Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProtKB - Q5S007 (LRRK2_HUMAN)

Protein

Leucine-rich repeat serine/threonine-protein kinase 2

Gene

LRRK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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). Plays a role in synaptic vesicle trafficking. Phosphorylates PRDX3. Has GTPase activity. May play a role in the phosphorylation of proteins central to Parkinson disease.7 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1906ATPPROSITE-ProRule annotation1
Active sitei1994Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1341 – 1348GTPPROSITE-ProRule annotation1 Publication8
Nucleotide bindingi1885 – 1893ATPPROSITE-ProRule annotation9
Nucleotide bindingi2098 – 2121GTPPROSITE-ProRule annotationAdd BLAST24
Nucleotide bindingi2295 – 2298GTPPROSITE-ProRule annotation4

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionGTPase activation, Kinase, Serine/threonine-protein kinase, Transferase
Biological processAutophagy, Differentiation
LigandATP-binding, GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-8857538 PTK6 promotes HIF1A stabilization
SignaLinkiQ5S007
SIGNORiQ5S007

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000188906.13
HGNCiHGNC:18618 LRRK2
MIMi609007 gene
neXtProtiNX_Q5S007

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Parkinson disease 8 (PARK8)33 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients.
See also OMIM:607060
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054741712M → V in PARK8. 1 PublicationCorresponds to variant dbSNP:rs199566791EnsemblClinVar.1
Natural variantiVAR_024935793R → M in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs35173587EnsemblClinVar.1
Natural variantiVAR_024936930Q → R in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs281865045EnsemblClinVar.1
Natural variantiVAR_0249381067R → Q in PARK8. 1 PublicationCorresponds to variant dbSNP:rs111341148EnsemblClinVar.1
Natural variantiVAR_0249391096S → C in PARK8; unknown pathological significance. Corresponds to variant dbSNP:rs76535406EnsemblClinVar.1
Natural variantiVAR_0249401122I → V in PARK8. 2 PublicationsCorresponds to variant dbSNP:rs34805604EnsemblClinVar.1
Natural variantiVAR_0249411228S → T in PARK8. 1 PublicationCorresponds to variant dbSNP:rs60185966EnsemblClinVar.1
Natural variantiVAR_0249431371I → V in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs17466213EnsemblClinVar.1
Natural variantiVAR_0249451441R → C in PARK8; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate. 6 PublicationsCorresponds to variant dbSNP:rs33939927EnsemblClinVar.1
Natural variantiVAR_0249461441R → G in PARK8; shows a progressive reduction in neurite length and branching. 5 PublicationsCorresponds to variant dbSNP:rs33939927EnsemblClinVar.1
Natural variantiVAR_0249471441R → H in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs34995376EnsemblClinVar.1
Natural variantiVAR_0249481514R → Q in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs35507033EnsemblClinVar.1
Natural variantiVAR_0249491542P → S in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs33958906EnsemblClinVar.1
Natural variantiVAR_0249501598V → E in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs721710EnsemblClinVar.1
Natural variantiVAR_0249541699Y → C in PARK8; shows no progressive reduction in neurite length and branching. 5 PublicationsCorresponds to variant dbSNP:rs35801418EnsemblClinVar.1
Natural variantiVAR_0547441728R → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs145364431EnsemblClinVar.1
Natural variantiVAR_0547451728R → L in PARK8. 1 PublicationCorresponds to variant dbSNP:rs145364431EnsemblClinVar.1
Natural variantiVAR_0249551869M → T in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs35602796EnsemblClinVar.1
Natural variantiVAR_0249561941R → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs77428810EnsemblClinVar.1
Natural variantiVAR_0249572012I → T in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs34015634EnsemblClinVar.1
Natural variantiVAR_0249582019G → 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. 28 PublicationsCorresponds to variant dbSNP:rs34637584EnsemblClinVar.1
Natural variantiVAR_0249592020I → 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. 6 PublicationsCorresponds to variant dbSNP:rs35870237EnsemblClinVar.1
Natural variantiVAR_0547472141T → M in PARK8. 1 PublicationCorresponds to variant dbSNP:rs111691891EnsemblClinVar.1
Natural variantiVAR_0547482143R → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs201271001EnsemblClinVar.1
Natural variantiVAR_0249632356T → I in PARK8. 1 PublicationCorresponds to variant dbSNP:rs113511708EnsemblClinVar.1
Natural variantiVAR_0547502466L → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs281865057EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1343T → G: Decreased kinase activity; when associated with Q-1398. 1 Publication1
Mutagenesisi1398R → Q: Decreased kinase activity; when associated with G-1343. 1 Publication1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

