UniProtKB - Q5S007 (LRRK2_HUMAN)
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Protein
Leucine-rich repeat serine/threonine-protein kinase 2
Gene
LRRK2
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 1906 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 1994 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 1341 – 1348 | GTPPROSITE-ProRule annotation1 Publication | 8 | |
Nucleotide bindingi | 1885 – 1893 | ATPPROSITE-ProRule annotation | 9 | |
Nucleotide bindingi | 2098 – 2121 | GTPPROSITE-ProRule annotationAdd BLAST | 24 | |
Nucleotide bindingi | 2295 – 2298 | GTPPROSITE-ProRule annotation | 4 |
GO - Molecular functioni
- actin binding Source: ParkinsonsUK-UCL
- ATP binding Source: UniProtKB-KW
- beta-catenin destruction complex binding Source: ParkinsonsUK-UCL
- clathrin binding Source: ParkinsonsUK-UCL
- co-receptor binding Source: ParkinsonsUK-UCL
- GTPase activator activity Source: UniProtKB
- GTPase activity Source: BHF-UCL
- GTP binding Source: UniProtKB
- GTP-dependent protein kinase activity Source: BHF-UCL
- identical protein binding Source: IntAct
- ion channel binding Source: UniProtKB
- kinase activity Source: UniProtKB
- MAP kinase kinase activity Source: BHF-UCL
- microtubule binding Source: ParkinsonsUK-UCL
- peroxidase inhibitor activity Source: ParkinsonsUK-UCL
- protein homodimerization activity Source: UniProtKB
- protein kinase A binding Source: ParkinsonsUK-UCL
- protein kinase activity Source: UniProtKB
- protein serine/threonine kinase activity Source: UniProtKB
- receptor signaling complex scaffold activity Source: ParkinsonsUK-UCL
- Rho GTPase binding Source: BHF-UCL
- SNARE binding Source: ParkinsonsUK-UCL
- syntaxin-1 binding Source: ParkinsonsUK-UCL
- tubulin binding Source: BHF-UCL
GO - Biological processi
- activation of MAPK activity Source: ParkinsonsUK-UCL
- activation of MAPKK activity Source: BHF-UCL
- autophagy Source: UniProtKB-KW
- calcium-mediated signaling Source: ParkinsonsUK-UCL
- canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
- cellular protein localization Source: ParkinsonsUK-UCL
- cellular response to dopamine Source: ParkinsonsUK-UCL
- cellular response to manganese ion Source: ParkinsonsUK-UCL
- cellular response to oxidative stress Source: ParkinsonsUK-UCL
- cellular response to starvation Source: ParkinsonsUK-UCL
- determination of adult lifespan Source: BHF-UCL
- endocytosis Source: ParkinsonsUK-UCL
- excitatory postsynaptic potential Source: ParkinsonsUK-UCL
- exploration behavior Source: BHF-UCL
- Golgi organization Source: ParkinsonsUK-UCL
- GTP metabolic process Source: BHF-UCL
- intracellular distribution of mitochondria Source: BHF-UCL
- intracellular signal transduction Source: ParkinsonsUK-UCL
- locomotory exploration behavior Source: Ensembl
- lysosome organization Source: ParkinsonsUK-UCL
- MAPK cascade Source: UniProtKB
- mitochondrion localization Source: ParkinsonsUK-UCL
- mitochondrion organization Source: ParkinsonsUK-UCL
- negative regulation of autophagosome assembly Source: ParkinsonsUK-UCL
- negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
- negative regulation of excitatory postsynaptic potential Source: ParkinsonsUK-UCL
- negative regulation of GTPase activity Source: MGI
- negative regulation of hydrogen peroxide-induced cell death Source: ParkinsonsUK-UCL
- negative regulation of late endosome to lysosome transport Source: ParkinsonsUK-UCL
- negative regulation of macroautophagy Source: ParkinsonsUK-UCL
- negative regulation of neuron death Source: ParkinsonsUK-UCL
- negative regulation of neuron projection development Source: Ensembl
- negative regulation of protein binding Source: ParkinsonsUK-UCL
- negative regulation of protein phosphorylation Source: ParkinsonsUK-UCL
- negative regulation of protein processing Source: ParkinsonsUK-UCL
- negative regulation of protein processing involved in protein targeting to mitochondrion Source: ParkinsonsUK-UCL
- negative regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
- negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation Source: ParkinsonsUK-UCL
- neuromuscular junction development Source: BHF-UCL
- neuron death Source: BHF-UCL
- neuron projection arborization Source: Ensembl
