LRRK2_HUMAN
ID LRRK2_HUMAN Reviewed; 2527 AA.
AC Q5S007; A6NJU2; Q6ZS50; Q8NCX9;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Leucine-rich repeat serine/threonine-protein kinase 2;
DE EC=2.7.11.1 {ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421};
DE EC=3.6.5.- {ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29212815};
DE AltName: Full=Dardarin;
GN Name=LRRK2; Synonyms=PARK8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS PARK8
RP VAL-1122; CYS-1441; CYS-1699 AND THR-2020.
RC TISSUE=Brain;
RX PubMed=15541309; DOI=10.1016/j.neuron.2004.11.005;
RA Zimprich A., Biskup S., Leitner P., Lichtner P., Farrer M., Lincoln S.J.,
RA Kachergus J.M., Hulihan M.M., Uitti R.J., Calne D.B., Stoessl A.J.,
RA Pfeiffer R.F., Patenge N., Carballo Carbajal I., Vieregge P., Asmus F.,
RA Mueller-Myhsok B., Dickson D.W., Meitinger T., Strom T.M., Wszolek Z.K.,
RA Gasser T.;
RT "Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic
RT pathology.";
RL Neuron 44:601-607(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2128-2527.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP DISEASE.
RX PubMed=16081470; DOI=10.1093/brain/awh607;
RA Adams J.R., van Netten H., Schulzer M., Mak E., McKenzie J., Strongosky A.,
RA Sossi V., Ruth T.J., Lee C.S., Farrer M., Gasser T., Uitti R.J.,
RA Calne D.B., Wszolek Z.K., Stoessl A.J.;
RT "PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and
RT evidence for presymptomatic compensation.";
RL Brain 128:2777-2785(2005).
RN [5]
RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT PARK8 THR-2020.
RX PubMed=16321986; DOI=10.1093/hmg/ddi439;
RA Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E.,
RA Meitinger T., Kolch W., Prokisch H., Ueffing M.;
RT "The Parkinson disease causing LRRK2 mutation I2020T is associated with
RT increased kinase activity.";
RL Hum. Mol. Genet. 15:223-232(2006).
RN [6]
RP DISEASE.
RX PubMed=16087219; DOI=10.1016/j.mad.2005.06.010;
RA Toft M., Sando S.B., Melquist S., Ross O.A., White L.R., Aasly J.O.,
RA Farrer M.J.;
RT "LRRK2 mutations are not common in Alzheimer's disease.";
RL Mech. Ageing Dev. 126:1201-1205(2005).
RN [7]
RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS PARK8 CYS-1441 AND
RP SER-2019.
RX PubMed=16269541; DOI=10.1073/pnas.0507360102;
RA West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A.,
RA Dawson V.L., Dawson T.M.;
RT "Parkinson's disease-associated mutations in leucine-rich repeat kinase 2
RT augment kinase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:16842-16847(2005).
RN [8]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PRKN.
RX PubMed=16352719; DOI=10.1073/pnas.0508052102;
RA Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L.,
RA Dawson T.M., Ross C.A.;
RT "Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant
RT LRRK2 induces neuronal degeneration.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=16532471; DOI=10.1002/ana.20808;
RA Galter D., Westerlund M., Carmine A., Lindqvist E., Sydow O., Olson L.;
RT "LRRK2 expression linked to dopamine-innervated areas.";
RL Ann. Neurol. 59:714-719(2006).
RN [10]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17120249; DOI=10.1002/ana.21019;
RA Biskup S., Moore D.J., Celsi F., Higashi S., West A.B., Andrabi S.A.,
RA Kurkinen K., Yu S.W., Savitt J.M., Waldvogel H.J., Faull R.L., Emson P.C.,
RA Torp R., Ottersen O.P., Dawson T.M., Dawson V.L.;
RT "Localization of LRRK2 to membranous and vesicular structures in mammalian
RT brain.";
RL Ann. Neurol. 60:557-569(2006).
RN [11]
RP FUNCTION, CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; CYS-1699; SER-2019
RP AND THR-2020, AND VARIANT MET-1906.
RX PubMed=17114044; DOI=10.1016/j.neuron.2006.10.008;
RA MacLeod D., Dowman J., Hammond R., Leete T., Inoue K., Abeliovich A.;
RT "The familial Parkinsonism gene LRRK2 regulates neurite process
RT morphology.";
RL Neuron 52:587-593(2006).
RN [12]
RP FUNCTION.
RX PubMed=20949042; DOI=10.1371/journal.pone.0013191;
RA Zach S., Felk S., Gillardon F.;
RT "Signal transduction protein array analysis links LRRK2 to Ste20 kinases
RT and PKC zeta that modulate neuronal plasticity.";
RL PLoS ONE 5:E13191-E13191(2010).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRDX3, AND
RP CHARACTERIZATION OF VARIANT PARK8 SER-2019.
RX PubMed=21850687; DOI=10.1002/humu.21582;
RA Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J.,
RA Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.;
RT "Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3
RT exacerbating oxidative stress-induced neuronal death.";
RL Hum. Mutat. 32:1390-1397(2011).
RN [14]
RP FUNCTION, AND INTERACTION WITH TPCN2.
RX PubMed=22012985; DOI=10.1093/hmg/ddr481;
RA Gomez-Suaga P., Luzon-Toro B., Churamani D., Zhang L., Bloor-Young D.,
RA Patel S., Woodman P.G., Churchill G.C., Hilfiker S.;
RT "Leucine-rich repeat kinase 2 regulates autophagy through a calcium-
RT dependent pathway involving NAADP.";
RL Hum. Mol. Genet. 21:511-525(2012).
RN [15]
RP SUBUNIT, AND AUTOPHOSPHORYLATION.
RX PubMed=22952686; DOI=10.1371/journal.pone.0043472;
RA Civiero L., Vancraenenbroeck R., Belluzzi E., Beilina A., Lobbestael E.,
RA Reyniers L., Gao F., Micetic I., De Maeyer M., Bubacco L., Baekelandt V.,
RA Cookson M.R., Greggio E., Taymans J.M.;
RT "Biochemical characterization of highly purified leucine-rich repeat
RT kinases 1 and 2 demonstrates formation of homodimers.";
RL PLoS ONE 7:E43472-E43472(2012).
RN [16]
RP FUNCTION IN RETROGRADE TRANSPORT, INTERACTION WITH RAB29 AND VPS35,
RP SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT PARK8 SER-2019, AND
RP CHARACTERIZATION OF VARIANT MET-1906.
RX PubMed=23395371; DOI=10.1016/j.neuron.2012.11.033;
RA MacLeod D.A., Rhinn H., Kuwahara T., Zolin A., Di Paolo G., McCabe B.D.,
RA MacCabe B.D., Marder K.S., Honig L.S., Clark L.N., Small S.A.,
RA Abeliovich A.;
RT "RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and
RT Parkinson's disease risk.";
RL Neuron 77:425-439(2013).
RN [17]
RP WD REPEATS.
RX PubMed=23776530; DOI=10.1371/journal.pone.0065705;
RA Wang Y., Jiang F., Zhuo Z., Wu X.H., Wu Y.D.;
RT "A method for WD40 repeat detection and secondary structure prediction.";
RL PLoS ONE 8:E65705-E65705(2013).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, ELECTRON MICROSCOPY, WD REPEATS, AND
RP CHARACTERIZATION OF VARIANT ARG-2385.
RX PubMed=24687852; DOI=10.1128/mcb.00914-13;
RA Piccoli G., Onofri F., Cirnaru M.D., Kaiser C.J., Jagtap P.,
RA Kastenmuller A., Pischedda F., Marte A., von Zweydorf F., Vogt A.,
RA Giesert F., Pan L., Antonucci F., Kiel C., Zhang M., Weinkauf S.,
RA Sattler M., Sala C., Matteoli M., Ueffing M., Gloeckner C.J.;
RT "Leucine-rich repeat kinase 2 binds to neuronal vesicles through protein
RT interactions mediated by its C-terminal WD40 domain.";
RL Mol. Cell. Biol. 34:2147-2161(2014).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION
RP WITH RAB8A; RAB10 AND RAB12, CHARACTERIZATION OF VARIANTS PARK8 HIS-1441;
RP CYS-1441; GLY-1441; CYS-1699; HIS-1728; SER-2019; THR-2020; SER-2031 AND
RP ARG-2385, AND MUTAGENESIS OF ASP-1994.
RX PubMed=26824392; DOI=10.7554/elife.12813;
RA Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S.,
RA Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J.,
RA Morrow J.A., Reith A.D., Alessi D.R., Mann M.;
RT "Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates
RT a subset of Rab GTPases.";
RL Elife 5:0-0(2016).
RN [21]
RP FUNCTION, INTERACTION WITH MAPT, SUBCELLULAR LOCATION, CHARACTERIZATION OF
RP VARIANT PAR8 SER-2019, AND MUTAGENESIS OF LYS-1906; ASP-1994 AND ASP-2017.
RX PubMed=26014385; DOI=10.1007/s12035-015-9209-z;
RA Guerreiro P.S., Gerhardt E., Lopes da Fonseca T., Baehr M., Outeiro T.F.,
RA Eckermann K.;
RT "LRRK2 Promotes Tau Accumulation, Aggregation and Release.";
RL Mol. Neurobiol. 53:3124-3135(2016).
RN [22]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, CHARACTERIZATION OF VARIANTS PARK8
RP GLY-1441; CYS-1699 AND SER-2019, AND MUTAGENESIS OF ASP-2017.
RX PubMed=29125462; DOI=10.7554/elife.31012;
RA Steger M., Diez F., Dhekne H.S., Lis P., Nirujogi R.S., Karayel O.,
RA Tonelli F., Martinez T.N., Lorentzen E., Pfeffer S.R., Alessi D.R.,
RA Mann M.;
RT "Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation
RT establishes a connection to ciliogenesis.";
RL Elife 6:0-0(2017).
RN [23]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH APP,
RP PHOSPHORYLATION AT SER-910 AND SER-935, CHARACTERIZATION OF VARIANTS PARK8
RP GLY-1441 AND SER-2019, AND MUTAGENESIS OF ASP-1994.
RX PubMed=28720718; DOI=10.1126/scisignal.aam6790;
RA Chen Z.C., Zhang W., Chua L.L., Chai C., Li R., Lin L., Cao Z.,
RA Angeles D.C., Stanton L.W., Peng J.H., Zhou Z.D., Lim K.L., Zeng L.,
RA Tan E.K.;
RT "Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD
RT activity and neurotoxicity in Parkinson's disease.";
RL Sci. Signal. 10:0-0(2017).
RN [24]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, TISSUE SPECIFICITY,
RP CHARACTERIZATION OF VARIANT PARK8 SER-2019, AND PHOSPHORYLATION AT SER-935.
RX PubMed=29127255; DOI=10.1042/bcj20170803;
RA Fan Y., Howden A.J.M., Sarhan A.R., Lis P., Ito G., Martinez T.N.,
RA Brockmann K., Gasser T., Alessi D.R., Sammler E.M.;
RT "Interrogating Parkinson's disease LRRK2 kinase pathway activity by
RT assessing Rab10 phosphorylation in human neutrophils.";
RL Biochem. J. 475:23-44(2018).
RN [25]
RP FUNCTION, CATALYTIC ACTIVITY, AND VARIANTS PARK8 GLY-1441 AND SER-2019.
RX PubMed=30398148; DOI=10.7554/elife.40202;
RA Dhekne H.S., Yanatori I., Gomez R.C., Tonelli F., Diez F., Schuele B.,
RA Steger M., Alessi D.R., Pfeffer S.R.;
RT "A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and
RT Sonic hedgehog signaling in the brain.";
RL Elife 7:0-0(2018).
RN [26]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION AT SER-910; SER-935; SER-955; SER-973 AND SER-1292,
RP CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; CYS-1699;
RP HIS-1728; SER-2019; THR-2020; SER-2031 AND ARG-2385, AND MUTAGENESIS OF
RP CYS-727; LEU-728; LEU-729; LEU-760; LEU-761; LEU-762; LEU-789; LEU-790;
RP LEU-791; THR-1348 AND ASP-2017.
RX PubMed=29212815; DOI=10.15252/embj.201798099;
RA Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M.,
RA Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.;
RT "Rab29 activation of the Parkinson's disease-associated LRRK2 kinase.";
RL EMBO J. 37:1-18(2018).
RN [27]
RP ERRATUM OF PUBMED:29212815.
RX PubMed=30647193; DOI=10.15252/embj.2018101237;
RA Purlyte E., Dhekne H.S., Sarhan A.R., Gomez R., Lis P., Wightman M.,
RA Martinez T.N., Tonelli F., Pfeffer S.R., Alessi D.R.;
RL EMBO J. 38:0-0(2019).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1333-1516 IN COMPLEX WITH GDP,
RP FUNCTION, GTPASE ACTIVITY, ACTIVITY REGULATION, SUBUNIT, DOMAIN ROC, AND
RP MUTAGENESIS OF THR-1343 AND ARG-1398.
RX PubMed=18230735; DOI=10.1073/pnas.0709098105;
RA Deng J., Lewis P.A., Greggio E., Sluch E., Beilina A., Cookson M.R.;
RT "Structure of the ROC domain from the Parkinson's disease-associated
RT leucine-rich repeat kinase 2 reveals a dimeric GTPase.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:1499-1504(2008).
RN [29] {ECO:0007744|PDB:5MY9, ECO:0007744|PDB:5MYC}
RP X-RAY CRYSTALLOGRAPHY (1.33 ANGSTROMS) OF 929-941 IN COMPLEX WITH SFN,
RP INTERACTION WITH YWHAG, PHOSPHORYLATION AT SER-910; SER-935; SER-955;
RP SER-973 AND SER-1444, AND CHARACTERIZATION OF VARIANT PARK8 CYS-1441.
