GRB2_HUMAN
ID GRB2_HUMAN Reviewed; 217 AA.
AC P62993; P29354; Q14450; Q63057; Q63059;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Growth factor receptor-bound protein 2;
DE AltName: Full=Adapter protein GRB2;
DE AltName: Full=Protein Ash;
DE AltName: Full=SH2/SH3 adapter GRB2;
GN Name=GRB2; Synonyms=ASH;
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 1), FUNCTION, AND MUTAGENESIS OF PRO-49
RP AND GLY-203.
RC TISSUE=Brain;
RX PubMed=1322798; DOI=10.1016/0092-8674(92)90167-b;
RA Lowenstein E.J., Daly R.J., Batzer A.G., Li W., Margolis B., Lammers R.,
RA Ullrich A., Skolnik E.Y., Bar-Sagi D., Schlessinger J.;
RT "The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine
RT kinases to ras signaling.";
RL Cell 70:431-442(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal lung;
RX PubMed=1384039; DOI=10.1073/pnas.89.19.9015;
RA Matuoka K., Yamakawa A., Shibata M., Takenawa T.;
RT "Cloning of ASH, a ubiquitous protein composed of one Src homology region
RT (SH) 2 and two SH3 domains, from human and rat cDNA libraries.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9015-9019(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND FUNCTION.
RC TISSUE=Placenta;
RX PubMed=8178156; DOI=10.1126/science.8178156;
RA Fath I., Schweighoffer F., Rey I., Multon M.-C., Boiziau J., Duchesne M.,
RA Tocque B.;
RT "Cloning of a Grb2 isoform with apoptotic properties.";
RL Science 264:971-974(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Epidermis;
RX PubMed=10051406; DOI=10.1006/geno.1998.5692;
RA Bochmann H., Gehrisch S., Jaross W.;
RT "The gene structure of the human growth factor bound protein GRB2.";
RL Genomics 56:203-207(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [9]
RP PROTEIN SEQUENCE OF 11-20; 27-38; 77-109; 118-136; 143-149 AND 179-195, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP INTERACTION WITH CSF1R.
RX PubMed=8262059;
RA van der Geer P., Hunter T.;
RT "Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding
RT site, abrogates signal transduction by the murine CSF-1 receptor expressed
RT in Rat-2 fibroblasts.";
RL EMBO J. 12:5161-5172(1993).
RN [11]
RP INTERACTION WITH IRS1.
RX PubMed=8388384; DOI=10.1016/s0021-9258(18)82106-8;
RA Tobe K., Matuoka K., Tamemoto H., Ueki K., Kaburagi Y., Asai S.,
RA Noguchi T., Matsuda M., Tanaka S., Hattori S., Fukui Y., Akanuma Y.,
RA Yazaki Y., Takenawa T., Kadowaki T.;
RT "Insulin stimulates association of insulin receptor substrate-1 with the
RT protein abundant Src homology/growth factor receptor-bound protein 2.";
RL J. Biol. Chem. 268:11167-11171(1993).
RN [12]
RP INTERACTION WITH IRS1 AND SHC.
RX PubMed=8491186; DOI=10.1002/j.1460-2075.1993.tb05842.x;
RA Skolnik E.Y., Lee C.-H., Batzer A.G., Vicentini L.M., Zhou M., Daly R.J.,
RA Myers M.J. Jr., Backer J.M., Ullrich A., White M.F., Schlessinger J.;
RT "The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-
RT phosphorylated IRS1 and Shc: implications for insulin control of ras
RT signalling.";
RL EMBO J. 12:1929-1936(1993).
RN [13]
RP INTERACTION WITH SOS1, AND MUTAGENESIS OF PRO-49; GLU-89; SER-90 AND
RP GLY-203.
RC TISSUE=Brain;
RX PubMed=8493579; DOI=10.1126/science.8493579;
RA Chardin P., Camonis J.H., Gale N.W., van Aelst L., Wigler M.H.,
RA Bar-Sagi D.;
RT "Human Sos1: a guanine nucleotide exchange factor for Ras that binds to
RT GRB2.";
RL Science 260:1338-1343(1993).
RN [14]
RP IDENTIFICATION IN A COMPLEX WITH MUC1 AND SOS1, AND INTERACTION WITH MUC1
RP AND SOS1.
RX PubMed=7664271;
RA Pandey P., Kharbanda S., Kufe D.;
RT "Association of the DF3/MUC1 breast cancer antigen with Grb2 and the
RT Sos/Ras exchange protein.";
RL Cancer Res. 55:4000-4003(1995).
RN [15]
RP INTERACTION WITH INPP5D.
RX PubMed=8723348; DOI=10.1016/s0960-9822(02)00511-0;
RA Kavanaugh W.M., Pot D.A., Chin S.M., Deuter-Reinhard M., Jefferson A.B.,
RA Norris F.A., Masiarz F.R., Cousens L.S., Majerus P.W., Williams L.T.;
RT "Multiple forms of an inositol polyphosphate 5-phosphatase form signaling
RT complexes with Shc and Grb2.";
RL Curr. Biol. 6:438-445(1996).
RN [16]
RP INTERACTION WITH EPHB1.
RX PubMed=8798570; DOI=10.1074/jbc.271.38.23588;
RA Stein E., Cerretti D.P., Daniel T.O.;
RT "Ligand activation of ELK receptor tyrosine kinase promotes its association
RT with Grb10 and Grb2 in vascular endothelial cells.";
RL J. Biol. Chem. 271:23588-23593(1996).
RN [17]
RP INTERACTION WITH INPP5D.
RX PubMed=9108392;
RA Odai H., Sasaki K., Iwamatsu A., Nakamoto T., Ueno H., Yamagata T.,
RA Mitani K., Yazaki Y., Hirai H.;
RT "Purification and molecular cloning of SH2- and SH3-containing inositol
RT polyphosphate-5-phosphatase, which is involved in the signaling pathway of
RT granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-
RT Abl.";
RL Blood 89:2745-2756(1997).
RN [18]
RP INTERACTION WITH PTK2/FAK1.
RX PubMed=9148935; DOI=10.1074/jbc.272.20.13189;
RA Schlaepfer D.D., Hunter T.;
RT "Focal adhesion kinase overexpression enhances ras-dependent integrin
RT signaling to ERK2/mitogen-activated protein kinase through interactions
RT with and activation of c-Src.";
RL J. Biol. Chem. 272:13189-13195(1997).
RN [19]
RP INTERACTION WITH PTPNS1.
RX PubMed=9062191; DOI=10.1038/386181a0;
RA Kharitonenkov A., Chen Z., Sures I., Wang H., Schilling J., Ullrich A.;
RT "A family of proteins that inhibit signalling through tyrosine kinase
RT receptors.";
RL Nature 386:181-186(1997).
RN [20]
RP INTERACTION WITH AXL.
RX PubMed=9178760; DOI=10.1038/sj.onc.1201123;
RA Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R.,
RA Ullrich A., Bartram C.R., Janssen J.W.;
RT "Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is
RT mediated mainly by a multi-substrate docking-site.";
RL Oncogene 14:2619-2631(1997).
RN [21]
RP INTERACTION WITH SH2B2.
RX PubMed=9233773; DOI=10.1038/sj.onc.1201163;
RA Yokouchi M., Suzuki R., Masuhara M., Komiya S., Inoue A., Yoshimura A.;
RT "Cloning and characterization of APS, an adaptor molecule containing PH and
RT SH2 domains that is tyrosine phosphorylated upon B-cell receptor
RT stimulation.";
RL Oncogene 15:7-15(1997).
RN [22]
RP INTERACTION WITH LAT.
RX PubMed=9489702; DOI=10.1016/s0092-8674(00)80901-0;
RA Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E.;
RT "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to
RT cellular activation.";
RL Cell 92:83-92(1998).
RN [23]
RP INTERACTION WITH REPS2.
RX PubMed=9422736; DOI=10.1074/jbc.273.2.814;
RA Ikeda M., Ishida O., Hinoi T., Kishida S., Kikuchi A.;
RT "Identification and characterization of a novel protein interacting with
RT Ral-binding protein 1, a putative effector protein of Ral.";
RL J. Biol. Chem. 273:814-821(1998).
RN [24]
RP INTERACTION WITH IRS4.
RX PubMed=9553137; DOI=10.1074/jbc.273.17.10726;
RA Fantin V.R., Sparling J.D., Slot J.W., Keller S.R., Lienhard G.E.,
RA Lavan B.E.;
RT "Characterization of insulin receptor substrate 4 in human embryonic kidney
RT 293 cells.";
RL J. Biol. Chem. 273:10726-10732(1998).
RN [25]
RP INTERACTION WITH SHB, AND MUTAGENESIS OF PRO-49 AND PRO-206.
RX PubMed=9484780; DOI=10.1038/sj.onc.1201607;
RA Welsh M., Songyang Z., Frantz J.D., Trueb T., Reedquist K.A., Karlsson T.,
RA Miyazaki M., Cantley L.C., Band H., Shoelson S.E.;
RT "Stimulation through the T cell receptor leads to interactions between SHB
RT and several signaling proteins.";
RL Oncogene 16:891-901(1998).
RN [26]
RP INTERACTION WITH EGFR.
RX PubMed=10026169; DOI=10.1074/jbc.274.9.5542;
RA Braverman L.E., Quilliam L.A.;
RT "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing
RT adapter protein having similar binding and biological properties to Nck.";
RL J. Biol. Chem. 274:5542-5549(1999).
RN [27]
RP INTERACTION WITH CBLB.
RX PubMed=10022120; DOI=10.1038/sj.onc.1202411;
RA Elly C., Witte S., Zhang Z., Rosnet O., Lipkowitz S., Altman A., Liu Y.-C.;
RT "Tyrosine phosphorylation and complex formation of Cbl-b upon T cell
RT receptor stimulation.";
RL Oncogene 18:1147-1156(1999).
RN [28]
RP INTERACTION WITH CBL AND CBLB.
RX PubMed=10086340; DOI=10.1038/sj.onc.1202499;
RA Ettenberg S.A., Keane M.M., Nau M.M., Frankel M., Wang L.-M., Pierce J.H.,
RA Lipkowitz S.;
RT "cbl-b inhibits epidermal growth factor receptor signaling.";
RL Oncogene 18:1855-1866(1999).
RN [29]
RP INTERACTION WITH HEPATITIS C VIRUS/HCV PROTEIN NS5A (MICROBIAL INFECTION).
RX PubMed=10318918; DOI=10.1073/pnas.96.10.5533;
RA Tan S.-L., Nakao H., He Y., Vijaysri S., Neddermann P., Jacobs B.L.,
RA Mayer B.J., Katze M.G.;
RT "NS5A, a nonstructural protein of hepatitis C virus, binds growth factor
RT receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-
RT dependent manner and perturbs mitogenic signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:5533-5538(1999).
RN [30]
RP INTERACTION WITH RALGPS1.