- neuron projection morphogenesis Source: UniProtKB
- olfactory bulb development Source: ParkinsonsUK-UCL
- peptidyl-serine phosphorylation Source: BHF-UCL
- peptidyl-threonine phosphorylation Source: BHF-UCL
- phosphorylation Source: ParkinsonsUK-UCL
- positive regulation of autophagy Source: UniProtKB
- positive regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
- positive regulation of dopamine receptor signaling pathway Source: BHF-UCL
- positive regulation of histone deacetylase activity Source: Ensembl
- positive regulation of MAP kinase activity Source: ParkinsonsUK-UCL
- positive regulation of microglial cell activation Source: Ensembl
- positive regulation of nitric-oxide synthase biosynthetic process Source: Ensembl
- positive regulation of programmed cell death Source: UniProtKB
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
- positive regulation of protein autoubiquitination Source: ParkinsonsUK-UCL
- positive regulation of protein binding Source: ParkinsonsUK-UCL
- positive regulation of protein import into nucleus, translocation Source: Ensembl
- positive regulation of protein phosphorylation Source: ParkinsonsUK-UCL
- positive regulation of protein ubiquitination Source: UniProtKB
- positive regulation of synaptic vesicle endocytosis Source: Ensembl
- positive regulation of tumor necrosis factor secretion Source: Ensembl
- protein autophosphorylation Source: UniProtKB
- protein localization to mitochondrion Source: ParkinsonsUK-UCL
- protein phosphorylation Source: ParkinsonsUK-UCL
- reactive oxygen species metabolic process Source: ParkinsonsUK-UCL
- regulation of autophagy Source: ParkinsonsUK-UCL
- regulation of branching morphogenesis of a nerve Source: ParkinsonsUK-UCL
- regulation of CAMKK-AMPK signaling cascade Source: ParkinsonsUK-UCL
- regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
- regulation of dendritic spine morphogenesis Source: ParkinsonsUK-UCL
- regulation of dopamine receptor signaling pathway Source: ParkinsonsUK-UCL
- regulation of kidney size Source: BHF-UCL
- regulation of locomotion Source: BHF-UCL
- regulation of lysosomal lumen pH Source: ParkinsonsUK-UCL
- regulation of membrane potential Source: BHF-UCL
- regulation of mitochondrial depolarization Source: ParkinsonsUK-UCL
- regulation of mitochondrial fission Source: ParkinsonsUK-UCL
- regulation of neuroblast proliferation Source: ParkinsonsUK-UCL
- regulation of neuron death Source: ParkinsonsUK-UCL
- regulation of neuron maturation Source: ParkinsonsUK-UCL
- regulation of protein kinase A signaling Source: ParkinsonsUK-UCL
- regulation of retrograde transport, endosome to Golgi Source: ParkinsonsUK-UCL
- regulation of synaptic transmission, glutamatergic Source: ParkinsonsUK-UCL
- regulation of synaptic vesicle exocytosis Source: ParkinsonsUK-UCL
- regulation of synaptic vesicle transport Source: ParkinsonsUK-UCL
- response to oxidative stress Source: BHF-UCL
- spermatogenesis Source: Ensembl
- striatum development Source: Ensembl
- tangential migration from the subventricular zone to the olfactory bulb Source: ParkinsonsUK-UCL
- Wnt signalosome assembly Source: ParkinsonsUK-UCL
Keywordsi
Molecular function | GTPase activation, Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Autophagy, Differentiation |
Ligand | ATP-binding, GTP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-HSA-8857538. PTK6 promotes HIF1A stabilization. |
SignaLinki | Q5S007. |
SIGNORi | Q5S007. |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000188906.13. |
HGNCi | HGNC:18618. LRRK2. |
MIMi | 609007. gene. |
neXtProti | NX_Q5S007. |
Subcellular locationi
Keywords - Cellular componenti
Cell junction, Cell projection, Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Membrane, Mitochondrion, Mitochondrion inner membrane, Mitochondrion outer membrane, SynapsePathology & 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:607060Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_054741 | 712 | M → V in PARK8. 1 PublicationCorresponds to variant dbSNP:rs199566791Ensembl. | 1 | |
Natural variantiVAR_024935 | 793 | R → M in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs35173587Ensembl. | 1 | |
Natural variantiVAR_024936 | 930 | Q → R in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs281865045Ensembl. | 1 | |