RX PubMed=28202711; DOI=10.1042/bcj20161078;
RA Stevers L.M., de Vries R.M., Doveston R.G., Milroy L.G., Brunsveld L.,
RA Ottmann C.;
RT "Structural interface between LRRK2 and 14-3-3 protein.";
RL Biochem. J. 474:1273-1287(2017).
RN [30] {ECO:0007744|PDB:6DLO, ECO:0007744|PDB:6DLP}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 2142-2527, FUNCTION, CATALYTIC
RP ACTIVITY, SUBUNIT, DOMAIN, PHOSPHORYLATION AT SER-935 AND SER-1292,
RP CHARACTERIZATION OF VARIANTS PARK8 GLY-1441; SER-2019; ASP-2175; TYR-2189;
RP ILE-2356; ARG-2385; MET-2390 AND ILE-2439, AND MUTAGENESIS OF ASP-2017;
RP LEU-2343; PHE-2344; SER-2345; TYR-2346; HIS-2391; ARG-2394; GLU-2395;
RP MET-2408 AND SER-2409.
RX PubMed=30635421; DOI=10.1073/pnas.1817889116;
RA Zhang P., Fan Y., Ru H., Wang L., Magupalli V.G., Taylor S.S., Alessi D.R.,
RA Wu H.;
RT "Crystal structure of the WD40 domain dimer of LRRK2.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:1579-1584(2019).
RN [31]
RP VARIANTS PARK8 GLY-1441 AND CYS-1699, AND TISSUE SPECIFICITY.
RX PubMed=15541308; DOI=10.1016/j.neuron.2004.10.023;
RA Paisan-Ruiz C., Jain S., Evans E.W., Gilks W.P., Simon J., van der Brug M.,
RA Lopez de Munain A., Aparicio S., Gil A.M., Khan N.L., Johnson J.,
RA Martinez J.R., Nicholl D., Carrera I.M., Pena A.S., de Silva R., Lees A.J.,
RA Marti-Masso J.F., Perez-Tur J., Wood N.W., Singleton A.B.;
RT "Cloning of the gene containing mutations that cause PARK8-linked
RT Parkinson's disease.";
RL Neuron 44:595-600(2004).
RN [32]
RP VARIANT PARK8 SER-2019.
RX PubMed=15726496; DOI=10.1086/429256;
RA Kachergus J.M., Mata I.F., Hulihan M., Taylor J.P., Lincoln S., Aasly J.O.,
RA Gibson J.M., Ross O.A., Lynch T., Wiley J., Payami H., Nutt J.,
RA Maraganore D.M., Czyzewski K., Styczynska M., Wszolek Z.K., Farrer M.J.,
RA Toft M.;
RT "Identification of a novel LRRK2 mutation linked to autosomal dominant
RT parkinsonism: evidence of a common founder across European populations.";
RL Am. J. Hum. Genet. 76:672-680(2005).
RN [33]
RP VARIANT PARK8 SER-2019.
RX PubMed=15732108; DOI=10.1002/ana.20401;
RA Hernandez D.G., Paisan-Ruiz C., McInerney-Leo A., Jain S.,
RA Meyer-Lindenberg A., Evans E.W., Berman K.F., Johnson J., Auburger G.,
RA Schaeffer A.A., Lopez G.J., Nussbaum R.L., Singleton A.B.;
RT "Clinical and positron emission tomography of Parkinson's disease caused by
RT LRRK2.";
RL Ann. Neurol. 57:453-456(2005).
RN [34]
RP VARIANT PARK8/PD SER-2019.
RX PubMed=15852371; DOI=10.1002/ana.20456;
RA Aasly J.O., Toft M., Fernandez-Mata I., Kachergus J.M., Hulihan M.,
RA White L.R., Farrer M.J.;
RT "Clinical features of LRRK2-associated Parkinson's disease in central
RT Norway.";
RL Ann. Neurol. 57:762-765(2005).
RN [35]
RP VARIANT PARK8 SER-2019.
RX PubMed=16240353; DOI=10.1002/ana.20636;
RG French Parkinson's disease genetics study group;
RA Lesage S., Ibanez P., Lohmann E., Pollak P., Tison F., Tazir M.,
RA Leutenegger A.-L., Guimaraes J., Bonnet A.-M., Agid Y., Duerr A., Brice A.;
RT "G2019S LRRK2 mutation in French and North African families with
RT Parkinson's disease.";
RL Ann. Neurol. 58:784-787(2005).
RN [36]
RP VARIANT PARK8 THR-2020.
RX PubMed=15880653; DOI=10.1002/ana.20484;
RA Funayama M., Hasegawa K., Ohta E., Kawashima N., Komiyama M., Kowa H.,
RA Tsuji S., Obata F.;
RT "An LRRK2 mutation as a cause for the parkinsonism in the original PARK8
RT family.";
RL Ann. Neurol. 57:918-921(2005).
RN [37]
RP VARIANT PARK8 SER-2019.
RX PubMed=15929036; DOI=10.1002/ana.20510;
RA Deng H., Le W., Guo Y., Hunter C.B., Xie W., Jankovic J.;
RT "Genetic and clinical identification of Parkinson's disease patients with
RT LRRK2 G2019S mutation.";
RL Ann. Neurol. 57:933-934(2005).
RN [38]
RP VARIANTS PARK8 MET-793; ARG-930; CYS-1096 THR-1228; SER-2019 AND THR-2020,
RP AND VARIANT LYS-551.
RX PubMed=16251215; DOI=10.1093/brain/awh666;
RA Berg D., Schweitzer K., Leitner P., Zimprich A., Lichtner P., Belcredi P.,
RA Bruessel T., Schulte C., Maass S., Naegele T.;
RT "Type and frequency of mutations in the LRRK2 gene in familial and sporadic
RT Parkinson's disease.";
RL Brain 128:3000-3011(2005).
RN [39]
RP VARIANTS PARK8 CYS-1699; HIS-1941; SER-2019 AND ILE-2356.
RX PubMed=16272164; DOI=10.1093/brain/awh667;
RA Khan N.L., Jain S., Lynch J.M., Pavese N., Abou-Sleiman P.M., Holton J.L.,
RA Healy D.G., Gilks W.P., Sweeney M.G., Ganguly M., Gibbons V., Gandhi S.,
RA Vaughan J., Eunson L.H., Katzenschlager R., Gayton J., Lennox G.,
RA Revesz T., Nicholl D., Bhatia K.P., Quinn N., Brooks D., Lees A.J.,
RA Davis M.B., Piccini P., Singleton A.B., Wood N.W.;
RT "Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial
RT Parkinson's disease: clinical, pathological, olfactory and functional
RT imaging and genetic data.";
RL Brain 128:2786-2796(2005).
RN [40]
RP VARIANTS PARK8 VAL-1371; CYS-1441 AND SER-2019.
RX PubMed=16333314; DOI=10.1038/sj.ejhg.5201539;
RA Di Fonzo A., Tassorelli C., De Mari M., Chien H.F., Ferreira J., Rohe C.F.,
RA Riboldazzi G., Antonini A., Albani G., Mauro A., Marconi R., Abbruzzese G.,
RA Lopiano L., Fincati E., Guidi M., Marini P., Stocchi F., Onofrj M.,
RA Toni V., Tinazzi M., Fabbrini G., Lamberti P., Vanacore N., Meco G.,
RA Leitner P., Uitti R.J., Wszolek Z.K., Gasser T., Simons E.J.,
RA Breedveld G.J., Goldwurm S., Pezzoli G., Sampaio C., Barbosa E.,
RA Martignoni E., Oostra B.A., Bonifati V.;
RT "Comprehensive analysis of the LRRK2 gene in sixty families with
RT Parkinson's disease.";
RL Eur. J. Hum. Genet. 14:322-331(2006).
RN [41]
RP VARIANT PARK8 SER-2019.
RX PubMed=16272257; DOI=10.1136/jmg.2005.035568;
RA Goldwurm S., Di Fonzo A., Simons E.J., Rohe C.F., Zini M., Canesi M.,
RA Tesei S., Zecchinelli A., Antonini A., Mariani C., Meucci N., Sacilotto G.,
RA Sironi F., Salani G., Ferreira J., Chien H.F., Fabrizio E., Vanacore N.,
RA Dalla Libera A., Stocchi F., Diroma C., Lamberti P., Sampaio C., Meco G.,
RA Barbosa E., Bertoli-Avella A.M., Breedveld G.J., Oostra B.A., Pezzoli G.,
RA Bonifati V.;
RT "The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late
RT onset Parkinson's disease and originates from a common ancestor.";
RL J. Med. Genet. 42:E65-E65(2005).
RN [42]
RP VARIANT PARK8 SER-2019.
RX PubMed=15680455; DOI=10.1016/s0140-6736(05)70235-x;
RG The Parkinson study group-PROGENI investigators;
RA Nichols W.C., Pankratz N., Hernandez D., Paisan-Ruiz C., Jain S.,
RA Halter C.A., Michaels V.E., Reed T., Rudolph A., Shults C.W., Singleton A.,
RA Foroud T.;
RT "Genetic screening for a single common LRRK2 mutation in familial
RT Parkinson's disease.";
RL Lancet 365:410-412(2005).
RN [43]
RP VARIANT PARK8 SER-2019.
RX PubMed=15680456; DOI=10.1016/s0140-6736(05)70236-1;
RG The Italian Parkinson genetics network;
RA Di Fonzo A., Rohe C.F., Ferreira J., Chien H.F., Vacca L., Stocchi F.,
RA Guedes L., Fabrizio E., Manfredi M., Vanacore N., Goldwurm S.,
RA Breedveld G.J., Sampaio C., Meco G., Barbosa E., Oostra B.A., Bonifati V.;
RT "A frequent LRRK2 gene mutation associated with autosomal dominant
RT Parkinson's disease.";
RL Lancet 365:412-415(2005).
RN [44]
RP VARIANT PARK8 SER-2019.
RX PubMed=15680457; DOI=10.1016/s0140-6736(05)70237-3;
RA Gilks W.P., Abou-Sleiman P.M., Gandhi S., Jain S., Singleton A., Lees A.J.,
RA Shaw K., Bhatia K.P., Bonifati V., Quinn N.P., Lynch J.M., Healy D.G.,
RA Holton J.L., Revesz T., Wood N.W.;
RT "A common LRRK2 mutation in idiopathic Parkinson's disease.";
RL Lancet 365:415-416(2005).
RN [45]
RP VARIANT PARK8 SER-2019.
RX PubMed=15811454; DOI=10.1016/s0140-6736(05)74809-1;
RA Toft M., Mata I.F., Kachergus J.M., Ross O.A., Farrer M.J.;
RT "LRRK2 mutations and Parkinsonism.";
RL Lancet 365:1229-1230(2005).
RN [46]
RP VARIANT SER-2019.
RX PubMed=16001413; DOI=10.1002/mds.20618;
RA Kay D.M., Kramer P., Higgins D.S., Zabetian C.P., Payami H.;
RT "Escaping Parkinson's disease: a neurologically healthy octogenarian with
RT the LRRK2 G2019S mutation.";
RL Mov. Disord. 20:1077-1078(2005).
RN [47]
RP VARIANT PARK8 SER-2019.
RX PubMed=16250030; DOI=10.1002/mds.20751;
RA Kay D.M., Zabetian C.P., Factor S.A., Nutt J.G., Samii A., Griffith A.,
RA Bird T.D., Kramer P., Higgins D.S., Payami H.;
RT "Parkinson's disease and LRRK2: frequency of a common mutation in U.S.
RT movement disorder clinics.";
RL Mov. Disord. 21:519-523(2006).
RN [48]
RP VARIANTS PARK8 CYS-1441; GLY-1441; HIS-1441; GLN-1514; SER-1542; GLU-1598;
RP CYS-1699; THR-1869; THR-2012; SER-2019; THR-2020 AND ARG-2385, AND VARIANTS
RP PRO-119; LYS-551; VAL-723; MET-793; VAL-1122; ALA-1262; HIS-1398; PRO-1628;
RP THR-1646; THR-1647; ASP-2081; LEU-2119; ILE-2261 AND THR-2397.
RX PubMed=16172858; DOI=10.1007/s10048-005-0005-1;
RA Mata I.F., Kachergus J.M., Taylor J.P., Lincoln S., Aasly J., Lynch T.,
RA Hulihan M.M., Cobb S.A., Wu R.-M., Lu C.-S., Lahoz C., Wszolek Z.K.,
RA Farrer M.J.;
RT "Lrrk2 pathogenic substitutions in Parkinson's disease.";
RL Neurogenetics 6:171-177(2005).
RN [49]
RP VARIANTS PARK8 VAL-1371 AND SER-2019, AND VARIANTS HIS-1398 AND THR-2397.
RX PubMed=16157901; DOI=10.1212/01.wnl.0000167552.79769.b3;
RA Paisan-Ruiz C., Lang A.E., Kawarai T., Sato C., Salehi-Rad S., Fisman G.K.,
RA Al-Khairallah T., St George-Hyslop P.H., Singleton A., Rogaeva E.;
RT "LRRK2 gene in Parkinson disease: mutation analysis and case control
RT association study.";
RL Neurology 65:696-700(2005).
RN [50]
RP VARIANT PARK8 GLN-1067.
RX PubMed=16247070; DOI=10.1212/01.wnl.0000180517.70572.37;
RA Skipper L., Shen H., Chua E., Bonnard C., Kolatkar P., Tan L.C.S.,
RA Jamora R.D., Puvan K., Puong K.Y., Zhao Y., Pavanni R., Wong M.C., Yuen Y.,
RA Farrer M., Liu J.J., Tan E.K.;
RT "Analysis of LRRK2 functional domains in nondominant Parkinson disease.";
RL Neurology 65:1319-1321(2005).
