND SER-1292,
RP   CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; SER-2019; ASP-2175; TYR-2189;
RP   ILE-2356; ARG-2385; MET-2390 AND ILE-2439, AND MUTAGENESIS OF ASP-2017;
RP   LEU-2343; PHE-2344; SER-2345; TYR-2346; HIS-2391; ARG-2394; GLU-2395;
RP   MET-2408 AND SER-2409.
RX   PubMed=30635421; DOI=10.1073/pnas.1817889116;
RA   Zhang P., Fan Y., Ru H., Wang L., Magupalli V.G., Taylor S.S., Alessi D.R.,
RA   Wu H.;
RT   "Crystal structure of the WD40 domain dimer of LRRK2.";
RL   Proc. Natl. Acad. Sci. U.S.A. 116:1579-1584(2019).
RN   [33]
RP   VARIANTS PARK8 GLY-1441 AND CYS-1699, AND TISSUE SPECIFICITY.
RX   PubMed=15541308; DOI=10.1016/j.neuron.2004.10.023;
RA   Paisan-Ruiz C., Jain S., Evans E.W., Gilks W.P., Simon J., van der Brug M.,
RA   Lopez de Munain A., Aparicio S., Gil A.M., Khan N.L., Johnson J.,
RA   Martinez J.R., Nicholl D., Carrera I.M., Pena A.S., de Silva R., Lees A.J.,
RA   Marti-Masso J.F., Perez-Tur J., Wood N.W., Singleton A.B.;
RT   "Cloning of the gene containing mutations that cause PARK8-linked
RT   Parkinson's disease.";
RL   Neuron 44:595-600(2004).
RN   [34]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=15726496; DOI=10.1086/429256;
RA   Kachergus J.M., Mata I.F., Hulihan M., Taylor J.P., Lincoln S., Aasly J.O.,
RA   Gibson J.M., Ross O.A., Lynch T., Wiley J., Payami H., Nutt J.,
RA   Maraganore D.M., Czyzewski K., Styczynska M., Wszolek Z.K., Farrer M.J.,
RA   Toft M.;
RT   "Identification of a novel LRRK2 mutation linked to autosomal dominant
RT   parkinsonism: evidence of a common founder across European populations.";
RL   Am. J. Hum. Genet. 76:672-680(2005).
RN   [35]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=15732108; DOI=10.1002/ana.20401;
RA   Hernandez D.G., Paisan-Ruiz C., McInerney-Leo A., Jain S.,
RA   Meyer-Lindenberg A., Evans E.W., Berman K.F., Johnson J., Auburger G.,
RA   Schaeffer A.A., Lopez G.J., Nussbaum R.L., Singleton A.B.;
RT   "Clinical and positron emission tomography of Parkinson's disease caused by
RT   LRRK2.";
RL   Ann. Neurol. 57:453-456(2005).
RN   [36]
RP   VARIANT PARK8/PD SER-2019.
RX   PubMed=15852371; DOI=10.1002/ana.20456;
RA   Aasly J.O., Toft M., Fernandez-Mata I., Kachergus J.M., Hulihan M.,
RA   White L.R., Farrer M.J.;
RT   "Clinical features of LRRK2-associated Parkinson's disease in central
RT   Norway.";
RL   Ann. Neurol. 57:762-765(2005).
RN   [37]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=16240353; DOI=10.1002/ana.20636;
RG   French Parkinson's disease genetics study group;
RA   Lesage S., Ibanez P., Lohmann E., Pollak P., Tison F., Tazir M.,
RA   Leutenegger A.-L., Guimaraes J., Bonnet A.-M., Agid Y., Duerr A., Brice A.;
RT   "G2019S LRRK2 mutation in French and North African families with
RT   Parkinson's disease.";
RL   Ann. Neurol. 58:784-787(2005).
RN   [38]
RP   VARIANT PARK8 THR-2020.
RX   PubMed=15880653; DOI=10.1002/ana.20484;
RA   Funayama M., Hasegawa K., Ohta E., Kawashima N., Komiyama M., Kowa H.,
RA   Tsuji S., Obata F.;
RT   "An LRRK2 mutation as a cause for the parkinsonism in the original PARK8
RT   family.";
RL   Ann. Neurol. 57:918-921(2005).
RN   [39]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=15929036; DOI=10.1002/ana.20510;
RA   Deng H., Le W., Guo Y., Hunter C.B., Xie W., Jankovic J.;
RT   "Genetic and clinical identification of Parkinson's disease patients with
RT   LRRK2 G2019S mutation.";
RL   Ann. Neurol. 57:933-934(2005).
RN   [40]
RP   VARIANTS PARK8 MET-793; ARG-930; CYS-1096; THR-1228; SER-2019 AND THR-2020,
RP   AND VARIANT LYS-551.
RX   PubMed=16251215; DOI=10.1093/brain/awh666;
RA   Berg D., Schweitzer K., Leitner P., Zimprich A., Lichtner P., Belcredi P.,
RA   Bruessel T., Schulte C., Maass S., Naegele T.;
RT   "Type and frequency of mutations in the LRRK2 gene in familial and sporadic
RT   Parkinson's disease.";
RL   Brain 128:3000-3011(2005).
RN   [41]
RP   VARIANTS PARK8 CYS-1699; HIS-1941; SER-2019 AND ILE-2356.
RX   PubMed=16272164; DOI=10.1093/brain/awh667;
RA   Khan N.L., Jain S., Lynch J.M., Pavese N., Abou-Sleiman P.M., Holton J.L.,
RA   Healy D.G., Gilks W.P., Sweeney M.G., Ganguly M., Gibbons V., Gandhi S.,
RA   Vaughan J., Eunson L.H., Katzenschlager R., Gayton J., Lennox G.,
RA   Revesz T., Nicholl D., Bhatia K.P., Quinn N., Brooks D., Lees A.J.,
RA   Davis M.B., Piccini P., Singleton A.B., Wood N.W.;
RT   "Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial
RT   Parkinson's disease: clinical, pathological, olfactory and functional
RT   imaging and genetic data.";
RL   Brain 128:2786-2796(2005).
RN   [42]
RP   VARIANTS PARK8 VAL-1371; CYS-1441 AND SER-2019.
RX   PubMed=16333314; DOI=10.1038/sj.ejhg.5201539;
RA   Di Fonzo A., Tassorelli C., De Mari M., Chien H.F., Ferreira J., Rohe C.F.,
RA   Riboldazzi G., Antonini A., Albani G., Mauro A., Marconi R., Abbruzzese G.,
RA   Lopiano L., Fincati E., Guidi M., Marini P., Stocchi F., Onofrj M.,
RA   Toni V., Tinazzi M., Fabbrini G., Lamberti P., Vanacore N., Meco G.,
RA   Leitner P., Uitti R.J., Wszolek Z.K., Gasser T., Simons E.J.,
RA   Breedveld G.J., Goldwurm S., Pezzoli G., Sampaio C., Barbosa E.,
RA   Martignoni E., Oostra B.A., Bonifati V.;
RT   "Comprehensive analysis of the LRRK2 gene in sixty families with
RT   Parkinson's disease.";
RL   Eur. J. Hum. Genet. 14:322-331(2006).
RN   [43]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=16272257; DOI=10.1136/jmg.2005.035568;
RA   Goldwurm S., Di Fonzo A., Simons E.J., Rohe C.F., Zini M., Canesi M.,
RA   Tesei S., Zecchinelli A., Antonini A., Mariani C., Meucci N., Sacilotto G.,
RA   Sironi F., Salani G., Ferreira J., Chien H.F., Fabrizio E., Vanacore N.,
RA   Dalla Libera A., Stocchi F., Diroma C., Lamberti P., Sampaio C., Meco G.,
RA   Barbosa E., Bertoli-Avella A.M., Breedveld G.J., Oostra B.A., Pezzoli G.,
RA   Bonifati V.;
RT   "The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late
RT   onset Parkinson's disease and originates from a common ancestor.";
RL   J. Med. Genet. 42:E65-E65(2005).
RN   [44]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=15680455; DOI=10.1016/s0140-6736(05)17828-3;
RG   The Parkinson study group-PROGENI investigators;
RA   Nichols W.C., Pankratz N., Hernandez D., Paisan-Ruiz C., Jain S.,
RA   Halter C.A., Michaels V.E., Reed T., Rudolph A., Shults C.W., Singleton A.,
RA   Foroud T.;
RT   "Genetic screening for a single common LRRK2 mutation in familial
RT   Parkinson's disease.";
RL   Lancet 365:410-412(2005).
RN   [45]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=15680456; DOI=10.1016/s0140-6736(05)17829-5;
RG   The Italian Parkinson genetics network;
RA   Di Fonzo A., Rohe C.F., Ferreira J., Chien H.F., Vacca L., Stocchi F.,
RA   Guedes L., Fabrizio E., Manfredi M., Vanacore N., Goldwurm S.,
RA   Breedveld G.J., Sampaio C., Meco G., Barbosa E., Oostra B.A., Bonifati V.;
RT   "A frequent LRRK2 gene mutation associated with autosomal dominant
RT   Parkinson's disease.";
RL   Lancet 365:412-415(2005).
RN   [46]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=15680457; DOI=10.1016/s0140-6736(05)17830-1;
RA   Gilks W.P., Abou-Sleiman P.M., Gandhi S., Jain S., Singleton A., Lees A.J.,
RA   Shaw K., Bhatia K.P., Bonifati V., Quinn N.P., Lynch J.M., Healy D.G.,
RA   Holton J.L., Revesz T., Wood N.W.;
RT   "A common LRRK2 mutation in idiopathic Parkinson's disease.";
RL   Lancet 365:415-416(2005).
RN   [47]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=15811454; DOI=10.1016/s0140-6736(05)74809-1;
RA   Toft M., Mata I.F., Kachergus J.M., Ross O.A., Farrer M.J.;
RT   "LRRK2 mutations and Parkinsonism.";
RL   Lancet 365:1229-1230(2005).
RN   [48]
RP   VARIANT SER-2019.
RX   PubMed=16001413; DOI=10.1002/mds.20618;
RA   Kay D.M., Kramer P., Higgins D.S., Zabetian C.P., Payami H.;
RT   "Escaping Parkinson's disease: a neurologically healthy octogenarian with
RT   the LRRK2 G2019S mutation.";
RL   Mov. Disord. 20:1077-1078(2005).
RN   [49]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=16250030; DOI=10.1002/mds.20751;
RA   Kay D.M., Zabetian C.P., Factor S.A., Nutt J.G., Samii A., Griffith A.,
RA   Bird T.D., Kramer P., Higgins D.S., Payami H.;
RT   "Parkinson's disease and LRRK2: frequency of a common mutation in U.S.
RT   movement disorder clinics.";
RL   Mov. Disord. 21:519-523(2006).
RN   [50]
RP   VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; GLN-1514; SER-1542; GLU-1598;
RP   PRO-1628; CYS-1699; THR-1869; THR-2012; SER-2019; THR-2020 AND ARG-2385,
RP   AND VARIANTS PRO-119; LYS-551; VAL-723; MET-793; VAL-1122; ALA-1262;
RP   HIS-1398; THR-1646; THR-1647; ASP-2081; LEU-2119; ILE-2261 AND THR-2397.
RX   PubMed=16172858; DOI=10.1007/s10048-005-0005-1;
RA   Mata I.F., Kachergus J.M., Taylor J.P., Lincoln S., Aasly J., Lynch T.,
RA   Hulihan M.M., Cobb S.A., Wu R.-M., Lu C.-S., Lahoz C., Wszolek Z.K.,
RA   Farrer M.J.;
RT   "Lrrk2 pathogenic substitutions in Parkinson's disease.";
RL   Neurogenetics 6:171-177(2005).
RN   [51]
RP   VARIANTS PARK8 VAL-1371 AND SER-2019, AND VARIANTS HIS-1398 AND THR-2397.
RX   PubMed=16157901; DOI=10.1212/01.wnl.0000167552.79769.b3;
RA   Paisan-Ruiz C., Lang A.E., Kawarai T., Sato C., Salehi-Rad S., Fisman G.K.,
RA   Al-Khairallah T., St George-Hyslop P.H., Singleton A., Rogaeva E.;
RT   "LRRK2 gene in Parkinson disease: mutation analysis and case control
RT   association study.";
RL   Neurology 65:696-700(2005).
RN   [52]
RP   VARIANT PARK8 GLN-1067.
RX   PubMed=16247070; DOI=10.1212/01.wnl.0000180517.70572.37;
RA   Skipper L., Shen H., Chua E., Bonnard C., Kolatkar P., Tan L.C.S.,
RA   Jamora R.D., Puvan K., Puong K.Y., Zhao Y., Pavanni R., Wong M.C., Yuen Y.,
RA   Farrer M., Liu J.J., Tan E.K.;
RT   "Analysis of LRRK2 functional domains in nondominant Parkinson disease.";
RL   Neurology 65:1319-1321(2005).
