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Q5S007

- LRRK2_HUMAN

UniProt

Q5S007 - LRRK2_HUMAN

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Protein
Leucine-rich repeat serine/threonine-protein kinase 2
Gene
LRRK2, PARK8
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes. Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose 6 phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner. Regulates neuronal process morphology in the intact central nervous system (CNS). Phosphorylates PRDX3. May also have GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease.

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei1906 – 19061ATP By similarity
Active sitei1994 – 19941Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1341 – 13488GTP Reviewed prediction
Nucleotide bindingi1885 – 18939ATP By similarity
Nucleotide bindingi2098 – 212124GTP Reviewed prediction
Add
BLAST
Nucleotide bindingi2295 – 22984GTP Reviewed prediction

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. GTP binding Source: UniProtKB
  3. GTP-dependent protein kinase activity Source: UniProtKB
  4. GTPase activator activity Source: UniProtKB
  5. GTPase activity Source: BHF-UCL
  6. MAP kinase kinase activity Source: BHF-UCL
  7. Rho GTPase binding Source: BHF-UCL
  8. SNARE binding Source: ParkinsonsUK-UCL
  9. actin binding Source: ParkinsonsUK-UCL
  10. clathrin binding Source: ParkinsonsUK-UCL
  11. glycoprotein binding Source: ParkinsonsUK-UCL
  12. identical protein binding Source: IntAct
  13. ion channel binding Source: UniProtKB
  14. protein binding Source: UniProtKB
  15. protein homodimerization activity Source: UniProtKB
  16. protein kinase A binding Source: ParkinsonsUK-UCL
  17. protein kinase activity Source: UniProtKB
  18. protein serine/threonine kinase activity Source: UniProtKB
  19. syntaxin-1 binding Source: ParkinsonsUK-UCL
  20. tubulin binding Source: BHF-UCL
Complete GO annotation...

GO - Biological processi

  1. GTP catabolic process Source: BHF-UCL
  2. MAPK cascade Source: UniProtKB
  3. activation of MAPK activity Source: GOC
  4. activation of MAPKK activity Source: BHF-UCL
  5. autophagy Source: UniProtKB-KW
  6. cellular response to organic cyclic compound Source: Ensembl
  7. determination of adult lifespan Source: BHF-UCL
  8. exploration behavior Source: BHF-UCL
  9. intracellular distribution of mitochondria Source: BHF-UCL
  10. negative regulation of GTPase activity Source: MGI
  11. negative regulation of late endosome to lysosome transport Source: ParkinsonsUK-UCL
  12. negative regulation of protein binding Source: ParkinsonsUK-UCL
  13. neuromuscular junction development Source: BHF-UCL
  14. neuron death Source: BHF-UCL
  15. olfactory bulb development Source: BHF-UCL
  16. peptidyl-serine phosphorylation Source: BHF-UCL
  17. peptidyl-threonine phosphorylation Source: BHF-UCL
  18. positive regulation of GTPase activity Source: GOC
  19. positive regulation of autophagy Source: UniProtKB
  20. positive regulation of dopamine receptor signaling pathway Source: BHF-UCL
  21. positive regulation of programmed cell death Source: UniProtKB
  22. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
  23. positive regulation of protein phosphorylation Source: BHF-UCL
  24. positive regulation of protein ubiquitination Source: UniProtKB
  25. protein autophosphorylation Source: UniProtKB
  26. regulation of branching morphogenesis of a nerve Source: BHF-UCL
  27. regulation of dendritic spine morphogenesis Source: BHF-UCL
  28. regulation of kidney size Source: BHF-UCL
  29. regulation of locomotion Source: BHF-UCL
  30. regulation of membrane potential Source: BHF-UCL
  31. regulation of mitochondrial depolarization Source: ParkinsonsUK-UCL
  32. regulation of neuroblast proliferation Source: ParkinsonsUK-UCL
  33. regulation of neuron death Source: ParkinsonsUK-UCL
  34. regulation of neuron maturation Source: BHF-UCL
  35. regulation of synaptic vesicle exocytosis Source: ParkinsonsUK-UCL
  36. regulation of synaptic vesicle transport Source: ParkinsonsUK-UCL
  37. response to oxidative stress Source: BHF-UCL
  38. small GTPase mediated signal transduction Source: InterPro
  39. tangential migration from the subventricular zone to the olfactory bulb Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

GTPase activation, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Autophagy, Differentiation

Keywords - Ligandi

ATP-binding, GTP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ5S007.

Names & Taxonomyi

Protein namesi
Recommended name:
Leucine-rich repeat serine/threonine-protein kinase 2 (EC:2.7.11.1)
Alternative name(s):
Dardarin
Gene namesi
Name:LRRK2
Synonyms:PARK8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:18618. LRRK2.

Subcellular locationi

Membrane; Peripheral membrane protein. Cytoplasm. Perikaryon. Mitochondrion. Golgi apparatus. Cell projectionaxon. Cell projectiondendrite. Endoplasmic reticulum By similarity. Cytoplasmic vesicle By similarity. Endosome By similarity. Lysosome By similarity. Mitochondrion outer membrane By similarity. Mitochondrion inner membrane By similarity. Mitochondrion matrix By similarity
Note: Predominantly associated with intracytoplasmic vesicular and membranous structures By similarity. Localized in the cytoplasm and associated with cellular membrane structures. Predominantly associated with the mitochondrial outer membrane of the mitochondria. Colocalized with RAB29 along tubular structures emerging from Golgi apparatus. Localizes in intracytoplasmic punctate structures of neuronal perikarya and dendritic and axonal processes.

