ID BCR_HUMAN Reviewed; 1271 AA. AC P11274; P78501; Q12842; Q4LE80; Q6NZI3; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 03-APR-2007, sequence version 2. DT 27-MAR-2024, entry version 252. DE RecName: Full=Breakpoint cluster region protein {ECO:0000305}; DE EC=2.7.11.1 {ECO:0000269|PubMed:1657398}; DE AltName: Full=Renal carcinoma antigen NY-REN-26; GN Name=BCR {ECO:0000312|HGNC:HGNC:1014}; Synonyms=BCR1, D22S11; 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] (ISOFORM 2), AND VARIANT SER-796. RX PubMed=3285291; RA Lifshitz B., Fainstein E., Marcelle C., Shtivelman E., Amson R., Gale R.P., RA Canaani E.; RT "bcr genes and transcripts."; RL Oncogene 2:113-117(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CHROMOSOMAL TRANSLOCATION. RX PubMed=7665185; DOI=10.1006/geno.1995.1008; RA Chissoe S.L., Bodenteich A., Wang Y.-F., Wang Y.-P., Burian D., RA Clifton S.W., Crabtree J., Freeman A., Iyer K., Jian L., Ma Y., RA McLaury H.-J., Pan H.-Q., Sarhan O.H., Toth S., Wang Z., Zhang G., RA Heisterkamp N., Groffen J., Roe B.A.; RT "Sequence and analysis of the human ABL gene, the BCR gene, and regions RT involved in the Philadelphia chromosomal translocation."; RL Genomics 27:67-82(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-796. RC TISSUE=Brain; RA Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., RA Okazaki N., Koga H., Nagase T., Ohara O.; RT "Preparation of a set of expression-ready clones of mammalian long cDNAs RT encoding large proteins by the ORF trap cloning method."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-872, CHROMOSOMAL TRANSLOCATION, INVOLVEMENT RP IN CML, AND VARIANT SER-796. RX PubMed=3107980; DOI=10.1002/j.1460-2075.1987.tb04727.x; RA Hariharan I.K., Adams J.M.; RT "cDNA sequence for human bcr, the gene that translocates to the abl RT oncogene in chronic myeloid leukaemia."; RL EMBO J. 6:115-119(1987). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-693, AND INVOLVEMENT IN CML. RX PubMed=3540951; DOI=10.1073/pnas.83.24.9768; RA Mes-Masson A.-M., McLaughlin J., Daley G.Q., Paskind M., Witte O.N.; RT "Overlapping cDNA clones define the complete coding region for the P210c- RT abl gene product associated with chronic myelogenous leukemia cells RT containing the Philadelphia chromosome."; RL Proc. Natl. Acad. Sci. U.S.A. 83:9768-9772(1986). RN [6] RP ERRATUM OF PUBMED:3540951, AND SEQUENCE REVISION. RA Mes-Masson A.M., McLaughlin J., Daley G.Q., Paskind M., Witte O.N.; RL Proc. Natl. Acad. Sci. U.S.A. 84:2507-2507(1987). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 683-1271 (ISOFORM 1). RX PubMed=2989703; DOI=10.1038/315758a0; RA Heisterkamp N., Stam K., Groffen J., de Klein A., Grosveld G.; RT "Structural organization of the bcr gene and its role in the Ph' RT translocation."; RL Nature 315:758-761(1985). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-46 AND 275-426. RX PubMed=2263470; DOI=10.1093/nar/18.23.7119; RA Zhu Q.S., Heisterkamp N., Groffen J.; RT "Unique organization of the human BCR gene promoter."; RL Nucleic Acids Res. 18:7119-7125(1990). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 56-426. RX PubMed=2825022; DOI=10.1038/330386a0; RA Fainstein E., Marcelle C., Rosner A., Canaani E., Gale R.P., Dreazen O., RA Smith S.D., Croce C.M.; RT "A new fused transcript in Philadelphia chromosome positive acute RT lymphocytic leukaemia."; RL Nature 330:386-388(1987). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 362-438, AND ALTERNATIVE SPLICING. RX PubMed=2915904; RA Romero P., Beran M., Shtalrid M., Andersson B., Talpaz M., Blick M.; RT "Alternative 5' end of the bcr-abl transcript in chronic myelogenous RT leukemia."; RL Oncogene 4:93-98(1989). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 670-842, INVOLVEMENT IN CML, AND RP VARIANT SER-796. RX PubMed=2407300; RA Selleri L., von Lindern M., Hermans A., Meijer D., Torelli G., Grosveld G.; RT "Chronic myeloid leukemia may be associated with several bcr-abl RT transcripts including the acute lymphoid leukemia-type 7 kb transcript."; RL Blood 75:1146-1153(1990). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-4. RX PubMed=1900918; DOI=10.1128/mcb.11.4.1854-1860.1991; RA Shah N.P., Witte O.N., Denny C.T.; RT "Characterization of the BCR promoter in Philadelphia chromosome-positive RT and -negative cell lines."; RL Mol. Cell. Biol. 11:1854-1860(1991). RN [13] RP FUNCTION. RX PubMed=1903516; DOI=10.1038/351400a0; RA Diekmann D., Brill S., Garrett M.D., Totty N., Hsuan J., Monfries C., RA Hall C., Lim L., Hall A.; RT "Bcr encodes a GTPase-activating protein for p21rac."; RL Nature 351:400-402(1991). RN [14] RP INTERACTION WITH ABL1 SH2-DOMAIN. RX PubMed=1712671; DOI=10.1016/0092-8674(91)90148-r; RA Pendergast A.M., Muller A.J., Havlik M.H., Maru Y., Witte O.N.; RT "BCR sequences essential for transformation by the BCR-ABL oncogene bind to RT the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner."; RL Cell 66:161-171(1991). RN [15] RP FUNCTION AS PROTEIN KINASE, AND CATALYTIC ACTIVITY. RX PubMed=1657398; DOI=10.1016/0092-8674(91)90521-y; RA Maru Y., Witte O.N.; RT "The BCR gene encodes a novel serine/threonine kinase activity within a RT single exon."; RL Cell 67:459-468(1991). RN [16] RP FUNCTION, AND DOMAIN. RX PubMed=7479768; DOI=10.1073/pnas.92.22.10282; RA Chuang T.H., Xu X., Kaartinen V., Heisterkamp N., Groffen J., Bokoch G.M.; RT "Abr and Bcr are multifunctional regulators of the Rho GTP-binding protein RT family."; RL Proc. Natl. Acad. Sci. U.S.A. 92:10282-10286(1995). RN [17] RP PHOSPHORYLATION AT TYR-177 BY HCK, MUTAGENESIS OF TYR-177, AND INTERACTION RP WITH HCK AND GRB2. RX PubMed=9407116; DOI=10.1074/jbc.272.52.33260; RA Warmuth M., Bergmann M., Priess A., Hauslmann K., Emmerich B., Hallek M.; RT "The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent RT mechanism and phosphorylates the Grb2-binding site of Bcr."; RL J. Biol. Chem. 272:33260-33270(1997). RN [18] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal-cell RT carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1264, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=15144186; DOI=10.1021/ac035352d; RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., RA Peters E.C.; RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [20] RP INTERACTION WITH FES/FPS; ABL1; PIK3R1 AND GRB2, MUTAGENESIS OF TYR-177, RP PHOSPHORYLATION AT TYR-246, AND FUNCTION. RX PubMed=15302586; DOI=10.1016/j.yexcr.2004.05.010; RA Laurent C.E., Smithgall T.E.; RT "The c-Fes tyrosine kinase cooperates with the breakpoint cluster region RT protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent RT manner."; RL Exp. Cell Res. 299:188-198(2004). RN [21] RP INTERACTION WITH PDZK1, AND MUTAGENESIS OF 1269-THR--GLU-1271 AND VAL-1271. RX PubMed=15494376; DOI=10.1242/jcs.01472; RA Malmberg E.K., Andersson C.X., Gentzsch M., Chen J.H., Mengos A., Cui L., RA Hansson G.C., Riordan J.R.; RT "Bcr (breakpoint cluster region) protein binds to PDZ-domains of scaffold RT protein PDZK1 and vesicle coat protein Mint3."; RL J. Cell Sci. 117:5535-5541(2004). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [23] RP FUNCTION, AND MUTAGENESIS OF ARG-1090 AND ASN-1202. RX PubMed=17116687; DOI=10.1128/mcb.00756-06; RA Cho Y.J., Cunnick J.M., Yi S.J., Kaartinen V., Groffen J., Heisterkamp N.; RT "Abr and Bcr, two homologous Rac GTPase-activating proteins, control RT multiple cellular functions of murine macrophages."; RL Mol. Cell. Biol. 27:899-911(2007). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-459, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-177; SER-459 AND SER-1264, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122; SER-215 AND SER-459, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [29] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122; SER-139; SER-202; RP SER-215; SER-222; SER-356; SER-377; SER-459; SER-463; SER-473; SER-488; RP TYR-554; THR-641; TYR-644; THR-693 AND SER-894, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-459, AND IDENTIFICATION BY RP 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 [32] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 3-72, AND HOMOTETRAMERIZATION. RX PubMed=11780146; DOI=10.1038/nsb747; RA Zhao X., Ghaffari S., Lodish H., Malashkevich V.N., Kim P.S.; RT "Structure of the Bcr-Abl oncoprotein oligomerization domain."; RL Nat. Struct. Biol. 9:117-120(2002). RN [33] RP FUNCTION, INTERACTION WITH DLG4, AND MUTAGENESIS OF VAL-1271. RX PubMed=20962234; DOI=10.1523/jneurosci.1711-10.2010; RA Oh D., Han S., Seo J., Lee J.R., Choi J., Groffen J., Kim K., Cho Y.S., RA Choi H.S., Shin H., Woo J., Won H., Park S.K., Kim S.Y., Jo J., RA Whitcomb D.J., Cho K., Kim H., Bae Y.C., Heisterkamp N., Choi S.Y., Kim E.; RT "Regulation of synaptic Rac1 activity, long-term potentiation maintenance, RT and learning and memory by BCR and ABR Rac GTPase-activating proteins."; RL J. Neurosci. 30:14134-14144(2010). RN [34] RP FUNCTION, AND MUTAGENESIS OF 689-ASN-GLU-690. RX PubMed=23940119; DOI=10.1083/jcb.201304133; RA Dubash A.D., Koetsier J.L., Amargo E.V., Najor N.A., Harmon R.M., RA Green K.J.; RT "The GEF Bcr activates RhoA/MAL signaling to promote keratinocyte RT differentiation via desmoglein-1."; RL J. Cell Biol. 202:653-666(2013). RN [35] RP INTERACTION WITH SH2D5. RX PubMed=25331951; DOI=10.1074/jbc.m114.615112; RA Gray E.J., Petsalaki E., James D.A., Bagshaw R.D., Stacey M.M., Rocks O., RA Gingras A.C., Pawson T.; RT "src homology 2 domain containing protein 5 (sh2d5) binds the breakpoint RT cluster region protein, BCR, and regulates levels of Rac1-GTP."; RL J. Biol. Chem. 289:35397-35408(2014). RN [36] RP VARIANTS [LARGE SCALE ANALYSIS] PRO-400; MET-413; GLU-752; SER-796; RP CYS-910; ILE-949; LYS-1037; MET-1091; ALA-1096; GLY-1104; ASN-1106; RP THR-1149; LYS-1161; GLU-1187; MET-1189; GLY-1204 AND ARG-1235. 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 -!- FUNCTION: Protein with a unique structure having two opposing CC regulatory activities toward small GTP-binding proteins. The C-terminus CC is a GTPase-activating protein (GAP) domain which stimulates GTP CC hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of CC GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the CC active GTP-bound form (PubMed:7479768, PubMed:1903516, CC PubMed:17116687). The central Dbl homology (DH) domain functions as CC guanine nucleotide exchange factor (GEF) that modulates the GTPases CC CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 CC from the GDP-bound to the GTP-bound form (PubMed:7479768, CC PubMed:23940119). The amino terminus contains an intrinsic kinase CC activity (PubMed:1657398). Functions as an important negative regulator CC of neuronal RAC1 activity (By similarity). Regulates macrophage CC functions such as CSF1-directed motility and phagocytosis through the CC modulation of RAC1 activity (PubMed:17116687). Plays a major role as a CC RHOA GEF in keratinocytes being involved in focal adhesion formation CC and keratinocyte differentiation (PubMed:23940119). CC {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:1657398, CC ECO:0000269|PubMed:17116687, ECO:0000269|PubMed:1903516, CC ECO:0000269|PubMed:23940119, ECO:0000269|PubMed:7479768}. 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:1657398}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000269|PubMed:1657398}; 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:1657398}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609; CC Evidence={ECO:0000269|PubMed:1657398}; CC -!- SUBUNIT: Homotetramer. Interacts with PDZK1 (PubMed:15494376). May CC interact with CCPG1 (By similarity). Interacts with FES/FPS, ABL1, CC PIK3R1 and GRB2 (PubMed:15302586, PubMed:1712671, PubMed:9407116). CC Interacts with HCK (PubMed:9407116). Interacts with SH2D5 CC (PubMed:25331951). Interacts with DLG4 (PubMed:20962234). CC {ECO:0000250|UniProtKB:Q6PAJ1, ECO:0000269|PubMed:15302586, CC ECO:0000269|PubMed:15494376, ECO:0000269|PubMed:1712671, CC ECO:0000269|PubMed:20962234, ECO:0000269|PubMed:25331951, CC ECO:0000269|PubMed:9407116}. CC -!