DisGeNETi120892
GeneReviewsiLRRK2
MalaCardsiLRRK2
MIMi168600 phenotype
607060 phenotype
OpenTargetsiENSG00000188906
Orphaneti2828 Young adult-onset Parkinsonism
PharmGKBiPA134968052

Chemistry databases

ChEMBLiCHEMBL1075104
GuidetoPHARMACOLOGYi2059

Polymorphism and mutation databases

BioMutaiLRRK2
DMDMi294862450

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862381 – 2527Leucine-rich repeat serine/threonine-protein kinase 2Add BLAST2527

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei935PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated.

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ5S007
MaxQBiQ5S007
PaxDbiQ5S007
PeptideAtlasiQ5S007
PRIDEiQ5S007
ProteomicsDBi63755

PTM databases

iPTMnetiQ5S007
PhosphoSitePlusiQ5S007

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.4 Publications

Gene expression databases

BgeeiENSG00000188906 Expressed in 166 organ(s), highest expression level in visceral pleura
CleanExiHS_LRRK2
ExpressionAtlasiQ5S007 baseline and differential
GenevisibleiQ5S007 HS

Organism-specific databases

HPAiCAB037160
HPA014293

Interactioni

Subunit structurei

Homodimer. Interacts with PRKN, PRDX3, RAB29, TPCN2 and VPS35.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself68EBI-5323863,EBI-5323863
AGO2Q9UKV83EBI-5323863,EBI-528269
AKT1P317496EBI-5323863,EBI-296087
ANKS4BQ8N8V42EBI-5323863,EBI-9658517
ARFGAP1Q8N6T3-26EBI-5323863,EBI-6288865
Arfgap1Q628487EBI-5323863,EBI-4398879From Rattus norvegicus.
ARHGEF7Q141557EBI-5323863,EBI-717515
BAG2O958163EBI-5323863,EBI-355275
BAG3O958172EBI-5323863,EBI-747185
BAG5Q9UL1512EBI-5323863,EBI-356517
BCL2P10415-12EBI-5323863,EBI-4370304
CDC37Q165437EBI-5323863,EBI-295634
CDC42P609533EBI-5323863,EBI-81752
CDC42EP3Q9UKI22EBI-5323863,EBI-723480
CHGBP050603EBI-5323863,EBI-712619
Ckmt1P302752EBI-5323863,EBI-773103From Mus musculus.
CSNK1A1P48729-12EBI-5323863,EBI-10106282
CUEDC1Q9NWM32EBI-5323863,EBI-5838167
DAPK1P533552EBI-5323863,EBI-358616
DNM1Q051934EBI-5323863,EBI-713135
Dnm1P390533EBI-5323863,EBI-397785From Mus musculus.
DNM1LO0042911EBI-5323863,EBI-724571
DNM1LO00429-32EBI-5323863,EBI-6896746
DVL1O14640-27EBI-5323863,EBI-6504027
DVL2O146413EBI-5323863,EBI-740850
DVL3Q929974EBI-5323863,EBI-739789
ECHS1P300842EBI-5323863,EBI-719602
FADDQ131584EBI-5323863,EBI-494804
GAKO1497611EBI-5323863,EBI-714707
GSK3BP498417EBI-5323863,EBI-373586
HSPA8P111425EBI-5323863,EBI-351896
LDHBP071952EBI-5323863,EBI-358748
LRP6O755814EBI-5323863,EBI-910915
LRRK1Q38SD25EBI-5323863,EBI-1050422
MAP1BP468215EBI-5323863,EBI-9517186
MAP2K3P467345EBI-5323863,EBI-602462
MAP2K6P525644EBI-5323863,EBI-448135
MAP2K7O147333EBI-5323863,EBI-492605
MAPTP10636-23EBI-5323863,EBI-7796412
MAPTP10636-89EBI-5323863,EBI-366233
MATKP426792EBI-5323863,EBI-751664
MBPP026873EBI-5323863,EBI-908215From Bos taurus.
Mfn1Q811U43EBI-5323863,EBI-9029118From Mus musculus.
MFN2O951403EBI-5323863,EBI-3324756
MSNP2603817EBI-5323863,EBI-528768
NDUFAF7Q7L5922EBI-5323863,EBI-2555519
NEK1Q96PY62EBI-5323863,EBI-373615
NFATC2Q134693EBI-5323863,EBI-716258
NUP133Q8WUM02EBI-5323863,EBI-295695