GO - Cellular componenti

  1. axon Source: Ensembl
  2. cytoplasm Source: UniProtKB
  3. cytoplasmic side of mitochondrial outer membrane Source: UniProtKB
  4. cytosol Source: ParkinsonsUK-UCL
  5. dendrite cytoplasm Source: BHF-UCL
  6. extracellular space Source: UniProt
  7. extracellular vesicular exosome Source: UniProt
  8. inclusion body Source: ParkinsonsUK-UCL
  9. membrane raft Source: Ensembl
  10. mitochondrial membrane Source: ParkinsonsUK-UCL
  11. mitochondrion Source: UniProtKB
  12. neuron projection Source: BHF-UCL
  13. neuronal cell body Source: BHF-UCL
  14. plasma membrane Source: Ensembl
  15. synaptic vesicle Source: Ensembl
  16. trans-Golgi network Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Membrane, Mitochondrion, Mitochondrion inner membrane, Mitochondrion outer membrane

Pathology & Biotechi

Involvement in diseasei

Parkinson disease 8 (PARK8) [MIM:607060]: A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients.
Note: The disease is caused by mutations affecting the gene represented in this entry.35 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti712 – 7121M → V in PARK8. 1 Publication
VAR_054741
Natural varianti793 – 7931R → M in PARK8; unknown pathological significance. 3 Publications
Corresponds to variant rs35173587 [ dbSNP | Ensembl ].
VAR_024935
Natural varianti930 – 9301Q → R in PARK8; unknown pathological significance. 1 Publication
VAR_024936
Natural varianti1067 – 10671R → Q in PARK8. 1 Publication
VAR_024938
Natural varianti1096 – 10961S → C in PARK8; unknown pathological significance. 1 Publication
VAR_024939
Natural varianti1122 – 11221I → V in PARK8. 2 Publications
Corresponds to variant rs34805604 [ dbSNP | Ensembl ].
VAR_024940
Natural varianti1228 – 12281S → T in PARK8. 1 Publication
VAR_024941
Natural varianti1371 – 13711I → V in PARK8; unknown pathological significance. 2 Publications
Corresponds to variant rs17466213 [ dbSNP | Ensembl ].
VAR_024943
Natural varianti1441 – 14411R → G in PARK8; shows a progressive reduction in neurite length and branching.
Corresponds to variant rs33939927 [ dbSNP | Ensembl ].
VAR_024946
Natural varianti1441 – 14411R → H in PARK8; pathogenicity has yet to be confirmed. 2 Publications
Corresponds to variant rs34995376 [ dbSNP | Ensembl ].
VAR_024947
Natural varianti1514 – 15141R → Q in PARK8; pathogenicity has yet to be confirmed; might have an effect on protein structure. 3 Publications
Corresponds to variant rs35507033 [ dbSNP | Ensembl ].
VAR_024948
Natural varianti1542 – 15421P → S in PARK8; pathogenicity has yet to be confirmed; might have an effect on protein structure. 3 Publications
Corresponds to variant rs33958906 [ dbSNP | Ensembl ].
VAR_024949
Natural varianti1598 – 15981V → E in PARK8; pathogenicity has yet to be confirmed; might have an effect on protein structure. 1 Publication
Corresponds to variant rs721710 [ dbSNP | Ensembl ].
VAR_024950
Natural varianti1699 – 16991Y → C in PARK8; shows no progressive reduction in neurite length and branching.
Corresponds to variant rs35801418 [ dbSNP | Ensembl ].
VAR_024954
Natural varianti1728 – 17281R → H in PARK8. 1 Publication
VAR_054744
Natural varianti1728 – 17281R → L in PARK8. 1 Publication
VAR_054745
Natural varianti1869 – 18691M → T in PARK8; pathogenicity has yet to be confirmed. 2 Publications
Corresponds to variant rs35602796 [ dbSNP | Ensembl ].
VAR_024955
Natural varianti1941 – 19411R → H in PARK8. 1 Publication
VAR_024956
Natural varianti2012 – 20121I → T in PARK8; pathogenicity uncertain. 1 Publication
Corresponds to variant rs34015634 [ dbSNP | Ensembl ].
VAR_024957
Natural varianti2019 – 20191G → S in PARK8; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate; results in increased PRDX3 phosphorylation promoting dysregulation of mitochondrial function and oxidative damage; does not inhibit interaction with RAB29; shows a progressive reduction in neurite length and branching; shows distinctive spheroid-like inclusions within both neuronal processes and at intracellular membranous structures; shows lysosomal swelling and reduced retrograde transport of selective cargo between lysosomes and the Golgi apparatus; shows apoptotic mechanism of cell death. 26 Publications
Corresponds to variant rs34637584 [ dbSNP | Ensembl ].
VAR_024958
Natural varianti2020 – 20201I → T in PARK8; significant increase in autophosphorylation of about 40% in comparison to wild-type protein in vitro; shows a progressive reduction in neurite length and branching. 5 Publications
Corresponds to variant rs35870237 [ dbSNP | Ensembl ].
VAR_024959
Natural varianti2141 – 21411T → M in PARK8. 1 Publication
VAR_054747
Natural varianti2143 – 21431R → H in PARK8. 1 Publication
VAR_054748
Natural varianti2356 – 23561T → I in PARK8. 1 Publication
VAR_024963
Natural varianti2466 – 24661L → H in PARK8. 1 Publication
VAR_054750

Keywords - Diseasei

Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

MIMi168600. phenotype.
607060. phenotype.
Orphaneti2828. Young adult-onset Parkinsonism.
PharmGKBiPA134968052.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 25272527Leucine-rich repeat serine/threonine-protein kinase 2
PRO_0000086238Add
BLAST

Post-translational modificationi

Autophosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ5S007.
PaxDbiQ5S007.
PRIDEiQ5S007.

PTM databases

PhosphoSiteiQ5S007.

Expressioni

Tissue specificityi

Expressed in the brain. Expressed in pyramidal neurons in all cortical laminae of the visual cortex, in neurons of the substantia nigra pars compacta and caudate putamen (at protein level). Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas.

Gene expression databases

ArrayExpressiQ5S007.
BgeeiQ5S007.
CleanExiHS_LRRK2.
GenevestigatoriQ5S007.

Organism-specific databases

HPAiCAB037160.
HPA014293.

Interactioni

Subunit structurei

Homodimer. Interacts with PARK2, PRDX3, RAB29, TPCN2 and VPS35.

