LRRK1_HUMAN
ID LRRK1_HUMAN Reviewed; 2015 AA.
AC Q38SD2; Q6NVH5; Q6NYC0; Q6ZNL9; Q6ZNM9; Q96JN5; Q9H5S3;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Leucine-rich repeat serine/threonine-protein kinase 1;
DE EC=2.7.11.1;
GN Name=LRRK1 {ECO:0000312|EMBL:AAY67799.1};
GN Synonyms=KIAA1790 {ECO:0000312|EMBL:BAB47419.1};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAH68080.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1576-2015 (ISOFORM 1).
RC TISSUE=Pancreas {ECO:0000312|EMBL:AAH68080.1}, and
RC Skin {ECO:0000312|EMBL:AAH66655.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAY67799.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 28-2015 (ISOFORM 1), FUNCTION, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, GTP-BINDING, AND
RP MUTAGENESIS OF LYS-651; LYS-746; PHE-1022; LYS-1270 AND ILE-1412.
RX PubMed=16243488; DOI=10.1016/j.cellsig.2005.08.015;
RA Korr D., Toschi L., Donner P., Pohlenz H.-P., Kreft B., Weiss B.;
RT "LRRK1 protein kinase activity is stimulated upon binding of GTP to its Roc
RT domain.";
RL Cell. Signal. 18:910-920(2006).
RN [4] {ECO:0000305, ECO:0000312|EMBL:BAC85472.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 145-364 AND 905-2015 (ISOFORM 1).
RC TISSUE=Lung {ECO:0000312|EMBL:BAB15547.1},
RC Macrophage {ECO:0000312|EMBL:BAC85472.1}, and
RC Spleen {ECO:0000312|EMBL:BAC85125.1};
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5] {ECO:0000305, ECO:0000312|EMBL:BAB47419.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 646-2015 (ISOFORM 1).
RC TISSUE=Brain {ECO:0000312|EMBL:BAB47419.1};
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [6]
RP SUBUNIT, AND LACK OF 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 [7]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-1803; PHE-1824; ASN-1847 AND GLY-1927.
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).
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:16243488};
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:16243488};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16243488};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:16243488};
CC -!- ACTIVITY REGULATION: Binding of GTP stimulates kinase activity.
CC {ECO:0000269|PubMed:16243488}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22952686}.
CC -!- INTERACTION:
CC Q38SD2; P00519: ABL1; NbExp=3; IntAct=EBI-1050422, EBI-375543;
CC Q38SD2; Q9UL15: BAG5; NbExp=3; IntAct=EBI-1050422, EBI-356517;
CC Q38SD2; P53355: DAPK1; NbExp=2; IntAct=EBI-1050422, EBI-358616;
CC Q38SD2; P00533: EGFR; NbExp=2; IntAct=EBI-1050422, EBI-297353;
CC Q38SD2; Q38SD2: LRRK1; NbExp=3; IntAct=EBI-1050422, EBI-1050422;
CC Q38SD2; Q5S007: LRRK2; NbExp=5; IntAct=EBI-1050422, EBI-5323863;
CC Q38SD2-1; Q96SN8: CDK5RAP2; NbExp=2; IntAct=EBI-16165296, EBI-308374;
CC Q38SD2-2; P06756: ITGAV; NbExp=3; IntAct=EBI-25929016, EBI-298282;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16243488}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q38SD2-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334};
CC IsoId=Q38SD2-2; Sequence=VSP_040119, VSP_040120;
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. ROCO subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY67799.1; Type=Miscellaneous discrepancy; Note=The cDNA contains a duplication of exon 3.; Evidence={ECO:0000305};
CC Sequence=BAB15547.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC85472.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AC090907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC066655; AAH66655.1; -; mRNA.
DR EMBL; BC068080; AAH68080.1; -; mRNA.
DR EMBL; DQ013130; AAY67799.1; ALT_SEQ; mRNA.
DR EMBL; AK026772; BAB15547.1; ALT_INIT; mRNA.
DR EMBL; AK130975; BAC85472.1; ALT_INIT; mRNA.