RX PubMed=10747847; DOI=10.1074/jbc.c000085200;
RA Rebhun J.F., Chen H., Quilliam L.A.;
RT "Identification and characterization of a new family of guanine nucleotide
RT exchange factors for the ras-related GTPase Ral.";
RL J. Biol. Chem. 275:13406-13410(2000).
RN [31]
RP INTERACTION WITH ERBB4.
RX PubMed=10867024; DOI=10.1074/jbc.c901015199;
RA Sweeney C., Lai C., Riese D.J. II, Diamonti A.J., Cantley L.C.,
RA Carraway K.L. III;
RT "Ligand discrimination in signaling through an ErbB4 receptor homodimer.";
RL J. Biol. Chem. 275:19803-19807(2000).
RN [32]
RP INTERACTION WITH SKAP2.
RX PubMed=10942756; DOI=10.1074/jbc.m001439200;
RA Asazuma N., Wilde J.I., Berlanga O., Leduc M., Leo A., Schweighoffer E.,
RA Tybulewicz V., Bon C., Liu S.K., McGlade C.J., Schraven B., Watson S.P.;
RT "Interaction of linker for activation of T cells with multiple adapter
RT proteins in platelets activated by the glycoprotein VI-selective ligand,
RT convulxin.";
RL J. Biol. Chem. 275:33427-33434(2000).
RN [33]
RP INTERACTION WITH PTPRE.
RX PubMed=10980613; DOI=10.1038/sj.onc.1203790;
RA Gil-Henn H., Volohonsky G., Toledano-Katchalski H., Gandre S., Elson A.;
RT "Generation of novel cytoplasmic forms of protein tyrosine phosphatase
RT epsilon by proteolytic processing and translational control.";
RL Oncogene 19:4375-4384(2000).
RN [34]
RP INTERACTION WITH SIT1.
RX PubMed=11433379;
RX DOI=10.1002/1521-4141(200106)31:6<1825::aid-immu1825>3.0.co;2-v;
RA Pfrepper K.-I., Marie-Cardine A., Simeoni L., Kuramitsu Y., Leo A.,
RA Spicka J., Hilgert I., Scherer J., Schraven B.;
RT "Structural and functional dissection of the cytoplasmic domain of the
RT transmembrane adaptor protein SIT (SHP2-interacting transmembrane adaptor
RT protein).";
RL Eur. J. Immunol. 31:1825-1836(2001).
RN [35]
RP INTERACTION WITH HEPATITIS E VIRUS/HEV ORF3 PROTEIN (MICROBIAL INFECTION).
RX PubMed=11518702; DOI=10.1074/jbc.m101546200;
RA Korkaya H., Jameel S., Gupta D., Tyagi S., Kumar R., Zafrullah M.,
RA Mazumdar M., Lal S.K., Xiaofang L., Sehgal D., Das S.R., Sahal D.;
RT "The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and
RT activates MAPK.";
RL J. Biol. Chem. 276:42389-42400(2001).
RN [36]
RP IDENTIFICATION IN A COMPLEX WITH PIK3C2B AND EGFR, AND INTERACTION WITH
RP PIK3C2B.
RX PubMed=11533253; DOI=10.1128/mcb.21.19.6660-6667.2001;
RA Wheeler M., Domin J.;
RT "Recruitment of the class II phosphoinositide 3-kinase C2beta to the
RT epidermal growth factor receptor: role of Grb2.";
RL Mol. Cell. Biol. 21:6660-6667(2001).
RN [37]
RP INTERACTION WITH NISCH.
RX PubMed=11912194; DOI=10.1074/jbc.m111838200;
RA Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E.;
RT "Insulin receptor substrate 4 associates with the protein IRAS.";
RL J. Biol. Chem. 277:19439-19447(2002).
RN [38]
RP INTERACTION WITH SKAP1.
RX PubMed=12171928; DOI=10.1074/jbc.m206023200;
RA Wu L., Yu Z., Shen S.-H.;
RT "SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway
RT upon T cell receptor activation.";
RL J. Biol. Chem. 277:40420-40427(2002).
RN [39]
RP INTERACTION WITH LAX1.
RX PubMed=12359715; DOI=10.1074/jbc.m208946200;
RA Zhu M., Janssen E., Leung K., Zhang W.;
RT "Molecular cloning of a novel gene encoding a membrane-associated adaptor
RT protein (LAX) in lymphocyte signaling.";
RL J. Biol. Chem. 277:46151-46158(2002).
RN [40]
RP INTERACTION WITH LAT2.
RX PubMed=12486104; DOI=10.1084/jem.20021405;
RA Brdicka T., Imrich M., Angelisova P., Brdickova N., Horvath O., Spicka J.,
RA Hilgert I., Luskova P., Draber P., Novak P., Engels N., Wienands J.,
RA Simeoni L., Oesterreicher J., Aguado E., Malissen M., Schraven B.,
RA Horejsi V.;
RT "Non-T cell activation linker (NTAL): a transmembrane adaptor protein
RT involved in immunoreceptor signaling.";
RL J. Exp. Med. 196:1617-1626(2002).
RN [41]
RP INTERACTION WITH PTPRJ.
RX PubMed=12475979; DOI=10.1074/jbc.m210656200;
RA Palka H.L., Park M., Tonks N.K.;
RT "Hepatocyte growth factor receptor tyrosine kinase met is a substrate of
RT the receptor protein-tyrosine phosphatase DEP-1.";
RL J. Biol. Chem. 278:5728-5735(2003).
RN [42]
RP INTERACTION WITH EPHB1 AND SHC1.
RX PubMed=12925710; DOI=10.1083/jcb.200302073;
RA Vindis C., Cerretti D.P., Daniel T.O., Huynh-Do U.;
RT "EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote
RT chemotaxis.";
RL J. Cell Biol. 162:661-671(2003).
RN [43]
RP INTERACTION WITH LAT2.
RX PubMed=12514734; DOI=10.1038/ni882;
RA Janssen E., Zhu M., Zhang W., Koonpaew S., Zhang W.;
RT "LAB: a new membrane-associated adaptor molecule in B cell activation.";
RL Nat. Immunol. 4:117-123(2003).
RN [44]
RP INTERACTION WITH NTRK1.
RX PubMed=15488758; DOI=10.1016/j.ccr.2004.09.011;
RA Tacconelli A., Farina A.R., Cappabianca L., Desantis G., Tessitore A.,
RA Vetuschi A., Sferra R., Rucci N., Argenti B., Screpanti I., Gulino A.,
RA Mackay A.R.;
RT "TrkA alternative splicing: a regulated tumor-promoting switch in human
RT neuroblastoma.";
RL Cancer Cell 6:347-360(2004).
RN [45]
RP INTERACTION WITH FLT4.
RX PubMed=15102829; DOI=10.1074/jbc.m314015200;
RA Wang J.F., Zhang X., Groopman J.E.;
RT "Activation of vascular endothelial growth factor receptor-3 and its
RT downstream signaling promote cell survival under oxidative stress.";
RL J. Biol. Chem. 279:27088-27097(2004).
RN [46]
RP REVIEW ON INTERACTION WITH KIT AND ROLE IN KIT SIGNALING.
RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6;
RA Ronnstrand L.;
RT "Signal transduction via the stem cell factor receptor/c-Kit.";
RL Cell. Mol. Life Sci. 61:2535-2548(2004).
RN [47]
RP INTERACTION WITH BCR.
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 [48]
RP REVIEW ON ROLE IN KIT SIGNALING.
RX PubMed=16129412; DOI=10.1016/j.bbrc.2005.08.055;
RA Roskoski R. Jr.;
RT "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.";
RL Biochem. Biophys. Res. Commun. 337:1-13(2005).
RN [49]
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 [50]
RP INTERACTION WITH HCST.
RX PubMed=16582911; DOI=10.1038/ni1325;
RA Upshaw J.L., Arneson L.N., Schoon R.A., Dick C.J., Billadeau D.D.,
RA Leibson P.J.;
RT "NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and
RT phosphatidylinositol-3-kinase in human natural killer cells.";
RL Nat. Immunol. 7:524-532(2006).
RN [51]
RP INTERACTION WITH SPRY2.
RX PubMed=17974561; DOI=10.1074/jbc.m705457200;
RA Chandramouli S., Yu C.Y., Yusoff P., Lao D.H., Leong H.F., Mizuno K.,
RA Guy G.R.;
RT "Tesk1 interacts with Spry2 to abrogate its inhibition of ERK
RT phosphorylation downstream of receptor tyrosine kinase signaling.";
RL J. Biol. Chem. 283:1679-1691(2008).
RN [52]
RP INTERACTION WITH GAPT.
RX PubMed=18559951; DOI=10.1189/jlb.0208087;
RA Liu Y., Zhang W.;
RT "Identification of a new transmembrane adaptor protein that constitutively
RT binds Grb2 in B cells.";
RL J. Leukoc. Biol. 84:842-851(2008).
RN [53]
RP INTERACTION WITH ADAM15.
RX PubMed=18296648; DOI=10.1158/1541-7786.mcr-07-2028;
RA Zhong J.L., Poghosyan Z., Pennington C.J., Scott X., Handsley M.M.,
RA Warn A., Gavrilovic J., Honert K., Kruger A., Span P.N., Sweep F.C.,
RA Edwards D.R.;
RT "Distinct functions of natural ADAM-15 cytoplasmic domain variants in human
RT mammary carcinoma.";
RL Mol. Cancer Res. 6:383-394(2008).
RN [54]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-211, 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 [55]
RP INTERACTION WITH EGFR.
RX PubMed=19836242; DOI=10.1016/j.cub.2009.09.048;
RA Tarcic G., Boguslavsky S.K., Wakim J., Kiuchi T., Liu A., Reinitz F.,
RA Nathanson D., Takahashi T., Mischel P.S., Ng T., Yarden Y.;
RT "An unbiased screen identifies DEP-1 tumor suppressor as a phosphatase
RT controlling EGFR endocytosis.";
RL Curr. Biol. 19:1788-1798(2009).
RN [56]
RP INTERACTION WITH AXL; LTK; PDGFRL AND TNK2, AND FUNCTION.
RX PubMed=19815557; DOI=10.1074/jbc.m109.072660;
RA Pao-Chun L., Chan P.M., Chan W., Manser E.;
RT "Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is
RT mediated by Grb2: an analysis of ACK1 effects on Axl signaling.";
RL J. Biol. Chem. 284:34954-34963(2009).
RN [57]
RP INTERACTION WITH KIF26A.
RX PubMed=19914172; DOI=10.1016/j.cell.2009.10.023;
RA Zhou R., Niwa S., Homma N., Takei Y., Hirokawa N.;
RT "KIF26A is an unconventional kinesin and regulates GDNF-Ret signaling in
RT enteric neuronal development.";
RL Cell 139:802-813(2009).
RN [58]
RP INTERACTION WITH GAREM1.
