GRB2_MOUSE
ID GRB2_MOUSE Reviewed; 217 AA.
AC Q60631; Q61240;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Growth factor receptor-bound protein 2;
DE AltName: Full=Adapter protein GRB2;
DE AltName: Full=SH2/SH3 adapter GRB2;
GN Name=Grb2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=7689150; DOI=10.1128/mcb.13.9.5500-5512.1993;
RA Suen K., Bustelo X.R., Pawson T., Barbacid M.;
RT "Molecular cloning of the mouse grb2 gene: differential interaction of the
RT Grb2 adaptor protein with epidermal growth factor and nerve growth factor
RT receptors.";
RL Mol. Cell. Biol. 13:5500-5512(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=BALB/cJ;
RA Tanaka S.;
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Mammary gland;
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 [4]
RP PROTEIN SEQUENCE OF 125-136, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hippocampus;
RA Lubec G., Klug S.;
RL Submitted (MAR-2007) to UniProtKB.
RN [5]
RP INTERACTION WITH PTK2/FAK1.
RX PubMed=7997267; DOI=10.1038/372786a0;
RA Schlaepfer D.D., Hanks S.K., Hunter T., van der Geer P.;
RT "Integrin-mediated signal transduction linked to Ras pathway by GRB2
RT binding to focal adhesion kinase.";
RL Nature 372:786-791(1994).
RN [6]
RP INTERACTION WITH PDGFRA AND PTPN11.
RX PubMed=8943348; DOI=10.1128/mcb.16.12.6926;
RA Bazenet C.E., Gelderloos J.A., Kazlauskas A.;
RT "Phosphorylation of tyrosine 720 in the platelet-derived growth factor
RT alpha receptor is required for binding of Grb2 and SHP-2 but not for
RT activation of Ras or cell proliferation.";
RL Mol. Cell. Biol. 16:6926-6936(1996).
RN [7]
RP INTERACTION WITH CSF1R, AND PHOSPHORYLATION.
RX PubMed=9312046; DOI=10.1093/emboj/16.19.5880;
RA Bourette R.P., Myles G.M., Choi J.L., Rohrschneider L.R.;
RT "Sequential activation of phoshatidylinositol 3-kinase and phospholipase C-
RT gamma2 by the M-CSF receptor is necessary for differentiation signaling.";
RL EMBO J. 16:5880-5893(1997).
RN [8]
RP INTERACTION WITH REPS1.
RC TISSUE=Muscle;
RX PubMed=9395447; DOI=10.1074/jbc.272.50.31230;
RA Yamaguchi A., Urano T., Goi T., Feig L.A.;
RT "An eps homology (EH) domain protein that binds to the ral-GTPase target,
RT RalBP1.";
RL J. Biol. Chem. 272:31230-31234(1997).
RN [9]
RP INTERACTION WITH FLT1.
RX PubMed=9722576; DOI=10.1074/jbc.273.36.23410;
RA Ito N., Wernstedt C., Engstrom U., Claesson-Welsh L.;
RT "Identification of vascular endothelial growth factor receptor-1 tyrosine
RT phosphorylation sites and binding of SH2 domain-containing molecules.";
RL J. Biol. Chem. 273:23410-23418(1998).
RN [10]
RP INTERACTION WITH DAB2.
RX PubMed=9569023; DOI=10.1038/sj.onc.1201678;
RA Xu X.X., Yi T., Tang B., Lambeth J.D.;
RT "Disabled-2 (Dab2) is an SH3 domain-binding partner of Grb2.";
RL Oncogene 16:1561-1569(1998).
RN [11]
RP INTERACTION WITH KIT.
RX PubMed=10377264; DOI=10.1042/bj3410211;
RA Thommes K., Lennartsson J., Carlberg M., Ronnstrand L.;
RT "Identification of Tyr-703 and Tyr-936 as the primary association sites for
RT Grb2 and Grb7 in the c-Kit/stem cell factor receptor.";
RL Biochem. J. 341:211-216(1999).
RN [12]
RP INTERACTION WITH GAB2.