DR EMBL; AK131075; BAC85125.1; -; mRNA.
DR EMBL; AB058693; BAB47419.1; -; mRNA.
DR CCDS; CCDS42086.1; -. [Q38SD2-1]
DR RefSeq; NP_078928.3; NM_024652.5. [Q38SD2-1]
DR RefSeq; XP_011520314.1; XM_011522012.2. [Q38SD2-1]
DR RefSeq; XP_011520315.1; XM_011522013.2. [Q38SD2-1]
DR AlphaFoldDB; Q38SD2; -.
DR SMR; Q38SD2; -.
DR BioGRID; 122823; 89.
DR DIP; DIP-50235N; -.
DR IntAct; Q38SD2; 96.
DR STRING; 9606.ENSP00000373600; -.
DR iPTMnet; Q38SD2; -.
DR PhosphoSitePlus; Q38SD2; -.
DR BioMuta; LRRK1; -.
DR DMDM; 313104220; -.
DR EPD; Q38SD2; -.
DR jPOST; Q38SD2; -.
DR MassIVE; Q38SD2; -.
DR MaxQB; Q38SD2; -.
DR PaxDb; Q38SD2; -.
DR PeptideAtlas; Q38SD2; -.
DR PRIDE; Q38SD2; -.
DR ProteomicsDB; 61644; -. [Q38SD2-1]
DR ProteomicsDB; 61645; -. [Q38SD2-2]
DR ABCD; Q38SD2; 2 sequenced antibodies.
DR Antibodypedia; 2085; 202 antibodies from 29 providers.
DR DNASU; 79705; -.
DR Ensembl; ENST00000388948.8; ENSP00000373600.3; ENSG00000154237.13. [Q38SD2-1]
DR Ensembl; ENST00000532029.6; ENSP00000433268.2; ENSG00000154237.13. [Q38SD2-2]
DR GeneID; 79705; -.
DR KEGG; hsa:79705; -.
DR MANE-Select; ENST00000388948.8; ENSP00000373600.3; NM_024652.6; NP_078928.3.
DR UCSC; uc002bwq.2; human. [Q38SD2-1]
DR CTD; 79705; -.
DR DisGeNET; 79705; -.
DR GeneCards; LRRK1; -.
DR HGNC; HGNC:18608; LRRK1.
DR HPA; ENSG00000154237; Low tissue specificity.
DR MalaCards; LRRK1; -.
DR MIM; 610986; gene.
DR neXtProt; NX_Q38SD2; -.
DR OpenTargets; ENSG00000154237; -.
DR Orphanet; 500548; Osteosclerotic metaphyseal dysplasia.
DR PharmGKB; PA134892363; -.
DR VEuPathDB; HostDB:ENSG00000154237; -.
DR eggNOG; KOG0192; Eukaryota.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000160363; -.
DR HOGENOM; CLU_001731_0_0_1; -.
DR InParanoid; Q38SD2; -.
DR OMA; CHICAAA; -.
DR OrthoDB; 14978at2759; -.
DR PhylomeDB; Q38SD2; -.
DR TreeFam; TF313679; -.
DR PathwayCommons; Q38SD2; -.
DR SignaLink; Q38SD2; -.
DR SIGNOR; Q38SD2; -.
DR BioGRID-ORCS; 79705; 13 hits in 1103 CRISPR screens.
DR ChiTaRS; LRRK1; human.
DR GeneWiki; LRRK1; -.
DR GenomeRNAi; 79705; -.
DR Pharos; Q38SD2; Tbio.
DR PRO; PR:Q38SD2; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q38SD2; protein.
DR Bgee; ENSG00000154237; Expressed in lymph node and 134 other tissues.
DR ExpressionAtlas; Q38SD2; baseline and differential.
DR Genevisible; Q38SD2; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IBA:GO_Central.
DR GO; GO:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0036035; P:osteoclast development; IEA:Ensembl.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IGI:ParkinsonsUK-UCL.
DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR Gene3D; 3.80.10.10; -; 3.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR032171; COR.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR001611; Leu-rich_rpt.
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; IPR020859; ROC_dom.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF16095; COR; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00248; ANK; 3.
