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Q5S007

- LRRK2_HUMAN

UniProt

Q5S007 - LRRK2_HUMAN

Protein

Leucine-rich repeat serine/threonine-protein kinase 2

Gene

LRRK2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 2 (20 Apr 2010)
      Previous versions | rss
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    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.5 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei1906 – 19061ATPPROSITE-ProRule annotation
    Active sitei1994 – 19941Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi1341 – 13488GTPPROSITE-ProRule annotation
    Nucleotide bindingi1885 – 18939ATPPROSITE-ProRule annotation
    Nucleotide bindingi2098 – 212124GTPPROSITE-ProRule annotationAdd
    BLAST
    Nucleotide bindingi2295 – 22984GTPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. actin binding Source: ParkinsonsUK-UCL
    2. ATP binding Source: UniProtKB-KW
    3. clathrin binding Source: ParkinsonsUK-UCL
    4. enzyme inhibitor activity Source: ParkinsonsUK-UCL
    5. glycoprotein binding Source: ParkinsonsUK-UCL
    6. GTPase activator activity Source: UniProtKB
    7. GTPase activity Source: BHF-UCL
    8. GTP binding Source: UniProtKB
    9. GTP-dependent protein kinase activity Source: UniProtKB
    10. identical protein binding Source: IntAct
    11. ion channel binding Source: UniProtKB
    12. kinase activity Source: UniProtKB
    13. MAP kinase kinase activity Source: BHF-UCL
    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. Rho GTPase binding Source: BHF-UCL
    20. SNARE binding Source: ParkinsonsUK-UCL
    21. syntaxin-1 binding Source: ParkinsonsUK-UCL
    22. tubulin binding Source: BHF-UCL

    GO - Biological processi

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

    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.By similarity

    GO - Cellular componenti

    1. axon Source: UniProtKB
    2. cytoplasm Source: UniProtKB
    3. cytoplasmic side of mitochondrial outer membrane Source: UniProtKB
    4. cytoplasmic vesicle Source: UniProtKB
    5. cytosol Source: ParkinsonsUK-UCL
    6. dendrite Source: UniProtKB
    7. dendrite cytoplasm Source: BHF-UCL
    8. endoplasmic reticulum Source: UniProtKB
    9. endosome Source: UniProtKB
    10. extracellular space Source: UniProt
    11. extracellular vesicular exosome Source: UniProt
    12. Golgi apparatus Source: UniProtKB
    13. inclusion body Source: ParkinsonsUK-UCL
    14. lysosome Source: UniProtKB
    15. membrane raft Source: Ensembl
    16. mitochondrial inner membrane Source: UniProtKB
    17. mitochondrial matrix Source: UniProtKB
    18. mitochondrial membrane Source: ParkinsonsUK-UCL
    19. mitochondrial outer membrane Source: UniProtKB
    20. mitochondrion Source: UniProtKB
    21. neuronal cell body Source: BHF-UCL
    22. neuron projection Source: BHF-UCL
    23. perikaryon Source: UniProtKB
    24. plasma membrane Source: Ensembl
    25. synaptic vesicle Source: Ensembl
    26. trans-Golgi network Source: Ensembl

    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.28 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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.
    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. 4 Publications
    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. 4 Publications
    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. 24 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. 4 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 2PRO_0000086238Add
    BLAST

    Post-translational modificationi

    Autophosphorylated.

    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.4 Publications

    Gene expression databases

    ArrayExpressiQ5S007.
    BgeeiQ5S007.
    CleanExiHS_LRRK2.
    GenevestigatoriQ5S007.

    Organism-specific databases

    HPAiCAB037160.
    HPA014293.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with PARK2, PRDX3, RAB29, TPCN2 and VPS35.5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself54EBI-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
    BAG2O958162EBI-5323863,EBI-355275
    BAG3O958172EBI-5323863,EBI-747185
    BAG5Q9UL1512EBI-5323863,EBI-356517
    CDC37Q165437EBI-5323863,EBI-295634
    CDC42P609533EBI-5323863,EBI-81752
    CHGBP050602EBI-5323863,EBI-712619
    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
    ECHS1P300842EBI-5323863,EBI-719602
    FADDQ131584EBI-5323863,EBI-494804
    GAKO1497610EBI-5323863,EBI-714707
    GSK3BP498417EBI-5323863,EBI-373586
    HSPA8P111425EBI-5323863,EBI-351896
    LDHBP071952EBI-5323863,EBI-358748
    LRP6O755813EBI-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 a different organism.
    Mfn1Q811U43EBI-5323863,EBI-9029118From a different organism.
    MFN2O951403EBI-5323863,EBI-3324756
    MSNP2603812EBI-5323863,EBI-528768
    NEK1Q96PY62EBI-5323863,EBI-373615
    NFATC2Q134693EBI-5323863,EBI-716258
    NUP133Q8WUM02EBI-5323863,EBI-295695
    OPA1O603133EBI-5323863,EBI-1054131
    PAK6Q9NQU52EBI-5323863,EBI-1053685
    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.
    RAB7L1O149667EBI-5323863,EBI-372165
    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
    RPS15P628418EBI-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
    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.
    TUBBP074374EBI-5323863,EBI-350864
    TUBB4AP043504EBI-5323863,EBI-355007
    YWHABP319465EBI-5323863,EBI-359815
    YWHAEP622586EBI-5323863,EBI-356498
    YWHAGP619814EBI-5323863,EBI-359832
    YwhagP619836EBI-5323863,EBI-359821From a different organism.
    YWHAHQ049173EBI-5323863,EBI-306940
    YWHAQP273488EBI-5323863,EBI-359854
    YWHAZP631049EBI-5323863,EBI-347088

    Protein-protein interaction databases

    BioGridi125700. 139 interactions.
    DIPiDIP-29684N.
    IntActiQ5S007. 520 interactions.
    MINTiMINT-7997594.
    STRINGi9606.ENSP00000298910.

    Structurei

    Secondary structure

    1
    2527
    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ5S007.

    Family & Domainsi

    Domains and Repeats

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

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili319 – 34830Sequence AnalysisAdd
    BLAST

    Compositional bias

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

    Sequence similaritiesi

    Contains 12 LRR (leucine-rich) repeats.Curated
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 Roc domain.PROSITE-ProRule annotation

    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

    « Hide

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti212 – 2121L → S in AAV63975. (PubMed:15541309)Curated

    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.
    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. 5 Publications
    VAR_024945
    Natural varianti1441 – 14411R → G in PARK8; shows a progressive reduction in neurite length and branching. 4 Publications
    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. 2 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. 4 Publications
    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. 1 Publication
    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. 24 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. 4 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. 1 Publication
    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 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...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 125700. 139 interactions.
    DIPi DIP-29684N.
    IntActi Q5S007. 520 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

    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: October 1, 2014
    This is version 115 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