Binary interactionsi

WithEntry#Exp.IntActNotes
itself52EBI-5323863,EBI-5323863
AGO2Q9UKV83EBI-5323863,EBI-528269
AKT1P317496EBI-5323863,EBI-296087
ARFGAP1Q8N6T3-26EBI-5323863,EBI-6288865
Arfgap1Q628487EBI-5323863,EBI-4398879From a different organism.
ARHGEF7Q141556EBI-5323863,EBI-717515
CDC37Q165437EBI-5323863,EBI-295634
CDC42P609533EBI-5323863,EBI-81752
Ckmt1P302752EBI-5323863,EBI-773103From a different organism.
DAPK1P533552EBI-5323863,EBI-358616
DNM1Q051934EBI-5323863,EBI-713135
Dnm1P390533EBI-5323863,EBI-397785From a different organism.
DNM1LO0042911EBI-5323863,EBI-724571
DNM1LO00429-32EBI-5323863,EBI-6896746
DVL1O14640-27EBI-5323863,EBI-6504027
DVL2O146413EBI-5323863,EBI-740850
DVL3Q929974EBI-5323863,EBI-739789
FADDQ131584EBI-5323863,EBI-494804
GSK3BP498417EBI-5323863,EBI-373586
HSPA8P111423EBI-5323863,EBI-351896
LDHBP071952EBI-5323863,EBI-358748
LRP6O755813EBI-5323863,EBI-910915
LRRK1Q38SD25EBI-5323863,EBI-1050422
MAP2K3P467345EBI-5323863,EBI-602462
MAP2K6P525644EBI-5323863,EBI-448135
MAP2K7O147333EBI-5323863,EBI-492605
MAPTP10636-23EBI-5323863,EBI-7796412
MAPTP10636-89EBI-5323863,EBI-366233
MBPP026873EBI-5323863,EBI-908215From a different organism.
Mfn1Q811U43EBI-5323863,EBI-9029118From a different organism.
MFN2O951403EBI-5323863,EBI-3324756
MSNP260386EBI-5323863,EBI-528768
NFATC2Q134693EBI-5323863,EBI-716258
OPA1O603133EBI-5323863,EBI-1054131
PARK2O602603EBI-5323863,EBI-716346
PRDX3P3004812EBI-5323863,EBI-748336
PRKACAP176126EBI-5323863,EBI-476586
Prkar2bP123693EBI-5323863,EBI-6096160From a different organism.
RAB5BP610204EBI-5323863,EBI-399401
Rab5bP610212EBI-5323863,EBI-8320093From a different organism.
Rab7l1Q634813EBI-5323863,EBI-6513837From a different organism.
RAC1P630005EBI-5323863,EBI-413628
RPL10AP629062EBI-5323863,EBI-356860
RPL13P263732EBI-5323863,EBI-356849
RPL14P509142EBI-5323863,EBI-356746
RPL23AP627502EBI-5323863,EBI-353254
RPS11P622803EBI-5323863,EBI-1047710
RPS15P628417EBI-5323863,EBI-372635
RPS16P622492EBI-5323863,EBI-352480
RPS2P158802EBI-5323863,EBI-443446
RPS23P622662EBI-5323863,EBI-353072
RPS27P426772EBI-5323863,EBI-356336
RPS3P233962EBI-5323863,EBI-351193
SH3GL2Q999622EBI-5323863,EBI-77938
SLC25A4P122352EBI-5323863,EBI-359074
SLC25A5P051412EBI-5323863,EBI-355133
SLC25A6P122362EBI-5323863,EBI-356254
SNAPINO952955EBI-5323863,EBI-296723
SNCAP378406EBI-5323863,EBI-985879
Spag9Q58A652EBI-5323863,EBI-6530207From a different organism.
TUBBP074373EBI-5323863,EBI-350864
TUBB4AP043504EBI-5323863,EBI-355007
YWHABP319463EBI-5323863,EBI-359815
YWHAEP622585EBI-5323863,EBI-356498
YWHAGP619813EBI-5323863,EBI-359832
YwhagP619836EBI-5323863,EBI-359821From a different organism.
YWHAHQ049173EBI-5323863,EBI-306940
YWHAQP273487EBI-5323863,EBI-359854
YWHAZP631047EBI-5323863,EBI-347088

Protein-protein interaction databases

BioGridi125700. 139 interactions.
DIPiDIP-29684N.
IntActiQ5S007. 407 interactions.
MINTiMINT-7997594.
STRINGi9606.ENSP00000298910.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi1336 – 13416
Helixi1347 – 13548
Beta strandi1370 – 13778
Beta strandi1389 – 13957
Helixi1398 – 14025
Helixi1406 – 14116
Beta strandi1412 – 14209
Helixi1421 – 14233
Helixi1425 – 14295
Helixi1431 – 144111
Beta strandi1446 – 14527
Helixi1454 – 14563
Helixi1459 – 147214
Turni1473 – 14753
Beta strandi1481 – 14877
Helixi1495 – 150915

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZEJX-ray2.00A/B1333-1516[»]
3D6TX-ray2.43B1335-1505[»]
ProteinModelPortaliQ5S007.
SMRiQ5S007. Positions 1335-1512.

Miscellaneous databases

EvolutionaryTraceiQ5S007.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati983 – 100422LRR 1
Add
BLAST
Repeati1012 – 103322LRR 2
Add
BLAST
Repeati1036 – 105722LRR 3
Add
BLAST
Repeati1059 – 108022LRR 4
Add
BLAST
Repeati1084 – 110522LRR 5
Add
BLAST
Repeati1108 – 112922LRR 6
Add
BLAST
Repeati1130 – 115021LRR 7
Add
BLAST
Repeati1174 – 119623LRR 8
Add
BLAST
Repeati1197 – 121822LRR 9
Add
BLAST
Repeati1221 – 124121LRR 10
Add
BLAST
Repeati1246 – 126722LRR 11
Add
BLAST
Repeati1269 – 129123LRR 12
Add
BLAST
Domaini1328 – 1511184Roc
Add
BLAST
Domaini1879 – 2138260Protein kinase
Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili319 – 34830 Reviewed prediction
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi728 – 7314Poly-Leu

Sequence similaritiesi

Contains 1 Roc domain.

Keywords - Domaini

Coiled coil, Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiCOG4886.
HOGENOMiHOG000293315.
HOVERGENiHBG081937.
InParanoidiQ5S007.
KOiK08844.
OMAiFKIRDQP.
PhylomeDBiQ5S007.
TreeFamiTF313679.