DR SMART; SM00369; LRR_TYP; 8.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS51450; LRR; 11.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS51424; ROC; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; ATP-binding; Cytoplasm; GTP-binding;
KW Kinase; Leucine-rich repeat; Magnesium; Manganese; Metal-binding;
KW Nucleotide-binding; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..2015
FT /note="Leucine-rich repeat serine/threonine-protein kinase
FT 1"
FT /id="PRO_0000233377"
FT REPEAT 86..116
FT /note="ANK 1"
FT REPEAT 119..148
FT /note="ANK 2"
FT REPEAT 152..182
FT /note="ANK 3"
FT REPEAT 193..222
FT /note="ANK 4"
FT REPEAT 279..300
FT /note="LRR 1"
FT REPEAT 303..324
FT /note="LRR 2"
FT REPEAT 330..351
FT /note="LRR 3"
FT REPEAT 353..374
FT /note="LRR 4"
FT REPEAT 381..402
FT /note="LRR 5"
FT REPEAT 405..426
FT /note="LRR 6"
FT REPEAT 427..447
FT /note="LRR 7"
FT REPEAT 451..472
FT /note="LRR 8"
FT REPEAT 474..495
FT /note="LRR 9"
FT REPEAT 498..519
FT /note="LRR 10"
FT REPEAT 549..570
FT /note="LRR 11"
FT REPEAT 572..594
FT /note="LRR 12"
FT REPEAT 596..617
FT /note="LRR 13"
FT DOMAIN 632..826
FT /note="Roc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00758"
FT DOMAIN 1242..1525
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 26..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1788..1810
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1841..1899
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1841..1874
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1386
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1248..1256
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1270
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 255..264
FT /note="ALRVKWSHLR -> VSSHCLWSVF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040119"
FT VAR_SEQ 265..2015
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040120"
FT VARIANT 1803
FT /note="A -> T"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040674"
FT VARIANT 1824
FT /note="L -> F"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040675"
FT VARIANT 1847
FT /note="S -> N"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040676"
FT VARIANT 1927
FT /note="D -> G"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040677"
FT MUTAGEN 651
FT /note="K->A: Loss of GTP/GDP-binding."
FT /evidence="ECO:0000269|PubMed:16243488"
FT MUTAGEN 746
FT /note="K->G: No effect on GTP-binding but reduction in
FT subsequent stimulation of kinase activity."
FT /evidence="ECO:0000269|PubMed:16243488"
FT MUTAGEN 1022
FT /note="F->C: No effect on GTP-binding but loss of
FT subsequent stimulation of kinase activity."
FT /evidence="ECO:0000269|PubMed:16243488"
FT MUTAGEN 1270
FT /note="K->W: Loss of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:16243488"
FT MUTAGEN 1412
FT /note="I->T: No effect on GTP-binding but reduction in
FT subsequent stimulation of kinase activity."