RX PubMed=10068651;
RA Nishida K., Yoshida Y., Itoh M., Fukada T., Ohtani T., Shirogane T.,
RA Atsumi T., Takahashi-Tezuka M., Ishihara K., Hibi M., Hirano T.;
RT "Gab-family adapter proteins act downstream of cytokine and growth factor
RT receptors and T- and B-cell antigen receptors.";
RL Blood 93:1809-1816(1999).
RN [13]
RP INTERACTION WITH TEK/TIE2.
RX PubMed=10521483; DOI=10.1074/jbc.274.43.30896;
RA Jones N., Master Z., Jones J., Bouchard D., Gunji Y., Sasaki H., Daly R.,
RA Alitalo K., Dumont D.J.;
RT "Identification of Tek/Tie2 binding partners. Binding to a multifunctional
RT docking site mediates cell survival and migration.";
RL J. Biol. Chem. 274:30896-30905(1999).
RN [14]
RP INTERACTION WITH AJUBA.
RX PubMed=10330178; DOI=10.1128/mcb.19.6.4379;
RA Goyal R.K., Lin P., Kanungo J., Payne A.S., Muslin A.J., Longmore G.D.;
RT "Ajuba, a novel LIM protein, interacts with Grb2, augments mitogen-
RT activated protein kinase activity in fibroblasts, and promotes meiotic
RT maturation of Xenopus oocytes in a Grb2- and Ras-dependent manner.";
RL Mol. Cell. Biol. 19:4379-4389(1999).
RN [15]
RP INTERACTION WITH SNTA1.
RX PubMed=11551227; DOI=10.1021/bi010490n;
RA Oak S.A., Russo K., Petrucci T.C., Jarrett H.W.;
RT "Mouse alpha1-syntrophin binding to Grb2: further evidence of a role for
RT syntrophin in cell signaling.";
RL Biochemistry 40:11270-11278(2001).
RN [16]
RP INTERACTION WITH CLNK.
RX PubMed=11463797; DOI=10.1074/jbc.m106390200;
RA Goitsuka R., Tatsuno A., Ishiai M., Kurosaki T., Kitamura D.;
RT "MIST functions through distinct domains in immunoreceptor signaling in the
RT presence and absence of LAT.";
RL J. Biol. Chem. 276:36043-36050(2001).
RN [17]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PRNP.
RX PubMed=11571277; DOI=10.1074/jbc.m103289200;
RA Spielhaupter C., Schaetzl H.M.;
RT "PrPC directly interacts with proteins involved in signaling pathways.";
RL J. Biol. Chem. 276:44604-44612(2001).
RN [18]
RP INTERACTION WITH IRS4.
RX PubMed=11113178; DOI=10.1128/mcb.21.1.26-38.2001;
RA Tsuruzoe K., Emkey R., Kriauciunas K.M., Ueki K., Kahn C.R.;
RT "Insulin receptor substrate 3 (IRS-3) and IRS-4 impair IRS-1- and IRS-2-
RT mediated signaling.";
RL Mol. Cell. Biol. 21:26-38(2001).
RN [19]
RP INTERACTION WITH TOM1L1.
RX PubMed=11711534; DOI=10.1074/jbc.m106813200;
RA Seykora J.T., Mei L., Dotto G.P., Stein P.L.;
RT "'Srcasm: a novel Src activating and signaling molecule.";
RL J. Biol. Chem. 277:2812-2822(2002).
RN [20]
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 [21]
RP INTERACTION WITH LIME1.
RX PubMed=14610044; DOI=10.1084/jem.20030232;
RA Hur E.M., Son M., Lee O.-H., Choi Y.B., Park C., Lee H., Yun Y.;
RT "LIME, a novel transmembrane adaptor protein, associates with p56lck and
RT mediates T cell activation.";
RL J. Exp. Med. 198:1463-1473(2003).
RN [22]
RP INTERACTION WITH LAT2.