Family and domain databases

Gene3Di1.25.10.10. 2 hits.
1.25.40.20. 1 hit.
2.130.10.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR020683. Ankyrin_rpt-contain_dom.
IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR011009. Kinase-like_dom.
IPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR013684. MIRO-like.
IPR027417. P-loop_NTPase.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR020859. ROC_GTPase.
IPR008271. Ser/Thr_kinase_AS.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00560. LRR_1. 1 hit.
PF12799. LRR_4. 1 hit.
PF13855. LRR_8. 1 hit.
PF08477. Miro. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SMARTiSM00369. LRR_TYP. 1 hit.
SM00320. WD40. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 2 hits.
SSF50978. SSF50978. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF56112. SSF56112. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51450. LRR. 11 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS51424. ROC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5S007-1 [UniParc]FASTAAdd to Basket

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MASGSCQGCE EDEETLKKLI VRLNNVQEGK QIETLVQILE DLLVFTYSER     50
ASKLFQGKNI HVPLLIVLDS YMRVASVQQV GWSLLCKLIE VCPGTMQSLM 100
GPQDVGNDWE VLGVHQLILK MLTVHNASVN LSVIGLKTLD LLLTSGKITL 150
LILDEESDIF MLIFDAMHSF PANDEVQKLG CKALHVLFER VSEEQLTEFV 200
ENKDYMILLS ALTNFKDEEE IVLHVLHCLH SLAIPCNNVE VLMSGNVRCY 250
NIVVEAMKAF PMSERIQEVS CCLLHRLTLG NFFNILVLNE VHEFVVKAVQ 300
QYPENAALQI SALSCLALLT ETIFLNQDLE EKNENQENDD EGEEDKLFWL 350
EACYKALTWH RKNKHVQEAA CWALNNLLMY QNSLHEKIGD EDGHFPAHRE 400
VMLSMLMHSS SKEVFQASAN ALSTLLEQNV NFRKILLSKG IHLNVLELMQ 450
KHIHSPEVAE SGCKMLNHLF EGSNTSLDIM AAVVPKILTV MKRHETSLPV 500
QLEALRAILH FIVPGMPEES REDTEFHHKL NMVKKQCFKN DIHKLVLAAL 550
NRFIGNPGIQ KCGLKVISSI VHFPDALEML SLEGAMDSVL HTLQMYPDDQ 600
EIQCLGLSLI GYLITKKNVF IGTGHLLAKI LVSSLYRFKD VAEIQTKGFQ 650
TILAILKLSA SFSKLLVHHS FDLVIFHQMS SNIMEQKDQQ FLNLCCKCFA 700
KVAMDDYLKN VMLERACDQN NSIMVECLLL LGADANQAKE GSSLICQVCE 750
KESSPKLVEL LLNSGSREQD VRKALTISIG KGDSQIISLL LRRLALDVAN 800
NSICLGGFCI GKVEPSWLGP LFPDKTSNLR KQTNIASTLA RMVIRYQMKS 850
AVEEGTASGS DGNFSEDVLS KFDEWTFIPD SSMDSVFAQS DDLDSEGSEG 900
SFLVKKKSNS ISVGEFYRDA VLQRCSPNLQ RHSNSLGPIF DHEDLLKRKR 950
KILSSDDSLR SSKLQSHMRH SDSISSLASE REYITSLDLS ANELRDIDAL 1000
SQKCCISVHL EHLEKLELHQ NALTSFPQQL CETLKSLTHL DLHSNKFTSF 1050
PSYLLKMSCI ANLDVSRNDI GPSVVLDPTV KCPTLKQFNL SYNQLSFVPE 1100
NLTDVVEKLE QLILEGNKIS GICSPLRLKE LKILNLSKNH ISSLSENFLE 1150
ACPKVESFSA RMNFLAAMPF LPPSMTILKL SQNKFSCIPE AILNLPHLRS 1200
LDMSSNDIQY LPGPAHWKSL NLRELLFSHN QISILDLSEK AYLWSRVEKL 1250
HLSHNKLKEI PPEIGCLENL TSLDVSYNLE LRSFPNEMGK LSKIWDLPLD 1300
ELHLNFDFKH IGCKAKDIIR FLQQRLKKAV PYNRMKLMIV GNTGSGKTTL 1350
LQQLMKTKKS DLGMQSATVG IDVKDWPIQI RDKRKRDLVL NVWDFAGREE 1400
FYSTHPHFMT QRALYLAVYD LSKGQAEVDA MKPWLFNIKA RASSSPVILV 1450
GTHLDVSDEK QRKACMSKIT KELLNKRGFP AIRDYHFVNA TEESDALAKL 1500
RKTIINESLN FKIRDQLVVG QLIPDCYVEL EKIILSERKN VPIEFPVIDR 1550
KRLLQLVREN QLQLDENELP HAVHFLNESG VLLHFQDPAL QLSDLYFVEP 1600
KWLCKIMAQI LTVKVEGCPK HPKGIISRRD VEKFLSKKRK FPKNYMSQYF 1650
KLLEKFQIAL PIGEEYLLVP SSLSDHRPVI ELPHCENSEI IIRLYEMPYF 1700
PMGFWSRLIN RLLEISPYML SGRERALRPN RMYWRQGIYL NWSPEAYCLV 1750
GSEVLDNHPE SFLKITVPSC RKGCILLGQV VDHIDSLMEE WFPGLLEIDI 1800
CGEGETLLKK WALYSFNDGE EHQKILLDDL MKKAEEGDLL VNPDQPRLTI 1850
PISQIAPDLI LADLPRNIML NNDELEFEQA PEFLLGDGSF GSVYRAAYEG 1900
EEVAVKIFNK HTSLRLLRQE LVVLCHLHHP SLISLLAAGI RPRMLVMELA 1950
SKGSLDRLLQ QDKASLTRTL QHRIALHVAD GLRYLHSAMI IYRDLKPHNV 2000
LLFTLYPNAA IIAKIADYGI AQYCCRMGIK TSEGTPGFRA PEVARGNVIY 2050
NQQADVYSFG LLLYDILTTG GRIVEGLKFP NEFDELEIQG KLPDPVKEYG 2100
CAPWPMVEKL IKQCLKENPQ ERPTSAQVFD ILNSAELVCL TRRILLPKNV 2150
IVECMVATHH NSRNASIWLG CGHTDRGQLS FLDLNTEGYT SEEVADSRIL 2200
CLALVHLPVE KESWIVSGTQ SGTLLVINTE DGKKRHTLEK MTDSVTCLYC 2250
NSFSKQSKQK NFLLVGTADG KLAIFEDKTV KLKGAAPLKI LNIGNVSTPL 2300
MCLSESTNST ERNVMWGGCG TKIFSFSNDF TIQKLIETRT SQLFSYAAFS 2350
DSNIITVVVD TALYIAKQNS PVVEVWDKKT EKLCGLIDCV HFLREVMVKE 2400
NKESKHKMSY SGRVKTLCLQ KNTALWIGTG GGHILLLDLS TRRLIRVIYN 2450
FCNSVRVMMT AQLGSLKNVM LVLGYNRKNT EGTQKQKEIQ SCLTVWDINL 2500
PHEVQNLEKH IEVRKELAEK MRRTSVE 2527
Length:2,527
Mass (Da):286,103
Last modified:April 20, 2010 - v2
Checksum:i26142A0CECBBC3F4
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti50 – 501R → H.
Corresponds to variant rs2256408 [ dbSNP | Ensembl ].
VAR_024931
Natural varianti119 – 1191L → P.2 Publications
Corresponds to variant rs33995463 [ dbSNP | Ensembl ].
VAR_024932
Natural varianti228 – 2281C → S.1 Publication
Corresponds to variant rs56108242 [ dbSNP | Ensembl ].
VAR_054740
Natural varianti419 – 4191A → V.1 Publication
Corresponds to variant rs34594498 [ dbSNP | Ensembl ].
VAR_033903
Natural varianti551 – 5511N → K.4 Publications
Corresponds to variant rs7308720 [ dbSNP | Ensembl ].
VAR_024933
Natural varianti712 – 7121M → V in PARK8. 1 Publication
VAR_054741
Natural varianti716 – 7161A → V.1 Publication
VAR_054742
Natural varianti723 – 7231I → V.3 Publications
Corresponds to variant rs10878307 [ dbSNP | Ensembl ].
VAR_024934
Natural varianti755 – 7551P → L.
Corresponds to variant rs34410987 [ dbSNP | Ensembl ].
VAR_033904
Natural varianti793 – 7931R → M in PARK8; unknown pathological significance. 3 Publications
Corresponds to variant rs35173587 [ dbSNP | Ensembl ].
VAR_024935
Natural varianti871 – 8711K → E.1 Publication
VAR_054743
Natural varianti930 – 9301Q → R in PARK8; unknown pathological significance. 1 Publication
VAR_024936
Natural varianti944 – 9441D → Y.
Corresponds to variant rs17519916 [ dbSNP | Ensembl ].
VAR_024937
Natural varianti1067 – 10671R → Q in PARK8. 1 Publication