Natural variantiVAR_024938 | 1067 | R → Q in PARK8. 1 PublicationCorresponds to variant dbSNP:rs111341148Ensembl. | 1 | |
Natural variantiVAR_024939 | 1096 | S → C in PARK8; unknown pathological significance. Corresponds to variant dbSNP:rs76535406Ensembl. | 1 | |
Natural variantiVAR_024940 | 1122 | I → V in PARK8. 2 PublicationsCorresponds to variant dbSNP:rs34805604Ensembl. | 1 | |
Natural variantiVAR_024941 | 1228 | S → T in PARK8. 1 PublicationCorresponds to variant dbSNP:rs60185966Ensembl. | 1 | |
Natural variantiVAR_024943 | 1371 | I → V in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs17466213Ensembl. | 1 | |
Natural variantiVAR_024945 | 1441 | R → C in PARK8; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate. 6 PublicationsCorresponds to variant dbSNP:rs33939927Ensembl. | 1 | |
Natural variantiVAR_024946 | 1441 | R → G in PARK8; shows a progressive reduction in neurite length and branching. 5 PublicationsCorresponds to variant dbSNP:rs33939927Ensembl. | 1 | |
Natural variantiVAR_024947 | 1441 | R → H in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs34995376Ensembl. | 1 | |
Natural variantiVAR_024948 | 1514 | R → Q in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs35507033Ensembl. | 1 | |
Natural variantiVAR_024949 | 1542 | P → S in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs33958906Ensembl. | 1 | |
Natural variantiVAR_024950 | 1598 | V → E in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs721710Ensembl. | 1 | |
Natural variantiVAR_024954 | 1699 | Y → C in PARK8; shows no progressive reduction in neurite length and branching. 5 PublicationsCorresponds to variant dbSNP:rs35801418Ensembl. | 1 | |
Natural variantiVAR_054744 | 1728 | R → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs145364431Ensembl. | 1 | |
Natural variantiVAR_054745 | 1728 | R → L in PARK8. 1 PublicationCorresponds to variant dbSNP:rs145364431Ensembl. | 1 | |
Natural variantiVAR_024955 | 1869 | M → T in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs35602796Ensembl. | 1 | |
Natural variantiVAR_024956 | 1941 | R → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs77428810Ensembl. | 1 | |
Natural variantiVAR_024957 | 2012 | I → T in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs34015634Ensembl. | 1 | |
Natural variantiVAR_024958 | 2019 | G → S in PARK8; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate; results in increased PRDX3 phosphorylation promoting dysregulation of mitochondrial function and oxidative damage; 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:rs34637584Ensembl. | 1 | |
Natural variantiVAR_024959 | 2020 | I → 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:rs35870237Ensembl. | 1 | |
Natural variantiVAR_054747 | 2141 | T → M in PARK8. 1 PublicationCorresponds to variant dbSNP:rs111691891Ensembl. | 1 | |
Natural variantiVAR_054748 | 2143 | R → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs201271001Ensembl. | 1 | |
Natural variantiVAR_024963 | 2356 | T → I in PARK8. 1 PublicationCorresponds to variant dbSNP:rs113511708Ensembl. | 1 | |
Natural variantiVAR_054750 | 2466 | L → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs281865057Ensembl. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1343 | T → G: Decreased kinase activity; when associated with Q-1398. 1 Publication | 1 | |
Mutagenesisi | 1398 | R → Q: Decreased kinase activity; when associated with G-1343. 1 Publication | 1 |
Keywords - Diseasei
Disease mutation, Neurodegeneration, Parkinson disease, ParkinsonismOrganism-specific databases
DisGeNETi | 120892. |
GeneReviewsi | LRRK2. |
MalaCardsi | LRRK2. |
MIMi | 168600. phenotype. 607060. phenotype. |
OpenTargetsi | ENSG00000188906. |
Orphaneti | 2828. Young adult-onset Parkinsonism. |
PharmGKBi | PA134968052. |
Chemistry databases
ChEMBLi | CHEMBL1075104. |
GuidetoPHARMACOLOGYi | 2059. |
Polymorphism and mutation databases
BioMutai | LRRK2. |
DMDMi | 294862450. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086238 | 1 – 2527 | Leucine-rich repeat serine/threonine-protein kinase 2Add BLAST | 2527 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 935 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Autophosphorylated.