OPA1O603133EBI-5323863,EBI-1054131
PAK6Q9NQU52EBI-5323863,EBI-1053685
phoAP006342EBI-5323863,EBI-552958From Escherichia coli (strain K12).
PPP1CAP621366EBI-5323863,EBI-357253
PRDX3P3004812EBI-5323863,EBI-748336
PRKACAP176126EBI-5323863,EBI-476586
Prkar2bP123693EBI-5323863,EBI-6096160From Rattus norvegicus.
PRKNO602603EBI-5323863,EBI-716346
RAB10P610265EBI-5323863,EBI-726075
RAB12Q6IQ222EBI-5323863,EBI-4289591
RAB1BQ9H0U43EBI-5323863,EBI-1045214
RAB29O149667EBI-5323863,EBI-372165
Rab29Q634813EBI-5323863,EBI-6513837From Rattus norvegicus.
RAB32Q136376EBI-5323863,EBI-9837586
RAB5BP610209EBI-5323863,EBI-399401
Rab5bP610212EBI-5323863,EBI-8320093From Mus musculus.
RAB8AP610066EBI-5323863,EBI-722293
RAC1P630005EBI-5323863,EBI-413628
RGS2P412206EBI-5323863,EBI-712388
RPL10AP629062EBI-5323863,EBI-356860
RPL13P263732EBI-5323863,EBI-356849
RPL14P509142EBI-5323863,EBI-356746
RPL23AP627502EBI-5323863,EBI-353254
RPS11P622803EBI-5323863,EBI-1047710
RPS15P628419EBI-5323863,EBI-372635
RPS16P622492EBI-5323863,EBI-352480
RPS2P158802EBI-5323863,EBI-443446
RPS20P608662EBI-5323863,EBI-353105
RPS23P622662EBI-5323863,EBI-353072
RPS27P426772EBI-5323863,EBI-356336
RPS3P233962EBI-5323863,EBI-351193
SEC16AO150276EBI-5323863,EBI-357515
SH3GL2Q999624EBI-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 Mus musculus.
STUB1Q9UNE72EBI-5323863,EBI-357085
STUB1Q9UNE7-12EBI-5323863,EBI-15687717
Stub1Q9WUD12EBI-5323863,EBI-773027From Mus musculus.
TUBBP074374EBI-5323863,EBI-350864
TUBB4AP043504EBI-5323863,EBI-355007
WSB1Q9Y6I75EBI-5323863,EBI-1171494
YWHABP319465EBI-5323863,EBI-359815
YWHAEP622586EBI-5323863,EBI-356498
YWHAGP619814EBI-5323863,EBI-359832
YwhagP619836EBI-5323863,EBI-359821From Rattus norvegicus.
YWHAHQ049173EBI-5323863,EBI-306940
YWHAQP273488EBI-5323863,EBI-359854
YWHAZP631049EBI-5323863,EBI-347088
ZRANB2O952182EBI-5323863,EBI-1051583

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi125700, 156 interactors
CORUMiQ5S007
DIPiDIP-29684N
IntActiQ5S007, 619 interactors
MINTiQ5S007
STRINGi9606.ENSP00000298910

Chemistry databases

BindingDBiQ5S007

Structurei

Secondary structure

12527
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ5S007
SMRiQ5S007
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ5S007

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati983 – 1004LRR 1Add BLAST22
Repeati1012 – 1033LRR 2Add BLAST22
Repeati1036 – 1057LRR 3Add BLAST22
Repeati1059 – 1080LRR 4Add BLAST22
Repeati1084 – 1105LRR 5Add BLAST22
Repeati1108 – 1129LRR 6Add BLAST22
Repeati1130 – 1150LRR 7Add BLAST21
Repeati1174 – 1196LRR 8Add BLAST23
Repeati1197 – 1218LRR 9Add BLAST22
Repeati1221 – 1241LRR 10Add BLAST21
Repeati1246 – 1267LRR 11Add BLAST22
Repeati1269 – 1291LRR 12Add BLAST23
Domaini1328 – 1511RocPROSITE-ProRule annotationAdd BLAST184
Domaini1879 – 2138Protein kinasePROSITE-ProRule annotationAdd BLAST260
Repeati2139 – 2183WD 1Add BLAST45
Repeati2188 – 2228WD 2Add BLAST41
Repeati2233 – 2276WD 3Add BLAST44
Repeati2281 – 2327WD 4Add BLAST47
Repeati2333 – 2377WD 5Add BLAST45
Repeati2402 – 2438WD 6Add BLAST37
Repeati2443 – 2497WD 7Add BLAST55