VAR_024938
Natural varianti1096 – 10961S → C in PARK8; unknown pathological significance. 1 Publication
VAR_024939
Natural varianti1122 – 11221I → V in PARK8. 2 Publications
Corresponds to variant rs34805604 [ dbSNP | Ensembl ].
VAR_024940
Natural varianti1228 – 12281S → T in PARK8. 1 Publication
VAR_024941
Natural varianti1262 – 12621P → A.1 Publication
Corresponds to variant rs4640000 [ dbSNP | Ensembl ].
VAR_024942
Natural varianti1359 – 13591K → I Found in a renal cell carcinoma sample; somatic mutation. 1 Publication
VAR_064728
Natural varianti1371 – 13711I → V in PARK8; unknown pathological significance. 2 Publications
Corresponds to variant rs17466213 [ dbSNP | Ensembl ].
VAR_024943
Natural varianti1375 – 13751D → E.
Corresponds to variant rs28365226 [ dbSNP | Ensembl ].
VAR_047022
Natural varianti1398 – 13981R → H.4 Publications
Corresponds to variant rs7133914 [ dbSNP | Ensembl ].
VAR_024944
Natural varianti1441 – 14411R → C in PARK; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate. 6 Publications
VAR_024945
Natural varianti1441 – 14411R → G in PARK8; shows a progressive reduction in neurite length and branching.
Corresponds to variant rs33939927 [ dbSNP | Ensembl ].
VAR_024946
Natural varianti1441 – 14411R → H in PARK8; pathogenicity has yet to be confirmed. 2 Publications
Corresponds to variant rs34995376 [ dbSNP | Ensembl ].
VAR_024947
Natural varianti1514 – 15141R → Q in PARK8; pathogenicity has yet to be confirmed; might have an effect on protein structure. 3 Publications
Corresponds to variant rs35507033 [ dbSNP | Ensembl ].
VAR_024948
Natural varianti1542 – 15421P → S in PARK8; pathogenicity has yet to be confirmed; might have an effect on protein structure. 3 Publications
Corresponds to variant rs33958906 [ dbSNP | Ensembl ].
VAR_024949
Natural varianti1550 – 15501R → Q in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication
VAR_040678
Natural varianti1598 – 15981V → E in PARK8; pathogenicity has yet to be confirmed; might have an effect on protein structure. 1 Publication
Corresponds to variant rs721710 [ dbSNP | Ensembl ].
VAR_024950
Natural varianti1628 – 16281R → P May be associated with Parkinson disease in some populations. 3 Publications
Corresponds to variant rs33949390 [ dbSNP | Ensembl ].
VAR_024951
Natural varianti1646 – 16461M → T.2 Publications
Corresponds to variant rs35303786 [ dbSNP | Ensembl ].
VAR_024952
Natural varianti1647 – 16471S → T.2 Publications
Corresponds to variant rs11564148 [ dbSNP | Ensembl ].
VAR_024953
Natural varianti1699 – 16991Y → C in PARK8; shows no progressive reduction in neurite length and branching.
Corresponds to variant rs35801418 [ dbSNP | Ensembl ].
VAR_024954
Natural varianti1723 – 17231R → P in an ovarian serous carcinoma sample; somatic mutation. 1 Publication
VAR_040679
Natural varianti1728 – 17281R → H in PARK8. 1 Publication
VAR_054744
Natural varianti1728 – 17281R → L in PARK8. 1 Publication
VAR_054745
Natural varianti1869 – 18691M → T in PARK8; pathogenicity has yet to be confirmed. 2 Publications
Corresponds to variant rs35602796 [ dbSNP | Ensembl ].
VAR_024955
Natural varianti1870 – 18701L → F.1 Publication
VAR_054746
Natural varianti1906 – 19061K → M Does not inhibit interaction with RAB29; shows a progressive increase in neurite length and branching.
VAR_071101
Natural varianti1941 – 19411R → H in PARK8. 1 Publication
VAR_024956
Natural varianti2012 – 20121I → T in PARK8; pathogenicity uncertain. 1 Publication
Corresponds to variant rs34015634 [ dbSNP | Ensembl ].
VAR_024957
Natural varianti2019 – 20191G → S in PARK8; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate; results in increased PRDX3 phosphorylation promoting dysregulation of mitochondrial function and oxidative damage; does not inhibit interaction with RAB29; shows a progressive reduction in neurite length and branching; shows distinctive spheroid-like inclusions within both neuronal processes and at intracellular membranous structures; shows lysosomal swelling and reduced retrograde transport of selective cargo between lysosomes and the Golgi apparatus; shows apoptotic mechanism of cell death. 26 Publications
Corresponds to variant rs34637584 [ dbSNP | Ensembl ].
VAR_024958
Natural varianti2020 – 20201I → T in PARK8; significant increase in autophosphorylation of about 40% in comparison to wild-type protein in vitro; shows a progressive reduction in neurite length and branching. 5 Publications
Corresponds to variant rs35870237 [ dbSNP | Ensembl ].
VAR_024959
Natural varianti2081 – 20811N → D.2 Publications
Corresponds to variant rs33995883 [ dbSNP | Ensembl ].
VAR_024960
Natural varianti2119 – 21191P → L.1 Publication
Corresponds to variant rs12423862 [ dbSNP | Ensembl ].
VAR_024961
Natural varianti2141 – 21411T → M in PARK8. 1 Publication
VAR_054747
Natural varianti2143 – 21431R → H in PARK8. 1 Publication
VAR_054748
Natural varianti2261 – 22611N → I.1 Publication
Corresponds to variant rs12581902 [ dbSNP | Ensembl ].
VAR_024962
Natural varianti2356 – 23561T → I in PARK8. 1 Publication
VAR_024963
Natural varianti2385 – 23851G → R Associated with Parkinson disease; under conditions of oxidative stress the variant protein is more toxic and is associated with a higher rate of apoptosis. 3 Publications
Corresponds to variant rs34778348 [ dbSNP | Ensembl ].
VAR_024964
Natural varianti2395 – 23951E → K.1 Publication
VAR_054749
Natural varianti2397 – 23971M → T.3 Publications
Corresponds to variant rs3761863 [ dbSNP | Ensembl ].
VAR_024965
Natural varianti2466 – 24661L → H in PARK8. 1 Publication
VAR_054750