RX PubMed=19509291; DOI=10.1074/jbc.m109.021139;
RA Tashiro K., Tsunematsu T., Okubo H., Ohta T., Sano E., Yamauchi E.,
RA Taniguchi H., Konishi H.;
RT "GAREM, a novel adaptor protein for growth factor receptor-bound protein 2,
RT contributes to cellular transformation through the activation of
RT extracellular signal-regulated kinase signaling.";
RL J. Biol. Chem. 284:20206-20214(2009).
RN [59]
RP 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 [60]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6; LYS-50 AND LYS-109, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [61]
RP INTERACTION WITH PTK2B/PYK2.
RX PubMed=20521079; DOI=10.1007/s00018-010-0411-x;
RA Shen X., Xi G., Radhakrishnan Y., Clemmons D.R.;
RT "Recruitment of Pyk2 to SHPS-1 signaling complex is required for IGF-I-
RT dependent mitogenic signaling in vascular smooth muscle cells.";
RL Cell. Mol. Life Sci. 67:3893-3903(2010).
RN [62]
RP INTERACTION WITH PTPN23, AND SUBCELLULAR LOCATION.
RX PubMed=21179510; DOI=10.1371/journal.pone.0014339;
RA Tanase C.A.;
RT "Histidine domain-protein tyrosine phosphatase interacts with Grb2 and
RT GrpL.";
RL PLoS ONE 5:E14339-E14339(2010).
RN [63]
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 [64]
RP INTERACTION WITH FCRL6.
RX PubMed=20933011; DOI=10.1016/j.imlet.2010.09.023;
RA Kulemzin S.V., Zamoshnikova A.Y., Yurchenko M.Y., Vitak N.Y.,
RA Najakshin A.M., Fayngerts S.A., Chikaev N.A., Reshetnikova E.S.,
RA Kashirina N.M., Peclo M.M., Rutkevich P.N., Shevelev A.Y.,
RA Yanushevskaya E.V., Baranov K.O., Mamonkin M., Vlasik T.N., Sidorenko S.P.,
RA Taranin A.V., Mechetina L.V.;
RT "FCRL6 receptor: expression and associated proteins.";
RL Immunol. Lett. 134:174-182(2011).
RN [65]
RP INTERACTION WITH ASAP3.
RX PubMed=22027826; DOI=10.1074/jbc.m111.278770;
RA Yu X., Wang F., Liu H., Adams G., Aikhionbare F., Liu D., Cao X., Fan L.,
RA Hu G., Chen Y., Frost A., Partridge E., Ding X., Yao X.;
RT "ACAP4 protein cooperates with Grb2 protein to orchestrate epidermal growth
RT factor-stimulated integrin beta1 recycling in cell migration.";
RL J. Biol. Chem. 286:43735-43747(2011).
RN [66]
RP INTERACTION WITH SCIMP.
RX PubMed=21930792; DOI=10.1128/mcb.05817-11;
RA Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M., Skopcova T.,
RA Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A., Brdicka T.;
RT "SCIMP, a transmembrane adapter protein involved in major
RT histocompatibility complex class II signaling.";
RL Mol. Cell. Biol. 31:4550-4562(2011).
RN [67]
RP INTERACTION WITH TESPA1.
RC TISSUE=Thymocyte;
RX PubMed=22561606; DOI=10.1038/ni.2301;
RA Wang D., Zheng M., Lei L., Ji J., Yao Y., Qiu Y., Ma L., Lou J., Ouyang C.,
RA Zhang X., He Y., Chi J., Wang L., Kuang Y., Wang J., Cao X., Lu L.;
RT "Tespa1 is involved in late thymocyte development through the regulation of
RT TCR-mediated signaling.";
RL Nat. Immunol. 13:560-568(2012).
RN [68]
RP RETRACTED PAPER.
RX PubMed=31462771; DOI=10.1038/s41586-019-1511-x;
RA Niu J., Sun Y., Chen B., Zheng B., Jarugumilli G.K., Walker S.R.,
RA Hata A.N., Mino-Kenudson M., Frank D.A., Wu X.;
RT "Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through
RT S-palmitoylation.";
RL Nature 573:139-143(2019).
RN [69]
RP RETRACTION NOTICE OF PUBMED:31462771.
RX PubMed=32555452; DOI=10.1038/s41586-020-2414-6;
RA Niu J., Sun Y., Chen B., Zheng B., Jarugumilli G.K., Walker S.R.,
RA Hata A.N., Mino-Kenudson M., Frank D.A., Wu X.;
RL Nature 583:154-154(2020).
RN [70]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [71]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [72]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1/HHV1 PROTEIN UL46 (MICROBIAL
RP INFECTION).
RX PubMed=23946459; DOI=10.1128/jvi.01702-13;
RA Strunk U., Saffran H.A., Wu F.W., Smiley J.R.;
RT "Role of herpes simplex virus VP11/12 tyrosine-based motifs in binding and
RT activation of the Src family kinase Lck and recruitment of p85, Grb2, and
RT Shc.";
RL J. Virol. 87:11276-11286(2013).
RN [73]
RP INTERACTION WITH RHEX.
RX PubMed=25092874; DOI=10.1084/jem.20130624;
RA Verma R., Su S., McCrann D.J., Green J.M., Leu K., Young P.R., Schatz P.J.,
RA Silva J.C., Stokes M.P., Wojchowski D.M.;
RT "RHEX, a novel regulator of human erythroid progenitor cell expansion and
RT erythroblast development.";
RL J. Exp. Med. 211:1715-1722(2014).
RN [74]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [75]
RP INTERACTION WITH PRR14.
RX PubMed=27041574; DOI=10.1038/onc.2016.93;
RA Yang M., Lewinska M., Fan X., Zhu J., Yuan Z.M.;
RT "PRR14 is a novel activator of the PI3K pathway promoting lung
RT carcinogenesis.";
RL Oncogene 35:5527-5538(2016).
RN [76]
RP INTERACTION WITH DENND2B.
RX PubMed=29030480; DOI=10.15252/embr.201744034;
RA Ioannou M.S., Kulasekaran G., Fotouhi M., Morein J.J., Han C., Tse S.,
RA Nossova N., Han T., Mannard E., McPherson P.S.;
RT "Intersectin-s interaction with DENND2B facilitates recycling of epidermal
RT growth factor receptor.";
RL EMBO Rep. 18:2119-2130(2017).
RN [77]
RP STRUCTURE BY NMR OF 58-164.
RX PubMed=8794768; DOI=10.1021/bi952615s;
RA Thornton K.H., Mueller W.T., McConnell P., Zhu G., Saltiel A.R.,
RA Thanabal V.;
RT "Nuclear magnetic resonance solution structure of the growth factor
RT receptor-bound protein 2 Src homology 2 domain.";
RL Biochemistry 35:11852-11864(1996).
RN [78]
RP STRUCTURE BY NMR OF 52-163.
RA Senior M.M., Frederick A.F., Black S., Murgolo N.J., Perkins L.M.,
RA Wilson O., Snow M.E., Wang Y.-S.;
RT "The three-dimensional solution structure of the Src homology domain-2 of
RT the growth factor receptor-bound protein-2.";
RL J. Biomol. NMR 11:153-164(1998).
RN [79]
RP STRUCTURE BY NMR OF 157-215.
RX PubMed=7881903; DOI=10.1016/s0969-2126(94)00106-5;
RA Kohda D., Terasawa H., Ichikawa S., Ogura K., Hatanaka H., Mandiyan V.,
RA Ullrich A., Schlessinger J., Inagaki F.;
RT "Solution structure and ligand-binding site of the carboxy-terminal SH3
RT domain of GRB2.";
RL Structure 2:1029-1040(1994).
RN [80]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS).
RX PubMed=7716522; DOI=10.1126/science.7716522;
RA Maignan S., Guilloteau J.-P., Fromage N., Arnoux B., Becquart J.,
RA Ducruix A.;
RT "Crystal structure of the mammalian Grb2 adaptor.";
RL Science 268:291-293(1995).
RN [81]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 56-153.
RX PubMed=9642078; DOI=10.1006/jmbi.1998.1790;
RA Rahuel J., Garcia-Echeverria C., Furet P., Strauss A., Caravatti G.,
RA Fretz H., Schoepfer J., Gay B.;
RT "Structural basis for the high affinity of amino-aromatic SH2
RT phosphopeptide ligands.";
RL J. Mol. Biol. 279:1013-1022(1998).
RN [82]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 47-163.
RX PubMed=10090780; DOI=10.1021/jm9811007;
RA Ettmayer P., France D., Gounarides J., Jarosinski M., Martin M.-S.,
RA Rondeau J.-M., Sabio M., Topiol S., Weidmann B., Zurini M., Bair K.W.;
RT "Structural and conformational requirements for high-affinity binding to
RT the SH2 domain of Grb2(1).";
RL J. Med. Chem. 42:971-980(1999).
RN [83]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 57-152.
RX PubMed=10395476; DOI=10.1021/jm991013u;
RA Furet P., Garcia-Echeverria C., Gay B., Schoepfer J., Zeller M., Rahuel J.;
RT "Structure-based design, synthesis, and X-ray crystallography of a
RT high- affinity antagonist of the Grb2-SH2 domain containing an asparagine
RT mimetic.";
RL J. Med. Chem. 42:2358-2363(1999).
RN [84]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 52-160 IN COMPLEX WITH MET.
RX PubMed=11063574; DOI=10.1021/bi0012336;
RA Schiering N., Casale E., Caccia P., Giordano P., Battistini C.;
RT "Dimer formation through domain swapping in the crystal structure of the
RT Grb2-SH2-Ac-pYVNV complex.";
RL Biochemistry 39:13376-13382(2000).
RN [85]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 56-151 IN COMPLEX WITH THE
RP TYROSINE PHOSPHORYLATED PEPTIDE TYR-VAL-ASN-VAL-GLN-ASN AND IN COMPLEX WITH
RP A PEPTIDE INHIBITOR.
RX PubMed=11827484; DOI=10.1006/jmbi.2001.5299;
RA Nioche P., Liu W.-Q., Broutin I., Charbonnier F., Latreille M.-T.,
RA Vidal M., Roques B., Garbay C., Ducruix A.;
RT "Crystal structures of the SH2 domain of Grb2: highlight on the binding of
RT a new high-affinity inhibitor.";
RL J. Mol. Biol. 315:1167-1177(2002).
RN [86]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 158-211 IN COMPLEX WITH GAB2.
RX PubMed=19523899; DOI=10.1016/j.str.2009.03.017;
RA Harkiolaki M., Tsirka T., Lewitzky M., Simister P.C., Joshi D., Bird L.E.,
RA Jones E.Y., O'Reilly N., Feller S.M.;
RT "Distinct binding modes of two epitopes in Gab2 that interact with the SH3C
RT domain of Grb2.";
RL Structure 17:809-822(2009).