RN   [53]
RP   VARIANTS PARK8 MET-793; THR-1869 AND SER-2019.
RX   PubMed=16157908; DOI=10.1212/01.wnl.0000169023.51764.b0;
RA   Farrer M., Stone J., Mata I.F., Lincoln S., Kachergus J., Hulihan M.,
RA   Strain K.J., Maraganore D.M.;
RT   "LRRK2 mutations in Parkinson disease.";
RL   Neurology 65:738-740(2005).
RN   [54]
RP   VARIANTS PARK8 CYS-1441; HIS-1441 AND SER-2019.
RX   PubMed=16157909; DOI=10.1212/01.wnl.0000172630.22804.73;
RA   Zabetian C.P., Samii A., Mosley A.D., Roberts J.W., Leis B.C., Yearout D.,
RA   Raskind W.H., Griffith A.;
RT   "A clinic-based study of the LRRK2 gene in Parkinson disease yields new
RT   mutations.";
RL   Neurology 65:741-744(2005).
RN   [55]
RP   VARIANT PARK8 GLY-1441.
RX   PubMed=15925109; DOI=10.1016/j.neulet.2005.03.033;
RA   Mata I.F., Taylor J.P., Kachergus J., Hulihan M., Huerta C., Lahoz C.,
RA   Blazquez M., Guisasola L.M., Salvador C., Ribacoba R., Martinez C.,
RA   Farrer M., Alvarez V.;
RT   "LRRK2 R1441G in Spanish patients with Parkinson's disease.";
RL   Neurosci. Lett. 382:309-311(2005).
RN   [56]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=16298482; DOI=10.1016/j.neulet.2005.10.083;
RA   Infante J., Rodriguez E., Combarros O., Mateo I., Fontalba A., Pascual J.,
RA   Oterino A., Polo J.M., Leno C., Berciano J.;
RT   "LRRK2 G2019S is a common mutation in Spanish patients with late-onset
RT   Parkinson's disease.";
RL   Neurosci. Lett. 395:224-226(2006).
RN   [57]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=16102999; DOI=10.1016/j.parkreldis.2005.05.004;
RA   Gosal D., Ross O.A., Wiley J., Irvine G.B., Johnston J.A., Toft M.,
RA   Mata I.F., Kachergus J., Hulihan M., Taylor J.P., Lincoln S.J.,
RA   Farrer M.J., Lynch T., Mark Gibson J.;
RT   "Clinical traits of LRRK2-associated Parkinson's disease in Ireland: a link
RT   between familial and idiopathic PD.";
RL   Parkinsonism Relat. Disord. 11:349-352(2005).
RN   [58]
RP   VARIANTS PARK8 CYS-1441; GLY-1441 AND SER-2019.
RX   PubMed=16533964; DOI=10.1001/archneur.63.3.377;
RA   Gaig C., Ezquerra M., Marti M.J., Munoz E., Valldeoriola F., Tolosa E.;
RT   "LRRK2 mutations in Spanish patients with Parkinson disease: frequency,
RT   clinical features, and incomplete penetrance.";
RL   Arch. Neurol. 63:377-382(2006).
RN   [59]
RP   CHARACTERIZATION OF VARIANT ARG-2385, AND ASSOCIATION WITH PARKINSON
RP   DISEASE.
RX   PubMed=17019612; DOI=10.1007/s00439-006-0268-0;
RA   Tan E.K., Zhao Y., Skipper L., Tan M.G., Di Fonzo A., Sun L.,
RA   Fook-Chong S., Tang S., Chua E., Yuen Y., Tan L., Pavanni R., Wong M.C.,
RA   Kolatkar P., Lu C.S., Bonifati V., Liu J.J.;
RT   "The LRRK2 Gly2385Arg variant is associated with Parkinson's disease:
RT   genetic and functional evidence.";
RL   Hum. Genet. 120:857-863(2007).
RN   [60]
RP   VARIANTS [LARGE SCALE ANALYSIS] PRO-119; VAL-419; LYS-551; VAL-723;
RP   HIS-1398; GLN-1514; SER-1542; GLN-1550 AND PRO-1723.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
RN   [61]
RP   VARIANTS PARK8 VAL-712; LEU-1728; HIS-1728; SER-2019; MET-2141; HIS-2143
RP   AND HIS-2466, AND VARIANTS SER-228; VAL-716; GLU-871; PHE-1870 AND
RP   LYS-2395.
RX   PubMed=18213618; DOI=10.1002/humu.20668;
RA   Paisan-Ruiz C., Nath P., Washecka N., Gibbs J.R., Singleton A.B.;
RT   "Comprehensive analysis of LRRK2 in publicly available Parkinson's disease
RT   cases and neurologically normal controls.";
RL   Hum. Mutat. 29:485-490(2008).
RN   [62]
RP   VARIANT ILE-1359.
RX   PubMed=21248752; DOI=10.1038/nature09639;
RA   Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA   Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA   Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA   Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA   Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA   Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA   Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA   Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT   "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT   PBRM1 in renal carcinoma.";
RL   Nature 469:539-542(2011).
RN   [63]
RP   VARIANTS PARK8 PRO-1628 AND ARG-2385.
RX   PubMed=21641266; DOI=10.1016/j.parkreldis.2010.11.008;
RA   Bardien S., Lesage S., Brice A., Carr J.;
RT   "Genetic characteristics of leucine-rich repeat kinase 2 (LRRK2) associated
RT   Parkinson's disease.";
RL   Parkinsonism Relat. Disord. 17:501-508(2011).
RN   [64]
RP   VARIANTS LYS-551; VAL-723; HIS-1398; GLN-1514; SER-1542; PRO-1628;
RP   THR-1646; THR-1647; ASP-2081 AND THR-2397.
RX   PubMed=22415848; DOI=10.1002/humu.22075;
RA   Rubio J.P., Topp S., Warren L., St Jean P.L., Wegmann D., Kessner D.,
RA   Novembre J., Shen J., Fraser D., Aponte J., Nangle K., Cardon L.R.,
RA   Ehm M.G., Chissoe S.L., Whittaker J.C., Nelson M.R., Mooser V.E.;
RT   "Deep sequencing of the LRRK2 gene in 14,002 individuals reveals evidence
RT   of purifying selection and independent origin of the p.Arg1628Pro mutation
RT   in Europe.";
RL   Hum. Mutat. 33:1087-1098(2012).
RN   [65]
RP   VARIANT PARK8 SER-2019.
RX   PubMed=22956510; DOI=10.1002/mds.25132;
RA   Kilarski L.L., Pearson J.P., Newsway V., Majounie E., Knipe M.D.,
RA   Misbahuddin A., Chinnery P.F., Burn D.J., Clarke C.E., Marion M.H.,
RA   Lewthwaite A.J., Nicholl D.J., Wood N.W., Morrison K.E.,
RA   Williams-Gray C.H., Evans J.R., Sawcer S.J., Barker R.A.,
RA   Wickremaratchi M.M., Ben-Shlomo Y., Williams N.M., Morris H.R.;
RT   "Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-
RT   1) and LRRK2 in early-onset Parkinson's disease.";
RL   Mov. Disord. 27:1522-1529(2012).
RN   [66]
RP   CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; CYS-1699 AND SER-2019,
RP   CHARACTERIZATION OF VARIANT ARG-2385, FUNCTION, SUBCELLULAR LOCATION,
RP   INTERACTION WITH SEC16A, AND MUTAGENESIS OF LYS-1347 AND ASP-1994.
RX   PubMed=25201882; DOI=10.15252/embj.201487807;
RA   Cho H.J., Yu J., Xie C., Rudrabhatla P., Chen X., Wu J., Parisiadou L.,
RA   Liu G., Sun L., Ma B., Ding J., Liu Z., Cai H.;
RT   "Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow
RT   ER-Golgi export.";
RL   EMBO J. 33:2314-2331(2014).
CC   -!- FUNCTION: Serine/threonine-protein kinase which phosphorylates a broad
CC       range of proteins involved in multiple processes such as neuronal
CC       plasticity, innate immunity, autophagy, and vesicle trafficking
CC       (PubMed:20949042, PubMed:22012985, PubMed:26824392, PubMed:27830463,
CC       PubMed:29125462, PubMed:28720718, PubMed:29127255, PubMed:30398148,
CC       PubMed:29212815, PubMed:30635421, PubMed:21850687, PubMed:23395371,
CC       PubMed:17114044, PubMed:24687852, PubMed:26014385, PubMed:25201882). Is
CC       a key regulator of RAB GTPases by regulating the GTP/GDP exchange and
CC       interaction partners of RABs through phosphorylation (PubMed:26824392,
CC       PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815,
CC       PubMed:29125462, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C,
CC       RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and
CC       RAB43 (PubMed:26824392, PubMed:28720718, PubMed:29127255,
CC       PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421,
CC       PubMed:23395371). Regulates the RAB3IP-catalyzed GDP/GTP exchange for
CC       RAB8A through the phosphorylation of 'Thr-72' on RAB8A
CC       (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1
CC       and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392).
CC       Regulates primary ciliogenesis through phosphorylation of RAB8A and
CC       RAB10, which promotes SHH signaling in the brain (PubMed:29125462,
CC       PubMed:30398148). Together with RAB29, plays a role in the retrograde
CC       trafficking pathway for recycling proteins, such as mannose-6-phosphate
CC       receptor (M6PR), between lysosomes and the Golgi apparatus in a
CC       retromer-dependent manner (PubMed:23395371). Regulates neuronal process
CC       morphology in the intact central nervous system (CNS)
CC       (PubMed:17114044). Plays a role in synaptic vesicle trafficking
CC       (PubMed:24687852). Plays an important role in recruiting SEC16A to
CC       endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi
CC       vesicle-mediated transport and ERES organization (PubMed:25201882).
CC       Positively regulates autophagy through a calcium-dependent activation
CC       of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process
CC       involves activation of nicotinic acid adenine dinucleotide phosphate
CC       (NAADP) receptors, increase in lysosomal pH, and calcium release from
CC       lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By
CC       phosphorylating APP on 'Thr-743', which promotes the production and the
CC       nuclear translocation of the APP intracellular domain (AICD), regulates
CC       dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive
CC       regulator of innate immunity by mediating phosphorylation of RIPK2
CC       downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation
CC       (PubMed:27830463). Independent of its kinase activity, inhibits the
CC       proteasomal degradation of MAPT, thus promoting MAPT oligomerization
CC       and secretion (PubMed:26014385). In addition, has GTPase activity via
CC       its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735,
CC       PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:29212815).
CC       {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735,
CC       ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687,
CC       ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371,
CC       ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882,
CC       ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392,
CC       ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718,
CC       ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255,
CC       ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148,
CC       ECO:0000269|PubMed:30635421}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.1; Evidence={ECO:0000269|PubMed:26824392,
CC         ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462,
CC         ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815,
CC         ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC         Evidence={ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463,
CC         ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462,
CC         ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815,
CC         ECO:0000269|PubMed:30398148};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC         Evidence={ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:26824392,
CC         ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462,
CC         ECO:0000269|PubMed:29212815};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718,
CC         ECO:0000269|PubMed:29125462};
CC   -!- ACTIVITY REGULATION: Kinase activity is regulated by the GTPase
CC       activity of the ROC domain (PubMed:29212815, PubMed:18230735). GTP-
CC       bound LLRK2 kinase activity is stimulated by RAB29 (PubMed:29212815).
CC       Inhibited by small molecule inhibitor MLi-2 (PubMed:26824392,
CC       PubMed:29127255). {ECO:0000269|PubMed:18230735,
CC       ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:29127255,
CC       ECO:0000269|PubMed:29212815}.
CC   -!- SUBUNIT: Homodimer (PubMed:22952686, PubMed:18230735, PubMed:30635421).
CC       Interacts with PRKN, PRDX3, and TPCN2 (PubMed:16352719,
CC       PubMed:21850687, PubMed:22012985). Interacts with VPS35 and RAB29
CC       (PubMed:23395371). Interacts (via ROC domain) with SEC16A
CC       (PubMed:25201882). Interacts with APP; interaction promotes
CC       phosphorylation of 'Thr-743' of APP (PubMed:28720718). Interacts with
CC       MAPT (PubMed:26014385). Interacts with RAB8A, RAB10, and RAB12
CC       (PubMed:26824392). Interacts with YWHAG; this interaction is dependent
CC       on phosphorylation of Ser-910 and either Ser-935 or Ser-1444
CC       (PubMed:28202711). Interacts with SFN; this interaction is dependent on
CC       phosphorylation of Ser-910 and/or Ser-935 (PubMed:28202711).
CC       {ECO:0000269|PubMed:16352719, ECO:0000269|PubMed:18230735,
CC       ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985,
CC       ECO:0000269|PubMed:22952686, ECO:0000269|PubMed:23395371,
CC       ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385,
CC       ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28202711,
CC       ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:30635421}.