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili319 – 348Sequence analysisAdd BLAST30

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi728 – 731Poly-Leu4

Domaini

The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins.1 Publication
The Roc domain mediates homodimerization and regulates kinase activity.1 Publication

Sequence similaritiesi

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.Curated

Keywords - Domaini

Coiled coil, Leucine-rich repeat, Repeat, WD repeat

Phylogenomic databases

eggNOGiENOG410IRBK Eukaryota
KOG0192 Eukaryota
COG1100 LUCA
COG4886 LUCA
GeneTreeiENSGT00910000144054
HOGENOMiHOG000293315
HOVERGENiHBG081937
InParanoidiQ5S007
KOiK08844
OMAiFKIRDQP
OrthoDBiEOG091G003N
PhylomeDBiQ5S007
TreeFamiTF313679

Family and domain databases

Gene3Di1.25.10.10, 2 hits
1.25.40.20, 1 hit
2.130.10.10, 1 hit
3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR036770 Ankyrin_rpt-contain_sf
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR032171 COR
IPR011009 Kinase-like_dom_sf
IPR001611 Leu-rich_rpt
IPR025875 Leu-rich_rpt_4
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR027417 P-loop_NTPase
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR020859 ROC_dom
IPR008271 Ser/Thr_kinase_AS
IPR005225 Small_GTP-bd_dom
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF16095 COR, 1 hit
PF12799 LRR_4, 1 hit
PF13855 LRR_8, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 7 hits
SM00220 S_TKc, 1 hit
SUPFAMiSSF48371 SSF48371, 2 hits
SSF50978 SSF50978, 1 hit
SSF52540 SSF52540, 1 hit
SSF56112 SSF56112, 1 hit
TIGRFAMsiTIGR00231 small_GTP, 1 hit
PROSITEiView protein in PROSITE
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