FT /evidence="ECO:0000269|PubMed:16243488"
FT CONFLICT 203
FT /note="K -> R (in Ref. 4; BAC85472)"
FT /evidence="ECO:0000305"
FT CONFLICT 1938
FT /note="G -> E (in Ref. 2; AAH66655 and 5; BAB47419)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2015 AA; 225393 MW; 38E77EDC7C84583B CRC64;
MAGMSQRPPS MYWCVGPEES AVCPERAMET LNGAGDTGGK PSTRGGDPAA RSRRTEGIRA
AYRRGDRGGA RDLLEEACDQ CASQLEKGQL LSIPAAYGDL EMVRYLLSKR LVELPTEPTD
DNPAVVAAYF GHTAVVQELL ESLPGPCSPQ RLLNWMLALA CQRGHLGVVK LLVLTHGADP
ESYAVRKNEF PVIVRLPLYA AIKSGNEDIA IFLLRHGAYF CSYILLDSPD PSKHLLRKYF
IEASPLPSSY PGKTALRVKW SHLRLPWVDL DWLIDISCQI TELDLSANCL ATLPSVIPWG
LINLRKLNLS DNHLGELPGV QSSDEIICSR LLEIDISSNK LSHLPPGFLH LSKLQKLTAS
KNCLEKLFEE ENATNWIGLR KLQELDISDN KLTELPALFL HSFKSLNSLN VSRNNLKVFP
DPWACPLKCC KASRNALECL PDKMAVFWKN HLKDVDFSEN ALKEVPLGLF QLDALMFLRL
QGNQLAALPP QEKWTCRQLK TLDLSRNQLG KNEDGLKTKR IAFFTTRGRQ RSGTEAASVL
EFPAFLSESL EVLCLNDNHL DTVPPSVCLL KSLSELYLGN NPGLRELPPE LGQLGNLWQL
DTEDLTISNV PAEIQKEGPK AMLSYLRAQL RKAEKCKLMK MIIVGPPRQG KSTLLEILQT
GRAPQVVHGE ATIRTTKWEL QRPAGSRAKV ESVEFNVWDI GGPASMATVN QCFFTDKALY
VVVWNLALGE EAVANLQFWL LNIEAKAPNA VVLVVGTHLD LIEAKFRVER IATLRAYVLA
LCRSPSGSRA TGFPDITFKH LHEISCKSLE GQEGLRQLIF HVTCSMKDVG STIGCQRLAG
RLIPRSYLSL QEAVLAEQQR RSRDDDVQYL TDRQLEQLVE QTPDNDIKDY EDLQSAISFL
IETGTLLHFP DTSHGLRNLY FLDPIWLSEC LQRIFNIKGS RSVAKNGVIR AEDLRMLLVG
TGFTQQTEEQ YFQFLAKFEI ALPVANDSYL LPHLLPSKPG LDTHGMRHPT ANTIQRVFKM
SFVPVGFWQR FIARMLISLA EMDLQLFENK KNTKSRNRKV TIYSFTGNQR NRCSTFRVKR
NQTIYWQEGL LVTFDGGYLS VESSDVNWKK KKSGGMKIVC QSEVRDFSAM AFITDHVNSL
IDQWFPALTA TESDGTPLME QYVPCPVCET AWAQHTDPSE KSEDVQYFDM EDCVLTAIER
DFISCPRHPD LPVPLQELVP ELFMTDFPAR LFLENSKLEH SEDEGSVLGQ GGSGTVIYRA
RYQGQPVAVK RFHIKKFKNF ANVPADTMLR HLRATDAMKN FSEFRQEASM LHALQHPCIV
ALIGISIHPL CFALELAPLS SLNTVLSENA RDSSFIPLGH MLTQKIAYQI ASGLAYLHKK
NIIFCDLKSD NILVWSLDVK EHINIKLSDY GISRQSFHEG ALGVEGTPGY QAPEIRPRIV
YDEKVDMFSY GMVLYELLSG QRPALGHHQL QIAKKLSKGI RPVLGQPEEV QFRRLQALMM
ECWDTKPEKR PLALSVVSQM KDPTFATFMY ELCCGKQTAF FSSQGQEYTV VFWDGKEESR
NYTVVNTEKG LMEVQRMCCP GMKVSCQLQV QRSLWTATED QKIYIYTLKG MCPLNTPQQA
LDTPAVVTCF LAVPVIKKNS YLVLAGLADG LVAVFPVVRG TPKDSCSYLC SHTANRSKFS
IADEDARQNP YPVKAMEVVN SGSEVWYSNG PGLLVIDCAS LEICRRLEPY MAPSMVTSVV
CSSEGRGEEV VWCLDDKANS LVMYHSTTYQ LCARYFCGVP SPLRDMFPVR PLDTEPPAAS
HTANPKVPEG DSIADVSIMY SEELGTQILI HQESLTDYCS MSSYSSSPPR QAARSPSSLP
SSPASSSSVP FSTDCEDSDM LHTPGAASDR SEHDLTPMDG ETFSQHLQAV KILAVRDLIW
VPRRGGDVIV IGLEKDSGAQ RGRVIAVLKA RELTPHGVLV DAAVVAKDTV VCTFENENTE
WCLAVWRGWG AREFDIFYQS YEELGRLEAC TRKRR
