BCR_HUMAN
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 03-AUG-2022, entry version 243.
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 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="http://atlasgeneticsoncology.org/Genes/BCRID55.html";
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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; 138.
DR ELM; P11274; -.
DR IntAct; P11274; 137.
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 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; P11274; -.
DR PeptideAtlas; P11274; -.
DR PRIDE; P11274; -.
DR ProteomicsDB; 52729; -. [P11274-1]
DR ProteomicsDB; 52730; -. [P11274-2]
DR Antibodypedia; 9277; 673 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 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; 585877; B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality.
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; EKSYNRT; -.
DR OrthoDB; 762492at2759; -.
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; 32 hits in 1118 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 180 other tissues.
DR ExpressionAtlas; P11274; baseline and differential.
DR Genevisible; P11274; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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; cd00160; RhoGEF; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR Gene3D; 4.10.280.30; -; 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; PTHR23182; 1.
DR Pfam; PF09036; Bcr-Abl_Oligo; 1.
DR Pfam; PF00168; C2; 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; SSF48065; SSF48065; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF69036; SSF69036; 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.
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 RHOA GEF 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 A-
FT 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