Keywords - PTMi
PhosphoproteinProteomic databases
MaxQBi | Q5S007. |
PaxDbi | Q5S007. |
PeptideAtlasi | Q5S007. |
PRIDEi | Q5S007. |
PTM databases
iPTMneti | Q5S007. |
PhosphoSitePlusi | Q5S007. |
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
Bgeei | ENSG00000188906. |
CleanExi | HS_LRRK2. |
ExpressionAtlasi | Q5S007. baseline and differential. |
Genevisiblei | Q5S007. HS. |
Organism-specific databases
HPAi | CAB037160. HPA014293. |
Interactioni
Subunit structurei
Homodimer. Interacts with PRKN, PRDX3, RAB29, TPCN2 and VPS35.6 Publications
Binary interactionsi
GO - Molecular functioni
- actin binding Source: ParkinsonsUK-UCL
- beta-catenin destruction complex binding Source: ParkinsonsUK-UCL
- clathrin binding Source: ParkinsonsUK-UCL
- co-receptor binding Source: ParkinsonsUK-UCL
- identical protein binding Source: IntAct
- ion channel binding Source: UniProtKB
- microtubule binding Source: ParkinsonsUK-UCL
- protein homodimerization activity Source: UniProtKB
- protein kinase A binding Source: ParkinsonsUK-UCL
- receptor signaling complex scaffold activity Source: ParkinsonsUK-UCL
- Rho GTPase binding Source: BHF-UCL
- SNARE binding Source: ParkinsonsUK-UCL
- syntaxin-1 binding Source: ParkinsonsUK-UCL
- tubulin binding Source: BHF-UCL
Protein-protein interaction databases
BioGridi | 125700. 157 interactors. |
CORUMi | Q5S007. |
DIPi | DIP-29684N. |
IntActi | Q5S007. 553 interactors. |
MINTi | Q5S007. |
STRINGi | 9606.ENSP00000298910. |
Chemistry databases
BindingDBi | Q5S007. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Helixi | 913 – 917 | Combined sources | 5 | |
Beta strandi | 1336 – 1341 | Combined sources | 6 | |
Helixi | 1347 – 1354 | Combined sources | 8 | |
Beta strandi | 1370 – 1377 | Combined sources | 8 | |
Beta strandi | 1389 – 1395 | Combined sources | 7 | |
Helixi | 1398 – 1402 | Combined sources | 5 | |
Helixi | 1406 – 1411 | Combined sources | 6 | |
Beta strandi | 1412 – 1420 | Combined sources | 9 | |
Helixi | 1421 – 1423 | Combined sources | 3 | |
Helixi | 1425 – 1429 | Combined sources | 5 | |
Helixi | 1431 – 1441 | Combined sources | 11 | |
Beta strandi | 1446 – 1452 | Combined sources | 7 | |
Helixi | 1454 – 1456 | Combined sources | 3 | |
Helixi | 1459 – 1472 | Combined sources | 14 | |
Turni | 1473 – 1475 | Combined sources | 3 | |
Beta strandi | 1481 – 1487 | Combined sources | 7 | |
Helixi | 1495 – 1509 | Combined sources | 15 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2ZEJ | X-ray | 2.00 | A/B | 1333-1516 | [»] | |
3D6T | X-ray | 2.43 | B | 1335-1505 | [»] | |
5MY9 | X-ray | 1.33 | P | 929-941 | [»] | |
5MYC | X-ray | 1.46 | P | 904-941 | [»] | |
ProteinModelPortali | Q5S007. | |||||
SMRi | Q5S007. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q5S007. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 983 – 1004 | LRR 1Add BLAST | 22 | |
Repeati | 1012 – 1033 | LRR 2Add BLAST | 22 | |
Repeati | 1036 – 1057 | LRR 3Add BLAST | 22 | |
Repeati | 1059 – 1080 | LRR 4Add BLAST | 22 | |
Repeati | 1084 – 1105 | LRR 5Add BLAST | 22 | |
Repeati | 1108 – 1129 | LRR 6Add BLAST | 22 | |
Repeati | 1130 – 1150 | LRR 7Add BLAST | 21 | |
Repeati | 1174 – 1196 | LRR 8Add BLAST | 23 | |
Repeati | 1197 – 1218 | LRR 9Add BLAST | 22 | |
Repeati | 1221 – 1241 | LRR 10Add BLAST | 21 | |
Repeati | 1246 – 1267 | LRR 11Add BLAST | 22 | |
Repeati | 1269 – 1291 | LRR 12Add BLAST | 23 | |
Domaini | 1328 – 1511 | RocPROSITE-ProRule annotationAdd BLAST | 184 | |
Domaini | 1879 – 2138 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 260 | |
Repeati | 2139 – 2183 | WD 1Add BLAST | 45 | |