RN [87]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 60-152 IN COMPLEX WITH CD28, AND
RP INTERACTION WITH CD28.
RX PubMed=24098653; DOI=10.1371/journal.pone.0074482;
RA Higo K., Ikura T., Oda M., Morii H., Takahashi J., Abe R., Ito N.;
RT "High resolution crystal structure of the Grb2 SH2 domain with a
RT phosphopeptide derived from CD28.";
RL PLoS ONE 8:E74482-E74482(2013).
CC -!- FUNCTION: Adapter protein that provides a critical link between cell
CC surface growth factor receptors and the Ras signaling pathway.
CC {ECO:0000269|PubMed:1322798, ECO:0000269|PubMed:19815557}.
CC -!- FUNCTION: [Isoform 2]: Does not bind to phosphorylated epidermal growth
CC factor receptor (EGFR) but inhibits EGF-induced transactivation of a
CC RAS-responsive element. Acts as a dominant negative protein over GRB2
CC and by suppressing proliferative signals, may trigger active programmed
CC cell death. {ECO:0000269|PubMed:8178156}.
CC -!- SUBUNIT: Associates (via SH2 domain) with activated EGF and PDGF
CC receptors (tyrosine phosphorylated) (PubMed:10026169, PubMed:19836242).
CC Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be
CC indirect (By similarity). Also associates to other cellular Tyr-
CC phosphorylated proteins such as SIT1, IRS1, IRS4, SHC and LNK; probably
CC via the concerted action of both its SH2 and SH3 domains
CC (PubMed:8388384, PubMed:8491186, PubMed:9553137, PubMed:11433379). It
CC also seems to interact with RAS in the signaling pathway leading to DNA
CC synthesis. Interacts with SOS1 (PubMed:8493579, PubMed:7664271). Forms
CC a complex with MUC1 and SOS1, through interaction of the SH3 domains
CC with SOS1 and the SH2 domain with phosphorylated MUC1 (PubMed:7664271).
CC Interacts with phosphorylated MET (PubMed:11063574, PubMed:11827484).
CC Interacts with phosphorylated TOM1L1 (By similarity). Interacts with
CC the phosphorylated C-terminus of SH2B2 (PubMed:9233773). Interacts with
CC phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR
CC activation (By similarity) (PubMed:9489702, PubMed:12359715,
CC PubMed:12486104, PubMed:12514734). Interacts with NISCH, PTPNS1 and
CC REPS2 (PubMed:9062191, PubMed:9422736, PubMed:11912194). Interacts with
CC syntrophin SNTA1 (By similarity). Interacts (via SH3 domains) with
CC REPS1 (By similarity). Interacts (via SH3 domains) with PIK3C2B
CC (PubMed:11533253). Interacts with CBL and CBLB (PubMed:10022120,
CC PubMed:10086340). Interacts with AJUBA and CLNK (By similarity).
CC Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By
CC similarity). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2
CC (PubMed:8723348, PubMed:9108392, PubMed:9484780, PubMed:10942756,
CC PubMed:12171928). Interacts with PTPN11 (By similarity). Interacts with
CC PRNP (By similarity). Interacts with RALGPS1 (PubMed:10747847).
CC Interacts with HCST (PubMed:16582911). Interacts with KDR (By
CC similarity). Interacts with FLT1 (tyrosine-phosphorylated) (By
CC similarity). Interacts with GAPT and PTPRE (PubMed:10980613,
CC PubMed:18559951). Interacts (via SH2 domain) with KIF26A
CC (PubMed:19914172). Interacts (via SH3 2) with GAB2 (PubMed:19523899).
CC Interacts with ADAM15 (PubMed:18296648). Interacts with THEMIS2 (By
CC similarity). Interacts (via SH2 domain) with AXL (phosphorylated)
CC (PubMed:9178760, PubMed:19815557). Interacts (via SH2 domain) with KIT
CC (phosphorylated) (PubMed:15526160, PubMed:16129412). Interacts with
CC PTPRJ and BCR (PubMed:12475979, PubMed:15302586). Interacts with PTPN23
CC (PubMed:21179510). Interacts with FLT4 (tyrosine phosphorylated)
CC (PubMed:15102829). Interacts with EPHB1 and SHC1; activates the
CC MAPK/ERK cascade to regulate cell migration (PubMed:8798570,
CC PubMed:12925710). Part of a complex including TNK2, GRB2, LTK and one
CC receptor tyrosine kinase (RTK) such as AXL and PDGFRL, in which GRB2
CC promotes RTK recruitment by TNK2 (PubMed:9178760, PubMed:19815557).
CC Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated)
CC (PubMed:8262059). Interacts with ERBB4 (PubMed:10867024). Interacts
CC with NTRK1 (phosphorylated upon ligand-binding) (PubMed:15488758).
CC Interacts with PTK2/FAK1 (tyrosine phosphorylated) (PubMed:9148935).
CC Interacts with PTK2B/PYK2 (tyrosine phosphorylated) (PubMed:20521079).
CC Interacts (via SH3 domains) with GAREM1 isoform 1 (via proline-rich
CC domain and tyrosine phosphorylated); the interaction occurs upon EGF
CC stimulation (PubMed:19509291). Interacts with DAB2 (By similarity).
CC Interacts with TESPA1 (PubMed:22561606). Interacts with PLCG1, LAT and
CC THEMIS upon TCR activation in thymocytes; the association is weaker in
CC the absence of TESPA1 (By similarity). Interacts with CD28
CC (PubMed:24098653). Interacts with RAB13; may recruit RAB13 to the
CC leading edge of migrating endothelial cells where it can activate RHOA
CC (By similarity). Interacts with ASAP3 (phosphorylated form)
CC (PubMed:22027826). Interacts (via SH2 domain) with PTPRH
CC (phosphorylated form) (By similarity). Interacts with PTPRO
CC (phosphorylated form) (By similarity). Interacts with PTPRB
CC (phosphorylated form) (By similarity). Interacts (via SH3 domain 2)
CC with PRR14 (via proline-rich region) (PubMed:27041574). Interacts with
CC FCRL6 (tyrosine phosphorylated form) (PubMed:20933011). Interacts with
CC RHEX (via tyrosine-phosphorylated form) (PubMed:25092874). Interacts
CC with DENND2B (PubMed:29030480). Interacts with SPRY2 (PubMed:17974561).
CC Interacts with LRRC8A (By similarity). {ECO:0000250|UniProtKB:Q60631,
CC ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10026169,
CC ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:10318918,
CC ECO:0000269|PubMed:10747847, ECO:0000269|PubMed:10867024,
CC ECO:0000269|PubMed:10942756, ECO:0000269|PubMed:10980613,
CC ECO:0000269|PubMed:11063574, ECO:0000269|PubMed:11433379,
CC ECO:0000269|PubMed:11518702, ECO:0000269|PubMed:11533253,
CC ECO:0000269|PubMed:11827484, ECO:0000269|PubMed:11912194,
CC ECO:0000269|PubMed:12171928, ECO:0000269|PubMed:12359715,
CC ECO:0000269|PubMed:12475979, ECO:0000269|PubMed:12486104,
CC ECO:0000269|PubMed:12514734, ECO:0000269|PubMed:12925710,
CC ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15302586,
CC ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:16582911,
CC ECO:0000269|PubMed:17974561, ECO:0000269|PubMed:18296648,
CC ECO:0000269|PubMed:18559951, ECO:0000269|PubMed:19509291,
CC ECO:0000269|PubMed:19523899, ECO:0000269|PubMed:19815557,
CC ECO:0000269|PubMed:19836242, ECO:0000269|PubMed:19914172,
CC ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:20933011,
CC ECO:0000269|PubMed:21179510, ECO:0000269|PubMed:21930792,
CC ECO:0000269|PubMed:22027826, ECO:0000269|PubMed:22561606,
CC ECO:0000269|PubMed:23946459, ECO:0000269|PubMed:24098653,
CC ECO:0000269|PubMed:25092874, ECO:0000269|PubMed:27041574,
CC ECO:0000269|PubMed:29030480, ECO:0000269|PubMed:7664271,
CC ECO:0000269|PubMed:8262059, ECO:0000269|PubMed:8388384,
CC ECO:0000269|PubMed:8491186, ECO:0000269|PubMed:8493579,
CC ECO:0000269|PubMed:8723348, ECO:0000269|PubMed:8798570,
CC ECO:0000269|PubMed:9062191, ECO:0000269|PubMed:9108392,
CC ECO:0000269|PubMed:9148935, ECO:0000269|PubMed:9178760,
CC ECO:0000269|PubMed:9233773, ECO:0000269|PubMed:9422736,
CC ECO:0000269|PubMed:9484780, ECO:0000269|PubMed:9489702,
CC ECO:0000269|PubMed:9553137}.
CC -!- SUBUNIT: [Isoform 1]: Interacts (via SH2-domain) with SCIMP; this
CC interaction is dependent on phosphorylation of SCIMP 'Tyr-69'.
CC {ECO:0000269|PubMed:21930792}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via SH3 domain) with
CC hepatitis E virus/HEV ORF3 protein. {ECO:0000269|PubMed:11518702}.
CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C virus/HCV
CC protein NS5A via its SH3 domains. {ECO:0000269|PubMed:10318918}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC protein UL46. {ECO:0000269|PubMed:23946459}.