RX PubMed=15477350; DOI=10.1084/jem.20041223;
RA Zhu M., Liu Y., Koonpaew S., Granillo O., Zhang W.;
RT "Positive and negative regulation of FcepsilonRI-mediated signaling by the
RT adaptor protein LAB/NTAL.";
RL J. Exp. Med. 200:991-1000(2004).
RN [23]
RP INTERACTION WITH LAT2.
RX PubMed=15477348; DOI=10.1084/jem.20041213;
RA Volna P., Lebduska P., Draberova L., Simova S., Heneberg P., Boubelik M.,
RA Bugajev V., Malissen B., Wilson B.S., Horejsi V., Malissen M., Draber P.;
RT "Negative regulation of mast cell signaling and function by the adaptor
RT LAB/NTAL.";
RL J. Exp. Med. 200:1001-1013(2004).
RN [24]
RP INTERACTION WITH LIME1.
RX PubMed=16249387; DOI=10.1182/blood-2005-05-1859;
RA Ahn E., Lee H., Yun Y.;
RT "LIME acts as a transmembrane adapter mediating BCR-dependent B-cell
RT activation.";
RL Blood 107:1521-1527(2006).
RN [25]
RP INTERACTION WITH KDR.
RX PubMed=16966330; DOI=10.1074/jbc.m603928200;
RA Lamalice L., Houle F., Huot J.;
RT "Phosphorylation of Tyr1214 within VEGFR-2 triggers the recruitment of Nck
RT and activation of Fyn leading to SAPK2/p38 activation and endothelial cell
RT migration in response to VEGF.";
RL J. Biol. Chem. 281:34009-34020(2006).
RN [26]
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 [27]
RP INTERACTION WITH THEMIS.
RX PubMed=19597498; DOI=10.1038/ni.1768;
RA Lesourne R., Uehara S., Lee J., Song K.-D., Li L., Pinkhasov J., Zhang Y.,
RA Weng N.-P., Wildt K.F., Wang L., Bosselut R., Love P.E.;
RT "Themis, a T cell-specific protein important for late thymocyte
RT development.";
RL Nat. Immunol. 10:840-847(2009).
RN [28]
RP INTERACTION WITH THEMIS.
RX PubMed=19597497; DOI=10.1038/ni.1769;
RA Johnson A.L., Aravind L., Shulzhenko N., Morgun A., Choi S.-Y.,
RA Crockford T.L., Lambe T., Domaschenz H., Kucharska E.M., Zheng L.,
RA Vinuesa C.G., Lenardo M.J., Goodnow C.C., Cornall R.J., Schwartz R.H.;
RT "Themis is a member of a new metazoan gene family and is required for the
RT completion of thymocyte positive selection.";
RL Nat. Immunol. 10:831-839(2009).
RN [29]
RP INTERACTION WITH THEMIS.
RX PubMed=19805304; DOI=10.1073/pnas.0908593106;
RA Patrick M.S., Oda H., Hayakawa K., Sato Y., Eshima K., Kirikae T.,
RA Iemura S., Shirai M., Abe T., Natsume T., Sasazuki T., Suzuki H.;
RT "Gasp, a Grb2-associating protein, is critical for positive selection of
RT thymocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:16345-16350(2009).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [31]
RP INTERACTION WITH PTPRH; PTPRO AND PTPRB.
RX PubMed=20398064; DOI=10.1111/j.1365-2443.2010.01398.x;
RA Murata Y., Mori M., Kotani T., Supriatna Y., Okazawa H., Kusakari S.,
RA Saito Y., Ohnishi H., Matozaki T.;
RT "Tyrosine phosphorylation of R3 subtype receptor-type protein tyrosine
RT phosphatases and their complex formations with Grb2 or Fyn.";
RL Genes Cells 15:513-524(2010).
RN [32]
RP INTERACTION WITH THEMIS2.
RX PubMed=20644716; DOI=10.1371/journal.pone.0011465;
RA Peirce M.J., Brook M., Morrice N., Snelgrove R., Begum S., Lanfrancotti A.,
RA Notley C., Hussell T., Cope A.P., Wait R.;
RT "Themis2/ICB1 is a signaling scaffold that selectively regulates macrophage
RT Toll-like receptor signaling and cytokine production.";
RL PLoS ONE 5:E11465-E11465(2010).