CC   -!- INTERACTION:
CC       Q5S007; Q9UKV8: AGO2; NbExp=3; IntAct=EBI-5323863, EBI-528269;
CC       Q5S007; O43865: AHCYL1; NbExp=3; IntAct=EBI-5323863, EBI-2371423;
CC       Q5S007; P31749: AKT1; NbExp=6; IntAct=EBI-5323863, EBI-296087;
CC       Q5S007; Q8N8V4: ANKS4B; NbExp=2; IntAct=EBI-5323863, EBI-9658517;
CC       Q5S007; O00203: AP3B1; NbExp=2; IntAct=EBI-5323863, EBI-1044383;
CC       Q5S007; Q8N6T3-2: ARFGAP1; NbExp=6; IntAct=EBI-5323863, EBI-6288865;
CC       Q5S007; Q14155: ARHGEF7; NbExp=7; IntAct=EBI-5323863, EBI-717515;
CC       Q5S007; O95816: BAG2; NbExp=3; IntAct=EBI-5323863, EBI-355275;
CC       Q5S007; O95817: BAG3; NbExp=2; IntAct=EBI-5323863, EBI-747185;
CC       Q5S007; Q9UL15: BAG5; NbExp=12; IntAct=EBI-5323863, EBI-356517;
CC       Q5S007; P10415-1: BCL2; NbExp=2; IntAct=EBI-5323863, EBI-4370304;
CC       Q5S007; Q13191: CBLB; NbExp=4; IntAct=EBI-5323863, EBI-744027;
CC       Q5S007; Q16543: CDC37; NbExp=7; IntAct=EBI-5323863, EBI-295634;
CC       Q5S007; P60953: CDC42; NbExp=3; IntAct=EBI-5323863, EBI-81752;
CC       Q5S007; Q9UKI2: CDC42EP3; NbExp=2; IntAct=EBI-5323863, EBI-723480;
CC       Q5S007; Q9Y6A4: CFAP20; NbExp=3; IntAct=EBI-5323863, EBI-1046872;
CC       Q5S007; P05060: CHGB; NbExp=3; IntAct=EBI-5323863, EBI-712619;
CC       Q5S007; Q9ULV4: CORO1C; NbExp=3; IntAct=EBI-5323863, EBI-351384;
CC       Q5S007; P48729-1: CSNK1A1; NbExp=2; IntAct=EBI-5323863, EBI-10106282;
CC       Q5S007; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-5323863, EBI-9087876;
CC       Q5S007; Q9NWM3: CUEDC1; NbExp=2; IntAct=EBI-5323863, EBI-5838167;
CC       Q5S007; P53355: DAPK1; NbExp=2; IntAct=EBI-5323863, EBI-358616;
CC       Q5S007; Q05193: DNM1; NbExp=4; IntAct=EBI-5323863, EBI-713135;
CC       Q5S007; O00429: DNM1L; NbExp=14; IntAct=EBI-5323863, EBI-724571;
CC       Q5S007; O00429-3: DNM1L; NbExp=2; IntAct=EBI-5323863, EBI-6896746;
CC       Q5S007; O14640-2: DVL1; NbExp=7; IntAct=EBI-5323863, EBI-6504027;
CC       Q5S007; O14641: DVL2; NbExp=5; IntAct=EBI-5323863, EBI-740850;
CC       Q5S007; Q92997: DVL3; NbExp=4; IntAct=EBI-5323863, EBI-739789;
CC       Q5S007; P30084: ECHS1; NbExp=4; IntAct=EBI-5323863, EBI-719602;
CC       Q5S007; Q05639: EEF1A2; NbExp=3; IntAct=EBI-5323863, EBI-354943;
CC       Q5S007; Q13158: FADD; NbExp=4; IntAct=EBI-5323863, EBI-494804;
CC       Q5S007; O14976: GAK; NbExp=11; IntAct=EBI-5323863, EBI-714707;
CC       Q5S007; P49841: GSK3B; NbExp=7; IntAct=EBI-5323863, EBI-373586;
CC       Q5S007; P11142: HSPA8; NbExp=6; IntAct=EBI-5323863, EBI-351896;
CC       Q5S007; Q71RC2: LARP4; NbExp=3; IntAct=EBI-5323863, EBI-2878091;
CC       Q5S007; Q4G0J3: LARP7; NbExp=3; IntAct=EBI-5323863, EBI-2371923;
CC       Q5S007; P07195: LDHB; NbExp=2; IntAct=EBI-5323863, EBI-358748;
CC       Q5S007; O75581: LRP6; NbExp=4; IntAct=EBI-5323863, EBI-910915;
CC       Q5S007; Q38SD2: LRRK1; NbExp=5; IntAct=EBI-5323863, EBI-1050422;
CC       Q5S007; Q5S007: LRRK2; NbExp=68; IntAct=EBI-5323863, EBI-5323863;
CC       Q5S007; PRO_0000018605 [P46821]: MAP1B; NbExp=5; IntAct=EBI-5323863, EBI-9517186;
CC       Q5S007; P46734: MAP2K3; NbExp=5; IntAct=EBI-5323863, EBI-602462;
CC       Q5S007; P52564: MAP2K6; NbExp=4; IntAct=EBI-5323863, EBI-448135;
CC       Q5S007; O14733: MAP2K7; NbExp=3; IntAct=EBI-5323863, EBI-492605;
CC       Q5S007; P10636-2: MAPT; NbExp=3; IntAct=EBI-5323863, EBI-7796412;
CC       Q5S007; P10636-8: MAPT; NbExp=9; IntAct=EBI-5323863, EBI-366233;
CC       Q5S007; P42679: MATK; NbExp=2; IntAct=EBI-5323863, EBI-751664;
CC       Q5S007; O95140: MFN2; NbExp=3; IntAct=EBI-5323863, EBI-3324756;
CC       Q5S007; P49406: MRPL19; NbExp=3; IntAct=EBI-5323863, EBI-1188518;
CC       Q5S007; P26038: MSN; NbExp=19; IntAct=EBI-5323863, EBI-528768;
CC       Q5S007; Q7L592: NDUFAF7; NbExp=2; IntAct=EBI-5323863, EBI-2555519;
CC       Q5S007; Q96PY6: NEK1; NbExp=2; IntAct=EBI-5323863, EBI-373615;
CC       Q5S007; Q13469: NFATC2; NbExp=3; IntAct=EBI-5323863, EBI-716258;
CC       Q5S007; Q8WUM0: NUP133; NbExp=4; IntAct=EBI-5323863, EBI-295695;
CC       Q5S007; O60313: OPA1; NbExp=5; IntAct=EBI-5323863, EBI-1054131;
CC       Q5S007; Q9NQU5: PAK6; NbExp=2; IntAct=EBI-5323863, EBI-1053685;
CC       Q5S007; P62136: PPP1CA; NbExp=6; IntAct=EBI-5323863, EBI-357253;
CC       Q5S007; Q12972: PPP1R8; NbExp=3; IntAct=EBI-5323863, EBI-716633;
CC       Q5S007; P63151: PPP2R2A; NbExp=4; IntAct=EBI-5323863, EBI-1048931;
CC       Q5S007; P30048: PRDX3; NbExp=14; IntAct=EBI-5323863, EBI-748336;
CC       Q5S007; P17612: PRKACA; NbExp=6; IntAct=EBI-5323863, EBI-476586;
CC       Q5S007; O60260: PRKN; NbExp=3; IntAct=EBI-5323863, EBI-716346;
CC       Q5S007; P61026: RAB10; NbExp=7; IntAct=EBI-5323863, EBI-726075;
CC       Q5S007; Q6IQ22: RAB12; NbExp=2; IntAct=EBI-5323863, EBI-4289591;
CC       Q5S007; Q9H0U4: RAB1B; NbExp=5; IntAct=EBI-5323863, EBI-1045214;
CC       Q5S007; O14966: RAB29; NbExp=15; IntAct=EBI-5323863, EBI-372165;
CC       Q5S007; Q13637: RAB32; NbExp=12; IntAct=EBI-5323863, EBI-9837586;
CC       Q5S007; P57729: RAB38; NbExp=4; IntAct=EBI-5323863, EBI-6552718;
CC       Q5S007; P61020: RAB5B; NbExp=9; IntAct=EBI-5323863, EBI-399401;
CC       Q5S007; P61006: RAB8A; NbExp=7; IntAct=EBI-5323863, EBI-722293;
CC       Q5S007; P63000: RAC1; NbExp=5; IntAct=EBI-5323863, EBI-413628;
CC       Q5S007; P41220: RGS2; NbExp=6; IntAct=EBI-5323863, EBI-712388;
CC       Q5S007; P62906: RPL10A; NbExp=4; IntAct=EBI-5323863, EBI-356860;
CC       Q5S007; P26373: RPL13; NbExp=4; IntAct=EBI-5323863, EBI-356849;
CC       Q5S007; P50914: RPL14; NbExp=2; IntAct=EBI-5323863, EBI-356746;
CC       Q5S007; P62750: RPL23A; NbExp=2; IntAct=EBI-5323863, EBI-353254;
CC       Q5S007; P62888: RPL30; NbExp=3; IntAct=EBI-5323863, EBI-353116;
CC       Q5S007; P49207: RPL34; NbExp=3; IntAct=EBI-5323863, EBI-1051893;
CC       Q5S007; Q9BUL9: RPP25; NbExp=3; IntAct=EBI-5323863, EBI-366570;
CC       Q5S007; P62280: RPS11; NbExp=5; IntAct=EBI-5323863, EBI-1047710;
CC       Q5S007; P62277: RPS13; NbExp=3; IntAct=EBI-5323863, EBI-351850;
CC       Q5S007; P62841: RPS15; NbExp=9; IntAct=EBI-5323863, EBI-372635;
CC       Q5S007; P62249: RPS16; NbExp=4; IntAct=EBI-5323863, EBI-352480;
CC       Q5S007; P62269: RPS18; NbExp=3; IntAct=EBI-5323863, EBI-352451;
CC       Q5S007; P15880: RPS2; NbExp=4; IntAct=EBI-5323863, EBI-443446;
CC       Q5S007; P60866: RPS20; NbExp=4; IntAct=EBI-5323863, EBI-353105;
CC       Q5S007; P62266: RPS23; NbExp=2; IntAct=EBI-5323863, EBI-353072;
CC       Q5S007; P42677: RPS27; NbExp=4; IntAct=EBI-5323863, EBI-356336;
CC       Q5S007; P23396: RPS3; NbExp=4; IntAct=EBI-5323863, EBI-351193;
CC       Q5S007; O15027: SEC16A; NbExp=8; IntAct=EBI-5323863, EBI-357515;
CC       Q5S007; P60896: SEM1; NbExp=3; IntAct=EBI-5323863, EBI-79819;
CC       Q5S007; P31947: SFN; NbExp=5; IntAct=EBI-5323863, EBI-476295;
CC       Q5S007; Q99961: SH3GL1; NbExp=3; IntAct=EBI-5323863, EBI-697911;
CC       Q5S007; Q99962: SH3GL2; NbExp=4; IntAct=EBI-5323863, EBI-77938;
CC       Q5S007; P12235: SLC25A4; NbExp=2; IntAct=EBI-5323863, EBI-359074;
CC       Q5S007; P05141: SLC25A5; NbExp=2; IntAct=EBI-5323863, EBI-355133;
CC       Q5S007; P12236: SLC25A6; NbExp=2; IntAct=EBI-5323863, EBI-356254;
CC       Q5S007; O95295: SNAPIN; NbExp=5; IntAct=EBI-5323863, EBI-296723;
CC       Q5S007; P37840: SNCA; NbExp=6; IntAct=EBI-5323863, EBI-985879;
CC       Q5S007; Q8NHS9: SPATA22; NbExp=3; IntAct=EBI-5323863, EBI-7067260;
CC       Q5S007; Q13501: SQSTM1; NbExp=18; IntAct=EBI-5323863, EBI-307104;
CC       Q5S007; Q9UNE7: STUB1; NbExp=4; IntAct=EBI-5323863, EBI-357085;
CC       Q5S007; Q9UNE7-1: STUB1; NbExp=2; IntAct=EBI-5323863, EBI-15687717;
CC       Q5S007; Q9BQ70: TCF25; NbExp=3; IntAct=EBI-5323863, EBI-745182;
CC       Q5S007; Q6P3X3: TTC27; NbExp=3; IntAct=EBI-5323863, EBI-1057046;
CC       Q5S007; P07437: TUBB; NbExp=6; IntAct=EBI-5323863, EBI-350864;
CC       Q5S007; Q13885: TUBB2A; NbExp=3; IntAct=EBI-5323863, EBI-711595;
CC       Q5S007; P04350: TUBB4A; NbExp=6; IntAct=EBI-5323863, EBI-355007;
CC       Q5S007; P68371: TUBB4B; NbExp=3; IntAct=EBI-5323863, EBI-351356;
CC       Q5S007; Q9BUF5: TUBB6; NbExp=3; IntAct=EBI-5323863, EBI-356735;
CC       Q5S007; Q53GS9: USP39; NbExp=3; IntAct=EBI-5323863, EBI-1044822;
CC       Q5S007; P21796: VDAC1; NbExp=3; IntAct=EBI-5323863, EBI-354158;
CC       Q5S007; Q9Y6I7: WSB1; NbExp=5; IntAct=EBI-5323863, EBI-1171494;
CC       Q5S007; P31946: YWHAB; NbExp=5; IntAct=EBI-5323863, EBI-359815;
CC       Q5S007; P62258: YWHAE; NbExp=8; IntAct=EBI-5323863, EBI-356498;
CC       Q5S007; P61981: YWHAG; NbExp=26; IntAct=EBI-5323863, EBI-359832;
CC       Q5S007; Q04917: YWHAH; NbExp=4; IntAct=EBI-5323863, EBI-306940;
CC       Q5S007; P27348: YWHAQ; NbExp=10; IntAct=EBI-5323863, EBI-359854;
CC       Q5S007; P63104: YWHAZ; NbExp=11; IntAct=EBI-5323863, EBI-347088;