- INTERACTION: CC P11274; P62993: GRB2; NbExp=9; IntAct=EBI-712838, EBI-401755; CC P11274; Q6ZV89-1: SH2D5; NbExp=2; IntAct=EBI-712838, EBI-15101685; CC P11274; Q9H2K2: TNKS2; NbExp=3; IntAct=EBI-712838, EBI-4398527; CC P11274; A2AM67: Sh2d5; Xeno; NbExp=7; IntAct=EBI-712838, EBI-15101945; CC P11274; Q8JZW5: Sh2d5; Xeno; NbExp=2; IntAct=EBI-712838, EBI-15101675; CC P11274-1; P18031: PTPN1; NbExp=3; IntAct=EBI-8658094, EBI-968788; CC -!- SUBCELLULAR LOCATION: Postsynaptic density CC {ECO:0000250|UniProtKB:Q6PAJ1}. Cell projection, dendritic spine CC {ECO:0000250|UniProtKB:Q6PAJ1}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q6PAJ1}. Synapse {ECO:0000250|UniProtKB:F1LXF1}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P11274-1; Sequence=Displayed; CC Name=2; CC IsoId=P11274-2; Sequence=VSP_024352; CC -!- DOMAIN: The region involved in binding to ABL1 SH2-domain is rich in CC serine residues and needs to be Ser/Thr phosphorylated prior to SH2 CC binding. This region is essential for the activation of the ABL1 CC tyrosine kinase and transforming potential of the chimeric BCR-ABL CC oncogene. CC -!- DOMAIN: The DH domain is involved in interaction with CCPG1. CC {ECO:0000250|UniProtKB:Q6PAJ1}. CC -!- DOMAIN: The amino terminus contains an intrinsic kinase activity. The CC central Dbl homology (DH) domain functions as a guanine nucleotide CC exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. CC Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to CC the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates CC GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique CC structure having two opposing regulatory activities toward small GTP- CC binding proteins. {ECO:0000305|PubMed:7479768}. CC -!- PTM: Autophosphorylated. Phosphorylated by FES/FPS on tyrosine CC residues, leading to down-regulation of the BCR kinase activity. CC Phosphorylation at Tyr-177 by HCK is important for interaction with CC GRB2. {ECO:0000269|PubMed:15302586, ECO:0000269|PubMed:9407116}. CC -!- DISEASE: Leukemia, chronic myeloid (CML) [MIM:608232]: A clonal CC myeloproliferative disorder of a pluripotent stem cell with a specific CC cytogenetic abnormality, the Philadelphia chromosome (Ph), involving CC myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T- CC lymphoid cells, but not marrow fibroblasts. CC {ECO:0000269|PubMed:2407300, ECO:0000269|PubMed:3107980, CC ECO:0000269|PubMed:3540951}. Note=The gene represented in this entry is CC involved in disease pathogenesis. CC -!- DISEASE: Note=A chromosomal aberration involving BCR has been found in CC patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) CC with ABL1. The translocation produces a BCR-ABL found also in acute CC myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). CC {ECO:0000269|PubMed:3107980, ECO:0000269|PubMed:7665185}. CC -!- SEQUENCE CAUTION: CC Sequence=BAE06073.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/55/BCR"; 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; Y00661; CAA68676.1; -; mRNA. DR EMBL; U07000; AAB60388.1; -; Genomic_DNA. DR EMBL; AB209991; BAE06073.1; ALT_INIT; mRNA. DR EMBL; X02596; CAA26441.1; -; mRNA. DR EMBL; M15025; AAA35594.1; -; Genomic_DNA. DR EMBL; X52828; CAA37010.1; -; Genomic_DNA. DR EMBL; X52829; CAA37011.1; -; Genomic_DNA. DR EMBL; X14676; CAA32806.1; -; mRNA. DR EMBL; M64437; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS13806.1; -. [P11274-1] DR CCDS; CCDS13807.1; -. [P11274-2] DR PIR; A26664; TVHUA2. DR PIR; A91064; TVHUBR. DR RefSeq; NP_004318.3; NM_004327.3. [P11274-1] DR RefSeq; NP_067585.2; NM_021574.2. [P11274-2] DR PDB; 1K1F; X-ray; 2.20 A; A/B/C/D/E/F/G/H=1-72. DR PDB; 2AIN; NMR; -; B=1266-1271. DR PDB; 5N6R; NMR; -; A=487-702. DR PDB; 5N7E; X-ray; 1.65 A; B=487-702. DR PDB; 5OC7; X-ray; 1.65 A; A/D=704-893. DR PDBsum; 1K1F; -. DR PDBsum; 2AIN; -. DR PDBsum; 5N6R; -. DR PDBsum; 5N7E; -. DR PDBsum; 5OC7; -. DR AlphaFoldDB; P11274; -. DR SASBDB; P11274; -. DR SMR; P11274; -. DR BioGRID; 107083; 220. DR ELM; P11274; -. DR IntAct; P11274; 143. DR MINT; P11274; -. DR STRING; 9606.ENSP00000303507; -. DR BindingDB; P11274; -. DR ChEMBL; CHEMBL5146; -. DR DrugBank; DB06616; Bosutinib. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB08901; Ponatinib. DR DrugCentral; P11274; -. DR GlyCosmos; P11274; 1 site, 1 glycan. DR GlyGen; P11274; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P11274; -. DR MetOSite; P11274; -. DR PhosphoSitePlus; P11274; -. DR BioMuta; BCR; -. DR DMDM; 143811366; -. DR EPD; P11274; -. DR jPOST; P11274; -. DR MassIVE; P11274; -. DR MaxQB; P11274; -. DR PaxDb; 9606-ENSP00000303507; -. DR PeptideAtlas; P11274; -. DR ProteomicsDB; 52729; -. [P11274-1] DR ProteomicsDB; 52730; -. [P11274-2] DR Pumba; P11274; -. DR Antibodypedia; 9277; 754 antibodies from 40 providers. DR DNASU; 613; -. DR Ensembl; ENST00000305877.13; ENSP00000303507.8; ENSG00000186716.21. [P11274-1] DR Ensembl; ENST00000359540.7; ENSP00000352535.3; ENSG00000186716.21. [P11274-2] DR GeneID; 613; -. DR KEGG; hsa:613; -. DR MANE-Select; ENST00000305877.13; ENSP00000303507.8; NM_004327.4; NP_004318.3. DR UCSC; uc002zww.4; human. [P11274-1] DR AGR; HGNC:1014; -. DR CTD; 613; -. DR DisGeNET; 613; -. DR GeneCards; BCR; -. DR HGNC; HGNC:1014; BCR. DR HPA; ENSG00000186716; Low tissue specificity. DR MalaCards; BCR; -. DR MIM; 151410; gene. DR MIM; 608232; phenotype. DR neXtProt; NX_P11274; -. DR OpenTargets; ENSG00000186716; -. DR Orphanet; 585909; B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2). DR Orphanet; 521; Chronic myeloid leukemia. DR Orphanet; 261330; Distal 22q11.2 microdeletion syndrome. DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia. DR PharmGKB; PA25321; -. DR VEuPathDB; HostDB:ENSG00000186716; -. DR eggNOG; KOG4269; Eukaryota. DR GeneTree; ENSGT00940000153491; -. DR HOGENOM; CLU_004164_0_0_1; -. DR InParanoid; P11274; -. DR OMA; IKVKISH; -. DR OrthoDB; 2916231at2759; -. DR PhylomeDB; P11274; -. DR TreeFam; TF105082; -. DR PathwayCommons; P11274; -. DR Reactome; R-HSA-1839117; Signaling by cytosolic FGFR1 fusion mutants. DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. DR Reactome; R-HSA-8980692; RHOA GTPase cycle. DR Reactome; R-HSA-9013026; RHOB GTPase cycle. DR Reactome; R-HSA-9013106; RHOC GTPase cycle. DR Reactome; R-HSA-9013148; CDC42 GTPase cycle. DR Reactome; R-HSA-9013149; RAC1 GTPase cycle. DR Reactome; R-HSA-9013404; RAC2 GTPase cycle. DR Reactome; R-HSA-9013423; RAC3 GTPase cycle. DR SignaLink; P11274; -. DR SIGNOR; P11274; -. DR BioGRID-ORCS; 613; 37 hits in 1202 CRISPR screens. DR ChiTaRS; BCR; human. DR EvolutionaryTrace; P11274; -. DR GeneWiki; BCR_(gene); -. DR GenomeRNAi; 613; -. DR Pharos; P11274; Tclin. DR PRO; PR:P11274; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P11274; Protein. DR Bgee; ENSG00000186716; Expressed in nucleus accumbens and 182 other cell types or tissues. DR ExpressionAtlas; P11274; baseline and differential. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:ProtInc. DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome. DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl. DR GO; GO:0090630; P:activation of GTPase activity; IDA:UniProtKB. DR GO; GO:0007420; P:brain development; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0060216; P:definitive hemopoiesis; IEA:Ensembl. DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB. DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl. DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl. DR GO; GO:0065002; P:intracellular protein transmembrane transport; IEA:Ensembl. DR GO; GO:0030216; P:keratinocyte differentiation; IMP:UniProtKB. DR GO; GO:1905517; P:macrophage migration; IEA:Ensembl. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISS:UniProtKB. DR GO; GO:0060313; P:negative regulation of blood vessel remodeling; IEA:Ensembl. DR GO; GO:0002692; P:negative regulation of cellular extravasation; IEA:Ensembl. DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl. DR GO; GO:1905522; P:negative regulation of macrophage migration; IEA:Ensembl. DR GO; GO:0043314; P:negative regulation of neutrophil degranulation; IEA:Ensembl. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:0060268; P:negative regulation of respiratory burst; IEA:Ensembl. DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl. DR GO; GO:0043312; P:neutrophil degranulation; IEA:Ensembl. DR GO; GO:0006909; P:phagocytosis; IEA:Ensembl. DR GO; GO:0050766; P:positive regulation of phagocytosis; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl. DR GO; GO:0051171; P:regulation of nitrogen compound metabolic process; IEA:Ensembl. DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IMP:UniProtKB. DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0043114; P:regulation of vascular permeability; IEA:Ensembl. DR GO; GO:0003014; P:renal system process; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0007264; P:small GTPase mediated signal transduction; IMP:UniProtKB. DR CDD; cd08686; C2_ABR; 1. DR CDD; cd13367; PH_BCR_vertebrate; 1. DR CDD; cd04387; RhoGAP_Bcr; 1. DR CDD; cd00160; RhoGEF; 1. DR DisProt; DP03016; -. DR Gene3D; 4.10.280.30; Bcr-Abl oncoprotein oligomerisation domain; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.20.900.10; Dbl homology (DH) domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.10.555.10; Rho GTPase activation protein; 1. DR InterPro; IPR037769; Abr/Bcr. DR InterPro; IPR015123; Bcr-Abl_oncoprot_oligo. DR InterPro; IPR036481; Bcr-Abl_oncoprot_oligo_sf. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR035899; DBL_dom_sf. DR InterPro; IPR000219; DH-domain. DR InterPro; IPR001331; GDS_CDC24_CS. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR InterPro; IPR008936; Rho_GTPase_activation_prot. DR InterPro; IPR000198; RhoGAP_dom. DR PANTHER; PTHR23182:SF3; BREAKPOINT CLUSTER REGION PROTEIN; 1. DR PANTHER; PTHR23182; BREAKPOINT CLUSTER REGION PROTEIN BCR; 1. DR Pfam; PF09036; Bcr-Abl_Oligo; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF19057; PH_19; 1. DR Pfam; PF00620; RhoGAP; 1. DR Pfam; PF00621; RhoGEF; 1. DR SMART; SM00239; C2; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00324; RhoGAP; 1. DR SMART; SM00325; RhoGEF; 1. DR SUPFAM; SSF69036; Bcr-Abl oncoprotein oligomerization domain; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF48065; DBL homology domain (DH-domain); 1. DR SUPFAM; SSF48350; GTPase activation domain, GAP; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS00741; DH_1; 1. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50238; RHOGAP; 1. DR Genevisible; P11274; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Cell projection; Chromosomal rearrangement; Coiled coil; GTPase activation; KW Guanine-nucleotide releasing factor; Kinase; Methylation; KW Nucleotide-binding; Phosphoprotein; Proto-oncogene; Reference proteome; KW Serine/threonine-protein kinase; Synapse; Transferase. FT CHAIN 1..1271 FT /note="Breakpoint cluster region protein" FT /id="PRO_0000080933" FT DOMAIN 498..691 FT /note="DH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062" FT DOMAIN 708..866 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 893..1020 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 1054..1248 FT /note="Rho-GAP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172" FT REGION 1..426 FT /note="Kinase" FT REGION 67..173 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 185..247 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 197..385 FT /note="Binding to ABL SH2-domain" FT REGION 286..392 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 416..476 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 28..55 FT /evidence="ECO:0000255" FT COMPBIAS 198..222 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 330..385 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 426..427 FT /note="Breakpoint for translocation to form BCR-ABL FT oncogene" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22223895" FT MOD_RES 122 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 139 