RN [51]
RP VARIANTS PARK8 MET-793; THR-1869 AND SER-2019.
RX PubMed=16157908; DOI=10.1212/01.wnl.0000169023.51764.b0;
RA Farrer M., Stone J., Mata I.F., Lincoln S., Kachergus J., Hulihan M.,
RA Strain K.J., Maraganore D.M.;
RT "LRRK2 mutations in Parkinson disease.";
RL Neurology 65:738-740(2005).
RN [52]
RP VARIANTS PARK8 CYS-1441; HIS-1441 AND SER-2019.
RX PubMed=16157909; DOI=10.1212/01.wnl.0000172630.22804.73;
RA Zabetian C.P., Samii A., Mosley A.D., Roberts J.W., Leis B.C., Yearout D.,
RA Raskind W.H., Griffith A.;
RT "A clinic-based study of the LRRK2 gene in Parkinson disease yields new
RT mutations.";
RL Neurology 65:741-744(2005).
RN [53]
RP VARIANT PARK8 GLY-1441.
RX PubMed=15925109; DOI=10.1016/j.neulet.2005.03.033;
RA Mata I.F., Taylor J.P., Kachergus J., Hulihan M., Huerta C., Lahoz C.,
RA Blazquez M., Guisasola L.M., Salvador C., Ribacoba R., Martinez C.,
RA Farrer M., Alvarez V.;
RT "LRRK2 R1441G in Spanish patients with Parkinson's disease.";
RL Neurosci. Lett. 382:309-311(2005).
RN [54]
RP VARIANT PARK8 SER-2019.
RX PubMed=16298482; DOI=10.1016/j.neulet.2005.10.083;
RA Infante J., Rodriguez E., Combarros O., Mateo I., Fontalba A., Pascual J.,
RA Oterino A., Polo J.M., Leno C., Berciano J.;
RT "LRRK2 G2019S is a common mutation in Spanish patients with late-onset
RT Parkinson's disease.";
RL Neurosci. Lett. 395:224-226(2006).
RN [55]
RP VARIANT PARK8 SER-2019.
RX PubMed=16102999; DOI=10.1016/j.parkreldis.2005.05.004;
RA Gosal D., Ross O.A., Wiley J., Irvine G.B., Johnston J.A., Toft M.,
RA Mata I.F., Kachergus J., Hulihan M., Taylor J.P., Lincoln S.J.,
RA Farrer M.J., Lynch T., Mark Gibson J.;
RT "Clinical traits of LRRK2-associated Parkinson's disease in Ireland: a link
RT between familial and idiopathic PD.";
RL Parkinsonism Relat. Disord. 11:349-352(2005).
RN [56]
RP VARIANTS PARK8 CYS-1441; GLY-1441 AND SER-2019.
RX PubMed=16533964; DOI=10.1001/archneur.63.3.377;
RA Gaig C., Ezquerra M., Marti M.J., Munoz E., Valldeoriola F., Tolosa E.;
RT "LRRK2 mutations in Spanish patients with Parkinson disease: frequency,
RT clinical features, and incomplete penetrance.";
RL Arch. Neurol. 63:377-382(2006).
RN [57]
RP CHARACTERIZATION OF VARIANT ARG-2385, AND ASSOCIATION WITH PARKINSON
RP DISEASE.
RX PubMed=17019612; DOI=10.1007/s00439-006-0268-0;
RA Tan E.K., Zhao Y., Skipper L., Tan M.G., Di Fonzo A., Sun L.,
RA Fook-Chong S., Tang S., Chua E., Yuen Y., Tan L., Pavanni R., Wong M.C.,
RA Kolatkar P., Lu C.S., Bonifati V., Liu J.J.;
RT "The LRRK2 Gly2385Arg variant is associated with Parkinson's disease:
RT genetic and functional evidence.";
RL Hum. Genet. 120:857-863(2007).
RN [58]
RP VARIANTS [LARGE SCALE ANALYSIS] PRO-119; VAL-419; LYS-551; VAL-723;
RP HIS-1398; GLN-1514; SER-1542; GLN-1550 AND PRO-1723.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [59]
RP VARIANTS PARK8 VAL-712; LEU-1728; HIS-1728; SER-2019; MET-2141; HIS-2143
RP AND HIS-2466, AND VARIANTS SER-228; VAL-716; GLU-871; PHE-1870 AND
RP LYS-2395.
RX PubMed=18213618; DOI=10.1002/humu.20668;
RA Paisan-Ruiz C., Nath P., Washecka N., Gibbs J.R., Singleton A.B.;
RT "Comprehensive analysis of LRRK2 in publicly available Parkinson's disease
RT cases and neurologically normal controls.";
RL Hum. Mutat. 29:485-490(2008).
RN [60]
RP VARIANT ILE-1359.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
RN [61]
RP ASSOCIATION OF VARIANTS PRO-1628 AND ARG-2385 WITH PARKINSON DISEASE.
RX PubMed=21641266; DOI=10.1016/j.parkreldis.2010.11.008;
RA Bardien S., Lesage S., Brice A., Carr J.;
RT "Genetic characteristics of leucine-rich repeat kinase 2 (LRRK2) associated
RT Parkinson's disease.";
RL Parkinsonism Relat. Disord. 17:501-508(2011).
RN [62]
RP VARIANTS LYS-551; VAL-723; HIS-1398; GLN-1514; SER-1542; PRO-1628;
RP THR-1646; THR-1647; ASP-2081 AND THR-2397.
RX PubMed=22415848; DOI=10.1002/humu.22075;
RA Rubio J.P., Topp S., Warren L., St Jean P.L., Wegmann D., Kessner D.,
RA Novembre J., Shen J., Fraser D., Aponte J., Nangle K., Cardon L.R.,
RA Ehm M.G., Chissoe S.L., Whittaker J.C., Nelson M.R., Mooser V.E.;
RT "Deep sequencing of the LRRK2 gene in 14,002 individuals reveals evidence
RT of purifying selection and independent origin of the p.Arg1628Pro mutation
RT in Europe.";
RL Hum. Mutat. 33:1087-1098(2012).
RN [63]
RP VARIANT PARK8 SER-2019.
RX PubMed=22956510; DOI=10.1002/mds.25132;
RA Kilarski L.L., Pearson J.P., Newsway V., Majounie E., Knipe M.D.,
RA Misbahuddin A., Chinnery P.F., Burn D.J., Clarke C.E., Marion M.H.,
RA Lewthwaite A.J., Nicholl D.J., Wood N.W., Morrison K.E.,
RA Williams-Gray C.H., Evans J.R., Sawcer S.J., Barker R.A.,
RA Wickremaratchi M.M., Ben-Shlomo Y., Williams N.M., Morris H.R.;
RT "Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-
RT 1) and LRRK2 in early-onset Parkinson's disease.";
RL Mov. Disord. 27:1522-1529(2012).
RN [64]
RP CHARACTERIZATION OF VARIANTS PARK8 CYS-1441; CYS-1699 AND SER-2019,
RP CHARACTERIZATION OF VARIANT ARG-2385, FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH SEC16A, AND MUTAGENESIS OF LYS-1347 AND ASP-1994.
RX PubMed=25201882; DOI=10.15252/embj.201487807;
RA Cho H.J., Yu J., Xie C., Rudrabhatla P., Chen X., Wu J., Parisiadou L.,
RA Liu G., Sun L., Ma B., Ding J., Liu Z., Cai H.;
RT "Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow
RT ER-Golgi export.";
RL EMBO J. 33:2314-2331(2014).
CC -!- FUNCTION: Serine/threonine-protein kinase which phosphorylates a broad
CC range of proteins involved in multiple processes such as neuronal
CC plasticity, autophagy, and vesicle trafficking (PubMed:20949042,
CC PubMed:22012985, PubMed:26824392, PubMed:29125462, PubMed:28720718,
CC PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:30635421,
CC PubMed:21850687, PubMed:23395371, PubMed:17114044, PubMed:24687852,
CC PubMed:26014385, PubMed:25201882). Is a key regulator of RAB GTPases by
CC regulating the GTP/GDP exchange and interaction partners of RABs
CC through phosphorylation (PubMed:26824392, PubMed:28720718,
CC PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462,
CC PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A,
CC RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43
CC (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148,
CC PubMed:29212815, PubMed:29125462, PubMed:30635421, PubMed:23395371).
CC Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the
CC phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the
CC interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-
CC 72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through
CC phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the
CC brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a
CC role in the retrograde trafficking pathway for recycling proteins, such
CC as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi
CC apparatus in a retromer-dependent manner (PubMed:23395371). Regulates
CC neuronal process morphology in the intact central nervous system (CNS)
CC (PubMed:17114044). Plays a role in synaptic vesicle trafficking
CC (PubMed:24687852). Plays an important role in recruiting SEC16A to
CC endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi
CC vesicle-mediated transport and ERES organization (PubMed:25201882).
CC Positively regulates autophagy through a calcium-dependent activation
CC of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process
CC involves activation of nicotinic acid adenine dinucleotide phosphate
CC (NAADP) receptors, increase in lysosomal pH, and calcium release from
CC lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By
CC phosphorylating APP on 'Thr-743', which promotes the production and the
CC nuclear translocation of the APP intracellular domain (AICD), regulates
CC dopaminergic neuron apoptosis (PubMed:28720718). Independent of its
CC kinase activity, inhibits the proteosomal degradation of MAPT, thus
CC promoting MAPT oligomerization and secretion (PubMed:26014385). In
CC addition, has GTPase activity via its Roc domain which regulates LRRK2
CC kinase activity (PubMed:18230735, PubMed:26824392, PubMed:29125462,
CC PubMed:28720718, PubMed:29212815). {ECO:0000269|PubMed:17114044,
CC ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042,
CC ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985,
CC ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852,
CC ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385,
CC ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718,
CC ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255,
CC ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148,
CC ECO:0000269|PubMed:30635421}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:26824392,
CC ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462,
CC ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815,
CC ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718,
CC ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255,
CC ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:26824392,
CC ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462,
CC ECO:0000269|PubMed:29212815};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718,
CC ECO:0000269|PubMed:29125462};
CC -!- ACTIVITY REGULATION: Kinase activity is regulated by the GTPase
CC activity of the ROC domain (PubMed:29212815, PubMed:18230735). GTP-
CC bound LLRK2 kinase activity is stimulated by RAB29 (PubMed:29212815).
CC Inhibited by small molecule inhibitor MLi-2 (PubMed:26824392,
CC PubMed:29127255). {ECO:0000269|PubMed:18230735,
CC ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:29127255,
CC ECO:0000269|PubMed:29212815}.
CC -!- SUBUNIT: Homodimer (PubMed:22952686, PubMed:18230735, PubMed:30635421).
CC Interacts with PRKN, PRDX3, and TPCN2 (PubMed:16352719,
CC PubMed:21850687, PubMed:22012985). Interacts with VPS35 and RAB29
CC (PubMed:23395371). Interacts (via ROC domain) with SEC16A
CC (PubMed:25201882). Interacts with APP; interaction promotes
CC phosphorylation of 'Thr-743' of APP (PubMed:28720718). Interacts with
CC MAPT (PubMed:26014385). Interacts with RAB8A, RAB10, and RAB12
CC (PubMed:26824392). Interacts with YWHAG; this interaction is dependent
CC on phosphorylation of Ser-910 and either Ser-935 or Ser-1444
CC (PubMed:28202711). Interacts with SFN; this interaction is dependent on
CC phosphorylation of Ser-910 and/or Ser-935 (PubMed:28202711).
CC {ECO:0000269|PubMed:16352719, ECO:0000269|PubMed:18230735,
CC ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985,
CC ECO:0000269|PubMed:22952686, ECO:0000269|PubMed:23395371,
CC ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385,
CC ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28202711,
CC ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:30635421}.