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti212 – 2121L → S in AAV63975. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY792511 mRNA. Translation: AAV63975.1.
AC079630 Genomic DNA. No translation available.
AC084290 Genomic DNA. No translation available.
AC107023 Genomic DNA. No translation available.
AL834529 mRNA. Translation: CAD39185.1.
CCDSiCCDS31774.1.
RefSeqiNP_940980.3. NM_198578.3.
UniGeneiHs.187636.

Genome annotation databases

EnsembliENST00000298910; ENSP00000298910; ENSG00000188906.
GeneIDi120892.
KEGGihsa:120892.
UCSCiuc001rmg.4. human.

Polymorphism databases

DMDMi294862450.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY792511 mRNA. Translation: AAV63975.1 .
AC079630 Genomic DNA. No translation available.
AC084290 Genomic DNA. No translation available.
AC107023 Genomic DNA. No translation available.
AL834529 mRNA. Translation: CAD39185.1 .
CCDSi CCDS31774.1.
RefSeqi NP_940980.3. NM_198578.3.
UniGenei Hs.187636.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2ZEJ X-ray 2.00 A/B 1333-1516 [» ]
3D6T X-ray 2.43 B 1335-1505 [» ]
ProteinModelPortali Q5S007.
SMRi Q5S007. Positions 1335-1512.
ModBasei Search...

Protein-protein interaction databases

BioGridi 125700. 139 interactions.
DIPi DIP-29684N.
IntActi Q5S007. 407 interactions.
MINTi MINT-7997594.
STRINGi 9606.ENSP00000298910.

Chemistry

BindingDBi Q5S007.
ChEMBLi CHEMBL1075104.
GuidetoPHARMACOLOGYi 2059.

PTM databases

PhosphoSitei Q5S007.

Polymorphism databases

DMDMi 294862450.

Proteomic databases

MaxQBi Q5S007.
PaxDbi Q5S007.
PRIDEi Q5S007.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000298910 ; ENSP00000298910 ; ENSG00000188906 .
GeneIDi 120892.
KEGGi hsa:120892.
UCSCi uc001rmg.4. human.

Organism-specific databases

CTDi 120892.
GeneCardsi GC12P040590.
GeneReviewsi LRRK2.
HGNCi HGNC:18618. LRRK2.
HPAi CAB037160.
HPA014293.
MIMi 168600. phenotype.
607060. phenotype.
609007. gene.
neXtProti NX_Q5S007.
Orphaneti 2828. Young adult-onset Parkinsonism.
PharmGKBi PA134968052.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG4886.
HOGENOMi HOG000293315.
HOVERGENi HBG081937.
InParanoidi Q5S007.
KOi K08844.
OMAi FKIRDQP.
PhylomeDBi Q5S007.
TreeFami TF313679.

Enzyme and pathway databases

SignaLinki Q5S007.

Miscellaneous databases

EvolutionaryTracei Q5S007.
GeneWikii LRRK2.
GenomeRNAii 120892.
NextBioi 80641.
PROi Q5S007.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q5S007.
Bgeei Q5S007.
CleanExi HS_LRRK2.
Genevestigatori Q5S007.