Q5S007-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MASGSCQGCE EDEETLKKLI VRLNNVQEGK QIETLVQILE DLLVFTYSER 
        60         70         80         90        100
ASKLFQGKNI HVPLLIVLDS YMRVASVQQV GWSLLCKLIE VCPGTMQSLM 
       110        120        130        140        150
GPQDVGNDWE VLGVHQLILK MLTVHNASVN LSVIGLKTLD LLLTSGKITL 
       160        170        180        190        200
LILDEESDIF MLIFDAMHSF PANDEVQKLG CKALHVLFER VSEEQLTEFV 
       210        220        230        240        250
ENKDYMILLS ALTNFKDEEE IVLHVLHCLH SLAIPCNNVE VLMSGNVRCY 
       260        270        280        290        300
NIVVEAMKAF PMSERIQEVS CCLLHRLTLG NFFNILVLNE VHEFVVKAVQ 
       310        320        330        340        350
QYPENAALQI SALSCLALLT ETIFLNQDLE EKNENQENDD EGEEDKLFWL 
       360        370        380        390        400
EACYKALTWH RKNKHVQEAA CWALNNLLMY QNSLHEKIGD EDGHFPAHRE 
       410        420        430        440        450
VMLSMLMHSS SKEVFQASAN ALSTLLEQNV NFRKILLSKG IHLNVLELMQ 
       460        470        480        490        500
KHIHSPEVAE SGCKMLNHLF EGSNTSLDIM AAVVPKILTV MKRHETSLPV 
       510        520        530        540        550
QLEALRAILH FIVPGMPEES REDTEFHHKL NMVKKQCFKN DIHKLVLAAL 
       560        570        580        590        600
NRFIGNPGIQ KCGLKVISSI VHFPDALEML SLEGAMDSVL HTLQMYPDDQ 
       610        620        630        640        650
EIQCLGLSLI GYLITKKNVF IGTGHLLAKI LVSSLYRFKD VAEIQTKGFQ 
       660        670        680        690        700
TILAILKLSA SFSKLLVHHS FDLVIFHQMS SNIMEQKDQQ FLNLCCKCFA 
       710        720        730        740        750
KVAMDDYLKN VMLERACDQN NSIMVECLLL LGADANQAKE GSSLICQVCE 
       760        770        780        790        800
KESSPKLVEL LLNSGSREQD VRKALTISIG KGDSQIISLL LRRLALDVAN 
       810        820        830        840        850
NSICLGGFCI GKVEPSWLGP LFPDKTSNLR KQTNIASTLA RMVIRYQMKS 
       860        870        880        890        900
AVEEGTASGS DGNFSEDVLS KFDEWTFIPD SSMDSVFAQS DDLDSEGSEG 
       910        920        930        940        950
SFLVKKKSNS ISVGEFYRDA VLQRCSPNLQ RHSNSLGPIF DHEDLLKRKR 
       960        970        980        990       1000
KILSSDDSLR SSKLQSHMRH SDSISSLASE REYITSLDLS ANELRDIDAL 
      1010       1020       1030       1040       1050
SQKCCISVHL EHLEKLELHQ NALTSFPQQL CETLKSLTHL DLHSNKFTSF 
      1060       1070       1080       1090       1100
PSYLLKMSCI ANLDVSRNDI GPSVVLDPTV KCPTLKQFNL SYNQLSFVPE 
      1110       1120       1130       1140       1150
NLTDVVEKLE QLILEGNKIS GICSPLRLKE LKILNLSKNH ISSLSENFLE 
      1160       1170       1180       1190       1200
ACPKVESFSA RMNFLAAMPF LPPSMTILKL SQNKFSCIPE AILNLPHLRS 
      1210       1220       1230       1240       1250
LDMSSNDIQY LPGPAHWKSL NLRELLFSHN QISILDLSEK AYLWSRVEKL 
      1260       1270       1280       1290       1300
HLSHNKLKEI PPEIGCLENL TSLDVSYNLE LRSFPNEMGK LSKIWDLPLD 
      1310       1320       1330       1340       1350
ELHLNFDFKH IGCKAKDIIR FLQQRLKKAV PYNRMKLMIV GNTGSGKTTL 
      1360       1370       1380       1390       1400
LQQLMKTKKS DLGMQSATVG IDVKDWPIQI RDKRKRDLVL NVWDFAGREE 
      1410       1420       1430       1440       1450
FYSTHPHFMT QRALYLAVYD LSKGQAEVDA MKPWLFNIKA RASSSPVILV 
      1460       1470       1480       1490       1500
GTHLDVSDEK QRKACMSKIT KELLNKRGFP AIRDYHFVNA TEESDALAKL 
      1510       1520       1530       1540       1550
RKTIINESLN FKIRDQLVVG QLIPDCYVEL EKIILSERKN VPIEFPVIDR 
      1560       1570       1580       1590       1600
KRLLQLVREN QLQLDENELP HAVHFLNESG VLLHFQDPAL QLSDLYFVEP 
      1610       1620       1630       1640       1650
KWLCKIMAQI LTVKVEGCPK HPKGIISRRD VEKFLSKKRK FPKNYMSQYF 
      1660       1670       1680       1690       1700
KLLEKFQIAL PIGEEYLLVP SSLSDHRPVI ELPHCENSEI IIRLYEMPYF 
      1710       1720       1730       1740       1750
PMGFWSRLIN RLLEISPYML SGRERALRPN RMYWRQGIYL NWSPEAYCLV 
      1760       1770       1780       1790       1800
GSEVLDNHPE SFLKITVPSC RKGCILLGQV VDHIDSLMEE WFPGLLEIDI 
      1810       1820       1830       1840       1850