CC       Q5S007; O95218: ZRANB2; NbExp=2; IntAct=EBI-5323863, EBI-1051583;
CC       Q5S007; Q62848: Arfgap1; Xeno; NbExp=7; IntAct=EBI-5323863, EBI-4398879;
CC       Q5S007; O55143: Atp2a2; Xeno; NbExp=13; IntAct=EBI-5323863, EBI-770763;
CC       Q5S007; P30275: Ckmt1; Xeno; NbExp=2; IntAct=EBI-5323863, EBI-773103;
CC       Q5S007; P39053: Dnm1; Xeno; NbExp=3; IntAct=EBI-5323863, EBI-397785;
CC       Q5S007; P02687: MBP; Xeno; NbExp=3; IntAct=EBI-5323863, EBI-908215;
CC       Q5S007; Q811U4: Mfn1; Xeno; NbExp=3; IntAct=EBI-5323863, EBI-9029118;
CC       Q5S007; P00634: phoA; Xeno; NbExp=2; IntAct=EBI-5323863, EBI-552958;
CC       Q5S007; P12369: Prkar2b; Xeno; NbExp=3; IntAct=EBI-5323863, EBI-6096160;
CC       Q5S007; Q63481: Rab29; Xeno; NbExp=3; IntAct=EBI-5323863, EBI-6513837;
CC       Q5S007; P61021: Rab5b; Xeno; NbExp=2; IntAct=EBI-5323863, EBI-8320093;
CC       Q5S007; Q58A65: Spag9; Xeno; NbExp=2; IntAct=EBI-5323863, EBI-6530207;
CC       Q5S007; Q9WUD1: Stub1; Xeno; NbExp=2; IntAct=EBI-5323863, EBI-773027;
CC       Q5S007; P61983: Ywhag; Xeno; NbExp=6; IntAct=EBI-5323863, EBI-359821;
CC   -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle {ECO:0000269|PubMed:16321986,
CC       ECO:0000269|PubMed:16352719, ECO:0000269|PubMed:26014385}. Perikaryon
CC       {ECO:0000269|PubMed:17120249}. Golgi apparatus membrane
CC       {ECO:0000269|PubMed:16321986, ECO:0000269|PubMed:23395371}; Peripheral
CC       membrane protein {ECO:0000269|PubMed:16321986}. Cell projection, axon
CC       {ECO:0000269|PubMed:17120249}. Cell projection, dendrite
CC       {ECO:0000269|PubMed:17120249, ECO:0000269|PubMed:21850687}. Endoplasmic
CC       reticulum membrane {ECO:0000269|PubMed:16321986,
CC       ECO:0000269|PubMed:25201882}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:16321986}. Cytoplasmic vesicle, secretory vesicle,
CC       synaptic vesicle membrane {ECO:0000269|PubMed:24687852}. Endosome
CC       {ECO:0000250|UniProtKB:Q5S006}. Lysosome {ECO:0000269|PubMed:17120249}.
CC       Mitochondrion outer membrane {ECO:0000269|PubMed:16269541,
CC       ECO:0000269|PubMed:16321986, ECO:0000269|PubMed:17120249,
CC       ECO:0000269|PubMed:29212815}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:16269541, ECO:0000269|PubMed:16321986,
CC       ECO:0000269|PubMed:17120249, ECO:0000269|PubMed:29212815}. Cytoplasm,
CC       cytoskeleton {ECO:0000269|PubMed:35266954}. Note=Colocalized with RAB29
CC       along tubular structures emerging from Golgi apparatus
CC       (PubMed:23395371). Localizes to endoplasmic reticulum exit sites
CC       (ERES), also known as transitional endoplasmic reticulum (tER)
CC       (PubMed:25201882). {ECO:0000269|PubMed:23395371,
CC       ECO:0000269|PubMed:25201882}.
CC   -!- TISSUE SPECIFICITY: Expressed in pyramidal neurons in all cortical
CC       laminae of the visual cortex, in neurons of the substantia nigra pars
CC       compacta and caudate putamen (at protein level). Expressed in
CC       neutrophils (at protein level) (PubMed:29127255). Expressed in the
CC       brain. Expressed throughout the adult brain, but at a lower level than
CC       in heart and liver. Also expressed in placenta, lung, skeletal muscle,
CC       kidney and pancreas. In the brain, expressed in the cerebellum,
CC       cerebral cortex, medulla, spinal cord occipital pole, frontal lobe,
CC       temporal lobe and putamen. Expression is particularly high in brain
CC       dopaminoceptive areas. {ECO:0000269|PubMed:15541308,
CC       ECO:0000269|PubMed:15541309, ECO:0000269|PubMed:16532471,
CC       ECO:0000269|PubMed:17120249, ECO:0000269|PubMed:29127255}.
CC   -!- DOMAIN: The seven-bladed WD repeat region is critical for synaptic
CC       vesicle trafficking and mediates interaction with multiple vesicle-
CC       associated presynaptic proteins (PubMed:24687852). It also mediates
CC       homodimerization and regulates kinase activity (PubMed:30635421).
CC       {ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:30635421}.
CC   -!- DOMAIN: The Roc domain mediates homodimerization and regulates kinase
CC       activity. {ECO:0000269|PubMed:18230735}.
CC   -!- PTM: Autophosphorylated (PubMed:28202711, PubMed:28720718,
CC       PubMed:29127255, PubMed:29212815, PubMed:30635421). Phosphorylation of
CC       Ser-910 and either Ser-935 or Ser-1444 facilitates interaction with
CC       YWHAG (PubMed:28202711). Phosphorylation of Ser-910 and/or Ser-935
CC       facilitates interaction with SFN (PubMed:28202711).
CC       {ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:28720718,
CC       ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815,
CC       ECO:0000269|PubMed:30635421}.
CC   -!- PTM: Ubiquitinated by TRIM1; undergoes 'Lys-48'-linked
CC       polyubiquitination leading to proteasomal degradation.
CC       {ECO:0000269|PubMed:35266954}.
CC   -!- DISEASE: Parkinson disease 8 (PARK8) [MIM:607060]: A slowly progressive
CC       neurodegenerative disorder characterized by bradykinesia, rigidity,
CC       resting tremor, postural instability, neuronal loss in the substantia
CC       nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy
CC       bodies in some patients. {ECO:0000269|PubMed:15541308,
CC       ECO:0000269|PubMed:15541309, ECO:0000269|PubMed:15680455,
CC       ECO:0000269|PubMed:15680456, ECO:0000269|PubMed:15680457,
CC       ECO:0000269|PubMed:15726496, ECO:0000269|PubMed:15732108,
CC       ECO:0000269|PubMed:15811454, ECO:0000269|PubMed:15852371,
CC       ECO:0000269|PubMed:15880653, ECO:0000269|PubMed:15925109,
CC       ECO:0000269|PubMed:15929036, ECO:0000269|PubMed:16102999,
CC       ECO:0000269|PubMed:16157901, ECO:0000269|PubMed:16157908,
CC       ECO:0000269|PubMed:16157909, ECO:0000269|PubMed:16172858,
CC       ECO:0000269|PubMed:16240353, ECO:0000269|PubMed:16247070,
CC       ECO:0000269|PubMed:16250030, ECO:0000269|PubMed:16251215,
CC       ECO:0000269|PubMed:16269541, ECO:0000269|PubMed:16272164,
CC       ECO:0000269|PubMed:16272257, ECO:0000269|PubMed:16298482,
CC       ECO:0000269|PubMed:16321986, ECO:0000269|PubMed:16333314,
CC       ECO:0000269|PubMed:16533964, ECO:0000269|PubMed:17114044,
CC       ECO:0000269|PubMed:18213618, ECO:0000269|PubMed:21641266,
CC       ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22956510,
CC       ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:25201882,
CC       ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28202711,
CC       ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462,
CC       ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815,
CC       ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC       protein kinase family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AY792511; AAV63975.1; -; mRNA.
DR   EMBL; AC079630; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC084290; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC107023; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL834529; CAD39185.1; -; mRNA.
DR   CCDS; CCDS31774.1; -.
DR   RefSeq; NP_940980.3; NM_198578.3.
DR   PDB; 2ZEJ; X-ray; 2.00 A; A/B=1333-1516.
DR   PDB; 3D6T; X-ray; 2.43 A; B=1335-1505.
DR   PDB; 5MY9; X-ray; 1.33 A; P=929-941.
DR   PDB; 5MYC; X-ray; 1.46 A; P=904-941.
DR   PDB; 6DLO; X-ray; 2.70 A; A/B=2142-2527.
DR   PDB; 6DLP; X-ray; 4.00 A; A/B=2142-2527.
DR   PDB; 6OJE; X-ray; 1.95 A; A/B=1329-1520.
DR   PDB; 6OJF; X-ray; 1.60 A; A/B=1329-1520.
DR   PDB; 6VNO; EM; 3.50 A; A=1327-2527.
DR   PDB; 6VP6; EM; 3.47 A; A/B/C=1327-2527.
DR   PDB; 6VP7; EM; 3.50 A; A=1327-2527.
DR   PDB; 6XAF; X-ray; 1.97 A; A/B=1329-1520.
DR   PDB; 6XR4; EM; 14.00 A; A/B=1-2527.
DR   PDB; 7LHT; EM; 3.50 A; A/B=1-2527.
DR   PDB; 7LHW; EM; 3.70 A; A=1-2527.
DR   PDB; 7LI3; EM; 3.80 A; A=1-2527.
DR   PDB; 7LI4; EM; 3.10 A; A=1-2527.
DR   PDB; 7THY; EM; 5.20 A; A=1332-1525.
DR   PDB; 7THZ; EM; 5.00 A; A=1332-1525.
DR   PDB; 8TXZ; EM; 3.05 A; A=1334-2527.
DR   PDB; 8TYQ; EM; 2.99 A; A=1-2527.
DR   PDB; 8TZB; EM; 3.10 A; A=1-2527.
DR   PDB; 8TZC; EM; 2.70 A; A=1333-2527.
DR   PDB; 8TZE; EM; 2.90 A; A=1-2527.
DR   PDB; 8TZF; EM; 3.40 A; A=1-2527.
DR   PDB; 8TZG; EM; 2.70 A; A=1333-2522.
DR   PDB; 8TZH; EM; 3.90 A; A=1-2527.
DR   PDBsum; 2ZEJ; -.
DR   PDBsum; 3D6T; -.
DR   PDBsum; 5MY9; -.
DR   PDBsum; 5MYC; -.
DR   PDBsum; 6DLO; -.
DR   PDBsum; 6DLP; -.
DR   PDBsum; 6OJE; -.
DR   PDBsum; 6OJF; -.
DR   PDBsum; 6VNO; -.
DR   PDBsum; 6VP6; -.
DR   PDBsum; 6VP7; -.
DR   PDBsum; 6XAF; -.
DR   PDBsum; 6XR4; -.
DR   PDBsum; 7LHT; -.
DR   PDBsum; 7LHW; -.
DR   PDBsum; 7LI3; -.
DR   PDBsum; 7LI4; -.
DR   PDBsum; 7THY; -.
DR   PDBsum; 7THZ; -.
DR   PDBsum; 8TXZ; -.
DR   PDBsum; 8TYQ; -.
DR   PDBsum; 8TZB; -.
DR   PDBsum; 8TZC; -.
DR   PDBsum; 8TZE; -.
DR   PDBsum; 8TZF; -.
DR   PDBsum; 8TZG; -.
DR   PDBsum; 8TZH; -.
DR   AlphaFoldDB; Q5S007; -.
DR   EMDB; EMD-20825; -.
DR   EMDB; EMD-20826; -.