RN [33]
RP INTERACTION WITH RAB13.
RX PubMed=21543326; DOI=10.1074/jbc.m111.245209;
RA Wu C., Agrawal S., Vasanji A., Drazba J., Sarkaria S., Xie J., Welch C.M.,
RA Liu M., Anand-Apte B., Horowitz A.;
RT "Rab13-dependent trafficking of RhoA is required for directional migration
RT and angiogenesis.";
RL J. Biol. Chem. 286:23511-23520(2011).
RN [34]
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 [35]
RP INTERACTION WITH LAT; PLCG1 AND THEMIS.
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 [36]
RP INTERACTION WITH SCIMP.
RX PubMed=28290451; DOI=10.1038/icb.2017.10;
RA Luo L., Tong S.J., Wall A.A., Khromykh T., Sweet M.J., Stow J.L.;
RT "Development of SH2 probes and pull-down assays to detect pathogen-induced,
RT site-specific tyrosine phosphorylation of the TLR adaptor SCIMP.";
RL Immunol. Cell Biol. 95:564-570(2017).
RN [37]
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH SCIMP, AND TISSUE
RP SPECIFICITY.
RX PubMed=28098138; DOI=10.1038/ncomms14133;
RA Luo L., Bokil N.J., Wall A.A., Kapetanovic R., Lansdaal N.M., Marceline F.,
RA Burgess B.J., Tong S.J., Guo Z., Alexandrov K., Ross I.L., Hibbs M.L.,
RA Stow J.L., Sweet M.J.;
RT "SCIMP is a transmembrane non-TIR TLR adaptor that promotes proinflammatory
RT cytokine production from macrophages.";
RL Nat. Commun. 8:14133-14133(2017).
RN [38]
RP INTERACTION WITH LRRC8A.
RX PubMed=32930093; DOI=10.7554/elife.58941;
RA Kumar A., Xie L., Ta C.M., Hinton A.O., Gunasekar S.K., Minerath R.A.,
RA Shen K., Maurer J.M., Grueter C.E., Abel E.D., Meyer G., Sah R.;
RT "SWELL1 regulates skeletal muscle cell size, intracellular signaling,
RT adiposity and glucose metabolism.";
RL Elife 9:0-0(2020).
RN [39]
RP STRUCTURE BY NMR OF 1-65.
RX PubMed=9135122; DOI=10.1006/jmbi.1996.0886;
RA Wittekind M., Mapelli C., Lee V., Goldfarb V., Friedrichs M.S.,
RA Meyers C.A., Mueller L.;
RT "Solution structure of the Grb2 N-terminal SH3 domain complexed with a ten-
RT residue peptide derived from SOS: direct refinement against NOEs, J-
RT couplings and 1H and 13C chemical shifts.";
RL J. Mol. Biol. 267:933-952(1997).
CC -!- FUNCTION: Adapter protein that provides a critical link between cell
CC surface growth factor receptors and the Ras signaling pathway.
CC {ECO:0000250|UniProtKB:P62993}.
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:0000250|UniProtKB:P62993}.
CC -!- SUBUNIT: Associates (via SH2 domain) with activated EGF and PDGF
CC receptors (tyrosine phosphorylated) (By similarity). Interacts with
CC PDGFRA (tyrosine phosphorylated); the interaction may be indirect
CC (PubMed:8943348). Interacts with IRS4 (when Tyr-phosphorylated)
CC (PubMed:11113178). Also associates to other cellular Tyr-phosphorylated
CC proteins such as SIT1, IRS1, SHC and LNK; probably via the concerted
CC action of both its SH2 and SH3 domains (By similarity). It also seems
CC to interact with RAS in the signaling pathway leading to DNA synthesis.