Family and domain databases

Gene3Di 1.25.10.10. 2 hits.
1.25.40.20. 1 hit.
2.130.10.10. 1 hit.
3.40.50.300. 1 hit.
InterProi IPR020683. Ankyrin_rpt-contain_dom.
IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR011009. Kinase-like_dom.
IPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR013684. MIRO-like.
IPR027417. P-loop_NTPase.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR020859. ROC_GTPase.
IPR008271. Ser/Thr_kinase_AS.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR017986. WD40_repeat_dom.
[Graphical view ]
Pfami PF00560. LRR_1. 1 hit.
PF12799. LRR_4. 1 hit.
PF13855. LRR_8. 1 hit.
PF08477. Miro. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
PRINTSi PR00449. RASTRNSFRMNG.
SMARTi SM00369. LRR_TYP. 1 hit.
SM00320. WD40. 1 hit.
[Graphical view ]
SUPFAMi SSF48371. SSF48371. 2 hits.
SSF50978. SSF50978. 1 hit.
SSF52540. SSF52540. 1 hit.
SSF56112. SSF56112. 1 hit.
TIGRFAMsi TIGR00231. small_GTP. 1 hit.
PROSITEi PS51450. LRR. 11 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS51424. ROC. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANTS PARK8 VAL-1122; CYS-1441; CYS-1699 AND THR-2020.
    Tissue: Brain.
  2. "The finished DNA sequence of human chromosome 12."
    Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
    , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
    Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2128-2527.
    Tissue: Testis.
  4. "PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation."
    Adams J.R., van Netten H., Schulzer M., Mak E., McKenzie J., Strongosky A., Sossi V., Ruth T.J., Lee C.S., Farrer M., Gasser T., Uitti R.J., Calne D.B., Wszolek Z.K., Stoessl A.J.
    Brain 128:2777-2785(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISEASE.
  5. "The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity."
    Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M.
    Hum. Mol. Genet. 15:223-232(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 THR-2020.
  6. Cited for: DISEASE.
  7. "Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity."
    West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M.
    Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PARK8 CYS-1441 AND SER-2019.
  8. "Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant LRRK2 induces neuronal degeneration."
    Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L., Dawson T.M., Ross C.A.
    Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PARK2, POSSIBLE FUNCTION.
  9. Cited for: TISSUE SPECIFICITY.
  10. Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  11. "The familial Parkinsonism gene LRRK2 regulates neurite process morphology."
    MacLeod D., Dowman J., Hammond R., Leete T., Inoue K., Abeliovich A.
    Neuron 52:587-593(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699; SER-2019 AND THR-2020, VARIANT MET-1906.
  12. "Signal transduction protein array analysis links LRRK2 to Ste20 kinases and PKC zeta that modulate neuronal plasticity."
    Zach S., Felk S., Gillardon F.
    PLoS ONE 5:E13191-E13191(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death."
    Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.
    Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, CHARACTERIZATION OF VARIANT PARK8 SER-2019.
  14. "Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP."
    Gomez-Suaga P., Luzon-Toro B., Churamani D., Zhang L., Bloor-Young D., Patel S., Woodman P.G., Churchill G.C., Hilfiker S.
    Hum. Mol. Genet. 21:511-525(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TPCN2.
  15. "Biochemical characterization of highly purified leucine-rich repeat kinases 1 and 2 demonstrates formation of homodimers."
    Civiero L., Vancraenenbroeck R., Belluzzi E., Beilina A., Lobbestael E., Reyniers L., Gao F., Micetic I., De Maeyer M., Bubacco L., Baekelandt V., Cookson M.R., Greggio E., Taymans J.M.
    PLoS ONE 7:E43472-E43472(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, AUTOPHOSPHORYLATION.
  16. "RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk."
    MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D., MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A., Abeliovich A.
    Neuron 77:425-439(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN RETROGRADE TRANSPORT, INTERACTION WITH RAB29 AND VPS35, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 SER-2019, CHARACTERIZATION OF VARIANT MET-1906.
  17. Cited for: VARIANTS PARK8 GLY-1441 AND CYS-1699, TISSUE SPECIFICITY.
  18. "Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations."
    Kachergus J.M., Mata I.F., Hulihan M., Taylor J.P., Lincoln S., Aasly J.O., Gibson J.M., Ross O.A., Lynch T., Wiley J., Payami H., Nutt J., Maraganore D.M., Czyzewski K., Styczynska M., Wszolek Z.K., Farrer M.J., Toft M.
    Am. J. Hum. Genet. 76:672-680(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PARK8 SER-2019.
  19. Cited for: VARIANT PARK8 SER-2019.
  20. "Clinical features of LRRK2-associated Parkinson's disease in central Norway."
    Aasly J.O., Toft M., Fernandez-Mata I., Kachergus J.M., Hulihan M., White L.R., Farrer M.J.
    Ann. Neurol. 57:762-765(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PARK8/PD SER-2019.
  21. Cited for: VARIANT PARK8 SER-2019.
  22. "An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family."
    Funayama M., Hasegawa K., Ohta E., Kawashima N., Komiyama M., Kowa H., Tsuji S., Obata F.
    Ann. Neurol. 57:918-921(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PARK8 THR-2020.
  23. "Genetic and clinical identification of Parkinson's disease patients with LRRK2 G2019S mutation."
    Deng H., Le W., Guo Y., Hunter C.B., Xie W., Jankovic J.
    Ann. Neurol. 57:933-934(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PARK8 SER-2019.
  24. "Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease."