CC -!- INTERACTION:
CC P62993; Q9P2A4: ABI3; NbExp=3; IntAct=EBI-401755, EBI-742038;
CC P62993; P42684: ABL2; NbExp=2; IntAct=EBI-401755, EBI-1102694;
CC P62993; Q15027: ACAP1; NbExp=3; IntAct=EBI-401755, EBI-751746;
CC P62993; O14672: ADAM10; NbExp=5; IntAct=EBI-401755, EBI-1536151;
CC P62993; Q13444: ADAM15; NbExp=4; IntAct=EBI-401755, EBI-77818;
CC P62993; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-401755, EBI-10173507;
CC P62993; Q15109: AGER; NbExp=2; IntAct=EBI-401755, EBI-1646426;
CC P62993; O95994: AGR2; NbExp=5; IntAct=EBI-401755, EBI-712648;
CC P62993; Q01484: ANK2; NbExp=2; IntAct=EBI-401755, EBI-941975;
CC P62993; Q86SG2: ANKRD23; NbExp=3; IntAct=EBI-401755, EBI-5661893;
CC P62993; Q9BRR9: ARHGAP9; NbExp=3; IntAct=EBI-401755, EBI-750254;
CC P62993; P52566: ARHGDIB; NbExp=3; IntAct=EBI-401755, EBI-2806617;
CC P62993; Q12774: ARHGEF5; NbExp=7; IntAct=EBI-401755, EBI-602199;
CC P62993; Q03989: ARID5A; NbExp=3; IntAct=EBI-401755, EBI-948603;
CC P62993; Q66PJ3-4: ARL6IP4; NbExp=2; IntAct=EBI-401755, EBI-5280499;
CC P62993; Q9ULH1: ASAP1; NbExp=10; IntAct=EBI-401755, EBI-346622;
CC P62993; O43150: ASAP2; NbExp=3; IntAct=EBI-401755, EBI-310968;
CC P62993; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-401755, EBI-10254793;
CC P62993; P30530: AXL; NbExp=3; IntAct=EBI-401755, EBI-2850927;
CC P62993; P11274: BCR; NbExp=9; IntAct=EBI-401755, EBI-712838;
CC P62993; Q14457: BECN1; NbExp=3; IntAct=EBI-401755, EBI-949378;
CC P62993; Q8WV28: BLNK; NbExp=4; IntAct=EBI-401755, EBI-2623522;
CC P62993; O60885: BRD4; NbExp=2; IntAct=EBI-401755, EBI-723869;
CC P62993; P62324: BTG1; NbExp=3; IntAct=EBI-401755, EBI-742279;
CC P62993; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-401755, EBI-946029;
CC P62993; P22681: CBL; NbExp=13; IntAct=EBI-401755, EBI-518228;
CC P62993; Q13191: CBLB; NbExp=26; IntAct=EBI-401755, EBI-744027;
CC P62993; Q9BRT8: CBWD1; NbExp=3; IntAct=EBI-401755, EBI-1054417;
CC P62993; Q9BUN5-3: CCDC28B; NbExp=3; IntAct=EBI-401755, EBI-12920646;
CC P62993; Q9Y5K6: CD2AP; NbExp=3; IntAct=EBI-401755, EBI-298152;
CC P62993; Q8N684-3: CPSF7; NbExp=3; IntAct=EBI-401755, EBI-11523759;
CC P62993; P98082: DAB2; NbExp=2; IntAct=EBI-401755, EBI-1171238;
CC P62993; P14868: DARS1; NbExp=2; IntAct=EBI-401755, EBI-358730;
CC P62993; Q16643: DBN1; NbExp=4; IntAct=EBI-401755, EBI-351394;
CC P62993; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-401755, EBI-742054;
CC P62993; Q92841: DDX17; NbExp=3; IntAct=EBI-401755, EBI-746012;
CC P62993; O14490: DLGAP1; NbExp=3; IntAct=EBI-401755, EBI-1753207;
CC P62993; Q9P1A6: DLGAP2; NbExp=2; IntAct=EBI-401755, EBI-1753397;
CC P62993; Q9Y2H0: DLGAP4; NbExp=2; IntAct=EBI-401755, EBI-722139;
CC P62993; Q05193: DNM1; NbExp=5; IntAct=EBI-401755, EBI-713135;
CC P62993; P50570: DNM2; NbExp=8; IntAct=EBI-401755, EBI-346547;
CC P62993; Q14185: DOCK1; NbExp=5; IntAct=EBI-401755, EBI-446740;
CC P62993; Q8N1I0: DOCK4; NbExp=4; IntAct=EBI-401755, EBI-1059186;
CC P62993; Q7L190: DPPA4; NbExp=3; IntAct=EBI-401755, EBI-710457;
CC P62993; Q8N9I9: DTX3; NbExp=3; IntAct=EBI-401755, EBI-2340258;
CC P62993; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-401755, EBI-2349927;
CC P62993; P00533: EGFR; NbExp=45; IntAct=EBI-401755, EBI-297353;
CC P62993; Q9UI10: EIF2B4; NbExp=3; IntAct=EBI-401755, EBI-2340132;
CC P62993; P54762: EPHB1; NbExp=2; IntAct=EBI-401755, EBI-80252;
CC P62993; Q12929: EPS8; NbExp=3; IntAct=EBI-401755, EBI-375576;
CC P62993; P04626: ERBB2; NbExp=5; IntAct=EBI-401755, EBI-641062;
CC P62993; P21860: ERBB3; NbExp=3; IntAct=EBI-401755, EBI-720706;
CC P62993; Q9UJM3: ERRFI1; NbExp=16; IntAct=EBI-401755, EBI-2941912;
CC P62993; B7ZLH0: FAM22F; NbExp=6; IntAct=EBI-401755, EBI-10220102;
CC P62993; O15360: FANCA; NbExp=2; IntAct=EBI-401755, EBI-81570;
CC P62993; P21802: FGFR2; NbExp=5; IntAct=EBI-401755, EBI-1028658;
CC P62993; P21333: FLNA; NbExp=2; IntAct=EBI-401755, EBI-350432;
CC P62993; O75369: FLNB; NbExp=2; IntAct=EBI-401755, EBI-352089;
CC P62993; Q14315: FLNC; NbExp=2; IntAct=EBI-401755, EBI-489954;
CC P62993; Q13480: GAB1; NbExp=8; IntAct=EBI-401755, EBI-517684;
CC P62993; Q9UQC2: GAB2; NbExp=14; IntAct=EBI-401755, EBI-975200;
CC P62993; Q9H706: GAREM1; NbExp=11; IntAct=EBI-401755, EBI-3440103;
CC P62993; Q86UU5: GGN; NbExp=3; IntAct=EBI-401755, EBI-10259069;
CC P62993; Q9Y2X7: GIT1; NbExp=4; IntAct=EBI-401755, EBI-466061;
CC P62993; Q13322-4: GRB10; NbExp=3; IntAct=EBI-401755, EBI-12353035;
CC P62993; P62993: GRB2; NbExp=5; IntAct=EBI-401755, EBI-401755;
CC P62993; P61978: HNRNPK; NbExp=10; IntAct=EBI-401755, EBI-304185;
CC P62993; Q8IX15-3: HOMEZ; NbExp=3; IntAct=EBI-401755, EBI-10172004;
CC P62993; P11021: HSPA5; NbExp=4; IntAct=EBI-401755, EBI-354921;
CC P62993; Q9UKT9: IKZF3; NbExp=8; IntAct=EBI-401755, EBI-747204;
CC P62993; Q0VD86: INCA1; NbExp=4; IntAct=EBI-401755, EBI-6509505;
CC P62993; Q13352: ITGB3BP; NbExp=3; IntAct=EBI-401755, EBI-712105;
CC P62993; Q9NQC1-2: JADE2; NbExp=3; IntAct=EBI-401755, EBI-10311936;
CC P62993; Q07666: KHDRBS1; NbExp=8; IntAct=EBI-401755, EBI-1364;
CC P62993; Q6ZU52: KIAA0408; NbExp=3; IntAct=EBI-401755, EBI-739493;
CC P62993; P10721: KIT; NbExp=6; IntAct=EBI-401755, EBI-1379503;
CC P62993; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-401755, EBI-2796400;
CC P62993; P05787: KRT8; NbExp=3; IntAct=EBI-401755, EBI-297852;
CC P62993; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-401755, EBI-1048945;
CC P62993; O43561: LAT; NbExp=7; IntAct=EBI-401755, EBI-1222766;
CC P62993; Q13094: LCP2; NbExp=18; IntAct=EBI-401755, EBI-346946;
CC P62993; P48357: LEPR; NbExp=3; IntAct=EBI-401755, EBI-518596;
CC P62993; P25791: LMO2; NbExp=3; IntAct=EBI-401755, EBI-739696;
CC P62993; Q8TE12: LMX1A; NbExp=3; IntAct=EBI-401755, EBI-10692065;
CC P62993; Q8TBB1: LNX1; NbExp=4; IntAct=EBI-401755, EBI-739832;
CC P62993; Q14693: LPIN1; NbExp=3; IntAct=EBI-401755, EBI-5278370;
CC P62993; Q5SQ64: LY6G6F; NbExp=3; IntAct=EBI-401755, EBI-6963742;
CC P62993; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-401755, EBI-741037;
CC P62993; Q13163: MAP2K5; NbExp=2; IntAct=EBI-401755, EBI-307294;
CC P62993; Q92918: MAP4K1; NbExp=9; IntAct=EBI-401755, EBI-881;
CC P62993; Q8IVH8: MAP4K3; NbExp=2; IntAct=EBI-401755, EBI-1758170;
CC P62993; Q9Y4K4: MAP4K5; NbExp=6; IntAct=EBI-401755, EBI-1279;
CC P62993; A0JLT2-2: MED19; NbExp=3; IntAct=EBI-401755, EBI-13288755;
CC P62993; Q9H204: MED28; NbExp=3; IntAct=EBI-401755, EBI-514199;
CC P62993; A8MW99: MEI4; NbExp=3; IntAct=EBI-401755, EBI-19944212;
CC P62993; Q9HB07: MYG1; NbExp=3; IntAct=EBI-401755, EBI-709754;
CC P62993; P35579: MYH9; NbExp=3; IntAct=EBI-401755, EBI-350338;
CC P62993; Q8WX92: NELFB; NbExp=2; IntAct=EBI-401755, EBI-347721;
CC P62993; Q16236: NFE2L2; NbExp=2; IntAct=EBI-401755, EBI-2007911;
CC P62993; Q9GZT8: NIF3L1; NbExp=3; IntAct=EBI-401755, EBI-740897;
CC P62993; Q13177: PAK2; NbExp=2; IntAct=EBI-401755, EBI-1045887;
CC P62993; Q9NPB6-2: PARD6A; NbExp=3; IntAct=EBI-401755, EBI-10693102;
CC P62993; Q8N4B1-4: PHETA1; NbExp=3; IntAct=EBI-401755, EBI-14131832;
CC P62993; Q6ZUJ8: PIK3AP1; NbExp=5; IntAct=EBI-401755, EBI-2654168;
CC P62993; O00750: PIK3C2B; NbExp=5; IntAct=EBI-401755, EBI-641107;
CC P62993; P42336: PIK3CA; NbExp=5; IntAct=EBI-401755, EBI-2116585;
CC P62993; P27986: PIK3R1; NbExp=4; IntAct=EBI-401755, EBI-79464;
CC P62993; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-401755, EBI-9090282;
CC P62993; O00459: PIK3R2; NbExp=4; IntAct=EBI-401755, EBI-346930;
CC P62993; Q92569: PIK3R3; NbExp=4; IntAct=EBI-401755, EBI-79893;
CC P62993; P19174: PLCG1; NbExp=2; IntAct=EBI-401755, EBI-79387;