CGEGETLLKK WALYSFNDGE EHQKILLDDL MKKAEEGDLL VNPDQPRLTI 
      1860       1870       1880       1890       1900
PISQIAPDLI LADLPRNIML NNDELEFEQA PEFLLGDGSF GSVYRAAYEG 
      1910       1920       1930       1940       1950
EEVAVKIFNK HTSLRLLRQE LVVLCHLHHP SLISLLAAGI RPRMLVMELA 
      1960       1970       1980       1990       2000
SKGSLDRLLQ QDKASLTRTL QHRIALHVAD GLRYLHSAMI IYRDLKPHNV 
      2010       2020       2030       2040       2050
LLFTLYPNAA IIAKIADYGI AQYCCRMGIK TSEGTPGFRA PEVARGNVIY 
      2060       2070       2080       2090       2100
NQQADVYSFG LLLYDILTTG GRIVEGLKFP NEFDELEIQG KLPDPVKEYG 
      2110       2120       2130       2140       2150
CAPWPMVEKL IKQCLKENPQ ERPTSAQVFD ILNSAELVCL TRRILLPKNV 
      2160       2170       2180       2190       2200
IVECMVATHH NSRNASIWLG CGHTDRGQLS FLDLNTEGYT SEEVADSRIL 
      2210       2220       2230       2240       2250
CLALVHLPVE KESWIVSGTQ SGTLLVINTE DGKKRHTLEK MTDSVTCLYC 
      2260       2270       2280       2290       2300
NSFSKQSKQK NFLLVGTADG KLAIFEDKTV KLKGAAPLKI LNIGNVSTPL 
      2310       2320       2330       2340       2350
MCLSESTNST ERNVMWGGCG TKIFSFSNDF TIQKLIETRT SQLFSYAAFS 
      2360       2370       2380       2390       2400
DSNIITVVVD TALYIAKQNS PVVEVWDKKT EKLCGLIDCV HFLREVMVKE 
      2410       2420       2430       2440       2450
NKESKHKMSY SGRVKTLCLQ KNTALWIGTG GGHILLLDLS TRRLIRVIYN 
      2460       2470       2480       2490       2500
FCNSVRVMMT AQLGSLKNVM LVLGYNRKNT EGTQKQKEIQ SCLTVWDINL 
      2510       2520 
PHEVQNLEKH IEVRKELAEK MRRTSVE
Length:2,527
Mass (Da):286,103
Last modified:April 20, 2010 - v2
Checksum:i26142A0CECBBC3F4
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PC85E9PC85_HUMAN
Leucine-rich repeat serine/threonin...
LRRK2
1,271Annotation score:
A0A1B0GUQ3A0A1B0GUQ3_HUMAN
Leucine-rich repeat serine/threonin...
LRRK2
454Annotation score:
H7C3B6H7C3B6_HUMAN
Leucine-rich repeat serine/threonin...
LRRK2
207Annotation score:
C9JBF0C9JBF0_HUMAN
Leucine-rich repeat serine/threonin...
LRRK2
521Annotation score:
A0A2R8Y4F8A0A2R8Y4F8_HUMAN
Leucine-rich repeat serine/threonin...
LRRK2
78Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti212L → S in AAV63975 (PubMed:15541309).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02493150R → H. Corresponds to variant dbSNP:rs2256408Ensembl.1
Natural variantiVAR_024932119L → P2 PublicationsCorresponds to variant dbSNP:rs33995463EnsemblClinVar.1
Natural variantiVAR_054740228C → S1 PublicationCorresponds to variant dbSNP:rs56108242EnsemblClinVar.1
Natural variantiVAR_033903419A → V1 PublicationCorresponds to variant dbSNP:rs34594498EnsemblClinVar.1
Natural variantiVAR_024933551N → K4 PublicationsCorresponds to variant dbSNP:rs7308720EnsemblClinVar.1
Natural variantiVAR_054741712M → V in PARK8. 1 PublicationCorresponds to variant dbSNP:rs199566791EnsemblClinVar.1
Natural variantiVAR_054742716A → V1 PublicationCorresponds to variant dbSNP:rs281865043EnsemblClinVar.1
Natural variantiVAR_024934723I → V3 PublicationsCorresponds to variant dbSNP:rs10878307EnsemblClinVar.1
Natural variantiVAR_033904755P → L. Corresponds to variant dbSNP:rs34410987EnsemblClinVar.1
Natural variantiVAR_024935793R → M in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs35173587EnsemblClinVar.1
Natural variantiVAR_054743871K → E1 PublicationCorresponds to variant dbSNP:rs281865044EnsemblClinVar.1
Natural variantiVAR_024936930Q → R in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs281865045EnsemblClinVar.1
Natural variantiVAR_024937944D → Y. Corresponds to variant dbSNP:rs17519916EnsemblClinVar.1
Natural variantiVAR_0249381067R → Q in PARK8. 1 PublicationCorresponds to variant dbSNP:rs111341148EnsemblClinVar.1
Natural variantiVAR_0249391096S → C in PARK8; unknown pathological significance. Corresponds to variant dbSNP:rs76535406EnsemblClinVar.1
Natural variantiVAR_0249401122I → V in PARK8. 2 PublicationsCorresponds to variant dbSNP:rs34805604EnsemblClinVar.1
Natural variantiVAR_0249411228S → T in PARK8. 1 PublicationCorresponds to variant dbSNP:rs60185966EnsemblClinVar.1