CC Interacts with SOS1 (By similarity). Forms a complex with MUC1 and
CC SOS1, through interaction of the SH3 domains with SOS1 and the SH2
CC domain with phosphorylated MUC1 (By similarity). Interacts with
CC phosphorylated MET (By similarity). Interacts with phosphorylated
CC TOM1L1 (PubMed:11711534). Interacts with the phosphorylated C-terminus
CC of SH2B2 (By similarity). Interacts with phosphorylated SIT1, LAX1,
CC LAT, LAT2 and LIME1 upon TCR and/or BCR activation (By similarity)
CC (PubMed:16249387, PubMed:14610044, PubMed:15477350, PubMed:15477348,
CC PubMed:22561606). Interacts with NISCH, PTPNS1 and REPS2 (By
CC similarity). Interacts with syntrophin SNTA1 (PubMed:11551227).
CC Interacts (via SH3 domains) with REPS1 (PubMed:9395447). Interacts (via
CC SH3 domains) with PIK3C2B (By similarity). Interacts with CBL and CBLB
CC (By similarity). Interacts with AJUBA and CLNK (PubMed:10330178,
CC PubMed:11463797). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine
CC phosphorylated) (PubMed:10521483). Interacts with SHB, INPP5D/SHIP1,
CC SKAP1 and SKAP2 (By similarity). Interacts with PTPN11
CC (PubMed:8943348). Interacts with PRNP (PubMed:11571277). Interacts with
CC RALGPS1 (By similarity). Interacts also with HCST (PubMed:16582911).
CC Interacts with KDR (PubMed:16966330). Interacts with FLT1 (tyrosine-
CC phosphorylated) (PubMed:9722576). Interacts with GAPT and PTPRE (By
CC similarity). Interacts (via SH2 domain) with KIF26A (By similarity).
CC Interacts (via SH3 2) with GAB2 (PubMed:10068651). Interacts with
CC ADAM15 (By similarity). Interacts with THEMIS2 (PubMed:20644716).
CC Interacts (via SH2 domain) with AXL (phosphorylated) (By similarity).
CC Interacts (via SH2 domain) with KIT (phosphorylated) (PubMed:10377264).
CC Interacts with PTPRJ and BCR (By similarity). Interacts with PTPN23 (By
CC similarity). Interacts with FLT4 (tyrosine phosphorylated) (By
CC similarity). Interacts with EPHB1 and SHC1; activates the MAPK/ERK
CC cascade to regulate cell migration (PubMed:12925710). Part of a complex
CC including TNK2, GRB2 and one receptor tyrosine kinase (RTK) such as AXL
CC and PDGFRL, in which GRB2 promotes RTK recruitment by TNK2 (By
CC similarity). Interacts (via SH2 domain) with CSF1R (tyrosine
CC phosphorylated) (PubMed:9312046). Interacts with ERBB4 (By similarity).
CC Interacts with NTRK1 (phosphorylated upon ligand-binding) (By
CC similarity). Interacts with PTK2/FAK1 (tyrosine phosphorylated)
CC (PubMed:7997267). Interacts with PTK2B/PYK2 (tyrosine phosphorylated)
CC (By similarity). Interacts (via SH2-domain) with SCIMP; this
CC interaction is dependent on phosphorylation of SCIMP 'Tyr-58'
CC (PubMed:21930792, PubMed:28098138, PubMed:28290451). Interacts (via SH3
CC domains) with GAREM1 (via proline-rich domain and tyrosine
CC phosphorylated); the interaction occurs upon EGF stimulation (By
CC similarity). Interacts with DAB2 (PubMed:9569023). Interacts with
CC TESPA1 (By similarity). Interacts with THEMIS (PubMed:19597498,
CC PubMed:19597497, PubMed:19805304, PubMed:22561606). Interacts with
CC PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the
CC association is weaker in the absence of TESPA1 (PubMed:22561606).