Repeati | 2188 – 2228 | WD 2Add BLAST | 41 | |
Repeati | 2233 – 2276 | WD 3Add BLAST | 44 | |
Repeati | 2281 – 2327 | WD 4Add BLAST | 47 | |
Repeati | 2333 – 2377 | WD 5Add BLAST | 45 | |
Repeati | 2402 – 2438 | WD 6Add BLAST | 37 | |
Repeati | 2443 – 2497 | WD 7Add BLAST | 55 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 319 – 348 | Sequence analysisAdd BLAST | 30 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 728 – 731 | Poly-Leu | 4 |
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
Keywords - Domaini
Coiled coil, Leucine-rich repeat, Repeat, WD repeatPhylogenomic databases
eggNOGi | ENOG410IRBK. Eukaryota. KOG0192. Eukaryota. COG1100. LUCA. COG4886. LUCA. |
GeneTreei | ENSGT00910000144054. |
HOGENOMi | HOG000293315. |
HOVERGENi | HBG081937. |
InParanoidi | Q5S007. |
KOi | K08844. |
OMAi | FKIRDQP. |
OrthoDBi | EOG091G003N. |
PhylomeDBi | Q5S007. |
TreeFami | TF313679. |
Family and domain databases
Gene3Di | 1.25.10.10. 2 hits. 1.25.40.20. 1 hit. 2.130.10.10. 1 hit. 3.80.10.10. 2 hits. |
InterProi | View 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. |
Pfami | View protein in Pfam PF16095. COR. 1 hit. PF12799. LRR_4. 1 hit. PF13855. LRR_8. 1 hit. PF00069. Pkinase. 1 hit. |
SMARTi | View protein in SMART SM00369. LRR_TYP. 7 hits. SM00220. S_TKc. 1 hit. |
SUPFAMi | SSF48371. SSF48371. 2 hits. SSF50978. SSF50978. 1 hit. SSF52540. SSF52540. 1 hit. SSF56112. SSF56112. 1 hit. |
TIGRFAMsi | TIGR00231. small_GTP. 1 hit. |
PROSITEi | View 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. |
i Sequence
Sequence statusi: Complete.
Q5S007-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 212 | L → S in AAV63975 (PubMed:15541309).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_024931 | 50 | R → H. Corresponds to variant dbSNP:rs2256408Ensembl. | 1 | |
Natural variantiVAR_024932 | 119 | L → P2 PublicationsCorresponds to variant dbSNP:rs33995463Ensembl. | 1 | |
Natural variantiVAR_054740 | 228 | C → S1 PublicationCorresponds to variant dbSNP:rs56108242Ensembl. | 1 | |
Natural variantiVAR_033903 | 419 | A → V1 PublicationCorresponds to variant dbSNP:rs34594498Ensembl. | 1 | |
Natural variantiVAR_024933 | 551 | N → K4 PublicationsCorresponds to variant dbSNP:rs7308720Ensembl. | 1 | |
Natural variantiVAR_054741 | 712 | M → V in PARK8. 1 PublicationCorresponds to variant dbSNP:rs199566791Ensembl. | 1 | |
Natural variantiVAR_054742 | 716 | A → V1 PublicationCorresponds to variant dbSNP:rs281865043Ensembl. | 1 | |
Natural variantiVAR_024934 | 723 | I → V3 PublicationsCorresponds to variant dbSNP:rs10878307Ensembl. | 1 | |
Natural variantiVAR_033904 | 755 | P → L. Corresponds to variant dbSNP:rs34410987Ensembl. | 1 | |
Natural variantiVAR_024935 | 793 | R → M in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs35173587Ensembl. | 1 | |
Natural variantiVAR_054743 | 871 | K → E1 PublicationCorresponds to variant dbSNP:rs281865044Ensembl. | 1 | |
Natural variantiVAR_024936 | 930 | Q → R in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs281865045Ensembl. | 1 | |
Natural variantiVAR_024937 | 944 | D → Y. Corresponds to variant dbSNP:rs17519916Ensembl. | 1 | |
Natural variantiVAR_024938 | 1067 | R → Q in PARK8. 1 PublicationCorresponds to variant dbSNP:rs111341148Ensembl. | 1 | |
Natural variantiVAR_024939 | 1096 | S → C in PARK8; unknown pathological significance. Corresponds to variant dbSNP:rs76535406Ensembl. | 1 | |
Natural variantiVAR_024940 | 1122 | I → V in PARK8. 2 PublicationsCorresponds to variant dbSNP:rs34805604Ensembl. | 1 | |