Natural variantiVAR_0249421262P → A1 PublicationCorresponds to variant dbSNP:rs4640000EnsemblClinVar.1
Natural variantiVAR_0647281359K → I Found in a renal cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0249431371I → V in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs17466213EnsemblClinVar.1
Natural variantiVAR_0470221375D → E. Corresponds to variant dbSNP:rs28365226EnsemblClinVar.1
Natural variantiVAR_0249441398R → H4 PublicationsCorresponds to variant dbSNP:rs7133914EnsemblClinVar.1
Natural variantiVAR_0249451441R → C in PARK8; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate. 6 PublicationsCorresponds to variant dbSNP:rs33939927EnsemblClinVar.1
Natural variantiVAR_0249461441R → G in PARK8; shows a progressive reduction in neurite length and branching. 5 PublicationsCorresponds to variant dbSNP:rs33939927EnsemblClinVar.1
Natural variantiVAR_0249471441R → H in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs34995376EnsemblClinVar.1
Natural variantiVAR_0249481514R → Q in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs35507033EnsemblClinVar.1
Natural variantiVAR_0249491542P → S in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs33958906EnsemblClinVar.1
Natural variantiVAR_0406781550R → Q in an ovarian mucinous carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs200212150Ensembl.1
Natural variantiVAR_0249501598V → E in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs721710EnsemblClinVar.1
Natural variantiVAR_0249511628R → P May be associated with Parkinson disease in some populations. 3 PublicationsCorresponds to variant dbSNP:rs33949390EnsemblClinVar.1
Natural variantiVAR_0249521646M → T2 PublicationsCorresponds to variant dbSNP:rs35303786EnsemblClinVar.1
Natural variantiVAR_0249531647S → T2 PublicationsCorresponds to variant dbSNP:rs11564148EnsemblClinVar.1
Natural variantiVAR_0249541699Y → C in PARK8; shows no progressive reduction in neurite length and branching. 5 PublicationsCorresponds to variant dbSNP:rs35801418EnsemblClinVar.1
Natural variantiVAR_0406791723R → P in an ovarian serous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0547441728R → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs145364431EnsemblClinVar.1
Natural variantiVAR_0547451728R → L in PARK8. 1 PublicationCorresponds to variant dbSNP:rs145364431EnsemblClinVar.1
Natural variantiVAR_0249551869M → T in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs35602796EnsemblClinVar.1
Natural variantiVAR_0547461870L → F1 PublicationCorresponds to variant dbSNP:rs281865053EnsemblClinVar.1
Natural variantiVAR_0711011906K → M Does not inhibit interaction with RAB29; shows a progressive increase in neurite length and branching. 2 Publications1
Natural variantiVAR_0249561941R → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs77428810EnsemblClinVar.1
Natural variantiVAR_0249572012I → T in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs34015634EnsemblClinVar.1
Natural variantiVAR_0249582019G → 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. 28 PublicationsCorresponds to variant dbSNP:rs34637584EnsemblClinVar.1
Natural variantiVAR_0249592020I → 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. 6 PublicationsCorresponds to variant dbSNP:rs35870237EnsemblClinVar.1
Natural variantiVAR_0249602081N → D2 PublicationsCorresponds to variant dbSNP:rs33995883EnsemblClinVar.1
Natural variantiVAR_0249612119P → L1 PublicationCorresponds to variant dbSNP:rs12423862EnsemblClinVar.1
Natural variantiVAR_0547472141T → M in PARK8. 1 PublicationCorresponds to variant dbSNP:rs111691891EnsemblClinVar.1
Natural variantiVAR_0547482143R → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs201271001EnsemblClinVar.1
Natural variantiVAR_0249622261N → I1 PublicationCorresponds to variant dbSNP:rs12581902EnsemblClinVar.1
Natural variantiVAR_0249632356T → I in PARK8. 1 PublicationCorresponds to variant dbSNP:rs113511708EnsemblClinVar.1
Natural variantiVAR_0249642385G → 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; reduced binding to synaptic vesicles. 3 Publications