    Berg D., Schweitzer K., Leitner P., Zimprich A., Lichtner P., Belcredi P., Bruessel T., Schulte C., Maass S., Naegele T.
    Brain 128:3000-3011(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PARK8 MET-793; ARG-930; CYS-1096 THR-1228; SER-2019 AND THR-2020, VARIANT LYS-551.
  25. "Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson's disease: clinical, pathological, olfactory and functional imaging and genetic data."
    Khan N.L., Jain S., Lynch J.M., Pavese N., Abou-Sleiman P.M., Holton J.L., Healy D.G., Gilks W.P., Sweeney M.G., Ganguly M., Gibbons V., Gandhi S., Vaughan J., Eunson L.H., Katzenschlager R., Gayton J., Lennox G., Revesz T.
    , Nicholl D., Bhatia K.P., Quinn N., Brooks D., Lees A.J., Davis M.B., Piccini P., Singleton A.B., Wood N.W.
    Brain 128:2786-2796(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PARK8 CYS-1699; HIS-1941; SER-2019 AND ILE-2356.
  26. Cited for: VARIANTS PARK8 VAL-1371; CYS-1441 AND SER-2019.
  27. Cited for: VARIANT PARK8 SER-2019.
  28. Cited for: VARIANT PARK8 SER-2019.
  29. Cited for: VARIANT PARK8 SER-2019.
  30. Cited for: VARIANT PARK8 SER-2019.
  31. Cited for: VARIANT PARK8 SER-2019.
  32. "Escaping Parkinson's disease: a neurologically healthy octogenarian with the LRRK2 G2019S mutation."
    Kay D.M., Kramer P., Higgins D.S., Zabetian C.P., Payami H.
    Mov. Disord. 20:1077-1078(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT SER-2019.
  33. "Parkinson's disease and LRRK2: frequency of a common mutation in U.S. movement disorder clinics."
    Kay D.M., Zabetian C.P., Factor S.A., Nutt J.G., Samii A., Griffith A., Bird T.D., Kramer P., Higgins D.S., Payami H.
    Mov. Disord. 21:519-523(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PARK8 SER-2019.
  34. Cited for: VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; GLN-1514; SER-1542; GLU-1598; CYS-1699; THR-1869; THR-2012; SER-2019; THR-2020 AND ARG-2385, VARIANTS PRO-119; LYS-551; VAL-723; MET-793; VAL-1122; ALA-1262; HIS-1398; PRO-1628; THR-1646; THR-1647; ASP-2081; LEU-2119; ILE-2261 AND THR-2397.
  35. Cited for: VARIANTS PARK8 VAL-1371 AND SER-2019, VARIANTS HIS-1398 AND THR-2397.
  36. Cited for: VARIANT PARK8 GLN-1067.
  37. Cited for: VARIANTS PARK8 MET-793; THR-1869 AND SER-2019.
  38. "A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations."
    Zabetian C.P., Samii A., Mosley A.D., Roberts J.W., Leis B.C., Yearout D., Raskind W.H., Griffith A.
    Neurology 65:741-744(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PARK8 CYS-1441; HIS-1441 AND SER-2019.
  39. Cited for: VARIANT PARK8 GLY-1441.
  40. "LRRK2 G2019S is a common mutation in Spanish patients with late-onset Parkinson's disease."
    Infante J., Rodriguez E., Combarros O., Mateo I., Fontalba A., Pascual J., Oterino A., Polo J.M., Leno C., Berciano J.
    Neurosci. Lett. 395:224-226(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PARK8 SER-2019.
  41. "Clinical traits of LRRK2-associated Parkinson's disease in Ireland: a link between familial and idiopathic PD."
    Gosal D., Ross O.A., Wiley J., Irvine G.B., Johnston J.A., Toft M., Mata I.F., Kachergus J., Hulihan M., Taylor J.P., Lincoln S.J., Farrer M.J., Lynch T., Mark Gibson J.
    Parkinsonism Relat. Disord. 11:349-352(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PARK8 SER-2019.
  42. "LRRK2 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance."
    Gaig C., Ezquerra M., Marti M.J., Munoz E., Valldeoriola F., Tolosa E.
    Arch. Neurol. 63:377-382(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PARK8 CYS-1441; GLY-1441 AND SER-2019.
  43. "The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence."
    Tan E.K., Zhao Y., Skipper L., Tan M.G., Di Fonzo A., Sun L., Fook-Chong S., Tang S., Chua E., Yuen Y., Tan L., Pavanni R., Wong M.C., Kolatkar P., Lu C.S., Bonifati V., Liu J.J.
    Hum. Genet. 120:857-863(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANT ARG-2385, ASSOCIATION WITH PARKINSON DISEASE.
  44. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] PRO-119; VAL-419; LYS-551; VAL-723; HIS-1398; GLN-1514; SER-1542; GLN-1550 AND PRO-1723.
  45. "Comprehensive analysis of LRRK2 in publicly available Parkinson's disease cases and neurologically normal controls."
    Paisan-Ruiz C., Nath P., Washecka N., Gibbs J.R., Singleton A.B.
    Hum. Mutat. 29:485-490(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PARK8 VAL-712; LEU-1728; HIS-1728; SER-2019; MET-2141; HIS-2143 AND HIS-2466, VARIANTS SER-228; VAL-716; GLU-871; PHE-1870 AND LYS-2395.
  46. Cited for: VARIANT ILE-1359.
  47. "Genetic characteristics of leucine-rich repeat kinase 2 (LRRK2) associated Parkinson's disease."
    Bardien S., Lesage S., Brice A., Carr J.
    Parkinsonism Relat. Disord. 17:501-508(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ASSOCIATION OF VARIANTS PRO-1628 AND ARG-2385 WITH PARKINSON DISEASE.
  48. "Deep sequencing of the LRRK2 gene in 14,002 individuals reveals evidence of purifying selection and independent origin of the p.Arg1628Pro mutation in Europe."
    Rubio J.P., Topp S., Warren L., St Jean P.L., Wegmann D., Kessner D., Novembre J., Shen J., Fraser D., Aponte J., Nangle K., Cardon L.R., Ehm M.G., Chissoe S.L., Whittaker J.C., Nelson M.R., Mooser V.E.
    Hum. Mutat. 33:1087-1098(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS LYS-551; VAL-723; HIS-1398; GLN-1514; SER-1542; PRO-1628; THR-1646; THR-1647; ASP-2081 AND THR-2397.
  49. Cited for: VARIANT PARK8 SER-2019.

Entry informationi

Entry nameiLRRK2_HUMAN
AccessioniPrimary (citable) accession number: Q5S007
Secondary accession number(s): A6NJU2, Q6ZS50, Q8NCX9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2006
Last sequence update: April 20, 2010
Last modified: September 3, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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