DR   EMDB; EMD-21250; -.
DR   EMDB; EMD-21306; -.
DR   EMDB; EMD-21309; -.
DR   EMDB; EMD-21310; -.
DR   EMDB; EMD-21311; -.
DR   EMDB; EMD-21312; -.
DR   EMDB; EMD-23350; -.
DR   EMDB; EMD-23352; -.
DR   EMDB; EMD-23359; -.
DR   EMDB; EMD-23360; -.
DR   EMDB; EMD-25649; -.
DR   EMDB; EMD-25658; -.
DR   EMDB; EMD-25664; -.
DR   EMDB; EMD-25674; -.
DR   EMDB; EMD-25897; -.
DR   EMDB; EMD-25906; -.
DR   EMDB; EMD-25907; -.
DR   SMR; Q5S007; -.
DR   BioGRID; 125700; 511.
DR   CORUM; Q5S007; -.
DR   DIP; DIP-29684N; -.
DR   IntAct; Q5S007; 2328.
DR   MINT; Q5S007; -.
DR   STRING; 9606.ENSP00000298910; -.
DR   BindingDB; Q5S007; -.
DR   ChEMBL; CHEMBL1075104; -.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugCentral; Q5S007; -.
DR   GuidetoPHARMACOLOGY; 2059; -.
DR   TCDB; 8.A.23.1.54; the basigin (basigin) family.
DR   GlyGen; Q5S007; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q5S007; -.
DR   PhosphoSitePlus; Q5S007; -.
DR   BioMuta; LRRK2; -.
DR   DMDM; 294862450; -.
DR   EPD; Q5S007; -.
DR   jPOST; Q5S007; -.
DR   MassIVE; Q5S007; -.
DR   MaxQB; Q5S007; -.
DR   PaxDb; 9606-ENSP00000298910; -.
DR   PeptideAtlas; Q5S007; -.
DR   ProteomicsDB; 63755; -.
DR   ABCD; Q5S007; 2 sequenced antibodies.
DR   Antibodypedia; 2109; 1008 antibodies from 48 providers.
DR   DNASU; 120892; -.
DR   Ensembl; ENST00000298910.12; ENSP00000298910.7; ENSG00000188906.17.
DR   GeneID; 120892; -.
DR   KEGG; hsa:120892; -.
DR   MANE-Select; ENST00000298910.12; ENSP00000298910.7; NM_198578.4; NP_940980.4.
DR   UCSC; uc001rmg.5; human.
DR   AGR; HGNC:18618; -.
DR   CTD; 120892; -.
DR   DisGeNET; 120892; -.
DR   GeneCards; LRRK2; -.
DR   GeneReviews; LRRK2; -.
DR   HGNC; HGNC:18618; LRRK2.
DR   HPA; ENSG00000188906; Tissue enriched (lung).
DR   MalaCards; LRRK2; -.
DR   MIM; 168600; phenotype.
DR   MIM; 607060; phenotype.
DR   MIM; 609007; gene.
DR   neXtProt; NX_Q5S007; -.
DR   OpenTargets; ENSG00000188906; -.
DR   Orphanet; 411602; Hereditary late-onset Parkinson disease.
DR   Orphanet; 2828; Young-onset Parkinson disease.
DR   PharmGKB; PA134968052; -.
DR   VEuPathDB; HostDB:ENSG00000188906; -.
DR   eggNOG; KOG0192; Eukaryota.
DR   eggNOG; KOG0618; Eukaryota.
DR   eggNOG; KOG0619; Eukaryota.
DR   GeneTree; ENSGT00940000158267; -.
DR   HOGENOM; CLU_000815_0_0_1; -.
DR   InParanoid; Q5S007; -.
DR   OMA; FIVECMV; -.
DR   OrthoDB; 148126at2759; -.
DR   PhylomeDB; Q5S007; -.
DR   TreeFam; TF313679; -.
DR   PathwayCommons; Q5S007; -.
DR   Reactome; R-HSA-8857538; PTK6 promotes HIF1A stabilization.
DR   SignaLink; Q5S007; -.
DR   SIGNOR; Q5S007; -.
DR   BioGRID-ORCS; 120892; 21 hits in 1183 CRISPR screens.
DR   ChiTaRS; LRRK2; human.
DR   EvolutionaryTrace; Q5S007; -.
DR   GeneWiki; LRRK2; -.
DR   GenomeRNAi; 120892; -.
DR   Pharos; Q5S007; Tchem.
DR   PRO; PR:Q5S007; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q5S007; Protein.
DR   Bgee; ENSG00000188906; Expressed in buccal mucosa cell and 154 other cell types or tissues.
DR   ExpressionAtlas; Q5S007; baseline and differential.
DR   GO; GO:0044753; C:amphisome; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0044754; C:autolysosome; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0030424; C:axon; IDA:UniProtKB.
DR   GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central.
DR   GO; GO:0099400; C:caveola neck; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0032473; C:cytoplasmic side of mitochondrial outer membrane; IDA:UniProtKB.
DR   GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR   GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR   GO; GO:0032839; C:dendrite cytoplasm; IDA:BHF-UCL.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0070971; C:endoplasmic reticulum exit site; IDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005798; C:Golgi-associated vesicle; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0030426; C:growth cone; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR   GO; GO:0045121; C:membrane raft; IBA:GO_Central.
DR   GO; GO:0005902; C:microvillus; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR   GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR   GO; GO:0031966; C:mitochondrial membrane; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0097487; C:multivesicular body, internal vesicle; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0043005; C:neuron projection; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0043025; C:neuronal cell body; IDA:BHF-UCL.
DR   GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0098794; C:postsynapse; IEA:GOC.
DR   GO; GO:0099523; C:presynaptic cytosol; IEA:Ensembl.
DR   GO; GO:1990904; C:ribonucleoprotein complex; IEA:Ensembl.
DR   GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0043195; C:terminal bouton; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl.
DR   GO; GO:1990909; C:Wnt signalosome; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0003779; F:actin binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:1904713; F:beta-catenin destruction complex binding; NAS:ParkinsonsUK-UCL.
DR   GO; GO:0030276; F:clathrin binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0039706; F:co-receptor binding; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR   GO; GO:0034211; F:GTP-dependent protein kinase activity; IDA:BHF-UCL.
DR   GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR   GO; GO:0003924; F:GTPase activity; IDA:BHF-UCL.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0004706; F:JUN kinase kinase kinase activity; IDA:BHF-UCL.
DR   GO; GO:0016301; F:kinase activity; IDA:UniProtKB.
DR   GO; GO:0000287; F:magnesium ion binding; IMP:UniProtKB.
DR   GO; GO:0004709; F:MAP kinase kinase kinase activity; IDA:BHF-UCL.
DR   GO; GO:0008017; F:microtubule binding; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0036479; F:peroxidase inhibitor activity; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR   GO; GO:0051018; F:protein kinase A binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR   GO; GO:0030159; F:signaling receptor complex adaptor activity; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0031267; F:small GTPase binding; IPI:BHF-UCL.
DR   GO; GO:0000149; F:SNARE binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0017075; F:syntaxin-1 binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB.
DR   GO; GO:0015631; F:tubulin binding; IDA:BHF-UCL.
DR   GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0019722; P:calcium-mediated signaling; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; TAS:ParkinsonsUK-UCL.
DR   GO; GO:1903351; P:cellular response to dopamine; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0071287; P:cellular response to manganese ion; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0071407; P:cellular response to organic cyclic compound; IBA:GO_Central.
DR   GO; GO:0034599; P:cellular response to oxidative stress; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0009267; P:cellular response to starvation; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IBA:GO_Central.
DR   GO; GO:0008340; P:determination of adult lifespan; IMP:BHF-UCL.
DR   GO; GO:0006897; P:endocytosis; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0007029; P:endoplasmic reticulum organization; IMP:UniProtKB.
DR   GO; GO:0060079; P:excitatory postsynaptic potential; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0035640; P:exploration behavior; IMP:BHF-UCL.
DR   GO; GO:0007030; P:Golgi organization; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0046039; P:GTP metabolic process; IDA:BHF-UCL.
DR   GO; GO:0048312; P:intracellular distribution of mitochondria; IMP:BHF-UCL.
DR   GO; GO:0035556; P:intracellular signal transduction; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0007254; P:JNK cascade; IDA:BHF-UCL.
DR   GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl.
DR   GO; GO:0007040; P:lysosome organization; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0000165; P:MAPK cascade; IDA:UniProtKB.
DR   GO; GO:0051646; P:mitochondrion localization; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0007005; P:mitochondrion organization; IMP:ParkinsonsUK-UCL.
DR   GO; GO:1902902; P:negative regulation of autophagosome assembly; IMP:ParkinsonsUK-UCL.
DR   GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0090394; P:negative regulation of excitatory postsynaptic potential; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0034260; P:negative regulation of GTPase activity; IDA:MGI.
DR   GO; GO:1902823; P:negative regulation of late endosome to lysosome transport; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0016242; P:negative regulation of macroautophagy; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl.
DR   GO; GO:0032091; P:negative regulation of protein binding; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0010955; P:negative regulation of protein processing; IDA:ParkinsonsUK-UCL.
DR   GO; GO:1903217; P:negative regulation of protein processing involved in protein targeting to mitochondrion; IC:ParkinsonsUK-UCL.
DR   GO; GO:1903215; P:negative regulation of protein targeting to mitochondrion; IDA:ParkinsonsUK-UCL.
DR   GO; GO:1903125; P:negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0007528; P:neuromuscular junction development; IMP:BHF-UCL.
DR   GO; GO:0140058; P:neuron projection arborization; IEA:Ensembl.
DR   GO; GO:0048812; P:neuron projection morphogenesis; IMP:UniProtKB.
DR   GO; GO:0021772; P:olfactory bulb development; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0016310; P:phosphorylation; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR   GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IGI:ParkinsonsUK-UCL.
DR   GO; GO:0060161; P:positive regulation of dopamine receptor signaling pathway; IMP:BHF-UCL.
DR   GO; GO:0043406; P:positive regulation of MAP kinase activity; IMP:ParkinsonsUK-UCL.
DR   GO; GO:1903980; P:positive regulation of microglial cell activation; IEA:Ensembl.
DR   GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IEA:Ensembl.
DR   GO; GO:0043068; P:positive regulation of programmed cell death; IDA:UniProtKB.
DR   GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:BHF-UCL.
DR   GO; GO:1902499; P:positive regulation of protein autoubiquitination; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0032092; P:positive regulation of protein binding; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:BHF-UCL.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR   GO; GO:1900244; P:positive regulation of synaptic vesicle endocytosis; IEA:Ensembl.
DR   GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR   GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR   GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR   GO; GO:0008104; P:protein localization; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0070973; P:protein localization to endoplasmic reticulum exit site; IMP:UniProtKB.
DR   GO; GO:0070585; P:protein localization to mitochondrion; TAS:ParkinsonsUK-UCL.
DR   GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR   GO; GO:0010506; P:regulation of autophagy; IMP:ParkinsonsUK-UCL.
DR   GO; GO:2000172; P:regulation of branching morphogenesis of a nerve; IMP:ParkinsonsUK-UCL.
DR   GO; GO:1905289; P:regulation of CAMKK-AMPK signaling cascade; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR   GO; GO:0061001; P:regulation of dendritic spine morphogenesis; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0060159; P:regulation of dopamine receptor signaling pathway; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0060628; P:regulation of ER to Golgi vesicle-mediated transport; ISS:UniProtKB.
DR   GO; GO:0035564; P:regulation of kidney size; ISS:BHF-UCL.
DR   GO; GO:0040012; P:regulation of locomotion; IMP:BHF-UCL.
DR   GO; GO:0035751; P:regulation of lysosomal lumen pH; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0042391; P:regulation of membrane potential; IMP:BHF-UCL.
DR   GO; GO:0051900; P:regulation of mitochondrial depolarization; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0090140; P:regulation of mitochondrial fission; TAS:ParkinsonsUK-UCL.
DR   GO; GO:1902692; P:regulation of neuroblast proliferation; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0014041; P:regulation of neuron maturation; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0010738; P:regulation of protein kinase A signaling; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
DR   GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:ParkinsonsUK-UCL.
DR   GO; GO:1905279; P:regulation of retrograde transport, endosome to Golgi; IGI:ParkinsonsUK-UCL.
DR   GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; ISS:ParkinsonsUK-UCL.
DR   GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IMP:ParkinsonsUK-UCL.
DR   GO; GO:1902803; P:regulation of synaptic vesicle transport; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0006979; P:response to oxidative stress; IMP:BHF-UCL.
DR   GO; GO:0007266; P:Rho protein signal transduction; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR   GO; GO:0021756; P:striatum development; IEA:Ensembl.
DR   GO; GO:0022028; P:tangential migration from the subventricular zone to the olfactory bulb; IMP:ParkinsonsUK-UCL.