CC -!- INTERACTION:
CC Q5S007; Q9UKV8: AGO2; NbExp=3; IntAct=EBI-5323863, EBI-528269;
CC Q5S007; O43865: AHCYL1; NbExp=3; IntAct=EBI-5323863, EBI-2371423;
CC Q5S007; P31749: AKT1; NbExp=6; IntAct=EBI-5323863, EBI-296087;
CC Q5S007; Q8N8V4: ANKS4B; NbExp=2; IntAct=EBI-5323863, EBI-9658517;
CC Q5S007; O00203: AP3B1; NbExp=2; IntAct=EBI-5323863, EBI-1044383;
CC Q5S007; Q8N6T3-2: ARFGAP1; NbExp=6; IntAct=EBI-5323863, EBI-6288865;
CC Q5S007; Q14155: ARHGEF7; NbExp=7; IntAct=EBI-5323863, EBI-717515;
CC Q5S007; O95816: BAG2; NbExp=3; IntAct=EBI-5323863, EBI-355275;
CC Q5S007; O95817: BAG3; NbExp=2; IntAct=EBI-5323863, EBI-747185;
CC Q5S007; Q9UL15: BAG5; NbExp=12; IntAct=EBI-5323863, EBI-356517;
CC Q5S007; P10415-1: BCL2; NbExp=2; IntAct=EBI-5323863, EBI-4370304;
CC Q5S007; Q13191: CBLB; NbExp=4; IntAct=EBI-5323863, EBI-744027;
CC Q5S007; Q16543: CDC37; NbExp=7; IntAct=EBI-5323863, EBI-295634;
CC Q5S007; P60953: CDC42; NbExp=3; IntAct=EBI-5323863, EBI-81752;
CC Q5S007; Q9UKI2: CDC42EP3; NbExp=2; IntAct=EBI-5323863, EBI-723480;
CC Q5S007; Q9Y6A4: CFAP20; NbExp=3; IntAct=EBI-5323863, EBI-1046872;
CC Q5S007; P05060: CHGB; NbExp=3; IntAct=EBI-5323863, EBI-712619;
CC Q5S007; P48729-1: CSNK1A1; NbExp=2; IntAct=EBI-5323863, EBI-10106282;
CC Q5S007; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-5323863, EBI-9087876;
CC Q5S007; Q9NWM3: CUEDC1; NbExp=2; IntAct=EBI-5323863, EBI-5838167;
CC Q5S007; P53355: DAPK1; NbExp=2; IntAct=EBI-5323863, EBI-358616;
CC Q5S007; Q05193: DNM1; NbExp=4; IntAct=EBI-5323863, EBI-713135;
CC Q5S007; O00429: DNM1L; NbExp=14; IntAct=EBI-5323863, EBI-724571;
CC Q5S007; O00429-3: DNM1L; NbExp=2; IntAct=EBI-5323863, EBI-6896746;
CC Q5S007; O14640-2: DVL1; NbExp=7; IntAct=EBI-5323863, EBI-6504027;
CC Q5S007; O14641: DVL2; NbExp=5; IntAct=EBI-5323863, EBI-740850;
CC Q5S007; Q92997: DVL3; NbExp=4; IntAct=EBI-5323863, EBI-739789;
CC Q5S007; P30084: ECHS1; NbExp=4; IntAct=EBI-5323863, EBI-719602;
CC Q5S007; Q05639: EEF1A2; NbExp=3; IntAct=EBI-5323863, EBI-354943;
CC Q5S007; Q13158: FADD; NbExp=4; IntAct=EBI-5323863, EBI-494804;
CC Q5S007; O14976: GAK; NbExp=11; IntAct=EBI-5323863, EBI-714707;
CC Q5S007; P49841: GSK3B; NbExp=7; IntAct=EBI-5323863, EBI-373586;
CC Q5S007; P11142: HSPA8; NbExp=6; IntAct=EBI-5323863, EBI-351896;
CC Q5S007; Q71RC2: LARP4; NbExp=3; IntAct=EBI-5323863, EBI-2878091;
CC Q5S007; Q4G0J3: LARP7; NbExp=3; IntAct=EBI-5323863, EBI-2371923;
CC Q5S007; P07195: LDHB; NbExp=2; IntAct=EBI-5323863, EBI-358748;
CC Q5S007; O75581: LRP6; NbExp=4; IntAct=EBI-5323863, EBI-910915;
CC Q5S007; Q38SD2: LRRK1; NbExp=5; IntAct=EBI-5323863, EBI-1050422;
CC Q5S007; Q5S007: LRRK2; NbExp=68; IntAct=EBI-5323863, EBI-5323863;
CC Q5S007; PRO_0000018605 [P46821]: MAP1B; NbExp=5; IntAct=EBI-5323863, EBI-9517186;
CC Q5S007; P46734: MAP2K3; NbExp=5; IntAct=EBI-5323863, EBI-602462;
CC Q5S007; P52564: MAP2K6; NbExp=4; IntAct=EBI-5323863, EBI-448135;
CC Q5S007; O14733: MAP2K7; NbExp=3; IntAct=EBI-5323863, EBI-492605;
CC Q5S007; P10636-2: MAPT; NbExp=3; IntAct=EBI-5323863, EBI-7796412;
CC Q5S007; P10636-8: MAPT; NbExp=9; IntAct=EBI-5323863, EBI-366233;
CC Q5S007; P42679: MATK; NbExp=2; IntAct=EBI-5323863, EBI-751664;
CC Q5S007; O95140: MFN2; NbExp=3; IntAct=EBI-5323863, EBI-3324756;
CC Q5S007; P49406: MRPL19; NbExp=3; IntAct=EBI-5323863, EBI-1188518;
CC Q5S007; P26038: MSN; NbExp=19; IntAct=EBI-5323863, EBI-528768;
CC Q5S007; Q7L592: NDUFAF7; NbExp=2; IntAct=EBI-5323863, EBI-2555519;
CC Q5S007; Q96PY6: NEK1; NbExp=2; IntAct=EBI-5323863, EBI-373615;
CC Q5S007; Q13469: NFATC2; NbExp=3; IntAct=EBI-5323863, EBI-716258;
CC Q5S007; Q8WUM0: NUP133; NbExp=4; IntAct=EBI-5323863, EBI-295695;
CC Q5S007; O60313: OPA1; NbExp=5; IntAct=EBI-5323863, EBI-1054131;
CC Q5S007; Q9NQU5: PAK6; NbExp=2; IntAct=EBI-5323863, EBI-1053685;
CC Q5S007; P62136: PPP1CA; NbExp=6; IntAct=EBI-5323863, EBI-357253;
CC Q5S007; Q12972: PPP1R8; NbExp=3; IntAct=EBI-5323863, EBI-716633;
CC Q5S007; P63151: PPP2R2A; NbExp=4; IntAct=EBI-5323863, EBI-1048931;
CC Q5S007; P30048: PRDX3; NbExp=14; IntAct=EBI-5323863, EBI-748336;
CC Q5S007; P17612: PRKACA; NbExp=6; IntAct=EBI-5323863, EBI-476586;
CC Q5S007; O60260: PRKN; NbExp=3; IntAct=EBI-5323863, EBI-716346;
CC Q5S007; P61026: RAB10; NbExp=7; IntAct=EBI-5323863, EBI-726075;
CC Q5S007; Q6IQ22: RAB12; NbExp=2; IntAct=EBI-5323863, EBI-4289591;
CC Q5S007; Q9H0U4: RAB1B; NbExp=5; IntAct=EBI-5323863, EBI-1045214;
CC Q5S007; O14966: RAB29; NbExp=15; IntAct=EBI-5323863, EBI-372165;
CC Q5S007; Q13637: RAB32; NbExp=12; IntAct=EBI-5323863, EBI-9837586;
CC Q5S007; P57729: RAB38; NbExp=4; IntAct=EBI-5323863, EBI-6552718;
CC Q5S007; P61020: RAB5B; NbExp=9; IntAct=EBI-5323863, EBI-399401;
CC Q5S007; P61006: RAB8A; NbExp=7; IntAct=EBI-5323863, EBI-722293;
CC Q5S007; P63000: RAC1; NbExp=5; IntAct=EBI-5323863, EBI-413628;
CC Q5S007; P41220: RGS2; NbExp=6; IntAct=EBI-5323863, EBI-712388;
CC Q5S007; P62906: RPL10A; NbExp=4; IntAct=EBI-5323863, EBI-356860;
CC Q5S007; P26373: RPL13; NbExp=4; IntAct=EBI-5323863, EBI-356849;
CC Q5S007; P50914: RPL14; NbExp=2; IntAct=EBI-5323863, EBI-356746;
CC Q5S007; P62750: RPL23A; NbExp=2; IntAct=EBI-5323863, EBI-353254;
CC Q5S007; P62888: RPL30; NbExp=3; IntAct=EBI-5323863, EBI-353116;
CC Q5S007; P49207: RPL34; NbExp=3; IntAct=EBI-5323863, EBI-1051893;
CC Q5S007; Q9BUL9: RPP25; NbExp=3; IntAct=EBI-5323863, EBI-366570;
CC Q5S007; P62280: RPS11; NbExp=5; IntAct=EBI-5323863, EBI-1047710;
CC Q5S007; P62277: RPS13; NbExp=3; IntAct=EBI-5323863, EBI-351850;
CC Q5S007; P62841: RPS15; NbExp=9; IntAct=EBI-5323863, EBI-372635;
CC Q5S007; P62249: RPS16; NbExp=4; IntAct=EBI-5323863, EBI-352480;
CC Q5S007; P62269: RPS18; NbExp=3; IntAct=EBI-5323863, EBI-352451;
CC Q5S007; P15880: RPS2; NbExp=4; IntAct=EBI-5323863, EBI-443446;
CC Q5S007; P60866: RPS20; NbExp=4; IntAct=EBI-5323863, EBI-353105;
CC Q5S007; P62266: RPS23; NbExp=2; IntAct=EBI-5323863, EBI-353072;
CC Q5S007; P42677: RPS27; NbExp=4; IntAct=EBI-5323863, EBI-356336;
CC Q5S007; P23396: RPS3; NbExp=4; IntAct=EBI-5323863, EBI-351193;
CC Q5S007; O15027: SEC16A; NbExp=8; IntAct=EBI-5323863, EBI-357515;
CC Q5S007; P60896: SEM1; NbExp=3; IntAct=EBI-5323863, EBI-79819;
CC Q5S007; P31947: SFN; NbExp=5; IntAct=EBI-5323863, EBI-476295;
CC Q5S007; Q99961: SH3GL1; NbExp=3; IntAct=EBI-5323863, EBI-697911;
CC Q5S007; Q99962: SH3GL2; NbExp=4; IntAct=EBI-5323863, EBI-77938;
CC Q5S007; P12235: SLC25A4; NbExp=2; IntAct=EBI-5323863, EBI-359074;
CC Q5S007; P05141: SLC25A5; NbExp=2; IntAct=EBI-5323863, EBI-355133;
CC Q5S007; P12236: SLC25A6; NbExp=2; IntAct=EBI-5323863, EBI-356254;
CC Q5S007; O95295: SNAPIN; NbExp=5; IntAct=EBI-5323863, EBI-296723;
CC Q5S007; P37840: SNCA; NbExp=6; IntAct=EBI-5323863, EBI-985879;
CC Q5S007; Q8NHS9: SPATA22; NbExp=3; IntAct=EBI-5323863, EBI-7067260;
CC Q5S007; Q13501: SQSTM1; NbExp=18; IntAct=EBI-5323863, EBI-307104;
CC Q5S007; Q9UNE7: STUB1; NbExp=4; IntAct=EBI-5323863, EBI-357085;
CC Q5S007; Q9UNE7-1: STUB1; NbExp=2; IntAct=EBI-5323863, EBI-15687717;
CC Q5S007; Q9BQ70: TCF25; NbExp=3; IntAct=EBI-5323863, EBI-745182;
CC Q5S007; Q6P3X3: TTC27; NbExp=3; IntAct=EBI-5323863, EBI-1057046;
CC Q5S007; P07437: TUBB; NbExp=6; IntAct=EBI-5323863, EBI-350864;
CC Q5S007; Q13885: TUBB2A; NbExp=3; IntAct=EBI-5323863, EBI-711595;
CC Q5S007; P04350: TUBB4A; NbExp=6; IntAct=EBI-5323863, EBI-355007;
CC Q5S007; P68371: TUBB4B; NbExp=3; IntAct=EBI-5323863, EBI-351356;
CC Q5S007; Q9BUF5: TUBB6; NbExp=3; IntAct=EBI-5323863, EBI-356735;
CC Q5S007; Q53GS9: USP39; NbExp=3; IntAct=EBI-5323863, EBI-1044822;
CC Q5S007; P21796: VDAC1; NbExp=3; IntAct=EBI-5323863, EBI-354158;
CC Q5S007; Q9Y6I7: WSB1; NbExp=5; IntAct=EBI-5323863, EBI-1171494;
CC Q5S007; P31946: YWHAB; NbExp=5; IntAct=EBI-5323863, EBI-359815;
CC Q5S007; P62258: YWHAE; NbExp=8; IntAct=EBI-5323863, EBI-356498;
CC Q5S007; P61981: YWHAG; NbExp=26; IntAct=EBI-5323863, EBI-359832;
CC Q5S007; Q04917: YWHAH; NbExp=4; IntAct=EBI-5323863, EBI-306940;
CC Q5S007; P27348: YWHAQ; NbExp=10; IntAct=EBI-5323863, EBI-359854;
CC Q5S007; P63104: YWHAZ; NbExp=11; IntAct=EBI-5323863, EBI-347088;
CC Q5S007; O95218: ZRANB2; NbExp=2; IntAct=EBI-5323863, EBI-1051583;
CC Q5S007; Q62848: Arfgap1; Xeno; NbExp=7; IntAct=EBI-5323863, EBI-4398879;
CC Q5S007; O55143: Atp2a2; Xeno; NbExp=13; IntAct=EBI-5323863, EBI-770763;
CC Q5S007; P30275: Ckmt1; Xeno; NbExp=2; IntAct=EBI-5323863, EBI-773103;
CC Q5S007; P39053: Dnm1; Xeno; NbExp=3; IntAct=EBI-5323863, EBI-397785;
CC Q5S007; P02687: MBP; Xeno; NbExp=3; IntAct=EBI-5323863, EBI-908215;
CC Q5S007; Q811U4: Mfn1; Xeno; NbExp=3; IntAct=EBI-5323863, EBI-9029118;
CC Q5S007; P00634: phoA; Xeno; NbExp=2; IntAct=EBI-5323863, EBI-552958;
CC Q5S007; P12369: Prkar2b; Xeno; NbExp=3; IntAct=EBI-5323863, EBI-6096160;
CC Q5S007; Q63481: Rab29; Xeno; NbExp=3; IntAct=EBI-5323863, EBI-6513837;
CC Q5S007; P61021: Rab5b; Xeno; NbExp=2; IntAct=EBI-5323863, EBI-8320093;
CC Q5S007; Q58A65: Spag9; Xeno; NbExp=2; IntAct=EBI-5323863, EBI-6530207;
CC Q5S007; Q9WUD1: Stub1; Xeno; NbExp=2; IntAct=EBI-5323863, EBI-773027;
CC Q5S007; P61983: Ywhag; Xeno; NbExp=6; IntAct=EBI-5323863, EBI-359821;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle {ECO:0000269|PubMed:16321986,
CC ECO:0000269|PubMed:16352719, ECO:0000269|PubMed:26014385}. Perikaryon
CC {ECO:0000269|PubMed:17120249}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:16321986, ECO:0000269|PubMed:23395371}; Peripheral
CC membrane protein {ECO:0000269|PubMed:16321986}. Cell projection, axon
CC {ECO:0000269|PubMed:17120249}. Cell projection, dendrite
CC {ECO:0000269|PubMed:17120249, ECO:0000269|PubMed:21850687}. Endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:16321986,
CC ECO:0000269|PubMed:25201882}; Peripheral membrane protein
CC {ECO:0000269|PubMed:16321986}. Cytoplasmic vesicle, secretory vesicle,
CC synaptic vesicle membrane {ECO:0000269|PubMed:24687852}. Endosome
CC {ECO:0000250|UniProtKB:Q5S006}. Lysosome {ECO:0000269|PubMed:17120249}.