CC Interacts with CD28 (By similarity). Interacts with RAB13; may recruit
CC RAB13 to the leading edge of migrating endothelial cells where it can
CC activate RHOA (PubMed:21543326). Interacts with ASAP3 (phosphorylated
CC form) (By similarity). Interacts (via SH2 domain) with PTPRH
CC (phosphorylated form) (PubMed:20398064). Interacts with PTPRO
CC (phosphorylated form) (PubMed:20398064). Interacts with PTPRB
CC (phosphorylated form) (PubMed:20398064). Interacts (via SH3 domain 2)
CC with PRR14 (via proline-rich region) (By similarity). Interacts with
CC DENND2B (By similarity). Interacts with SPRY2 (By similarity).
CC Interacts with LRRC8A (PubMed:32930093). {ECO:0000250|UniProtKB:P62993,
CC ECO:0000269|PubMed:10068651, ECO:0000269|PubMed:10330178,
CC ECO:0000269|PubMed:10377264, ECO:0000269|PubMed:10521483,
CC ECO:0000269|PubMed:11113178, ECO:0000269|PubMed:11463797,
CC ECO:0000269|PubMed:11551227, ECO:0000269|PubMed:11571277,
CC ECO:0000269|PubMed:11711534, ECO:0000269|PubMed:12925710,
CC ECO:0000269|PubMed:14610044, ECO:0000269|PubMed:15477348,
CC ECO:0000269|PubMed:15477350, ECO:0000269|PubMed:16249387,
CC ECO:0000269|PubMed:16582911, ECO:0000269|PubMed:16966330,
CC ECO:0000269|PubMed:19597497, ECO:0000269|PubMed:19597498,
CC ECO:0000269|PubMed:19805304, ECO:0000269|PubMed:20398064,
CC ECO:0000269|PubMed:20644716, ECO:0000269|PubMed:21543326,
CC ECO:0000269|PubMed:21930792, ECO:0000269|PubMed:22561606,
CC ECO:0000269|PubMed:28098138, ECO:0000269|PubMed:28290451,
CC ECO:0000269|PubMed:32930093, ECO:0000269|PubMed:7997267,
CC ECO:0000269|PubMed:8943348, ECO:0000269|PubMed:9312046,
CC ECO:0000269|PubMed:9395447, ECO:0000269|PubMed:9569023,
CC ECO:0000269|PubMed:9722576}.
CC -!- INTERACTION:
CC Q60631; O54737: Blnk; NbExp=4; IntAct=EBI-1688, EBI-641814;
CC Q60631; P35991: Btk; NbExp=4; IntAct=EBI-1688, EBI-625119;
CC Q60631; B9EKI5: Cblb; NbExp=3; IntAct=EBI-1688, EBI-682463;
CC Q60631; P35329: Cd22; NbExp=4; IntAct=EBI-1688, EBI-300059;
CC Q60631; P98078: Dab2; NbExp=4; IntAct=EBI-1688, EBI-1391846;
CC Q60631; Q99JZ7: Errfi1; NbExp=3; IntAct=EBI-1688, EBI-643375;
CC Q60631; Q8C180: Frs2; NbExp=5; IntAct=EBI-1688, EBI-6880000;
CC Q60631; Q9QYY0: Gab1; NbExp=8; IntAct=EBI-1688, EBI-644784;
CC Q60631; Q60749: Khdrbs1; NbExp=2; IntAct=EBI-1688, EBI-519077;
CC Q60631; Q52KG5: Kif26a; NbExp=2; IntAct=EBI-1688, EBI-2480646;
CC Q60631; O54957: Lat; NbExp=5; IntAct=EBI-1688, EBI-6390034;
CC Q60631; Q62077: Plcg1; NbExp=2; IntAct=EBI-1688, EBI-300133;
CC Q60631; P04925: Prnp; NbExp=7; IntAct=EBI-1688, EBI-768613;
CC Q60631; P35235: Ptpn11; NbExp=3; IntAct=EBI-1688, EBI-397236;
CC Q60631; P18052: Ptpra; NbExp=4; IntAct=EBI-1688, EBI-6597520;
CC Q60631; Q91ZZ2: Rapgef1; NbExp=3; IntAct=EBI-1688, EBI-644719;
CC Q60631; P98083: Shc1; NbExp=8; IntAct=EBI-1688, EBI-300201;
CC Q60631; Q61234: Snta1; NbExp=3; IntAct=EBI-1688, EBI-295952;
CC Q60631; Q62245: Sos1; NbExp=7; IntAct=EBI-1688, EBI-1693;
CC Q60631; Q02384: Sos2; NbExp=5; IntAct=EBI-1688, EBI-395573;
CC Q60631; Q02858: Tek; NbExp=3; IntAct=EBI-1688, EBI-7099626;
CC Q60631; Q99PM9: Uck2; NbExp=3; IntAct=EBI-1688, EBI-644712;
CC Q60631-1; Q8BGW0-1: Themis; NbExp=3; IntAct=EBI-15532571, EBI-15806957;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P62993}. Cytoplasm
CC {ECO:0000250|UniProtKB:P62993}. Endosome
CC {ECO:0000250|UniProtKB:P62993}. Golgi apparatus
CC {ECO:0000269|PubMed:11571277}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q60631-1; Sequence=Displayed;
CC Name=2; Synonyms=GRB3-3;
CC IsoId=Q60631-2; Sequence=VSP_001841;
CC -!- TISSUE SPECIFICITY: Expressed in macrophages.