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 177 FT /note="Phosphotyrosine; by HCK" FT /evidence="ECO:0000269|PubMed:9407116, FT ECO:0007744|PubMed:19690332" FT MOD_RES 202 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 215 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 222 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 236 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 246 FT /note="Phosphotyrosine; by FES" FT /evidence="ECO:0000269|PubMed:15302586" FT MOD_RES 356 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 377 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 382 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 385 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 459 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 463 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 471 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q6PAJ1" FT MOD_RES 473 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 488 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 554 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 641 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 644 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 693 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 894 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1264 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15144186, FT ECO:0007744|PubMed:19690332" FT VAR_SEQ 961..1004 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:3285291" FT /id="VSP_024352" FT VARIANT 400 FT /note="S -> P (in a bladder transitional cell carcinoma FT sample; somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041883" FT VARIANT 413 FT /note="I -> M (in dbSNP:rs56321828)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041884" FT VARIANT 558 FT /note="K -> T (in dbSNP:rs4437065)" FT /id="VAR_051983" FT VARIANT 752 FT /note="D -> E (in dbSNP:rs12484731)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041885" FT VARIANT 796 FT /note="N -> S (in dbSNP:rs140504)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:2407300, ECO:0000269|PubMed:3107980, FT ECO:0000269|PubMed:3285291, ECO:0000269|Ref.3" FT /id="VAR_031552" FT VARIANT 910 FT /note="Y -> C (in dbSNP:rs35537221)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041886" FT VARIANT 949 FT /note="V -> I (in dbSNP:rs2229038)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041887" FT VARIANT 1037 FT /note="E -> K (in dbSNP:rs776552570)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_031553" FT VARIANT 1091 FT /note="V -> M (in dbSNP:rs778229520)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041888" FT VARIANT 1096 FT /note="T -> A (in dbSNP:rs745459086)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041889" FT VARIANT 1104 FT /note="A -> G (in dbSNP:rs11558696)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041890" FT VARIANT 1106 FT /note="D -> N (in dbSNP:rs879255379)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041891" FT VARIANT 1127 FT /note="T -> M (in dbSNP:rs35812689)" FT /id="VAR_031554" FT VARIANT 1149 FT /note="A -> T (in dbSNP:rs200099830)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041892" FT VARIANT 1161 FT /note="E -> K" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041893" FT VARIANT 1187 FT /note="K -> E (in dbSNP:rs1195127922)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041894" FT VARIANT 1189 FT /note="V -> M (in dbSNP:rs55816482)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041895" FT VARIANT 1204 FT /note="A -> G (in dbSNP:rs56265970)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041896" FT VARIANT 1235 FT /note="W -> R (in dbSNP:rs55719322)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041897" FT MUTAGEN 177 FT /note="Y->F: Abolishes interaction with FES and GRB2." FT /evidence="ECO:0000269|PubMed:15302586, FT ECO:0000269|PubMed:9407116" FT MUTAGEN 689..690 FT /note="NE->AA: Loss of RHOAGEF activity." FT /evidence="ECO:0000269|PubMed:23940119" FT MUTAGEN 1090 FT /note="R->A: Loss of GAP activity. Loss of GAP activity; FT when associated with A-1202." FT /evidence="ECO:0000269|PubMed:17116687" FT MUTAGEN 1202 FT /note="N->A: Loss of GAP activity; when associated with FT A-1090." FT /evidence="ECO:0000269|PubMed:17116687" FT MUTAGEN 1269..1271 FT /note="Missing: Abolishes interaction with PDZK1." FT /evidence="ECO:0000269|PubMed:15494376" FT MUTAGEN 1271 FT /note="V->A: Reduces interaction with PDZK1. Abolishes FT interaction with DLG4. No effect on synaptic localization." FT /evidence="ECO:0000269|PubMed:15494376, FT ECO:0000269|PubMed:20962234" FT CONFLICT 287 FT /note="M -> I (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 418 FT /note="G -> D (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 483 FT /note="E -> K (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 560 FT /note="F -> S (in Ref. 1; CAA68676)" FT /evidence="ECO:0000305" FT CONFLICT 690 FT /note="E -> D (in Ref. 11)" FT /evidence="ECO:0000305" FT CONFLICT 733 FT /note="D -> E (in Ref. 4; CAA26441)" FT /evidence="ECO:0000305" FT HELIX 4..14 FT /evidence="ECO:0007829|PDB:1K1F" FT HELIX 28..64 FT /evidence="ECO:0007829|PDB:1K1F" FT HELIX 492..521 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 524..531 FT /evidence="ECO:0007829|PDB:5N7E" FT STRAND 533..535 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 540..546 FT /evidence="ECO:0007829|PDB:5N7E" FT TURN 547..549 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 550..569 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 578..586 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 588..611 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 613..618 FT /evidence="ECO:0007829|PDB:5N7E" FT STRAND 630..634 FT /evidence="ECO:0007829|PDB:5N6R" FT HELIX 639..651 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 653..661 FT /evidence="ECO:0007829|PDB:5N7E" FT HELIX 670..687 FT /evidence="ECO:0007829|PDB:5N7E" FT STRAND 694..697 FT /evidence="ECO:0007829|PDB:5N6R" FT STRAND 709..719 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 722..740 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 751..758 FT /evidence="ECO:0007829|PDB:5OC7" FT HELIX 759..761 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 762..767 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 830..838 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 843..847 FT /evidence="ECO:0007829|PDB:5OC7" FT HELIX 851..865 FT /evidence="ECO:0007829|PDB:5OC7" FT HELIX 876..885 FT /evidence="ECO:0007829|PDB:5OC7" FT STRAND 1268..1271 FT /evidence="ECO:0007829|PDB:2AIN" SQ SEQUENCE 1271 AA; 142819 MW; 4BF66FA1E9D205FE CRC64; MVDPVGFAEA WKAQFPDSEP PRMELRSVGD IEQELERCKA SIRRLEQEVN QERFRMIYLQ TLLAKEKKSY DRQRWGFRRA AQAPDGASEP RASASRPQPA PADGADPPPA EEPEARPDGE GSPGKARPGT ARRPGAAASG ERDDRGPPAS VAALRSNFER IRKGHGQPGA DAEKPFYVNV EFHHERGLVK VNDKEVSDRI SSLGSQAMQM ERKKSQHGAG SSVGDASRPP YRGRSSESSC GVDGDYEDAE LNPRFLKDNL IDANGGSRPP WPPLEYQPYQ SIYVGGMMEG EGKGPLLRSQ STSEQEKRLT WPRRSYSPRS FEDCGGGYTP DCSSNENLTS SEEDFSSGQS SRVSPSPTTY RMFRDKSRSP SQNSQQSFDS SSPPTPQCHK RHRHCPVVVS EATIVGVRKT GQIWPNDGEG AFHGDADGSF GTPPGYGCAA DRAEEQRRHQ DGLPYIDDSP SSSPHLSSKG RGSRDALVSG ALESTKASEL DLEKGLEMRK WVLSGILASE ETYLSHLEAL LLPMKPLKAA ATTSQPVLTS QQIETIFFKV PELYEIHKEF YDGLFPRVQQ WSHQQRVGDL FQKLASQLGV YRAFVDNYGV AMEMAEKCCQ ANAQFAEISE NLRARSNKDA KDPTTKNSLE TLLYKPVDRV TRSTLVLHDL LKHTPASHPD HPLLQDALRI SQNFLSSINE EITPRRQSMT VKKGEHRQLL KDSFMVELVE GARKLRHVFL FTDLLLCTKL KKQSGGKTQQ YDCKWYIPLT DLSFQMVDEL EAVPNIPLVP DEELDALKIK ISQIKNDIQR EKRANKGSKA TERLKKKLSE QESLLLLMSP SMAFRVHSRN GKSYTFLISS DYERAEWREN IREQQKKCFR SFSLTSVELQ MLTNSCVKLQ TVHSIPLTIN KEDDESPGLY GFLNVIVHSA TGFKQSSNLY CTLEVDSFGY FVNKAKTRVY RDTAEPNWNE EFEIELEGSQ TLRILCYEKC YNKTKIPKED GESTDRLMGK GQVQLDPQAL QDRDWQRTVI AMNGIEVKLS VKFNSREFSL KRMPSRKQTG VFGVKIAVVT KRERSKVPYI VRQCVEEIER RGMEEVGIYR VSGVATDIQA LKAAFDVNNK DVSVMMSEMD VNAIAGTLKL YFRELPEPLF TDEFYPNFAE GIALSDPVAK ESCMLNLLLS LPEANLLTFL FLLDHLKRVA EKEAVNKMSL HNLATVFGPT LLRPSEKESK LPANPSQPIT MTDSWSLEVM SQVQVLLYFL QLEAIPAPDS KRQSILFSTE V //