CC P62993; O14939: PLD2; NbExp=4; IntAct=EBI-401755, EBI-1053996;
CC P62993; Q6IQ23-2: PLEKHA7; NbExp=3; IntAct=EBI-401755, EBI-12069346;
CC P62993; Q5SXH7-1: PLEKHS1; NbExp=2; IntAct=EBI-401755, EBI-26412802;
CC P62993; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-401755, EBI-10171633;
CC P62993; Q07869: PPARA; NbExp=3; IntAct=EBI-401755, EBI-78615;
CC P62993; Q08209: PPP3CA; NbExp=3; IntAct=EBI-401755, EBI-352922;
CC P62993; Q9Y478: PRKAB1; NbExp=2; IntAct=EBI-401755, EBI-719769;
CC P62993; O14744: PRMT5; NbExp=4; IntAct=EBI-401755, EBI-351098;
CC P62993; B1AHC3: PRR5-ARHGAP8; NbExp=3; IntAct=EBI-401755, EBI-17437404;
CC P62993; Q05397: PTK2; NbExp=4; IntAct=EBI-401755, EBI-702142;
CC P62993; P18031: PTPN1; NbExp=4; IntAct=EBI-401755, EBI-968788;
CC P62993; Q06124: PTPN11; NbExp=10; IntAct=EBI-401755, EBI-297779;
CC P62993; Q9Y2R2: PTPN22; NbExp=2; IntAct=EBI-401755, EBI-1211241;
CC P62993; Q9H3S7: PTPN23; NbExp=7; IntAct=EBI-401755, EBI-724478;
CC P62993; P29350: PTPN6; NbExp=3; IntAct=EBI-401755, EBI-78260;
CC P62993; P18433: PTPRA; NbExp=13; IntAct=EBI-401755, EBI-2609645;
CC P62993; O14522: PTPRT; NbExp=2; IntAct=EBI-401755, EBI-728180;
CC P62993; Q15907: RAB11B; NbExp=3; IntAct=EBI-401755, EBI-722234;
CC P62993; P06400: RB1; NbExp=4; IntAct=EBI-401755, EBI-491274;
CC P62993; Q9BWF3-2: RBM4; NbExp=3; IntAct=EBI-401755, EBI-25856809;
CC P62993; Q04864: REL; NbExp=3; IntAct=EBI-401755, EBI-307352;
CC P62993; Q8NFH8: REPS2; NbExp=8; IntAct=EBI-401755, EBI-7067016;
CC P62993; Q9H0X6: RNF208; NbExp=3; IntAct=EBI-401755, EBI-751555;
CC P62993; Q15428: SF3A2; NbExp=3; IntAct=EBI-401755, EBI-2462271;
CC P62993; Q15427: SF3B4; NbExp=2; IntAct=EBI-401755, EBI-348469;
CC P62993; Q9NRF2-2: SH2B1; NbExp=3; IntAct=EBI-401755, EBI-10691662;
CC P62993; Q9H788: SH2D4A; NbExp=4; IntAct=EBI-401755, EBI-747035;
CC P62993; Q9UPX8: SHANK2; NbExp=2; IntAct=EBI-401755, EBI-1570571;
CC P62993; Q9BYB0: SHANK3; NbExp=2; IntAct=EBI-401755, EBI-1752330;
CC P62993; P29353: SHC1; NbExp=28; IntAct=EBI-401755, EBI-78835;
CC P62993; P29353-1: SHC1; NbExp=3; IntAct=EBI-401755, EBI-8160716;
CC P62993; Q8WXH5: SOCS4; NbExp=3; IntAct=EBI-401755, EBI-3942425;
CC P62993; O14512: SOCS7; NbExp=3; IntAct=EBI-401755, EBI-1539606;
CC P62993; Q07889: SOS1; NbExp=26; IntAct=EBI-401755, EBI-297487;
CC P62993; Q07890: SOS2; NbExp=11; IntAct=EBI-401755, EBI-298181;
CC P62993; Q8IUW3: SPATA2L; NbExp=4; IntAct=EBI-401755, EBI-2510414;
CC P62993; O43597: SPRY2; NbExp=3; IntAct=EBI-401755, EBI-742487;
CC P62993; O43295: SRGAP3; NbExp=2; IntAct=EBI-401755, EBI-368166;
CC P62993; O95630: STAMBP; NbExp=9; IntAct=EBI-401755, EBI-396676;
CC P62993; O15056: SYNJ2; NbExp=2; IntAct=EBI-401755, EBI-310513;
CC P62993; Q6DHY5: TBC1D3G; NbExp=3; IntAct=EBI-401755, EBI-13092532;
CC P62993; Q8N1K5: THEMIS; NbExp=10; IntAct=EBI-401755, EBI-2873538;
CC P62993; Q8N1K5-1: THEMIS; NbExp=10; IntAct=EBI-401755, EBI-15102259;
CC P62993; Q08117: TLE5; NbExp=3; IntAct=EBI-401755, EBI-717810;
CC P62993; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-401755, EBI-10694905;
CC P62993; Q8NFB2: TMEM185A; NbExp=3; IntAct=EBI-401755, EBI-21757569;
CC P62993; Q13829: TNFAIP1; NbExp=3; IntAct=EBI-401755, EBI-2505861;
CC P62993; Q92973: TNPO1; NbExp=2; IntAct=EBI-401755, EBI-286693;
CC P62993; O75674: TOM1L1; NbExp=2; IntAct=EBI-401755, EBI-712991;
CC P62993; Q13625-3: TP53BP2; NbExp=3; IntAct=EBI-401755, EBI-10175039;
CC P62993; Q9ULW0: TPX2; NbExp=2; IntAct=EBI-401755, EBI-1037322;
CC P62993; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-401755, EBI-492476;
CC P62993; P14373: TRIM27; NbExp=3; IntAct=EBI-401755, EBI-719493;
CC P62993; O60636: TSPAN2; NbExp=6; IntAct=EBI-401755, EBI-3914288;
CC P62993; P42681: TXK; NbExp=3; IntAct=EBI-401755, EBI-7877438;
CC P62993; Q06418: TYRO3; NbExp=3; IntAct=EBI-401755, EBI-3951628;
CC P62993; Q16851: UGP2; NbExp=2; IntAct=EBI-401755, EBI-743729;
CC P62993; P15498: VAV1; NbExp=3; IntAct=EBI-401755, EBI-625518;
CC P62993; Q9UKW4: VAV3; NbExp=8; IntAct=EBI-401755, EBI-297568;
CC P62993; P55072: VCP; NbExp=3; IntAct=EBI-401755, EBI-355164;
CC P62993; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-401755, EBI-2559305;
CC P62993; Q92558: WASF1; NbExp=3; IntAct=EBI-401755, EBI-1548747;
CC P62993; O00401: WASL; NbExp=11; IntAct=EBI-401755, EBI-957615;
CC P62993; Q9Y2W2: WBP11; NbExp=4; IntAct=EBI-401755, EBI-714455;
CC P62993; O43516: WIPF1; NbExp=4; IntAct=EBI-401755, EBI-346356;
CC P62993; Q8TF74: WIPF2; NbExp=6; IntAct=EBI-401755, EBI-2850112;
CC P62993; Q9Y330: ZBTB12; NbExp=5; IntAct=EBI-401755, EBI-12377219;
CC P62993; O15156: ZBTB7B; NbExp=3; IntAct=EBI-401755, EBI-740434;
CC P62993; Q9UNY5: ZNF232; NbExp=3; IntAct=EBI-401755, EBI-749023;
CC P62993; Q9BYN7: ZNF341; NbExp=3; IntAct=EBI-401755, EBI-9089622;
CC P62993; Q6S9Z5: ZNF474; NbExp=3; IntAct=EBI-401755, EBI-17269964;
CC P62993; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-401755, EBI-4395669;
CC P62993; Q7Z783; NbExp=3; IntAct=EBI-401755, EBI-9088990;
CC P62993; P98078: Dab2; Xeno; NbExp=4; IntAct=EBI-401755, EBI-1391846;
CC P62993; P35570: Irs1; Xeno; NbExp=5; IntAct=EBI-401755, EBI-520230;
CC P62993; Q7VLE8: lspA1; Xeno; NbExp=2; IntAct=EBI-401755, EBI-26445163;
CC P62993; P34152: Ptk2; Xeno; NbExp=3; IntAct=EBI-401755, EBI-77070;
CC P62993; P35235: Ptpn11; Xeno; NbExp=7; IntAct=EBI-401755, EBI-397236;
CC P62993; Q62245: Sos1; Xeno; NbExp=4; IntAct=EBI-401755, EBI-1693;
CC P62993; Q810M5: Zdhhc19; Xeno; NbExp=2; IntAct=EBI-401755, EBI-22225085;
CC P62993; O92972; Xeno; NbExp=2; IntAct=EBI-401755, EBI-710506;
CC P62993; PRO_0000037647 [P26662]; Xeno; NbExp=3; IntAct=EBI-401755, EBI-9099462;
CC P62993; P27958; Xeno; NbExp=3; IntAct=EBI-401755, EBI-706378;
CC P62993-1; Q9UQC2-1: GAB2; NbExp=3; IntAct=EBI-15787932, EBI-15787947;
CC P62993-1; O43561-2: LAT; NbExp=3; IntAct=EBI-15787932, EBI-8070286;
CC P62993-1; Q62245: Sos1; Xeno; NbExp=2; IntAct=EBI-15787932, EBI-1693;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21179510}. Cytoplasm
CC {ECO:0000269|PubMed:21179510}. Endosome {ECO:0000269|PubMed:21179510}.
CC Golgi apparatus {ECO:0000250|UniProtKB:Q60631}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=Ash-L;
CC IsoId=P62993-1, P29354-1;
CC Sequence=Displayed;
CC Name=2; Synonyms=GRB3-3;
CC IsoId=P62993-2, P29354-2;
CC Sequence=VSP_001839;
CC -!- DOMAIN: The SH3 domains mediate interaction with RALGPS1 and SHB.
CC -!- SIMILARITY: Belongs to the GRB2/sem-5/DRK family. {ECO:0000305}.
CC -!- CAUTION: Was shown to interact with ZDHHC19, leading to recruitment of
CC STAT3. However, this study was later retracted.
CC {ECO:0000305|PubMed:31462771, ECO:0000305|PubMed:32555452}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GRB2ID386ch17q25.html";
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DR EMBL; M96995; AAA58448.1; -; mRNA.
DR EMBL; X62852; CAA44664.1; -; mRNA.
DR EMBL; L29511; AAC37549.1; -; mRNA.
DR EMBL; AF063618; AAC72075.1; -; Genomic_DNA.
DR EMBL; AF063614; AAC72075.1; JOINED; Genomic_DNA.
DR EMBL; AF063615; AAC72075.1; JOINED; Genomic_DNA.
DR EMBL; AF063616; AAC72075.1; JOINED; Genomic_DNA.
DR EMBL; AF063617; AAC72075.1; JOINED; Genomic_DNA.
DR EMBL; AF498925; AAM21073.1; -; mRNA.
DR EMBL; CR541942; CAG46740.1; -; mRNA.
DR EMBL; AC011933; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000631; AAH00631.1; -; mRNA.
DR CCDS; CCDS11721.1; -.
DR CCDS; CCDS11722.1; -. [P62993-2]
DR PIR; A43321; A43321.
DR RefSeq; NP_002077.1; NM_002086.4. [P62993-1]
DR RefSeq; NP_987102.1; NM_203506.2. [P62993-2]
DR PDB; 1AZE; NMR; -; A=1-56.
DR PDB; 1BM2; X-ray; 2.10 A; A=49-163.