CC {ECO:0000269|PubMed:28098138}.
CC -!- DOMAIN: The SH3 domains mediate interaction with RALGPS1 and SHB.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GRB2/sem-5/DRK family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Grb2 entry;
CC URL="https://en.wikipedia.org/wiki/Grb2";
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DR EMBL; U07617; AAB40022.1; -; mRNA.
DR EMBL; D85748; BAA12862.1; -; mRNA.
DR EMBL; BC052377; AAH52377.1; -; mRNA.
DR EMBL; BC085254; AAH85254.1; -; mRNA.
DR CCDS; CCDS25645.1; -. [Q60631-1]
DR PIR; A54688; A54688.
DR RefSeq; NP_001300865.1; NM_001313936.1. [Q60631-1]
DR RefSeq; NP_001300866.1; NM_001313937.1. [Q60631-1]
DR RefSeq; NP_032189.1; NM_008163.4. [Q60631-1]
DR PDB; 1GBQ; NMR; -; A=1-61.
DR PDB; 1GBR; NMR; -; A=1-59.
DR PDB; 2GBQ; NMR; -; A=1-59.
DR PDB; 3GBQ; NMR; -; A=1-59.
DR PDB; 4GBQ; NMR; -; A=1-59.
DR PDBsum; 1GBQ; -.
DR PDBsum; 1GBR; -.
DR PDBsum; 2GBQ; -.
DR PDBsum; 3GBQ; -.
DR PDBsum; 4GBQ; -.
DR AlphaFoldDB; Q60631; -.
DR SMR; Q60631; -.
DR BioGRID; 200046; 102.
DR CORUM; Q60631; -.
DR DIP; DIP-259N; -.
DR IntAct; Q60631; 77.
DR MINT; Q60631; -.
DR STRING; 10090.ENSMUSP00000021090; -.
DR BindingDB; Q60631; -.
DR ChEMBL; CHEMBL4830; -.
DR DrugCentral; Q60631; -.
DR iPTMnet; Q60631; -.
DR PhosphoSitePlus; Q60631; -.
DR SwissPalm; Q60631; -.
DR EPD; Q60631; -.
DR MaxQB; Q60631; -.
DR PaxDb; Q60631; -.
DR PeptideAtlas; Q60631; -.
DR PRIDE; Q60631; -.
DR ProteomicsDB; 271325; -. [Q60631-1]
DR ProteomicsDB; 271326; -. [Q60631-2]
DR Antibodypedia; 3408; 692 antibodies from 44 providers.
DR DNASU; 14784; -.
DR Ensembl; ENSMUST00000021090; ENSMUSP00000021090; ENSMUSG00000059923. [Q60631-1]
DR Ensembl; ENSMUST00000106497; ENSMUSP00000102106; ENSMUSG00000059923. [Q60631-1]
DR Ensembl; ENSMUST00000106499; ENSMUSP00000102108; ENSMUSG00000059923. [Q60631-2]
DR GeneID; 14784; -.