CC Mitochondrion outer membrane {ECO:0000269|PubMed:16269541,
CC ECO:0000269|PubMed:16321986, ECO:0000269|PubMed:17120249,
CC ECO:0000269|PubMed:29212815}; Peripheral membrane protein
CC {ECO:0000269|PubMed:16269541, ECO:0000269|PubMed:16321986,
CC ECO:0000269|PubMed:17120249, ECO:0000269|PubMed:29212815}.
CC Note=Colocalized with RAB29 along tubular structures emerging from
CC Golgi apparatus (PubMed:23395371). Localizes to endoplasmic reticulum
CC exit sites (ERES), also known as transitional endoplasmic reticulum
CC (tER) (PubMed:25201882). {ECO:0000269|PubMed:23395371,
CC ECO:0000269|PubMed:25201882}.
CC -!- TISSUE SPECIFICITY: Expressed in pyramidal neurons in all cortical
CC laminae of the visual cortex, in neurons of the substantia nigra pars
CC compacta and caudate putamen (at protein level). Expressed in
CC neutrophils (at protein level) (PubMed:29127255). Expressed in the
CC brain. Expressed throughout the adult brain, but at a lower level than
CC in heart and liver. Also expressed in placenta, lung, skeletal muscle,
CC kidney and pancreas. In the brain, expressed in the cerebellum,
CC cerebral cortex, medulla, spinal cord occipital pole, frontal lobe,
CC temporal lobe and putamen. Expression is particularly high in brain
CC dopaminoceptive areas. {ECO:0000269|PubMed:15541308,
CC ECO:0000269|PubMed:15541309, ECO:0000269|PubMed:16532471,
CC ECO:0000269|PubMed:17120249, ECO:0000269|PubMed:29127255}.
CC -!- DOMAIN: The seven-bladed WD repeat region is critical for synaptic
CC vesicle trafficking and mediates interaction with multiple vesicle-
CC associated presynaptic proteins (PubMed:24687852). It also mediates
CC homodimerization and regulates kinase activity (PubMed:30635421).
CC {ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:30635421}.
CC -!- DOMAIN: The Roc domain mediates homodimerization and regulates kinase
CC activity. {ECO:0000269|PubMed:18230735}.
CC -!- PTM: Autophosphorylated (PubMed:28202711, PubMed:28720718,
CC PubMed:29127255, PubMed:29212815, PubMed:30635421). Phosphorylation of
CC Ser-910 and either Ser-935 or Ser-1444 facilitates interaction with
CC YWHAG (PubMed:28202711). Phosphorylation of Ser-910 and/or Ser-935
CC facilitates interaction with SFN (PubMed:28202711).
CC {ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:28720718,
CC ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815,
CC ECO:0000269|PubMed:30635421}.
CC -!- DISEASE: Parkinson disease 8 (PARK8) [MIM:607060]: A slowly progressive
CC neurodegenerative disorder characterized by bradykinesia, rigidity,
CC resting tremor, postural instability, neuronal loss in the substantia
CC nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy
CC bodies in some patients. {ECO:0000269|PubMed:15541308,
CC ECO:0000269|PubMed:15541309, ECO:0000269|PubMed:15680455,
CC ECO:0000269|PubMed:15680456, ECO:0000269|PubMed:15680457,
CC ECO:0000269|PubMed:15726496, ECO:0000269|PubMed:15732108,
CC ECO:0000269|PubMed:15811454, ECO:0000269|PubMed:15852371,
CC ECO:0000269|PubMed:15880653, ECO:0000269|PubMed:15925109,
CC ECO:0000269|PubMed:15929036, ECO:0000269|PubMed:16102999,
CC ECO:0000269|PubMed:16157901, ECO:0000269|PubMed:16157908,
CC ECO:0000269|PubMed:16157909, ECO:0000269|PubMed:16172858,
CC ECO:0000269|PubMed:16240353, ECO:0000269|PubMed:16247070,
CC ECO:0000269|PubMed:16250030, ECO:0000269|PubMed:16251215,
CC ECO:0000269|PubMed:16269541, ECO:0000269|PubMed:16272164,
CC ECO:0000269|PubMed:16272257, ECO:0000269|PubMed:16298482,
CC ECO:0000269|PubMed:16321986, ECO:0000269|PubMed:16333314,
CC ECO:0000269|PubMed:16533964, ECO:0000269|PubMed:17114044,
CC ECO:0000269|PubMed:18213618, ECO:0000269|PubMed:21850687,
CC ECO:0000269|PubMed:22956510, ECO:0000269|PubMed:23395371,
CC ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26824392,
CC ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:28720718,
CC ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255,
CC ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148,
CC ECO:0000269|PubMed:30635421}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY792511; AAV63975.1; -; mRNA.
DR EMBL; AC079630; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC084290; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC107023; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL834529; CAD39185.1; -; mRNA.
DR CCDS; CCDS31774.1; -.
DR RefSeq; NP_940980.3; NM_198578.3.
DR PDB; 2ZEJ; X-ray; 2.00 A; A/B=1333-1516.
DR PDB; 3D6T; X-ray; 2.43 A; B=1335-1505.
DR PDB; 5MY9; X-ray; 1.33 A; P=929-941.
DR PDB; 5MYC; X-ray; 1.46 A; P=904-941.
DR PDB; 6DLO; X-ray; 2.70 A; A/B=2142-2527.
DR PDB; 6DLP; X-ray; 4.00 A; A/B=2142-2527.
DR PDB; 6OJE; X-ray; 1.95 A; A/B=1329-1520.
DR PDB; 6OJF; X-ray; 1.60 A; A/B=1329-1520.
DR PDB; 6VNO; EM; 3.50 A; A=1327-2527.
DR PDB; 6VP6; EM; 3.47 A; A/B/C=1327-2527.
DR PDB; 6VP7; EM; 3.50 A; A=1327-2527.
DR PDB; 6XAF; X-ray; 1.97 A; A/B=1329-1520.
DR PDB; 6XR4; EM; 14.00 A; A/B=1-2527.
DR PDB; 7LHT; EM; 3.50 A; A/B=1-2527.
DR PDB; 7LHW; EM; 3.70 A; A=1-2527.
DR PDB; 7LI3; EM; 3.80 A; A=1-2527.
DR PDB; 7LI4; EM; 3.10 A; A=1-2527.
DR PDBsum; 2ZEJ; -.
DR PDBsum; 3D6T; -.
DR PDBsum; 5MY9; -.
DR PDBsum; 5MYC; -.
DR PDBsum; 6DLO; -.
DR PDBsum; 6DLP; -.
DR PDBsum; 6OJE; -.
DR PDBsum; 6OJF; -.
DR PDBsum; 6VNO; -.
DR PDBsum; 6VP6; -.
DR PDBsum; 6VP7; -.
DR PDBsum; 6XAF; -.
DR PDBsum; 6XR4; -.
DR PDBsum; 7LHT; -.
DR PDBsum; 7LHW; -.
DR PDBsum; 7LI3; -.
DR PDBsum; 7LI4; -.
DR AlphaFoldDB; Q5S007; -.
DR SMR; Q5S007; -.
DR BioGRID; 125700; 506.
DR CORUM; Q5S007; -.
DR DIP; DIP-29684N; -.
DR IntAct; Q5S007; 2329.
DR MINT; Q5S007; -.
DR STRING; 9606.ENSP00000298910; -.
DR BindingDB; Q5S007; -.
DR ChEMBL; CHEMBL1075104; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q5S007; -.
DR GuidetoPHARMACOLOGY; 2059; -.
DR iPTMnet; Q5S007; -.
DR PhosphoSitePlus; Q5S007; -.
DR BioMuta; LRRK2; -.
DR DMDM; 294862450; -.
DR EPD; Q5S007; -.
DR jPOST; Q5S007; -.
DR MassIVE; Q5S007; -.
DR MaxQB; Q5S007; -.
DR PaxDb; Q5S007; -.
DR PeptideAtlas; Q5S007; -.
DR PRIDE; Q5S007; -.
DR ProteomicsDB; 63755; -.
DR ABCD; Q5S007; 2 sequenced antibodies.
DR Antibodypedia; 2109; 912 antibodies from 48 providers.
DR DNASU; 120892; -.
DR Ensembl; ENST00000298910.12; ENSP00000298910.7; ENSG00000188906.17.
DR GeneID; 120892; -.
DR KEGG; hsa:120892; -.
DR MANE-Select; ENST00000298910.12; ENSP00000298910.7; NM_198578.4; NP_940980.4.
DR UCSC; uc001rmg.5; human.
DR CTD; 120892; -.
DR DisGeNET; 120892; -.
DR GeneCards; LRRK2; -.
DR GeneReviews; LRRK2; -.
DR HGNC; HGNC:18618; LRRK2.
DR HPA; ENSG00000188906; Tissue enriched (lung).
DR MalaCards; LRRK2; -.
DR MIM; 168600; phenotype.
DR MIM; 607060; phenotype.
DR MIM; 609007; gene.
DR neXtProt; NX_Q5S007; -.
DR OpenTargets; ENSG00000188906; -.
DR Orphanet; 411602; Hereditary late-onset Parkinson disease.
DR Orphanet; 2828; Young-onset Parkinson disease.
DR PharmGKB; PA134968052; -.
DR VEuPathDB; HostDB:ENSG00000188906; -.
DR eggNOG; KOG0192; Eukaryota.
DR eggNOG; KOG0618; Eukaryota.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000158267; -.
DR HOGENOM; CLU_000815_0_0_1; -.
DR InParanoid; Q5S007; -.
DR OMA; WEVLGIH; -.
DR OrthoDB; 218804at2759; -.
DR PhylomeDB; Q5S007; -.
DR TreeFam; TF313679; -.
DR PathwayCommons; Q5S007; -.
DR Reactome; R-HSA-8857538; PTK6 promotes HIF1A stabilization.
DR SignaLink; Q5S007; -.
DR SIGNOR; Q5S007; -.
DR BioGRID-ORCS; 120892; 21 hits in 1105 CRISPR screens.
DR ChiTaRS; LRRK2; human.
DR EvolutionaryTrace; Q5S007; -.
DR GeneWiki; LRRK2; -.
DR GenomeRNAi; 120892; -.
DR Pharos; Q5S007; Tchem.
DR PRO; PR:Q5S007; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q5S007; protein.
DR Bgee; ENSG00000188906; Expressed in buccal mucosa cell and 152 other tissues.
DR ExpressionAtlas; Q5S007; baseline and differential.
DR Genevisible; Q5S007; HS.
DR GO; GO:0044753; C:amphisome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0044754; C:autolysosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0099400; C:caveola neck; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0032473; C:cytoplasmic side of mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0032839; C:dendrite cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0070971; C:endoplasmic reticulum exit site; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005798; C:Golgi-associated vesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030426; C:growth cone; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016234; C:inclusion body; IMP:ParkinsonsUK-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IBA:GO_Central.
DR GO; GO:0005902; C:microvillus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0097487; C:multivesicular body, internal vesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043005; C:neuron projection; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:BHF-UCL.
DR GO; GO:0043204; C:perikaryon; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0099523; C:presynaptic cytosol; IEA:Ensembl.
DR GO; GO:1990904; C:ribonucleoprotein complex; IEA:Ensembl.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043195; C:terminal bouton; TAS:ParkinsonsUK-UCL.
DR GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl.
DR GO; GO:1990909; C:Wnt signalosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0003779; F:actin binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:1904713; F:beta-catenin destruction complex binding; NAS:ParkinsonsUK-UCL.
DR GO; GO:0030276; F:clathrin binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0039706; F:co-receptor binding; TAS:ParkinsonsUK-UCL.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0034211; F:GTP-dependent protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IDA:BHF-UCL.
DR GO; GO:0016301; F:kinase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IMP:UniProtKB.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IDA:BHF-UCL.
DR GO; GO:0008017; F:microtubule binding; TAS:ParkinsonsUK-UCL.
DR GO; GO:0036479; F:peroxidase inhibitor activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0051018; F:protein kinase A binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IC:ParkinsonsUK-UCL.
DR GO; GO:0031267; F:small GTPase binding; IPI:BHF-UCL.
DR GO; GO:0000149; F:SNARE binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0017075; F:syntaxin-1 binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; IDA:BHF-UCL.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:ParkinsonsUK-UCL.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; TAS:ParkinsonsUK-UCL.
DR GO; GO:1903351; P:cellular response to dopamine; IMP:ParkinsonsUK-UCL.
DR GO; GO:0071287; P:cellular response to manganese ion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:0009267; P:cellular response to starvation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:BHF-UCL.
DR GO; GO:0006897; P:endocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0007029; P:endoplasmic reticulum organization; IMP:UniProtKB.
DR GO; GO:0060079; P:excitatory postsynaptic potential; ISS:ParkinsonsUK-UCL.
DR GO; GO:0035640; P:exploration behavior; IMP:BHF-UCL.
DR GO; GO:0007030; P:Golgi organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0046039; P:GTP metabolic process; IDA:BHF-UCL.