DR   GO; GO:1904887; P:Wnt signalosome assembly; IPI:ParkinsonsUK-UCL.
DR   CDD; cd09914; RocCOR; 1.
DR   CDD; cd14068; STKc_LRRK2; 1.
DR   Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 1.
DR   Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 2.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 2.
DR   Gene3D; 3.30.70.1390; ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
DR   InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR   InterPro; IPR011989; ARM-like.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR032171; COR.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR001611; Leu-rich_rpt.
DR   InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR020859; ROC_dom.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   InterPro; IPR005225; Small_GTP-bd_dom.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   InterPro; IPR036322; WD40_repeat_dom_sf.
DR   NCBIfam; TIGR00231; small_GTP; 1.
DR   PANTHER; PTHR48005; LEUCINE RICH REPEAT KINASE 2; 1.
DR   PANTHER; PTHR48005:SF13; SERINE_THREONINE-PROTEIN KINASE DDB_G0278509-RELATED; 1.
DR   Pfam; PF16095; COR; 1.
DR   Pfam; PF13855; LRR_8; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   Pfam; PF08477; Roc; 1.
DR   PRINTS; PR00449; RASTRNSFRMNG.
DR   SMART; SM00364; LRR_BAC; 8.
DR   SMART; SM00369; LRR_TYP; 7.
DR   SMART; SM00175; RAB; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF48371; ARM repeat; 2.
DR   SUPFAM; SSF52058; L domain-like; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF50978; WD40 repeat-like; 1.
DR   PROSITE; PS51450; LRR; 11.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   PROSITE; PS51424; ROC; 1.
DR   Genevisible; Q5S007; HS.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Autophagy; Cell projection; Coiled coil;
KW   Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Differentiation;
KW   Disease variant; Endoplasmic reticulum; Endosome; Golgi apparatus;
KW   GTP-binding; GTPase activation; Hydrolase; Kinase; Leucine-rich repeat;
KW   Lysosome; Membrane; Mitochondrion; Mitochondrion outer membrane;
KW   Neurodegeneration; Nucleotide-binding; Parkinson disease; Parkinsonism;
KW   Phosphoprotein; Reference proteome; Repeat;
KW   Serine/threonine-protein kinase; Synapse; Transferase; Ubl conjugation;
KW   WD repeat.
FT   CHAIN           1..2527
FT                   /note="Leucine-rich repeat serine/threonine-protein kinase
FT                   2"
FT                   /id="PRO_0000086238"
FT   REPEAT          983..1004
FT                   /note="LRR 1"
FT   REPEAT          1012..1033
FT                   /note="LRR 2"
FT   REPEAT          1036..1057
FT                   /note="LRR 3"
FT   REPEAT          1059..1080
FT                   /note="LRR 4"
FT   REPEAT          1084..1105
FT                   /note="LRR 5"
FT   REPEAT          1108..1129
FT                   /note="LRR 6"
FT   REPEAT          1130..1150
FT                   /note="LRR 7"
FT   REPEAT          1174..1196
FT                   /note="LRR 8"
FT   REPEAT          1197..1218
FT                   /note="LRR 9"
FT   REPEAT          1221..1241
FT                   /note="LRR 10"
FT   REPEAT          1246..1267
FT                   /note="LRR 11"
FT   REPEAT          1269..1291
FT                   /note="LRR 12"
FT   DOMAIN          1328..1511
FT                   /note="Roc"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00758"
FT   DOMAIN          1879..2138
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REPEAT          2139..2183
FT                   /note="WD 1"
FT   REPEAT          2188..2228
FT                   /note="WD 2"
FT   REPEAT          2233..2276
FT                   /note="WD 3"
FT   REPEAT          2281..2327
FT                   /note="WD 4"
FT   REPEAT          2333..2377
FT                   /note="WD 5"
FT   REPEAT          2402..2438
FT                   /note="WD 6"
FT   REPEAT          2443..2497
FT                   /note="WD 7"
FT   REGION          1..969
FT                   /note="Required for RAB29-mediated activation"
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   COILED          319..348
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        1994
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         1341..1348
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00758,
FT                   ECO:0000269|PubMed:18230735"
FT   BINDING         1885..1893
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         1906
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         2098..2121
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00758"
FT   BINDING         2295..2298
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00758"
FT   MOD_RES         910
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:28202711,
FT                   ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29212815"
FT   MOD_RES         935
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:28202711,
FT                   ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29127255,
FT                   ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30635421"
FT   MOD_RES         955
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:28202711,
FT                   ECO:0000269|PubMed:29212815"
FT   MOD_RES         973
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:28202711,
FT                   ECO:0000269|PubMed:29212815"
FT   MOD_RES         1292
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:29212815,
FT                   ECO:0000269|PubMed:30635421"
FT   MOD_RES         1444
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:28202711"
FT   VARIANT         50
FT                   /note="R -> H (in dbSNP:rs2256408)"
FT                   /id="VAR_024931"
FT   VARIANT         119
FT                   /note="L -> P (in dbSNP:rs33995463)"
FT                   /evidence="ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:17344846"
FT                   /id="VAR_024932"
FT   VARIANT         228
FT                   /note="C -> S (in dbSNP:rs56108242)"
FT                   /evidence="ECO:0000269|PubMed:18213618"
FT                   /id="VAR_054740"
FT   VARIANT         419
FT                   /note="A -> V (in dbSNP:rs34594498)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_033903"
FT   VARIANT         551
FT                   /note="N -> K (in dbSNP:rs7308720)"
FT                   /evidence="ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:16251215, ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:22415848"
FT                   /id="VAR_024933"
FT   VARIANT         712
FT                   /note="M -> V (in PARK8; dbSNP:rs199566791)"
FT                   /evidence="ECO:0000269|PubMed:18213618"
FT                   /id="VAR_054741"
FT   VARIANT         716
FT                   /note="A -> V (in dbSNP:rs281865043)"
FT                   /evidence="ECO:0000269|PubMed:18213618"
FT                   /id="VAR_054742"
FT   VARIANT         723
FT                   /note="I -> V (in dbSNP:rs10878307)"
FT                   /evidence="ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:22415848"
FT                   /id="VAR_024934"
FT   VARIANT         755
FT                   /note="P -> L (in dbSNP:rs34410987)"
FT                   /id="VAR_033904"
FT   VARIANT         793
FT                   /note="R -> M (in PARK8; uncertain significance;
FT                   dbSNP:rs35173587)"
FT                   /evidence="ECO:0000269|PubMed:16157908,
FT                   ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:16251215"
FT                   /id="VAR_024935"
FT   VARIANT         871
FT                   /note="K -> E (in dbSNP:rs281865044)"
FT                   /evidence="ECO:0000269|PubMed:18213618"
FT                   /id="VAR_054743"
FT   VARIANT         930
FT                   /note="Q -> R (in PARK8; uncertain significance;
FT                   dbSNP:rs281865045)"
FT                   /evidence="ECO:0000269|PubMed:16251215"
FT                   /id="VAR_024936"
FT   VARIANT         944
FT                   /note="D -> Y (in dbSNP:rs17519916)"
FT                   /id="VAR_024937"
FT   VARIANT         1067
FT                   /note="R -> Q (in PARK8; dbSNP:rs111341148)"
FT                   /evidence="ECO:0000269|PubMed:16247070"
FT                   /id="VAR_024938"
FT   VARIANT         1096
FT                   /note="S -> C (in PARK8; uncertain significance;
FT                   dbSNP:rs76535406)"
FT                   /evidence="ECO:0000269|PubMed:16251215"
FT                   /id="VAR_024939"
FT   VARIANT         1122
FT                   /note="I -> V (in PARK8; dbSNP:rs34805604)"
FT                   /evidence="ECO:0000269|PubMed:15541309,
FT                   ECO:0000269|PubMed:16172858"
FT                   /id="VAR_024940"
FT   VARIANT         1228
FT                   /note="S -> T (in PARK8; dbSNP:rs60185966)"
FT                   /evidence="ECO:0000269|PubMed:16251215"
FT                   /id="VAR_024941"
FT   VARIANT         1262
FT                   /note="P -> A (in dbSNP:rs4640000)"
FT                   /evidence="ECO:0000269|PubMed:16172858"
FT                   /id="VAR_024942"
FT   VARIANT         1359
FT                   /note="K -> I (found in a renal cell carcinoma sample;
FT                   somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:21248752"
FT                   /id="VAR_064728"
FT   VARIANT         1371
FT                   /note="I -> V (in PARK8; uncertain significance;
FT                   dbSNP:rs17466213)"
FT                   /evidence="ECO:0000269|PubMed:16157901,
FT                   ECO:0000269|PubMed:16333314"
FT                   /id="VAR_024943"
FT   VARIANT         1375
FT                   /note="D -> E (in dbSNP:rs28365226)"
FT                   /id="VAR_047022"
FT   VARIANT         1398
FT                   /note="R -> H (in dbSNP:rs7133914)"
FT                   /evidence="ECO:0000269|PubMed:16157901,
FT                   ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:22415848"
FT                   /id="VAR_024944"
FT   VARIANT         1441
FT                   /note="R -> C (in PARK8; shows an increase in activity in
FT                   both autophosphorylation and phosphorylation of a generic
FT                   substrate; loss of interaction with SEC16A; shows an
FT                   increase in activity in phosphorylation of RAB10; decreases
FT                   phosphorylation-dependent binding to YWHAG;
FT                   dbSNP:rs33939927)"
FT                   /evidence="ECO:0000269|PubMed:15541309,
FT                   ECO:0000269|PubMed:16157909, ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:16269541, ECO:0000269|PubMed:16333314,
FT                   ECO:0000269|PubMed:16533964, ECO:0000269|PubMed:25201882,
FT                   ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28202711,
FT                   ECO:0000269|PubMed:29212815"
FT                   /id="VAR_024945"
FT   VARIANT         1441
FT                   /note="R -> G (in PARK8; shows a progressive reduction in
FT                   neurite length and branching; shows an increase in activity
FT                   in phosphorylation of RAB8A and RAB10; decreases
FT                   phosphorylation-dependent binding to YWHAG;
FT                   dbSNP:rs33939927)"
FT                   /evidence="ECO:0000269|PubMed:15541308,
FT                   ECO:0000269|PubMed:15925109, ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:16533964, ECO:0000269|PubMed:17114044,
FT                   ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718,
FT                   ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29212815,
FT                   ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421"
FT                   /id="VAR_024946"
FT   VARIANT         1441
FT                   /note="R -> H (in PARK8; shows an increase in activity in
FT                   phosphorylation of RAB8A and RAB10; decreases
FT                   phosphorylation-dependent binding to YWHAG;
FT                   dbSNP:rs34995376)"
FT                   /evidence="ECO:0000269|PubMed:16157909,
FT                   ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:26824392,
FT                   ECO:0000269|PubMed:29212815"
FT                   /id="VAR_024947"
FT   VARIANT         1514
FT                   /note="R -> Q (in PARK8; uncertain significance;
FT                   dbSNP:rs35507033)"
FT                   /evidence="ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:22415848"
FT                   /id="VAR_024948"
FT   VARIANT         1542
FT                   /note="P -> S (in PARK8; uncertain significance;
FT                   dbSNP:rs33958906)"
FT                   /evidence="ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:22415848"
FT                   /id="VAR_024949"
FT   VARIANT         1550
FT                   /note="R -> Q (in an ovarian mucinous carcinoma sample;
FT                   somatic mutation; dbSNP:rs200212150)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040678"
FT   VARIANT         1598
FT                   /note="V -> E (in PARK8; uncertain significance;
FT                   dbSNP:rs721710)"
FT                   /evidence="ECO:0000269|PubMed:16172858"
FT                   /id="VAR_024950"
FT   VARIANT         1628
FT                   /note="R -> P (in PARK8; uncertain significance;
FT                   dbSNP:rs33949390)"
FT                   /evidence="ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:21641266, ECO:0000269|PubMed:22415848"
FT                   /id="VAR_024951"
FT   VARIANT         1646
FT                   /note="M -> T (in dbSNP:rs35303786)"
FT                   /evidence="ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:22415848"
FT                   /id="VAR_024952"
FT   VARIANT         1647
FT                   /note="S -> T (in dbSNP:rs11564148)"
FT                   /evidence="ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:22415848"
FT                   /id="VAR_024953"
FT   VARIANT         1699
FT                   /note="Y -> C (in PARK8; shows no progressive reduction in
FT                   neurite length and branching; no loss of interaction with
FT                   SEC16A; shows an increase in activity in phosphorylation of
FT                   RAB8A and RAB10; dbSNP:rs35801418)"
FT                   /evidence="ECO:0000269|PubMed:15541308,
FT                   ECO:0000269|PubMed:15541309, ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:16272164, ECO:0000269|PubMed:17114044,
FT                   ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26824392,
FT                   ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29212815"
FT                   /id="VAR_024954"
FT   VARIANT         1723
FT                   /note="R -> P (in an ovarian serous carcinoma sample;
FT                   somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040679"
FT   VARIANT         1728