DR PDB; 1BMB; X-ray; 1.80 A; A=49-168.
DR PDB; 1CJ1; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L=57-152.
DR PDB; 1FHS; NMR; -; A=53-163.
DR PDB; 1FYR; X-ray; 2.40 A; A/B/C/D=50-161.
DR PDB; 1GCQ; X-ray; 1.68 A; A/B=159-217.
DR PDB; 1GFC; NMR; -; A=159-215.
DR PDB; 1GFD; NMR; -; A=159-215.
DR PDB; 1GHU; NMR; -; A=60-158.
DR PDB; 1GRI; X-ray; 3.10 A; A/B=1-217.
DR PDB; 1IO6; NMR; -; A=159-215.
DR PDB; 1JYQ; X-ray; 2.00 A; A/B=60-151.
DR PDB; 1JYR; X-ray; 1.55 A; A=60-151.
DR PDB; 1JYU; X-ray; 2.75 A; A=60-151.
DR PDB; 1QG1; NMR; -; E=58-159.
DR PDB; 1TZE; X-ray; 2.10 A; E=55-152.
DR PDB; 1X0N; NMR; -; A=58-159.
DR PDB; 1ZFP; X-ray; 1.80 A; E=56-153.
DR PDB; 2AOA; X-ray; 1.99 A; A/B=55-153.
DR PDB; 2AOB; X-ray; 1.80 A; A/B/C/D=55-153.
DR PDB; 2H46; X-ray; 1.90 A; E=53-162.
DR PDB; 2H5K; X-ray; 3.25 A; A/B=53-162.
DR PDB; 2HUW; X-ray; 1.90 A; A/B=53-162.
DR PDB; 2VVK; X-ray; 1.60 A; A=161-214.
DR PDB; 2VWF; X-ray; 1.58 A; A=159-214.
DR PDB; 2W0Z; X-ray; 1.70 A; A=159-214.
DR PDB; 3C7I; X-ray; 1.70 A; A=53-162.
DR PDB; 3IMD; X-ray; 2.00 A; A/B=53-163.
DR PDB; 3IMJ; X-ray; 2.02 A; A/B=53-163.
DR PDB; 3IN7; X-ray; 2.00 A; A/C=53-163.
DR PDB; 3IN8; X-ray; 1.70 A; A=53-163.
DR PDB; 3KFJ; X-ray; 2.02 A; A=53-163.
DR PDB; 3MXC; X-ray; 2.00 A; A=55-152.
DR PDB; 3MXY; X-ray; 2.30 A; A=55-152.
DR PDB; 3N7Y; X-ray; 2.02 A; A/B/C=55-152.
DR PDB; 3N84; X-ray; 2.00 A; A/B/C/D/E/F=53-163.
DR PDB; 3N8M; X-ray; 2.00 A; A=53-163.
DR PDB; 3OV1; X-ray; 1.60 A; A=53-163.
DR PDB; 3OVE; X-ray; 1.82 A; A=53-163.
DR PDB; 3S8L; X-ray; 1.71 A; A=53-163.
DR PDB; 3S8N; X-ray; 1.71 A; A=53-163.
DR PDB; 3S8O; X-ray; 1.85 A; A=53-163.
DR PDB; 3WA4; X-ray; 1.35 A; A=60-152.
DR PDB; 4P9V; X-ray; 1.64 A; A=53-163.
DR PDB; 4P9Z; X-ray; 1.80 A; A=53-163.
DR PDB; 5CDW; X-ray; 2.60 A; A/B/C/E/G/H/K/L/O/P/U/V/Y/Z/c/d=54-153.
DR PDB; 6ICG; X-ray; 1.15 A; A/B=60-152.
DR PDB; 6ICH; X-ray; 2.00 A; A=60-152.
DR PDB; 6SDF; X-ray; 2.50 A; A/B=2-59.
DR PDB; 6VK2; NMR; -; A=55-150.
DR PDB; 6WM1; X-ray; 1.80 A; A/C=53-163.
DR PDB; 6WO2; X-ray; 2.00 A; A/B=53-163.
DR PDB; 7MPH; X-ray; 2.00 A; A/B/C/D/E/F=59-152.
DR PDBsum; 1AZE; -.
DR PDBsum; 1BM2; -.
DR PDBsum; 1BMB; -.
DR PDBsum; 1CJ1; -.
DR PDBsum; 1FHS; -.
DR PDBsum; 1FYR; -.
DR PDBsum; 1GCQ; -.
DR PDBsum; 1GFC; -.
DR PDBsum; 1GFD; -.
DR PDBsum; 1GHU; -.
DR PDBsum; 1GRI; -.
DR PDBsum; 1IO6; -.
DR PDBsum; 1JYQ; -.
DR PDBsum; 1JYR; -.
DR PDBsum; 1JYU; -.
DR PDBsum; 1QG1; -.
DR PDBsum; 1TZE; -.
DR PDBsum; 1X0N; -.
DR PDBsum; 1ZFP; -.
DR PDBsum; 2AOA; -.
DR PDBsum; 2AOB; -.
DR PDBsum; 2H46; -.
DR PDBsum; 2H5K; -.
DR PDBsum; 2HUW; -.
DR PDBsum; 2VVK; -.
DR PDBsum; 2VWF; -.
DR PDBsum; 2W0Z; -.
DR PDBsum; 3C7I; -.
DR PDBsum; 3IMD; -.
DR PDBsum; 3IMJ; -.
DR PDBsum; 3IN7; -.
DR PDBsum; 3IN8; -.
DR PDBsum; 3KFJ; -.
DR PDBsum; 3MXC; -.
DR PDBsum; 3MXY; -.
DR PDBsum; 3N7Y; -.
DR PDBsum; 3N84; -.
DR PDBsum; 3N8M; -.
DR PDBsum; 3OV1; -.
DR PDBsum; 3OVE; -.
DR PDBsum; 3S8L; -.
DR PDBsum; 3S8N; -.
DR PDBsum; 3S8O; -.
DR PDBsum; 3WA4; -.
DR PDBsum; 4P9V; -.
DR PDBsum; 4P9Z; -.
DR PDBsum; 5CDW; -.
DR PDBsum; 6ICG; -.
DR PDBsum; 6ICH; -.
DR PDBsum; 6SDF; -.
DR PDBsum; 6VK2; -.
DR PDBsum; 6WM1; -.
DR PDBsum; 6WO2; -.
DR PDBsum; 7MPH; -.
DR AlphaFoldDB; P62993; -.
DR BMRB; P62993; -.
DR SMR; P62993; -.
DR BioGRID; 109142; 680.
DR CORUM; P62993; -.
DR DIP; DIP-29229N; -.
DR ELM; P62993; -.
DR IntAct; P62993; 860.
DR MINT; P62993; -.
DR STRING; 9606.ENSP00000376345; -.
DR BindingDB; P62993; -.
DR ChEMBL; CHEMBL3663; -.
DR DrugBank; DB03276; 4-[(10s,14s,18s)-18-(2-Amino-2-Oxoethyl)-14-(1-Naphthylmethyl)-8,17,20-Trioxo-7,16,19-Triazaspiro[5.14]Icos-11-En-10-Yl]Benzylphosphonic Acid.
DR DrugBank; DB00061; Pegademase.
DR DrugCentral; P62993; -.
DR MoonDB; P62993; Predicted.
DR iPTMnet; P62993; -.
DR MetOSite; P62993; -.
DR PhosphoSitePlus; P62993; -.
DR BioMuta; GRB2; -.
DR DMDM; 51702266; -.
DR OGP; P62993; -.
DR SWISS-2DPAGE; P62993; -.
DR CPTAC; CPTAC-1421; -.
DR CPTAC; CPTAC-1422; -.
DR CPTAC; CPTAC-1423; -.
DR CPTAC; CPTAC-1424; -.
DR CPTAC; CPTAC-1425; -.
DR CPTAC; CPTAC-1609; -.
DR CPTAC; CPTAC-699; -.
DR EPD; P62993; -.
DR jPOST; P62993; -.
DR MassIVE; P62993; -.
DR MaxQB; P62993; -.
DR PaxDb; P62993; -.
DR PeptideAtlas; P62993; -.
DR PRIDE; P62993; -.
DR ProteomicsDB; 57462; -.
DR ProteomicsDB; 57463; -. [P62993-2]
DR TopDownProteomics; P62993-1; -. [P62993-1]
DR TopDownProteomics; P62993-2; -. [P62993-2]
DR ABCD; P62993; 8 sequenced antibodies.
DR Antibodypedia; 3408; 692 antibodies from 44 providers.
DR CPTC; P62993; 1 antibody.
DR DNASU; 2885; -.
DR Ensembl; ENST00000316615.9; ENSP00000317360.5; ENSG00000177885.15. [P62993-2]
DR Ensembl; ENST00000316804.10; ENSP00000339007.4; ENSG00000177885.15. [P62993-1]
DR Ensembl; ENST00000392562.5; ENSP00000376345.1; ENSG00000177885.15. [P62993-1]
DR Ensembl; ENST00000392563.5; ENSP00000376346.1; ENSG00000177885.15. [P62993-2]
DR Ensembl; ENST00000392564.5; ENSP00000376347.1; ENSG00000177885.15. [P62993-1]
DR Ensembl; ENST00000648046.1; ENSP00000496913.1; ENSG00000177885.15. [P62993-1]
DR GeneID; 2885; -.
DR KEGG; hsa:2885; -.
DR MANE-Select; ENST00000316804.10; ENSP00000339007.4; NM_002086.5; NP_002077.1.
DR UCSC; uc002jnx.5; human.
DR CTD; 2885; -.
DR DisGeNET; 2885; -.
DR GeneCards; GRB2; -.
DR HGNC; HGNC:4566; GRB2.
DR HPA; ENSG00000177885; Low tissue specificity.
DR MIM; 108355; gene.
DR neXtProt; NX_P62993; -.
DR OpenTargets; ENSG00000177885; -.
DR PharmGKB; PA28962; -.
DR VEuPathDB; HostDB:ENSG00000177885; -.
DR eggNOG; KOG3601; Eukaryota.
DR GeneTree; ENSGT00940000155738; -.
DR HOGENOM; CLU_073617_1_0_1; -.
DR InParanoid; P62993; -.
DR OMA; MVPEEML; -.
DR PhylomeDB; P62993; -.
DR TreeFam; TF354288; -.
DR PathwayCommons; P62993; -.