DR GO; GO:0048312; P:intracellular distribution of mitochondria; IMP:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:ParkinsonsUK-UCL.
DR GO; GO:0007254; P:JNK cascade; IDA:BHF-UCL.
DR GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl.
DR GO; GO:0007040; P:lysosome organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0000165; P:MAPK cascade; IDA:UniProtKB.
DR GO; GO:0051646; P:mitochondrion localization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0007005; P:mitochondrion organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:1902902; P:negative regulation of autophagosome assembly; IMP:ParkinsonsUK-UCL.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0090394; P:negative regulation of excitatory postsynaptic potential; ISS:ParkinsonsUK-UCL.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:MGI.
DR GO; GO:1903206; P:negative regulation of hydrogen peroxide-induced cell death; IMP:ParkinsonsUK-UCL.
DR GO; GO:1902823; P:negative regulation of late endosome to lysosome transport; TAS:ParkinsonsUK-UCL.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:1901215; P:negative regulation of neuron death; IGI:ParkinsonsUK-UCL.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0032091; P:negative regulation of protein binding; IMP:ParkinsonsUK-UCL.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:ParkinsonsUK-UCL.
DR GO; GO:0010955; P:negative regulation of protein processing; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903217; P:negative regulation of protein processing involved in protein targeting to mitochondrion; IC:ParkinsonsUK-UCL.
DR GO; GO:1903215; P:negative regulation of protein targeting to mitochondrion; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903125; P:negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0007528; P:neuromuscular junction development; IMP:BHF-UCL.
DR GO; GO:0070997; P:neuron death; IMP:BHF-UCL.
DR GO; GO:0140058; P:neuron projection arborization; IEA:Ensembl.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:UniProtKB.
DR GO; GO:0021772; P:olfactory bulb development; IMP:ParkinsonsUK-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0016310; P:phosphorylation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IGI:ParkinsonsUK-UCL.
DR GO; GO:0060161; P:positive regulation of dopamine receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:1901727; P:positive regulation of histone deacetylase activity; IEA:Ensembl.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903980; P:positive regulation of microglial cell activation; IEA:Ensembl.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IEA:Ensembl.
DR GO; GO:0043068; P:positive regulation of programmed cell death; IDA:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:BHF-UCL.
DR GO; GO:1902499; P:positive regulation of protein autoubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:1900244; P:positive regulation of synaptic vesicle endocytosis; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0008104; P:protein localization; ISS:ParkinsonsUK-UCL.
DR GO; GO:0070973; P:protein localization to endoplasmic reticulum exit site; IMP:UniProtKB.
DR GO; GO:0070585; P:protein localization to mitochondrion; TAS:ParkinsonsUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010506; P:regulation of autophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:2000172; P:regulation of branching morphogenesis of a nerve; IMP:ParkinsonsUK-UCL.
DR GO; GO:1905289; P:regulation of CAMKK-AMPK signaling cascade; IMP:ParkinsonsUK-UCL.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0060159; P:regulation of dopamine receptor signaling pathway; ISS:ParkinsonsUK-UCL.
DR GO; GO:0060628; P:regulation of ER to Golgi vesicle-mediated transport; ISS:UniProtKB.
DR GO; GO:0035564; P:regulation of kidney size; ISS:BHF-UCL.
DR GO; GO:0040012; P:regulation of locomotion; IMP:BHF-UCL.
DR GO; GO:0035751; P:regulation of lysosomal lumen pH; IMP:ParkinsonsUK-UCL.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:BHF-UCL.
DR GO; GO:0051900; P:regulation of mitochondrial depolarization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0090140; P:regulation of mitochondrial fission; TAS:ParkinsonsUK-UCL.
DR GO; GO:1902692; P:regulation of neuroblast proliferation; IMP:ParkinsonsUK-UCL.
DR GO; GO:1901214; P:regulation of neuron death; IMP:ParkinsonsUK-UCL.
DR GO; GO:0014041; P:regulation of neuron maturation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010738; P:regulation of protein kinase A signaling; ISS:ParkinsonsUK-UCL.
DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
DR GO; GO:1905279; P:regulation of retrograde transport, endosome to Golgi; IGI:ParkinsonsUK-UCL.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; ISS:ParkinsonsUK-UCL.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:1902803; P:regulation of synaptic vesicle transport; ISS:ParkinsonsUK-UCL.
DR GO; GO:0006979; P:response to oxidative stress; IMP:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0021756; P:striatum development; IEA:Ensembl.
DR GO; GO:0022028; P:tangential migration from the subventricular zone to the olfactory bulb; IMP:ParkinsonsUK-UCL.
DR GO; GO:1904887; P:Wnt signalosome assembly; IPI:ParkinsonsUK-UCL.
DR Gene3D; 1.25.10.10; -; 2.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR032171; COR.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR025875; Leu-rich_rpt_4.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR020859; ROC_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF16095; COR; 1.
DR Pfam; PF12799; LRR_4; 1.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48371; SSF48371; 2.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51450; LRR; 11.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS51424; ROC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Autophagy; Cell projection; Coiled coil;
KW Cytoplasmic vesicle; Differentiation; Disease variant;
KW Endoplasmic reticulum; Endosome; Golgi apparatus; GTP-binding;
KW GTPase activation; Hydrolase; Kinase; Leucine-rich repeat; Lysosome;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; Neurodegeneration;
KW Nucleotide-binding; Parkinson disease; Parkinsonism; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Synapse;
KW Transferase; WD repeat.
FT CHAIN 1..2527
FT /note="Leucine-rich repeat serine/threonine-protein kinase
FT 2"
FT /id="PRO_0000086238"
FT REPEAT 983..1004
FT /note="LRR 1"
FT REPEAT 1012..1033
FT /note="LRR 2"
FT REPEAT 1036..1057
FT /note="LRR 3"
FT REPEAT 1059..1080
FT /note="LRR 4"
FT REPEAT 1084..1105
FT /note="LRR 5"
FT REPEAT 1108..1129
FT /note="LRR 6"
FT REPEAT 1130..1150
FT /note="LRR 7"
FT REPEAT 1174..1196
FT /note="LRR 8"
FT REPEAT 1197..1218
FT /note="LRR 9"
FT REPEAT 1221..1241
FT /note="LRR 10"
FT REPEAT 1246..1267
FT /note="LRR 11"
FT REPEAT 1269..1291
FT /note="LRR 12"
FT DOMAIN 1328..1511
FT /note="Roc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00758"
FT DOMAIN 1879..2138
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 2139..2183
FT /note="WD 1"
FT REPEAT 2188..2228
FT /note="WD 2"
FT REPEAT 2233..2276
FT /note="WD 3"
FT REPEAT 2281..2327
FT /note="WD 4"
FT REPEAT 2333..2377
FT /note="WD 5"
FT REPEAT 2402..2438
FT /note="WD 6"
FT REPEAT 2443..2497
FT /note="WD 7"
FT REGION 1..969
FT /note="Required for RAB29-mediated activation"
FT /evidence="ECO:0000269|PubMed:29212815"
FT COILED 319..348
FT /evidence="ECO:0000255"
FT ACT_SITE 1994
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 1341..1348
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00758,
FT ECO:0000269|PubMed:18230735"
FT BINDING 1885..1893
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1906
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 2098..2121
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00758"
FT BINDING 2295..2298
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00758"
FT MOD_RES 910
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28202711,
FT ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29212815"
FT MOD_RES 935
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28202711,
FT ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29127255,
FT ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30635421"
FT MOD_RES 955
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28202711,
FT ECO:0000269|PubMed:29212815"
FT MOD_RES 973
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28202711,
FT ECO:0000269|PubMed:29212815"
FT MOD_RES 1292
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:29212815,
FT ECO:0000269|PubMed:30635421"
FT MOD_RES 1444
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28202711"
FT VARIANT 50
FT /note="R -> H (in dbSNP:rs2256408)"
FT /id="VAR_024931"
FT VARIANT 119
FT /note="L -> P (in dbSNP:rs33995463)"
FT /evidence="ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_024932"
FT VARIANT 228
FT /note="C -> S (in dbSNP:rs56108242)"
FT /evidence="ECO:0000269|PubMed:18213618"
FT /id="VAR_054740"
FT VARIANT 419
FT /note="A -> V (in dbSNP:rs34594498)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_033903"
FT VARIANT 551
FT /note="N -> K (in dbSNP:rs7308720)"
FT /evidence="ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:16251215, ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:22415848"
FT /id="VAR_024933"
FT VARIANT 712
FT /note="M -> V (in PARK8; dbSNP:rs199566791)"
FT /evidence="ECO:0000269|PubMed:18213618"
FT /id="VAR_054741"
FT VARIANT 716
FT /note="A -> V (in dbSNP:rs281865043)"
FT /evidence="ECO:0000269|PubMed:18213618"
FT /id="VAR_054742"
FT VARIANT 723
FT /note="I -> V (in dbSNP:rs10878307)"
FT /evidence="ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:22415848"
FT /id="VAR_024934"
FT VARIANT 755
FT /note="P -> L (in dbSNP:rs34410987)"
FT /id="VAR_033904"
FT VARIANT 793
FT /note="R -> M (in PARK8; unknown pathological significance;
FT dbSNP:rs35173587)"
FT /evidence="ECO:0000269|PubMed:16157908,
FT ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:16251215"
FT /id="VAR_024935"
FT VARIANT 871
FT /note="K -> E (in dbSNP:rs281865044)"
FT /evidence="ECO:0000269|PubMed:18213618"
FT /id="VAR_054743"
FT VARIANT 930
FT /note="Q -> R (in PARK8; unknown pathological significance;
FT dbSNP:rs281865045)"
FT /evidence="ECO:0000269|PubMed:16251215"
FT /id="VAR_024936"
FT VARIANT 944
FT /note="D -> Y (in dbSNP:rs17519916)"
FT /id="VAR_024937"
FT VARIANT 1067
FT /note="R -> Q (in PARK8; dbSNP:rs111341148)"
FT /evidence="ECO:0000269|PubMed:16247070"
FT /id="VAR_024938"
FT VARIANT 1096
FT /note="S -> C (in PARK8; unknown pathological significance;
FT dbSNP:rs76535406)"
FT /id="VAR_024939"
FT VARIANT 1122
FT /note="I -> V (in PARK8; dbSNP:rs34805604)"
FT /evidence="ECO:0000269|PubMed:15541309,
FT ECO:0000269|PubMed:16172858"
FT /id="VAR_024940"
FT VARIANT 1228
FT /note="S -> T (in PARK8; dbSNP:rs60185966)"
FT /evidence="ECO:0000269|PubMed:16251215"
FT /id="VAR_024941"
FT VARIANT 1262
FT /note="P -> A (in dbSNP:rs4640000)"
FT /evidence="ECO:0000269|PubMed:16172858"
FT /id="VAR_024942"
FT VARIANT 1359
FT /note="K -> I (found in a renal cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064728"
FT VARIANT 1371
FT /note="I -> V (in PARK8; unknown pathological significance;
FT dbSNP:rs17466213)"
FT /evidence="ECO:0000269|PubMed:16157901,
FT ECO:0000269|PubMed:16333314"
FT /id="VAR_024943"
FT VARIANT 1375
FT /note="D -> E (in dbSNP:rs28365226)"
FT /id="VAR_047022"
FT VARIANT 1398
FT /note="R -> H (in dbSNP:rs7133914)"
FT /evidence="ECO:0000269|PubMed:16157901,
FT ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:22415848"
FT /id="VAR_024944"
FT VARIANT 1441
FT /note="R -> C (in PARK8; shows an increase in activity in
FT both autophosphorylation and phosphorylation of a generic
FT substrate; loss of interaction with SEC16A; shows an
FT increase in activity in phosphorylation of RAB10; decreases
FT phosphorylation-dependent binding to YWHAG;
FT dbSNP:rs33939927)"
FT /evidence="ECO:0000269|PubMed:15541309,
FT ECO:0000269|PubMed:16157909, ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:16269541, ECO:0000269|PubMed:16333314,
FT ECO:0000269|PubMed:16533964, ECO:0000269|PubMed:25201882,
FT ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28202711,
FT ECO:0000269|PubMed:29212815"
FT /id="VAR_024945"
FT VARIANT 1441
FT /note="R -> G (in PARK8; shows a progressive reduction in
FT neurite length and branching; shows an increase in activity
FT in phosphorylation of RAB8A and RAB10; decreases
FT phosphorylation-dependent binding to YWHAG;
FT dbSNP:rs33939927)"
FT /evidence="ECO:0000269|PubMed:15541308,
FT ECO:0000269|PubMed:15925109, ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:16533964, ECO:0000269|PubMed:17114044,
FT ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718,
FT ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29212815,
FT ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421"
FT /id="VAR_024946"
FT VARIANT 1441
FT /note="R -> H (in PARK8; shows an increase in activity in
FT phosphorylation of RAB8A and RAB10; decreases
FT phosphorylation-dependent binding to YWHAG;
FT dbSNP:rs34995376)"
FT /evidence="ECO:0000269|PubMed:16157909,
FT ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:26824392,