FT                   /note="R -> H (in PARK8; shows an increase in activity in
FT                   phosphorylation of RAB8A and RAB10; dbSNP:rs145364431)"
FT                   /evidence="ECO:0000269|PubMed:18213618,
FT                   ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:29212815"
FT                   /id="VAR_054744"
FT   VARIANT         1728
FT                   /note="R -> L (in PARK8; dbSNP:rs145364431)"
FT                   /evidence="ECO:0000269|PubMed:18213618"
FT                   /id="VAR_054745"
FT   VARIANT         1869
FT                   /note="M -> T (in PARK8; uncertain significance;
FT                   dbSNP:rs35602796)"
FT                   /evidence="ECO:0000269|PubMed:16157908,
FT                   ECO:0000269|PubMed:16172858"
FT                   /id="VAR_024955"
FT   VARIANT         1870
FT                   /note="L -> F (in dbSNP:rs281865053)"
FT                   /evidence="ECO:0000269|PubMed:18213618"
FT                   /id="VAR_054746"
FT   VARIANT         1906
FT                   /note="K -> M (does not inhibit interaction with RAB29;
FT                   shows a progressive increase in neurite length and
FT                   branching)"
FT                   /evidence="ECO:0000269|PubMed:17114044,
FT                   ECO:0000269|PubMed:23395371"
FT                   /id="VAR_071101"
FT   VARIANT         1941
FT                   /note="R -> H (in PARK8; dbSNP:rs77428810)"
FT                   /evidence="ECO:0000269|PubMed:16272164"
FT                   /id="VAR_024956"
FT   VARIANT         2012
FT                   /note="I -> T (in PARK8; uncertain significance;
FT                   dbSNP:rs34015634)"
FT                   /evidence="ECO:0000269|PubMed:16172858"
FT                   /id="VAR_024957"
FT   VARIANT         2019
FT                   /note="G -> S (in PARK8; shows an increase in activity in
FT                   both autophosphorylation and phosphorylation of a generic
FT                   substrate; results in increased PRDX3 phosphorylation
FT                   promoting dysregulation of mitochondrial function and
FT                   oxidative damage; results in increased APP phosphorylation
FT                   on 'T-743' promoting neurotoxicity in dopaminergic neurons;
FT                   shows increased kinase activity in the phosphorylation of
FT                   RAB10; does not inhibit interaction with RAB29; shows a
FT                   progressive reduction in neurite length and branching;
FT                   shows distinctive spheroid-like inclusions within both
FT                   neuronal processes and at intracellular membranous
FT                   structures; shows lysosomal swelling and reduced retrograde
FT                   transport of selective cargo between lysosomes and the
FT                   Golgi apparatus; shows apoptotic mechanism of cell death;
FT                   no loss of interaction with SEC16A; dbSNP:rs34637584)"
FT                   /evidence="ECO:0000269|PubMed:15680455,
FT                   ECO:0000269|PubMed:15680456, ECO:0000269|PubMed:15680457,
FT                   ECO:0000269|PubMed:15726496, ECO:0000269|PubMed:15732108,
FT                   ECO:0000269|PubMed:15811454, ECO:0000269|PubMed:15852371,
FT                   ECO:0000269|PubMed:15929036, ECO:0000269|PubMed:16001413,
FT                   ECO:0000269|PubMed:16102999, ECO:0000269|PubMed:16157901,
FT                   ECO:0000269|PubMed:16157908, ECO:0000269|PubMed:16157909,
FT                   ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:16240353,
FT                   ECO:0000269|PubMed:16250030, ECO:0000269|PubMed:16251215,
FT                   ECO:0000269|PubMed:16269541, ECO:0000269|PubMed:16272164,
FT                   ECO:0000269|PubMed:16272257, ECO:0000269|PubMed:16298482,
FT                   ECO:0000269|PubMed:16333314, ECO:0000269|PubMed:16533964,
FT                   ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18213618,
FT                   ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22956510,
FT                   ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:25201882,
FT                   ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718,
FT                   ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255,
FT                   ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148,
FT                   ECO:0000269|PubMed:30635421"
FT                   /id="VAR_024958"
FT   VARIANT         2020
FT                   /note="I -> T (in PARK8; significant increase in
FT                   autophosphorylation of about 40% in comparison to wild-type
FT                   protein in vitro; shows a progressive reduction in neurite
FT                   length and branching; shows an increase in activity in
FT                   phosphorylation of RAB8A and RAB10; dbSNP:rs35870237)"
FT                   /evidence="ECO:0000269|PubMed:15541309,
FT                   ECO:0000269|PubMed:15880653, ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:16251215, ECO:0000269|PubMed:16321986,
FT                   ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:26824392,
FT                   ECO:0000269|PubMed:29212815"
FT                   /id="VAR_024959"
FT   VARIANT         2031
FT                   /note="T -> S (in PARK8; shows an increase in activity in
FT                   phosphorylation of RAB8A and RAB10; dbSNP:rs78029637)"
FT                   /evidence="ECO:0000269|PubMed:26824392,
FT                   ECO:0000269|PubMed:29212815"
FT                   /id="VAR_082047"
FT   VARIANT         2081
FT                   /note="N -> D (in dbSNP:rs33995883)"
FT                   /evidence="ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:22415848"
FT                   /id="VAR_024960"
FT   VARIANT         2119
FT                   /note="P -> L (in dbSNP:rs12423862)"
FT                   /evidence="ECO:0000269|PubMed:16172858"
FT                   /id="VAR_024961"
FT   VARIANT         2141
FT                   /note="T -> M (in PARK8; dbSNP:rs111691891)"
FT                   /evidence="ECO:0000269|PubMed:18213618"
FT                   /id="VAR_054747"
FT   VARIANT         2143
FT                   /note="R -> H (in PARK8; dbSNP:rs201271001)"
FT                   /evidence="ECO:0000269|PubMed:18213618"
FT                   /id="VAR_054748"
FT   VARIANT         2175
FT                   /note="D -> H (in PARK8; shows decreased WD domain
FT                   homodimerization; no effect on kinase activity;
FT                   dbSNP:rs72547981)"
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT                   /id="VAR_082048"
FT   VARIANT         2189
FT                   /note="Y -> C (in PARK8; no effect on WD domain
FT                   homodimerization; no effect on kinase activity;
FT                   dbSNP:rs35658131)"
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT                   /id="VAR_082049"
FT   VARIANT         2261
FT                   /note="N -> I (in dbSNP:rs12581902)"
FT                   /evidence="ECO:0000269|PubMed:16172858"
FT                   /id="VAR_024962"
FT   VARIANT         2356
FT                   /note="T -> I (in PARK8; shows decreased WD domain
FT                   homodimerization; no effect on kinase activity;
FT                   dbSNP:rs113511708)"
FT                   /evidence="ECO:0000269|PubMed:16272164,
FT                   ECO:0000269|PubMed:30635421"
FT                   /id="VAR_024963"
FT   VARIANT         2385
FT                   /note="G -> R (in PARK8; under conditions of oxidative
FT                   stress the variant protein is more toxic and is correlated
FT                   with a higher rate of apoptosis; reduced binding to
FT                   synaptic vesicles; no loss of interaction with SEC16A;
FT                   shows an increase in activity in phosphorylation of RAB8A
FT                   and RAB10; shows decreased WD domain homodimerization;
FT                   reduced autophosphorylation at Ser-935; dbSNP:rs34778348)"
FT                   /evidence="ECO:0000269|PubMed:16172858,
FT                   ECO:0000269|PubMed:17019612, ECO:0000269|PubMed:21641266,
FT                   ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882,
FT                   ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:29212815,
FT                   ECO:0000269|PubMed:30635421"
FT                   /id="VAR_024964"
FT   VARIANT         2390
FT                   /note="V -> M (in PARK8; shows decreased WD domain
FT                   homodimerization; no effect on kinase activity;
FT                   dbSNP:rs79546190)"
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT                   /id="VAR_082050"
FT   VARIANT         2395
FT                   /note="E -> K (in dbSNP:rs78964014)"
FT                   /evidence="ECO:0000269|PubMed:18213618"
FT                   /id="VAR_054749"
FT   VARIANT         2397
FT                   /note="M -> T (in dbSNP:rs3761863)"
FT                   /evidence="ECO:0000269|PubMed:16157901,
FT                   ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:22415848"
FT                   /id="VAR_024965"
FT   VARIANT         2439
FT                   /note="L -> I (in PARK8; shows decreased WD domain
FT                   homodimerization; no effect on kinase activity;
FT                   dbSNP:rs72547983)"
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT                   /id="VAR_082051"
FT   VARIANT         2466
FT                   /note="L -> H (in PARK8; dbSNP:rs281865057)"
FT                   /evidence="ECO:0000269|PubMed:18213618"
FT                   /id="VAR_054750"
FT   MUTAGEN         727
FT                   /note="C->D: Decreased kinase activity. Loss of
FT                   RAB29-mediated activation and autophosphorylation of S-910,
FT                   S-935, S-955, S-973 and S-1292. Decreased membrane
FT                   association; when associated with G-1441, C-1699 and
FT                   S-2019."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         728
FT                   /note="L->D: Decreased kinase activity. Loss of
FT                   RAB29-mediated activation and autophosphorylation of S-910,
FT                   S-935, S-955, S-973 and S-1292. Decreased membrane
FT                   association; when associated with G-1441, C-1699 and
FT                   S-2019."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         729
FT                   /note="L->D: Decreased kinase activity. Loss of
FT                   RAB29-mediated activation and autophosphorylation of S-910,
FT                   S-935, S-955, S-973 and S-1292. Decreased membrane
FT                   association; when associated with G-1441, C-1699 and
FT                   S-2019."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         760
FT                   /note="L->D: Decreased kinase activity and loss of
FT                   RAB29-mediated activation."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         761
FT                   /note="L->D: Decreased kinase activity and loss of
FT                   RAB29-mediated activation."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         762
FT                   /note="L->D: Decreased kinase activity and loss of
FT                   RAB29-mediated activation."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         789
FT                   /note="L->D: No effect on kinase activity and
FT                   RAB29-mediated activation."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         790
FT                   /note="L->D: No effect on kinase activity and
FT                   RAB29-mediated activation."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         791
FT                   /note="L->D: No effect on kinase activity and
FT                   RAB29-mediated activation."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         1343
FT                   /note="T->G: Decreased kinase activity; when associated
FT                   with Q-1398."
FT                   /evidence="ECO:0000269|PubMed:18230735"
FT   MUTAGEN         1347
FT                   /note="K->A: GTPase-dead mutant. Loss of interaction with
FT                   SEC16A and impaired ability to recruit SEC16A to
FT                   endoplasmic reticulum exit sites."
FT                   /evidence="ECO:0000269|PubMed:25201882"
FT   MUTAGEN         1348
FT                   /note="T->N: Loss of GTP binding. Inhibits
FT                   autophosphorylation and RAB10 phosphorylation; when
FT                   associated with G-1441, C-1699, or S-2019."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         1398
FT                   /note="R->Q: Decreased kinase activity; when associated
FT                   with G-1343."
FT                   /evidence="ECO:0000269|PubMed:18230735"
FT   MUTAGEN         1441
FT                   /note="R->G: Decreased membrane association when associated
FT                   with D-727, D-728, or D-729. Inhibits autophosphorylation
FT                   and RAB10 phosphorylation when associated with N-1348 or
FT                   A-2017."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         1699
FT                   /note="Y->C: Decreased membrane association when associated
FT                   with D-727, D-728, or D-729. Inhibits autophosphorylation
FT                   and RAB10 phosphorylation when associated with N-1348 or
FT                   A-2017."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         1906
FT                   /note="K->A: Loss of kinase activity. Decreases proteasomal
FT                   degradation of MAPT; when associated with N-1994 and
FT                   A-2017."
FT                   /evidence="ECO:0000269|PubMed:26014385"
FT   MUTAGEN         1906
FT                   /note="K->M: Loss of kinase activity and ability to enhance
FT                   NOD2 signaling."
FT                   /evidence="ECO:0000269|PubMed:27830463"
FT   MUTAGEN         1994
FT                   /note="D->A: Loss of kinase activity."
FT                   /evidence="ECO:0000269|PubMed:28720718"
FT   MUTAGEN         1994
FT                   /note="D->N: Loss of kinase activity. No loss of
FT                   interaction with SEC16A and no loss of ability to recruit
FT                   SEC16A to endoplasmic reticulum exit sites. Decreases
FT                   proteasomal degradation of MAPT; when associated with
FT                   A-1906 and A-2017."
FT                   /evidence="ECO:0000269|PubMed:25201882,
FT                   ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392"
FT   MUTAGEN         2017
FT                   /note="D->A: Loss of kinase activity. Decreases proteasomal
FT                   degradation of MAPT; when associated with A-1906 and
FT                   N-1994. Loss of phosphorylation of RAB10; when associated
FT                   with G-1441, C-1699, or S-2019."