DR Reactome; R-HSA-109704; PI3K Cascade. [P62993-1]
DR Reactome; R-HSA-112412; SOS-mediated signalling. [P62993-1]
DR Reactome; R-HSA-1236382; Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants. [P62993-1]
DR Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling. [P62993-1]
DR Reactome; R-HSA-1250347; SHC1 events in ERBB4 signaling. [P62993-1]
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. [P62993-1]
DR Reactome; R-HSA-1295596; Spry regulation of FGF signaling. [P62993-1]
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. [P62993-1]
DR Reactome; R-HSA-1433559; Regulation of KIT signaling. [P62993-1]
DR Reactome; R-HSA-167044; Signalling to RAS. [P62993-1]
DR Reactome; R-HSA-179812; GRB2 events in EGFR signaling. [P62993-1]
DR Reactome; R-HSA-180292; GAB1 signalosome. [P62993-1]
DR Reactome; R-HSA-180336; SHC1 events in EGFR signaling. [P62993-1]
DR Reactome; R-HSA-182971; EGFR downregulation. [P62993-1]
DR Reactome; R-HSA-1839117; Signaling by cytosolic FGFR1 fusion mutants. [P62993-1]
DR Reactome; R-HSA-186763; Downstream signal transduction. [P62993-1]
DR Reactome; R-HSA-1963640; GRB2 events in ERBB2 signaling. [P62993-1]
DR Reactome; R-HSA-1963642; PI3K events in ERBB2 signaling. [P62993-1]
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation. [P62993-1]
DR Reactome; R-HSA-210993; Tie2 Signaling. [P62993-1]
DR Reactome; R-HSA-2179392; EGFR Transactivation by Gastrin. [P62993-1]
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. [P62993-1]
DR Reactome; R-HSA-2424491; DAP12 signaling. [P62993-1]
DR Reactome; R-HSA-2428933; SHC-related events triggered by IGF1R. [P62993-1]
DR Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. [P62993-1]
DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. [P62993-1]
DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization. [P62993-1]
DR Reactome; R-HSA-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins. [P62993-1]
DR Reactome; R-HSA-375165; NCAM signaling for neurite out-growth. [P62993-1]
DR Reactome; R-HSA-388841; Costimulation by the CD28 family. [P62993-1]
DR Reactome; R-HSA-389359; CD28 dependent Vav1 pathway. [P62993-1]
DR Reactome; R-HSA-391160; Signal regulatory protein family interactions. [P62993-1]
DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling. [P62993-1]
DR Reactome; R-HSA-5637810; Constitutive Signaling by EGFRvIII. [P62993-1]
DR Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1. [P62993-1]
DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1. [P62993-1]
DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling. [P62993-1]
DR Reactome; R-HSA-5654695; PI-3K cascade:FGFR2. [P62993-1]
DR Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2. [P62993-1]
DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling. [P62993-1]
DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3. [P62993-1]
DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling. [P62993-1]
DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3. [P62993-1]
DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling. [P62993-1]
DR Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4. [P62993-1]
DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4. [P62993-1]
DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling. [P62993-1]
DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling. [P62993-1]
DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling. [P62993-1]
DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling. [P62993-1]
DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease. [P62993-1]
DR Reactome; R-HSA-5655291; Signaling by FGFR4 in disease. [P62993-1]
DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. [P62993-1]
DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease. [P62993-1]
DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs. [P62993-1]
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. [P62993-1]
DR Reactome; R-HSA-6807004; Negative regulation of MET activity. [P62993-1]
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. [P62993-1]
DR Reactome; R-HSA-74749; Signal attenuation. [P62993-1]
DR Reactome; R-HSA-74751; Insulin receptor signalling cascade. [P62993-1]
DR Reactome; R-HSA-8851805; MET activates RAS signaling. [P62993-1]
DR Reactome; R-HSA-8851907; MET activates PI3K/AKT signaling. [P62993-1]
DR Reactome; R-HSA-8853659; RET signaling. [P62993-1]
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. [P62993-1]
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. [P62993-1]
DR Reactome; R-HSA-8865999; MET activates PTPN11. [P62993-1]
DR Reactome; R-HSA-8875360; InlB-mediated entry of Listeria monocytogenes into host cell. [P62993-1]
DR Reactome; R-HSA-8875555; MET activates RAP1 and RAC1. [P62993-1]
DR Reactome; R-HSA-8875656; MET receptor recycling. [P62993-1]
DR Reactome; R-HSA-8983432; Interleukin-15 signaling.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle. [P62993-1]
DR Reactome; R-HSA-9026519; Activated NTRK2 signals through RAS. [P62993-1]
DR Reactome; R-HSA-9027284; Erythropoietin activates RAS. [P62993-1]
DR Reactome; R-HSA-9028335; Activated NTRK2 signals through PI3K. [P62993-1]
DR Reactome; R-HSA-9028731; Activated NTRK2 signals through FRS2 and FRS3. [P62993-1]
DR Reactome; R-HSA-9034864; Activated NTRK3 signals through RAS. [P62993-1]
DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling. [P62993-1]
DR Reactome; R-HSA-912631; Regulation of signaling by CBL. [P62993-1]
DR Reactome; R-HSA-9607240; FLT3 Signaling. [P62993-1]
DR Reactome; R-HSA-9634285; Constitutive Signaling by Overexpressed ERBB2. [P62993-1]
DR Reactome; R-HSA-9645135; STAT5 Activation. [P62993-1]
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis. [P62993-1]
DR Reactome; R-HSA-9664565; Signaling by ERBB2 KD Mutants. [P62993-1]
DR Reactome; R-HSA-9665348; Signaling by ERBB2 ECD mutants. [P62993-1]
DR Reactome; R-HSA-9665686; Signaling by ERBB2 TMD/JMD mutants. [P62993-1]
DR Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants. [P62993-1]
DR Reactome; R-HSA-9673767; Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants. [P62993-1]
DR Reactome; R-HSA-9673770; Signaling by PDGFRA extracellular domain mutants. [P62993-1]
DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-HSA-9702518; STAT5 activation downstream of FLT3 ITD mutants.
DR Reactome; R-HSA-9703465; Signaling by FLT3 fusion proteins. [P62993-1]
DR Reactome; R-HSA-9703648; Signaling by FLT3 ITD and TKD mutants.
DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants.
DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. [P62993-1]
DR SignaLink; P62993; -.
DR SIGNOR; P62993; -.
DR BioGRID-ORCS; 2885; 573 hits in 1095 CRISPR screens.
DR ChiTaRS; GRB2; human.
DR EvolutionaryTrace; P62993; -.
DR GeneWiki; GRB2; -.
DR GenomeRNAi; 2885; -.
DR Pharos; P62993; Tchem.
DR PRO; PR:P62993; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P62993; protein.
DR Bgee; ENSG00000177885; Expressed in monocyte and 198 other tissues.
DR ExpressionAtlas; P62993; baseline and differential.
DR Genevisible; P62993; HS.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:HGNC-UCL.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0070436; C:Grb2-EGFR complex; IDA:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0012506; C:vesicle membrane; IEA:Ensembl.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0043560; F:insulin receptor substrate binding; IPI:UniProtKB.
DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; IPI:UniProtKB.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0017124; F:SH3 domain binding; IDA:UniProtKB.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IEA:Ensembl.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IEA:Ensembl.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:BHF-UCL.
DR GO; GO:0035987; P:endodermal cell differentiation; IEA:Ensembl.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IPI:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IEA:Ensembl.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:BHF-UCL.
DR GO; GO:0007265; P:Ras protein signal transduction; TAS:UniProtKB.
DR GO; GO:0031623; P:receptor internalization; IMP:BHF-UCL.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0042770; P:signal transduction in response to DNA damage; IMP:BHF-UCL.
DR CDD; cd11949; SH3_GRB2_C; 1.
DR CDD; cd11946; SH3_GRB2_N; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR IDEAL; IID00459; -.
DR InterPro; IPR035643; GRB2_C_SH3.
DR InterPro; IPR035641; GRB2_N_SH3.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 2.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 2.
DR SUPFAM; SSF50044; SSF50044; 2.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Endosome; Golgi apparatus;
KW Host-virus interaction; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; SH2 domain; SH3 domain.
FT CHAIN 1..217
FT /note="Growth factor receptor-bound protein 2"
FT /id="PRO_0000088198"
FT DOMAIN 1..58
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 60..152
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 156..215
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 6
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 50
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 109
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 211
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 60..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8178156"
FT /id="VSP_001839"
FT MUTAGEN 49
FT /note="P->L: Ineffective in DNA synthesis. Abolishes
FT interaction with SHB; when associated with L-206. Abolishes
FT interaction with SOS1."
FT /evidence="ECO:0000269|PubMed:1322798,
FT ECO:0000269|PubMed:8493579, ECO:0000269|PubMed:9484780"
FT MUTAGEN 89
FT /note="E->K: No effect on the interaction with SOS1."
FT /evidence="ECO:0000269|PubMed:8493579"
FT MUTAGEN 90
FT /note="S->N: No effect on the interaction with SOS1."
FT /evidence="ECO:0000269|PubMed:8493579"
FT MUTAGEN 203
FT /note="G->R: Ineffective in DNA synthesis. Abolishes
FT interaction with SOS1."
FT /evidence="ECO:0000269|PubMed:1322798,
FT ECO:0000269|PubMed:8493579"
FT MUTAGEN 206
FT /note="P->L: Abolishes interaction with SHB; when
FT associated with L-49."
FT /evidence="ECO:0000269|PubMed:9484780"
FT STRAND 2..7
FT /evidence="ECO:0007829|PDB:6SDF"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:1GRI"
FT STRAND 24..28
FT /evidence="ECO:0007829|PDB:6SDF"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:6SDF"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:6SDF"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:6SDF"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:6SDF"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:3IMD"
FT HELIX 67..75
FT /evidence="ECO:0007829|PDB:6ICG"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:1FHS"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:6ICG"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:6ICG"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:6ICG"
FT STRAND 104..112
FT /evidence="ECO:0007829|PDB:6ICG"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:1GRI"
FT STRAND 118..122
FT /evidence="ECO:0007829|PDB:6ICG"
FT STRAND 124..127
FT /evidence="ECO:0007829|PDB:6ICG"
FT HELIX 128..135
FT /evidence="ECO:0007829|PDB:6ICG"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:6ICG"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:1FHS"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:1QG1"
FT STRAND 160..165
FT /evidence="ECO:0007829|PDB:2VWF"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:1IO6"
FT STRAND 182..187
FT /evidence="ECO:0007829|PDB:2VWF"
FT STRAND 190..198
FT /evidence="ECO:0007829|PDB:2VWF"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:2VWF"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:2VWF"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:2VWF"
SQ SEQUENCE 217 AA; 25206 MW; 83A4B0BA1B248DC4 CRC64;
MEAIAKYDFK ATADDELSFK RGDILKVLNE ECDQNWYKAE LNGKDGFIPK NYIEMKPHPW
FFGKIPRAKA EEMLSKQRHD GAFLIRESES APGDFSLSVK FGNDVQHFKV LRDGAGKYFL
WVVKFNSLNE LVDYHRSTSV SRNQQIFLRD IEQVPQQPTY VQALFDFDPQ EDGELGFRRG
DFIHVMDNSD PNWWKGACHG QTGMFPRNYV TPVNRNV