FT ECO:0000269|PubMed:29212815"
FT /id="VAR_024947"
FT VARIANT 1514
FT /note="R -> Q (in PARK8; unknown pathological significance;
FT dbSNP:rs35507033)"
FT /evidence="ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:22415848"
FT /id="VAR_024948"
FT VARIANT 1542
FT /note="P -> S (in PARK8; unknown pathological significance;
FT dbSNP:rs33958906)"
FT /evidence="ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:22415848"
FT /id="VAR_024949"
FT VARIANT 1550
FT /note="R -> Q (in an ovarian mucinous carcinoma sample;
FT somatic mutation; dbSNP:rs200212150)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040678"
FT VARIANT 1598
FT /note="V -> E (in PARK8; unknown pathological significance;
FT dbSNP:rs721710)"
FT /evidence="ECO:0000269|PubMed:16172858"
FT /id="VAR_024950"
FT VARIANT 1628
FT /note="R -> P (may be associated with Parkinson disease in
FT some populations; dbSNP:rs33949390)"
FT /evidence="ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:21641266, ECO:0000269|PubMed:22415848"
FT /id="VAR_024951"
FT VARIANT 1646
FT /note="M -> T (in dbSNP:rs35303786)"
FT /evidence="ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:22415848"
FT /id="VAR_024952"
FT VARIANT 1647
FT /note="S -> T (in dbSNP:rs11564148)"
FT /evidence="ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:22415848"
FT /id="VAR_024953"
FT VARIANT 1699
FT /note="Y -> C (in PARK8; shows no progressive reduction in
FT neurite length and branching; no loss of interaction with
FT SEC16A; shows an increase in activity in phosphorylation of
FT RAB8A and RAB10; dbSNP:rs35801418)"
FT /evidence="ECO:0000269|PubMed:15541308,
FT ECO:0000269|PubMed:15541309, ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:16272164, ECO:0000269|PubMed:17114044,
FT ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26824392,
FT ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29212815"
FT /id="VAR_024954"
FT VARIANT 1723
FT /note="R -> P (in an ovarian serous carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040679"
FT VARIANT 1728
FT /note="R -> H (in PARK8; shows an increase in activity in
FT phosphorylation of RAB8A and RAB10; dbSNP:rs145364431)"
FT /evidence="ECO:0000269|PubMed:18213618,
FT ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:29212815"
FT /id="VAR_054744"
FT VARIANT 1728
FT /note="R -> L (in PARK8; dbSNP:rs145364431)"
FT /evidence="ECO:0000269|PubMed:18213618"
FT /id="VAR_054745"
FT VARIANT 1869
FT /note="M -> T (in PARK8; unknown pathological significance;
FT dbSNP:rs35602796)"
FT /evidence="ECO:0000269|PubMed:16157908,
FT ECO:0000269|PubMed:16172858"
FT /id="VAR_024955"
FT VARIANT 1870
FT /note="L -> F (in dbSNP:rs281865053)"
FT /evidence="ECO:0000269|PubMed:18213618"
FT /id="VAR_054746"
FT VARIANT 1906
FT /note="K -> M (does not inhibit interaction with RAB29;
FT shows a progressive increase in neurite length and
FT branching)"
FT /evidence="ECO:0000269|PubMed:17114044,
FT ECO:0000269|PubMed:23395371"
FT /id="VAR_071101"
FT VARIANT 1941
FT /note="R -> H (in PARK8; dbSNP:rs77428810)"
FT /evidence="ECO:0000269|PubMed:16272164"
FT /id="VAR_024956"
FT VARIANT 2012
FT /note="I -> T (in PARK8; unknown pathological significance;
FT dbSNP:rs34015634)"
FT /evidence="ECO:0000269|PubMed:16172858"
FT /id="VAR_024957"
FT VARIANT 2019
FT /note="G -> S (in PARK8; shows an increase in activity in
FT both autophosphorylation and phosphorylation of a generic
FT substrate; results in increased PRDX3 phosphorylation
FT promoting dysregulation of mitochondrial function and
FT oxidative damage; results in increased APP phosphorylation
FT on 'T-743' promoting neurotoxicity in dopaminergic neurons;
FT shows increased kinase activity in the phosphorylation of
FT RAB10; does not inhibit interaction with RAB29; shows a
FT progressive reduction in neurite length and branching;
FT shows distinctive spheroid-like inclusions within both
FT neuronal processes and at intracellular membranous
FT structures; shows lysosomal swelling and reduced retrograde
FT transport of selective cargo between lysosomes and the
FT Golgi apparatus; shows apoptotic mechanism of cell death;
FT no loss of interaction with SEC16A; dbSNP:rs34637584)"
FT /evidence="ECO:0000269|PubMed:15680455,
FT ECO:0000269|PubMed:15680456, ECO:0000269|PubMed:15680457,
FT ECO:0000269|PubMed:15726496, ECO:0000269|PubMed:15732108,
FT ECO:0000269|PubMed:15811454, ECO:0000269|PubMed:15852371,
FT ECO:0000269|PubMed:15929036, ECO:0000269|PubMed:16001413,
FT ECO:0000269|PubMed:16102999, ECO:0000269|PubMed:16157901,
FT ECO:0000269|PubMed:16157908, ECO:0000269|PubMed:16157909,
FT ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:16240353,
FT ECO:0000269|PubMed:16250030, ECO:0000269|PubMed:16251215,
FT ECO:0000269|PubMed:16269541, ECO:0000269|PubMed:16272164,
FT ECO:0000269|PubMed:16272257, ECO:0000269|PubMed:16298482,
FT ECO:0000269|PubMed:16333314, ECO:0000269|PubMed:16533964,
FT ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18213618,
FT ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22956510,
FT ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:25201882,
FT ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:28720718,
FT ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255,
FT ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30398148,
FT ECO:0000269|PubMed:30635421"
FT /id="VAR_024958"
FT VARIANT 2020
FT /note="I -> T (in PARK8; significant increase in
FT autophosphorylation of about 40% in comparison to wild-type
FT protein in vitro; shows a progressive reduction in neurite
FT length and branching; shows an increase in activity in
FT phosphorylation of RAB8A and RAB10; dbSNP:rs35870237)"
FT /evidence="ECO:0000269|PubMed:15541309,
FT ECO:0000269|PubMed:15880653, ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:16251215, ECO:0000269|PubMed:16321986,
FT ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:26824392,
FT ECO:0000269|PubMed:29212815"
FT /id="VAR_024959"
FT VARIANT 2031
FT /note="T -> S (in PARK8; shows an increase in activity in
FT phosphorylation of RAB8A and RAB10; dbSNP:rs78029637)"
FT /evidence="ECO:0000269|PubMed:26824392,
FT ECO:0000269|PubMed:29212815"
FT /id="VAR_082047"
FT VARIANT 2081
FT /note="N -> D (in dbSNP:rs33995883)"
FT /evidence="ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:22415848"
FT /id="VAR_024960"
FT VARIANT 2119
FT /note="P -> L (in dbSNP:rs12423862)"
FT /evidence="ECO:0000269|PubMed:16172858"
FT /id="VAR_024961"
FT VARIANT 2141
FT /note="T -> M (in PARK8; dbSNP:rs111691891)"
FT /evidence="ECO:0000269|PubMed:18213618"
FT /id="VAR_054747"
FT VARIANT 2143
FT /note="R -> H (in PARK8; dbSNP:rs201271001)"
FT /evidence="ECO:0000269|PubMed:18213618"
FT /id="VAR_054748"
FT VARIANT 2175
FT /note="D -> H (in PARK8; shows decreased WD domain
FT homodimerization; no effect on kinase activity;
FT dbSNP:rs72547981)"
FT /evidence="ECO:0000269|PubMed:30635421"
FT /id="VAR_082048"
FT VARIANT 2189
FT /note="Y -> C (in PARK8; no effect on WD domain
FT homodimerization; no effect on kinase activity;
FT dbSNP:rs35658131)"
FT /evidence="ECO:0000269|PubMed:30635421"
FT /id="VAR_082049"
FT VARIANT 2261
FT /note="N -> I (in dbSNP:rs12581902)"
FT /evidence="ECO:0000269|PubMed:16172858"
FT /id="VAR_024962"
FT VARIANT 2356
FT /note="T -> I (in PARK8; shows decreased WD domain
FT homodimerization; no effect on kinase activity;
FT dbSNP:rs113511708)"
FT /evidence="ECO:0000269|PubMed:16272164,
FT ECO:0000269|PubMed:30635421"
FT /id="VAR_024963"
FT VARIANT 2385
FT /note="G -> R (in PARK8; under conditions of oxidative
FT stress the variant protein is more toxic and is associated
FT with a higher rate of apoptosis; reduced binding to
FT synaptic vesicles; no loss of interaction with SEC16A;
FT shows an increase in activity in phosphorylation of RAB8A
FT and RAB10; shows decreased WD domain homodimerization;
FT reduced autophosphorylation at Ser-935; dbSNP:rs34778348)"
FT /evidence="ECO:0000269|PubMed:16172858,
FT ECO:0000269|PubMed:17019612, ECO:0000269|PubMed:24687852,
FT ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26824392,
FT ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30635421"
FT /id="VAR_024964"
FT VARIANT 2390
FT /note="V -> M (in PARK8; shows decreased WD domain
FT homodimerization; no effect on kinase activity;
FT dbSNP:rs79546190)"
FT /evidence="ECO:0000269|PubMed:30635421"
FT /id="VAR_082050"
FT VARIANT 2395
FT /note="E -> K (in dbSNP:rs78964014)"
FT /evidence="ECO:0000269|PubMed:18213618"
FT /id="VAR_054749"
FT VARIANT 2397
FT /note="M -> T (in dbSNP:rs3761863)"
FT /evidence="ECO:0000269|PubMed:16157901,
FT ECO:0000269|PubMed:16172858, ECO:0000269|PubMed:22415848"
FT /id="VAR_024965"
FT VARIANT 2439
FT /note="L -> I (in PARK8; shows decreased WD domain
FT homodimerization; no effect on kinase activity;
FT dbSNP:rs72547983)"
FT /evidence="ECO:0000269|PubMed:30635421"
FT /id="VAR_082051"
FT VARIANT 2466
FT /note="L -> H (in PARK8; dbSNP:rs281865057)"
FT /evidence="ECO:0000269|PubMed:18213618"
FT /id="VAR_054750"
FT MUTAGEN 727
FT /note="C->D: Decreased kinase activity. Loss of RAB29-
FT mediated activation and autophosphorylation of S-910, S-
FT 935, S-955, S-973 and S-1292. Decreased membrane
FT association; when associated with G-1441, C-1699 and S-
FT 2019."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 728
FT /note="L->D: Decreased kinase activity. Loss of RAB29-
FT mediated activation and autophosphorylation of S-910, S-
FT 935, S-955, S-973 and S-1292. Decreased membrane
FT association; when associated with G-1441, C-1699 and S-
FT 2019."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 729
FT /note="L->D: Decreased kinase activity. Loss of RAB29-
FT mediated activation and autophosphorylation of S-910, S-
FT 935, S-955, S-973 and S-1292. Decreased membrane
FT association; when associated with G-1441, C-1699 and S-
FT 2019."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 760
FT /note="L->D: Decreased kinase activity and loss of RAB29-
FT mediated activation."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 761
FT /note="L->D: Decreased kinase activity and loss of RAB29-
FT mediated activation."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 762
FT /note="L->D: Decreased kinase activity and loss of RAB29-
FT mediated activation."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 789
FT /note="L->D: No effect on kinase activity and RAB29-
FT mediated activation."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 790
FT /note="L->D: No effect on kinase activity and RAB29-
FT mediated activation."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 791
FT /note="L->D: No effect on kinase activity and RAB29-
FT mediated activation."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 1343
FT /note="T->G: Decreased kinase activity; when associated
FT with Q-1398."
FT /evidence="ECO:0000269|PubMed:18230735"
FT MUTAGEN 1347
FT /note="K->A: GTPase-dead mutant. Loss of interaction with
FT SEC16A and impaired ability to recruit SEC16A to
FT endoplasmic reticulum exit sites."
FT /evidence="ECO:0000269|PubMed:25201882"
FT MUTAGEN 1348
FT /note="T->N: Loss of GTP binding. Inhibits
FT autophosphorylation and RAB10 phosphorylation; when
FT associated with G-1441, C-1699, or S-2019."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 1398
FT /note="R->Q: Decreased kinase activity; when associated
FT with G-1343."
FT /evidence="ECO:0000269|PubMed:18230735"
FT MUTAGEN 1441
FT /note="R->G: Decreased membrane association when associated
FT with D-727, D-728, or D-729. Inhibits autophosphorylation
FT and RAB10 phosphorylation when associated with N-1348 or A-
FT 2017."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 1699
FT /note="Y->C: Decreased membrane association when associated
FT with D-727, D-728, or D-729. Inhibits autophosphorylation
FT and RAB10 phosphorylation when associated with N-1348 or A-
FT 2017."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 1906
FT /note="K->A: Loss of kinase activity. Decreases proteosomal
FT degradation of MAPT; when associated with N-1994 and A-
FT 2017."
FT /evidence="ECO:0000269|PubMed:26014385"
FT MUTAGEN 1994
FT /note="D->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:28720718"
FT MUTAGEN 1994
FT /note="D->N: Loss of kinase activity. No loss of
FT interaction with SEC16A and no loss of ability to recruit
FT SEC16A to endoplasmic reticulum exit sites. Decreases
FT proteosomal degradation of MAPT; when associated with A-
FT 1906 and A-2017."
FT /evidence="ECO:0000269|PubMed:25201882,
FT ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392"
FT MUTAGEN 2017
FT /note="D->A: Loss of kinase activity. Decreases proteosomal
FT degradation of MAPT; when associated with A-1906 and N-
FT 1994. Loss of phosphorylation of RAB10; when associated
FT with G-1441, C-1699, or S-2019."
FT /evidence="ECO:0000269|PubMed:26014385,
FT ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29212815,
FT ECO:0000269|PubMed:30635421"
FT MUTAGEN 2019
FT /note="G->S: Decreased membrane association when associated
FT with D-727, D-728, or D-729. Inhibits autophosphorylation
FT and RAB10 phosphorylation when associated with N-1348 or A-
FT 2017."