Natural variantiVAR_024941 | 1228 | S → T in PARK8. 1 PublicationCorresponds to variant dbSNP:rs60185966Ensembl. | 1 | |
Natural variantiVAR_024942 | 1262 | P → A1 PublicationCorresponds to variant dbSNP:rs4640000Ensembl. | 1 | |
Natural variantiVAR_064728 | 1359 | K → I Found in a renal cell carcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_024943 | 1371 | I → V in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs17466213Ensembl. | 1 | |
Natural variantiVAR_047022 | 1375 | D → E. Corresponds to variant dbSNP:rs28365226Ensembl. | 1 | |
Natural variantiVAR_024944 | 1398 | R → H4 PublicationsCorresponds to variant dbSNP:rs7133914Ensembl. | 1 | |
Natural variantiVAR_024945 | 1441 | R → C in PARK8; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate. 6 PublicationsCorresponds to variant dbSNP:rs33939927Ensembl. | 1 | |
Natural variantiVAR_024946 | 1441 | R → G in PARK8; shows a progressive reduction in neurite length and branching. 5 PublicationsCorresponds to variant dbSNP:rs33939927Ensembl. | 1 | |
Natural variantiVAR_024947 | 1441 | R → H in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs34995376Ensembl. | 1 | |
Natural variantiVAR_024948 | 1514 | R → Q in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs35507033Ensembl. | 1 | |
Natural variantiVAR_024949 | 1542 | P → S in PARK8; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs33958906Ensembl. | 1 | |
Natural variantiVAR_040678 | 1550 | R → Q in an ovarian mucinous carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs200212150Ensembl. | 1 | |
Natural variantiVAR_024950 | 1598 | V → E in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs721710Ensembl. | 1 | |
Natural variantiVAR_024951 | 1628 | R → P May be associated with Parkinson disease in some populations. 3 PublicationsCorresponds to variant dbSNP:rs33949390Ensembl. | 1 | |
Natural variantiVAR_024952 | 1646 | M → T2 PublicationsCorresponds to variant dbSNP:rs35303786Ensembl. | 1 | |
Natural variantiVAR_024953 | 1647 | S → T2 PublicationsCorresponds to variant dbSNP:rs11564148Ensembl. | 1 | |
Natural variantiVAR_024954 | 1699 | Y → C in PARK8; shows no progressive reduction in neurite length and branching. 5 PublicationsCorresponds to variant dbSNP:rs35801418Ensembl. | 1 | |
Natural variantiVAR_040679 | 1723 | R → P in an ovarian serous carcinoma sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_054744 | 1728 | R → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs145364431Ensembl. | 1 | |
Natural variantiVAR_054745 | 1728 | R → L in PARK8. 1 PublicationCorresponds to variant dbSNP:rs145364431Ensembl. | 1 | |
Natural variantiVAR_024955 | 1869 | M → T in PARK8; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs35602796Ensembl. | 1 | |
Natural variantiVAR_054746 | 1870 | L → F1 PublicationCorresponds to variant dbSNP:rs281865053Ensembl. | 1 | |
Natural variantiVAR_071101 | 1906 | K → M Does not inhibit interaction with RAB29; shows a progressive increase in neurite length and branching. 2 Publications | 1 | |
Natural variantiVAR_024956 | 1941 | R → H in PARK8. 1 PublicationCorresponds to variant dbSNP:rs77428810Ensembl. | 1 | |
Natural variantiVAR_024957 | 2012 | I → T in PARK8; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs34015634Ensembl. | 1 | |
Natural variantiVAR_024958 | 2019 | G → S in PARK8; shows an increase in activity in both autophosphorylation and phosphorylation of a generic substrate; results in increased PRDX3 phosphorylation promoting dysregulation of mitochondrial function and oxidative damage; 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 Publications |