FT                   /evidence="ECO:0000269|PubMed:26014385,
FT                   ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29212815,
FT                   ECO:0000269|PubMed:30635421"
FT   MUTAGEN         2019
FT                   /note="G->S: Decreased membrane association when associated
FT                   with D-727, D-728, or D-729. Inhibits autophosphorylation
FT                   and RAB10 phosphorylation when associated with N-1348 or
FT                   A-2017."
FT                   /evidence="ECO:0000269|PubMed:29212815"
FT   MUTAGEN         2343
FT                   /note="L->D: Decreases WD domain homodimerization. No
FT                   effect on kinase activity."
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT   MUTAGEN         2344
FT                   /note="F->A: Decreases WD domain homodimerization. No
FT                   effect on kinase activity."
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT   MUTAGEN         2345
FT                   /note="S->D: Decreases WD domain homodimerization. No
FT                   effect on kinase activity."
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT   MUTAGEN         2346
FT                   /note="Y->A: Decreases WD domain homodimerization. No
FT                   effect on kinase activity."
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT   MUTAGEN         2391
FT                   /note="H->D: Increases kinase activity."
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT   MUTAGEN         2394
FT                   /note="R->E: Decreases WD domain homodimerization.
FT                   Increases kinase activity and autophosphorylation at
FT                   Ser-1292."
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT   MUTAGEN         2395
FT                   /note="E->R: Decreases WD domain homodimerization. No
FT                   effect on kinase activity."
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT   MUTAGEN         2408
FT                   /note="M->A,E: No effect on WD domain homodimerization. No
FT                   effect on kinase activity."
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT   MUTAGEN         2409
FT                   /note="S->A: Decreases WD domain homodimerization."
FT                   /evidence="ECO:0000269|PubMed:30635421"
FT   CONFLICT        212
FT                   /note="L -> S (in Ref. 1; AAV63975)"
FT                   /evidence="ECO:0000305"
FT   HELIX           560..570
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            571..574
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           585..595
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           603..606
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           607..610
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           626..637
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            638..640
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           645..656
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           660..662
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           663..666
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            667..670
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           671..678
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           689..702
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           706..714
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            715..720
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           722..730
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          740..742
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           744..750
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           755..762
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          763..765
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           768..780
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          784..787
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           788..794
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            798..801
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          802..804
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           815..818
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           819..821
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           834..852
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           913..917
FT                   /evidence="ECO:0007829|PDB:5MYC"
FT   STRAND          986..988
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           998..1000
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1001..1003
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1005..1009
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1010..1012
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1030..1032
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1054..1056
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1057..1059
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1087..1089
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1102..1105
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1111..1113
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1177..1179
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1190..1193
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1200..1202
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1214..1216
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1224..1226
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1242..1244
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1249..1251
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1262..1266
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1272..1274
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1286..1290
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1317..1327
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1329..1332
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1336..1341
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   HELIX           1347..1354
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   STRAND          1357..1359
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   STRAND          1365..1368
FT                   /evidence="ECO:0007829|PDB:6OJE"
FT   STRAND          1370..1378
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   STRAND          1382..1384
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   STRAND          1388..1395
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   HELIX           1398..1402
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   HELIX           1406..1410
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   STRAND          1411..1420
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   HELIX           1421..1423
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   HELIX           1426..1429
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   HELIX           1431..1441
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   STRAND          1447..1452
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   HELIX           1454..1456
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   HELIX           1459..1472
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   TURN            1473..1475
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   STRAND          1482..1487
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   STRAND          1490..1492
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1495..1513
FT                   /evidence="ECO:0007829|PDB:6OJF"
FT   HELIX           1518..1520
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1521..1524
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1525..1538
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1547..1549
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1550..1559
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1566..1568
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1569..1578
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1581..1583
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1588..1590
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1591..1594
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1595..1599
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1600..1606
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1607..1612
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1628..1638
FT                   /evidence="ECO:0007829|PDB:6VP6"
FT   HELIX           1645..1653
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1654..1657
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1670..1672
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1686..1692
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1696..1699
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1705..1708
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1709..1711
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1740..1743
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1746..1750
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1765..1770
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1771..1791
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1793..1795
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1811..1814
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1816..1819
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1825..1828
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1829..1833
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1834..1836
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1837..1841
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1849..1851
FT                   /evidence="ECO:0007829|PDB:6VP7"
FT   HELIX           1852..1855
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1857..1861
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1866..1868
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1872..1874
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1881..1883
FT                   /evidence="ECO:0007829|PDB:6VP6"
FT   TURN            1888..1890
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1896..1898
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1901..1906
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1910..1912
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           1914..1924
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1935..1939
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1940..1943
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1944..1948
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1951..1954
FT                   /evidence="ECO:0007829|PDB:6VP6"
FT   HELIX           1955..1961
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1963..1965
FT                   /evidence="ECO:0007829|PDB:6VP6"
FT   HELIX           1970..1985
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            1986..1989
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          1999..2001
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          2013..2015
FT                   /evidence="ECO:0007829|PDB:6VP6"
FT   HELIX           2018..2025
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          2036..2038
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           2041..2044
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          2046..2048
FT                   /evidence="ECO:0007829|PDB:6VP6"
FT   HELIX           2052..2067
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           2071..2076
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           2080..2088
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            2095..2097
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            2105..2107
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           2108..2114
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           2119..2121
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           2125..2130
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   TURN            2137..2139
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          2142..2145
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2152..2158
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2166..2171
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2173..2183
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   TURN            2184..2186
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2189..2197
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2199..2207
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   TURN            2208..2211
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2212..2219
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2224..2230
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2235..2237
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2245..2252
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2256..2258
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          2262..2267
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2270..2276
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   HELIX           2278..2281
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2282..2284
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          2288..2292
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2300..2304
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2315..2319
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2322..2330
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2335..2338
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   HELIX           2339..2343
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   HELIX           2347..2350
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2354..2367
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2371..2376
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   TURN            2378..2380
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2382..2388
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   HELIX           2389..2393
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   TURN            2397..2399
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   HELIX           2403..2406
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          2414..2419
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2421..2423
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2425..2432
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2434..2437
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   TURN            2439..2441
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2444..2448
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2451..2462
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   STRAND          2468..2475
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   HELIX           2482..2484
FT                   /evidence="ECO:0007829|PDB:7LI4"
FT   STRAND          2491..2497
FT                   /evidence="ECO:0007829|PDB:6DLO"
FT   HELIX           2500..2526
FT                   /evidence="ECO:0007829|PDB:7LI4"
SQ   SEQUENCE   2527 AA;  286103 MW;  26142A0CECBBC3F4 CRC64;
     MASGSCQGCE EDEETLKKLI VRLNNVQEGK QIETLVQILE DLLVFTYSER ASKLFQGKNI
     HVPLLIVLDS YMRVASVQQV GWSLLCKLIE VCPGTMQSLM GPQDVGNDWE VLGVHQLILK
     MLTVHNASVN LSVIGLKTLD LLLTSGKITL LILDEESDIF MLIFDAMHSF PANDEVQKLG
     CKALHVLFER VSEEQLTEFV ENKDYMILLS ALTNFKDEEE IVLHVLHCLH SLAIPCNNVE
     VLMSGNVRCY NIVVEAMKAF PMSERIQEVS CCLLHRLTLG NFFNILVLNE VHEFVVKAVQ
     QYPENAALQI SALSCLALLT ETIFLNQDLE EKNENQENDD EGEEDKLFWL EACYKALTWH
     RKNKHVQEAA CWALNNLLMY QNSLHEKIGD EDGHFPAHRE VMLSMLMHSS SKEVFQASAN
     ALSTLLEQNV NFRKILLSKG IHLNVLELMQ KHIHSPEVAE SGCKMLNHLF EGSNTSLDIM
     AAVVPKILTV MKRHETSLPV QLEALRAILH FIVPGMPEES REDTEFHHKL NMVKKQCFKN
     DIHKLVLAAL NRFIGNPGIQ KCGLKVISSI VHFPDALEML SLEGAMDSVL HTLQMYPDDQ
     EIQCLGLSLI GYLITKKNVF IGTGHLLAKI LVSSLYRFKD VAEIQTKGFQ TILAILKLSA
     SFSKLLVHHS FDLVIFHQMS SNIMEQKDQQ FLNLCCKCFA KVAMDDYLKN VMLERACDQN
     NSIMVECLLL LGADANQAKE GSSLICQVCE KESSPKLVEL LLNSGSREQD VRKALTISIG
     KGDSQIISLL LRRLALDVAN NSICLGGFCI GKVEPSWLGP LFPDKTSNLR KQTNIASTLA
     RMVIRYQMKS AVEEGTASGS DGNFSEDVLS KFDEWTFIPD SSMDSVFAQS DDLDSEGSEG
     SFLVKKKSNS ISVGEFYRDA VLQRCSPNLQ RHSNSLGPIF DHEDLLKRKR KILSSDDSLR
     SSKLQSHMRH SDSISSLASE REYITSLDLS ANELRDIDAL SQKCCISVHL EHLEKLELHQ
     NALTSFPQQL CETLKSLTHL DLHSNKFTSF PSYLLKMSCI ANLDVSRNDI GPSVVLDPTV
     KCPTLKQFNL SYNQLSFVPE NLTDVVEKLE QLILEGNKIS GICSPLRLKE LKILNLSKNH
     ISSLSENFLE ACPKVESFSA RMNFLAAMPF LPPSMTILKL SQNKFSCIPE AILNLPHLRS
     LDMSSNDIQY LPGPAHWKSL NLRELLFSHN QISILDLSEK AYLWSRVEKL HLSHNKLKEI
     PPEIGCLENL TSLDVSYNLE LRSFPNEMGK LSKIWDLPLD ELHLNFDFKH IGCKAKDIIR
     FLQQRLKKAV PYNRMKLMIV GNTGSGKTTL LQQLMKTKKS DLGMQSATVG IDVKDWPIQI
     RDKRKRDLVL NVWDFAGREE FYSTHPHFMT QRALYLAVYD LSKGQAEVDA MKPWLFNIKA
     RASSSPVILV GTHLDVSDEK QRKACMSKIT KELLNKRGFP AIRDYHFVNA TEESDALAKL
     RKTIINESLN FKIRDQLVVG QLIPDCYVEL EKIILSERKN VPIEFPVIDR KRLLQLVREN
     QLQLDENELP HAVHFLNESG VLLHFQDPAL QLSDLYFVEP KWLCKIMAQI LTVKVEGCPK
     HPKGIISRRD VEKFLSKKRK FPKNYMSQYF KLLEKFQIAL PIGEEYLLVP SSLSDHRPVI
     ELPHCENSEI IIRLYEMPYF PMGFWSRLIN RLLEISPYML SGRERALRPN RMYWRQGIYL
     NWSPEAYCLV GSEVLDNHPE SFLKITVPSC RKGCILLGQV VDHIDSLMEE WFPGLLEIDI
     CGEGETLLKK WALYSFNDGE EHQKILLDDL MKKAEEGDLL VNPDQPRLTI PISQIAPDLI
     LADLPRNIML NNDELEFEQA PEFLLGDGSF GSVYRAAYEG EEVAVKIFNK HTSLRLLRQE
     LVVLCHLHHP SLISLLAAGI RPRMLVMELA SKGSLDRLLQ QDKASLTRTL QHRIALHVAD
     GLRYLHSAMI IYRDLKPHNV LLFTLYPNAA IIAKIADYGI AQYCCRMGIK TSEGTPGFRA
     PEVARGNVIY NQQADVYSFG LLLYDILTTG GRIVEGLKFP NEFDELEIQG KLPDPVKEYG
     CAPWPMVEKL IKQCLKENPQ ERPTSAQVFD ILNSAELVCL TRRILLPKNV IVECMVATHH
     NSRNASIWLG CGHTDRGQLS FLDLNTEGYT SEEVADSRIL CLALVHLPVE KESWIVSGTQ
     SGTLLVINTE DGKKRHTLEK MTDSVTCLYC NSFSKQSKQK NFLLVGTADG KLAIFEDKTV
     KLKGAAPLKI LNIGNVSTPL MCLSESTNST ERNVMWGGCG TKIFSFSNDF TIQKLIETRT
     SQLFSYAAFS DSNIITVVVD TALYIAKQNS PVVEVWDKKT EKLCGLIDCV HFLREVMVKE
     NKESKHKMSY SGRVKTLCLQ KNTALWIGTG GGHILLLDLS TRRLIRVIYN FCNSVRVMMT
     AQLGSLKNVM LVLGYNRKNT EGTQKQKEIQ SCLTVWDINL PHEVQNLEKH IEVRKELAEK
     MRRTSVE
//