FT /evidence="ECO:0000269|PubMed:29212815"
FT MUTAGEN 2343
FT /note="L->D: Decreases WD domain homodimerization. No
FT effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:30635421"
FT MUTAGEN 2344
FT /note="F->A: Decreases WD domain homodimerization. No
FT effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:30635421"
FT MUTAGEN 2345
FT /note="S->D: Decreases WD domain homodimerization. No
FT effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:30635421"
FT MUTAGEN 2346
FT /note="Y->A: Decreases WD domain homodimerization. No
FT effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:30635421"
FT MUTAGEN 2391
FT /note="H->D: Increases kinase activity."
FT /evidence="ECO:0000269|PubMed:30635421"
FT MUTAGEN 2394
FT /note="R->E: Decreases WD domain homodimerization.
FT Increases kinase activity and autophosphorylation at Ser-
FT 1292."
FT /evidence="ECO:0000269|PubMed:30635421"
FT MUTAGEN 2395
FT /note="E->R: Decreases WD domain homodimerization. No
FT effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:30635421"
FT MUTAGEN 2408
FT /note="M->A,E: No effect on WD domain homodimerization. No
FT effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:30635421"
FT MUTAGEN 2409
FT /note="S->A: Decreases WD domain homodimerization."
FT /evidence="ECO:0000269|PubMed:30635421"
FT CONFLICT 212
FT /note="L -> S (in Ref. 1; AAV63975)"
FT /evidence="ECO:0000305"
FT HELIX 560..570
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 571..574
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 585..595
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 603..606
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 607..610
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 626..637
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 638..640
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 645..656
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 660..662
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 663..666
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 667..670
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 671..678
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 689..702
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 706..714
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 715..720
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 722..730
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 740..742
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 744..750
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 755..762
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 763..765
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 768..780
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 784..787
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 788..794
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 798..801
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 802..804
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 815..818
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 819..821
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 834..852
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 913..917
FT /evidence="ECO:0007829|PDB:5MYC"
FT STRAND 986..988
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 998..1000
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1001..1003
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1005..1009
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1010..1012
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1030..1032
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1054..1056
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1057..1059
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1087..1089
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1102..1105
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1111..1113
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1177..1179
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1190..1193
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1200..1202
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1214..1216
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1224..1226
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1242..1244
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1249..1251
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1262..1266
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1272..1274
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1286..1290
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1317..1327
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1329..1332
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1336..1341
FT /evidence="ECO:0007829|PDB:6OJF"
FT HELIX 1347..1354
FT /evidence="ECO:0007829|PDB:6OJF"
FT STRAND 1357..1359
FT /evidence="ECO:0007829|PDB:6OJF"
FT STRAND 1365..1368
FT /evidence="ECO:0007829|PDB:6OJE"
FT STRAND 1370..1378
FT /evidence="ECO:0007829|PDB:6OJF"
FT STRAND 1382..1384
FT /evidence="ECO:0007829|PDB:6OJF"
FT STRAND 1388..1395
FT /evidence="ECO:0007829|PDB:6OJF"
FT HELIX 1398..1402
FT /evidence="ECO:0007829|PDB:6OJF"
FT HELIX 1406..1410
FT /evidence="ECO:0007829|PDB:6OJF"
FT STRAND 1411..1420
FT /evidence="ECO:0007829|PDB:6OJF"
FT HELIX 1421..1423
FT /evidence="ECO:0007829|PDB:6OJF"
FT HELIX 1426..1429
FT /evidence="ECO:0007829|PDB:6OJF"
FT HELIX 1431..1441
FT /evidence="ECO:0007829|PDB:6OJF"
FT STRAND 1447..1452
FT /evidence="ECO:0007829|PDB:6OJF"
FT HELIX 1454..1456
FT /evidence="ECO:0007829|PDB:6OJF"
FT HELIX 1459..1472
FT /evidence="ECO:0007829|PDB:6OJF"
FT TURN 1473..1475
FT /evidence="ECO:0007829|PDB:6OJF"
FT STRAND 1482..1487
FT /evidence="ECO:0007829|PDB:6OJF"
FT STRAND 1490..1492
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1495..1513
FT /evidence="ECO:0007829|PDB:6OJF"
FT HELIX 1518..1520
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1521..1524
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1525..1538
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1547..1549
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1550..1559
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1566..1568
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1569..1578
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1581..1583
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1588..1590
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1591..1594
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1595..1599
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1600..1606
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1607..1612
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1628..1638
FT /evidence="ECO:0007829|PDB:6VP6"
FT HELIX 1645..1653
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1654..1657
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1670..1672
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1686..1692
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1696..1699
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1705..1708
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1709..1711
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1740..1743
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1746..1750
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1765..1770
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1771..1791
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1793..1795
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1811..1814
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1816..1819
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1825..1828
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1829..1833
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1834..1836
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1837..1841
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1849..1851
FT /evidence="ECO:0007829|PDB:6VP7"
FT HELIX 1852..1855
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1857..1861
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1866..1868
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1872..1874
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1881..1883
FT /evidence="ECO:0007829|PDB:6VP6"
FT TURN 1888..1890
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1896..1898
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1901..1906
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1910..1912
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 1914..1924
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1935..1939
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1940..1943
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1944..1948
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1951..1954
FT /evidence="ECO:0007829|PDB:6VP6"
FT HELIX 1955..1961
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1963..1965
FT /evidence="ECO:0007829|PDB:6VP6"
FT HELIX 1970..1985
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 1986..1989
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 1999..2001
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 2013..2015
FT /evidence="ECO:0007829|PDB:6VP6"
FT HELIX 2018..2025
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 2036..2038
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 2041..2044
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 2046..2048
FT /evidence="ECO:0007829|PDB:6VP6"
FT HELIX 2052..2067
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 2071..2076
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 2080..2088
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 2095..2097
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 2105..2107
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 2108..2114
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 2119..2121
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 2125..2130
FT /evidence="ECO:0007829|PDB:7LI4"
FT TURN 2137..2139
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 2142..2145
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2152..2158
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2166..2171
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2173..2183
FT /evidence="ECO:0007829|PDB:6DLO"
FT TURN 2184..2186
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2189..2197
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2199..2207
FT /evidence="ECO:0007829|PDB:6DLO"
FT TURN 2208..2211
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2212..2219
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2224..2230
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2235..2237
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2245..2252
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2256..2258
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 2262..2267
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2270..2276
FT /evidence="ECO:0007829|PDB:6DLO"
FT HELIX 2278..2281
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2282..2284
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 2288..2292
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2300..2304
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2315..2319
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2322..2330
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2335..2338
FT /evidence="ECO:0007829|PDB:6DLO"
FT HELIX 2339..2343
FT /evidence="ECO:0007829|PDB:6DLO"
FT HELIX 2347..2350
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2354..2367
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2371..2376
FT /evidence="ECO:0007829|PDB:6DLO"
FT TURN 2378..2380
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2382..2388
FT /evidence="ECO:0007829|PDB:6DLO"
FT HELIX 2389..2393
FT /evidence="ECO:0007829|PDB:6DLO"
FT TURN 2397..2399
FT /evidence="ECO:0007829|PDB:7LI4"
FT HELIX 2403..2406
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 2414..2419
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2421..2423
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2425..2432
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2434..2437
FT /evidence="ECO:0007829|PDB:6DLO"
FT TURN 2439..2441
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2444..2448
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2451..2462
FT /evidence="ECO:0007829|PDB:6DLO"
FT STRAND 2468..2475
FT /evidence="ECO:0007829|PDB:6DLO"
FT HELIX 2482..2484
FT /evidence="ECO:0007829|PDB:7LI4"
FT STRAND 2491..2497
FT /evidence="ECO:0007829|PDB:6DLO"
FT HELIX 2500..2526
FT /evidence="ECO:0007829|PDB:7LI4"
SQ SEQUENCE 2527 AA; 286103 MW; 26142A0CECBBC3F4 CRC64;
MASGSCQGCE EDEETLKKLI VRLNNVQEGK QIETLVQILE DLLVFTYSER ASKLFQGKNI
HVPLLIVLDS YMRVASVQQV GWSLLCKLIE VCPGTMQSLM GPQDVGNDWE VLGVHQLILK
MLTVHNASVN LSVIGLKTLD LLLTSGKITL LILDEESDIF MLIFDAMHSF PANDEVQKLG
CKALHVLFER VSEEQLTEFV ENKDYMILLS ALTNFKDEEE IVLHVLHCLH SLAIPCNNVE
VLMSGNVRCY NIVVEAMKAF PMSERIQEVS CCLLHRLTLG NFFNILVLNE VHEFVVKAVQ
QYPENAALQI SALSCLALLT ETIFLNQDLE EKNENQENDD EGEEDKLFWL EACYKALTWH
RKNKHVQEAA CWALNNLLMY QNSLHEKIGD EDGHFPAHRE VMLSMLMHSS SKEVFQASAN
ALSTLLEQNV NFRKILLSKG IHLNVLELMQ KHIHSPEVAE SGCKMLNHLF EGSNTSLDIM
AAVVPKILTV MKRHETSLPV QLEALRAILH FIVPGMPEES REDTEFHHKL NMVKKQCFKN
DIHKLVLAAL NRFIGNPGIQ KCGLKVISSI VHFPDALEML SLEGAMDSVL HTLQMYPDDQ
EIQCLGLSLI GYLITKKNVF IGTGHLLAKI LVSSLYRFKD VAEIQTKGFQ TILAILKLSA
SFSKLLVHHS FDLVIFHQMS SNIMEQKDQQ FLNLCCKCFA KVAMDDYLKN VMLERACDQN
NSIMVECLLL LGADANQAKE GSSLICQVCE KESSPKLVEL LLNSGSREQD VRKALTISIG
KGDSQIISLL LRRLALDVAN NSICLGGFCI GKVEPSWLGP LFPDKTSNLR KQTNIASTLA
RMVIRYQMKS AVEEGTASGS DGNFSEDVLS KFDEWTFIPD SSMDSVFAQS DDLDSEGSEG
SFLVKKKSNS ISVGEFYRDA VLQRCSPNLQ RHSNSLGPIF DHEDLLKRKR KILSSDDSLR
SSKLQSHMRH SDSISSLASE REYITSLDLS ANELRDIDAL SQKCCISVHL EHLEKLELHQ
NALTSFPQQL CETLKSLTHL DLHSNKFTSF PSYLLKMSCI ANLDVSRNDI GPSVVLDPTV
KCPTLKQFNL SYNQLSFVPE NLTDVVEKLE QLILEGNKIS GICSPLRLKE LKILNLSKNH
ISSLSENFLE ACPKVESFSA RMNFLAAMPF LPPSMTILKL SQNKFSCIPE AILNLPHLRS
LDMSSNDIQY LPGPAHWKSL NLRELLFSHN QISILDLSEK AYLWSRVEKL HLSHNKLKEI
PPEIGCLENL TSLDVSYNLE LRSFPNEMGK LSKIWDLPLD ELHLNFDFKH IGCKAKDIIR
FLQQRLKKAV PYNRMKLMIV GNTGSGKTTL LQQLMKTKKS DLGMQSATVG IDVKDWPIQI
RDKRKRDLVL NVWDFAGREE FYSTHPHFMT QRALYLAVYD LSKGQAEVDA MKPWLFNIKA
RASSSPVILV GTHLDVSDEK QRKACMSKIT KELLNKRGFP AIRDYHFVNA TEESDALAKL
RKTIINESLN FKIRDQLVVG QLIPDCYVEL EKIILSERKN VPIEFPVIDR KRLLQLVREN
QLQLDENELP HAVHFLNESG VLLHFQDPAL QLSDLYFVEP KWLCKIMAQI LTVKVEGCPK
HPKGIISRRD VEKFLSKKRK FPKNYMSQYF KLLEKFQIAL PIGEEYLLVP SSLSDHRPVI
ELPHCENSEI IIRLYEMPYF PMGFWSRLIN RLLEISPYML SGRERALRPN RMYWRQGIYL
NWSPEAYCLV GSEVLDNHPE SFLKITVPSC RKGCILLGQV VDHIDSLMEE WFPGLLEIDI
CGEGETLLKK WALYSFNDGE EHQKILLDDL MKKAEEGDLL VNPDQPRLTI PISQIAPDLI
LADLPRNIML NNDELEFEQA PEFLLGDGSF GSVYRAAYEG EEVAVKIFNK HTSLRLLRQE
LVVLCHLHHP SLISLLAAGI RPRMLVMELA SKGSLDRLLQ QDKASLTRTL QHRIALHVAD
GLRYLHSAMI IYRDLKPHNV LLFTLYPNAA IIAKIADYGI AQYCCRMGIK TSEGTPGFRA
PEVARGNVIY NQQADVYSFG LLLYDILTTG GRIVEGLKFP NEFDELEIQG KLPDPVKEYG
CAPWPMVEKL IKQCLKENPQ ERPTSAQVFD ILNSAELVCL TRRILLPKNV IVECMVATHH
NSRNASIWLG CGHTDRGQLS FLDLNTEGYT SEEVADSRIL CLALVHLPVE KESWIVSGTQ
SGTLLVINTE DGKKRHTLEK MTDSVTCLYC NSFSKQSKQK NFLLVGTADG KLAIFEDKTV
KLKGAAPLKI LNIGNVSTPL MCLSESTNST ERNVMWGGCG TKIFSFSNDF TIQKLIETRT
SQLFSYAAFS DSNIITVVVD TALYIAKQNS PVVEVWDKKT EKLCGLIDCV HFLREVMVKE
NKESKHKMSY SGRVKTLCLQ KNTALWIGTG GGHILLLDLS TRRLIRVIYN FCNSVRVMMT
AQLGSLKNVM LVLGYNRKNT EGTQKQKEIQ SCLTVWDINL PHEVQNLEKH IEVRKELAEK
MRRTSVE