DR KEGG; mmu:14784; -.
DR UCSC; uc007mii.1; mouse. [Q60631-2]
DR UCSC; uc007mij.1; mouse. [Q60631-1]
DR CTD; 2885; -.
DR MGI; MGI:95805; Grb2.
DR VEuPathDB; HostDB:ENSMUSG00000059923; -.
DR eggNOG; KOG3601; Eukaryota.
DR GeneTree; ENSGT00940000155738; -.
DR InParanoid; Q60631; -.
DR OMA; MVPEEML; -.
DR PhylomeDB; Q60631; -.
DR TreeFam; TF354288; -.
DR Reactome; R-MMU-109704; PI3K Cascade. [Q60631-1]
DR Reactome; R-MMU-112412; SOS-mediated signalling. [Q60631-1]
DR Reactome; R-MMU-1250347; SHC1 events in ERBB4 signaling. [Q60631-1]
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling. [Q60631-1]
DR Reactome; R-MMU-1295596; Spry regulation of FGF signaling. [Q60631-1]
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT. [Q60631-1]
DR Reactome; R-MMU-1433559; Regulation of KIT signaling. [Q60631-1]
DR Reactome; R-MMU-167044; Signalling to RAS. [Q60631-1]
DR Reactome; R-MMU-179812; GRB2 events in EGFR signaling. [Q60631-1]
DR Reactome; R-MMU-180292; GAB1 signalosome. [Q60631-1]
DR Reactome; R-MMU-180336; SHC1 events in EGFR signaling. [Q60631-1]
DR Reactome; R-MMU-182971; EGFR downregulation. [Q60631-1]
DR Reactome; R-MMU-186763; Downstream signal transduction. [Q60631-1]
DR Reactome; R-MMU-1963640; GRB2 events in ERBB2 signaling. [Q60631-1]
DR Reactome; R-MMU-1963642; PI3K events in ERBB2 signaling. [Q60631-1]
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation. [Q60631-1]
DR Reactome; R-MMU-210993; Tie2 Signaling. [Q60631-1]
DR Reactome; R-MMU-2179392; EGFR Transactivation by Gastrin. [Q60631-1]
DR Reactome; R-MMU-2424491; DAP12 signaling. [Q60631-1]
DR Reactome; R-MMU-2428933; SHC-related events triggered by IGF1R. [Q60631-1]
DR Reactome; R-MMU-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. [Q60631-1]
DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation. [Q60631-1]
DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization. [Q60631-1]
DR Reactome; R-MMU-354194; GRB2:SOS provides linkage to MAPK signaling for Integrins. [Q60631-1]
DR Reactome; R-MMU-375165; NCAM signaling for neurite out-growth. [Q60631-1]
DR Reactome; R-MMU-388841; Costimulation by the CD28 family. [Q60631-1]
DR Reactome; R-MMU-389359; CD28 dependent Vav1 pathway. [Q60631-1]
DR Reactome; R-MMU-391160; Signal regulatory protein family interactions. [Q60631-1]
DR Reactome; R-MMU-5654688; SHC-mediated cascade:FGFR1. [Q60631-1]
DR Reactome; R-MMU-5654689; PI-3K cascade:FGFR1. [Q60631-1]
DR Reactome; R-MMU-5654693; FRS-mediated FGFR1 signaling. [Q60631-1]
DR Reactome; R-MMU-5654695; PI-3K cascade:FGFR2. [Q60631-1]
DR Reactome; R-MMU-5654699; SHC-mediated cascade:FGFR2. [Q60631-1]
DR Reactome; R-MMU-5654700; FRS-mediated FGFR2 signaling. [Q60631-1]
DR Reactome; R-MMU-5654704; SHC-mediated cascade:FGFR3. [Q60631-1]
DR Reactome; R-MMU-5654706; FRS-mediated FGFR3 signaling. [Q60631-1]
DR Reactome; R-MMU-5654710; PI-3K cascade:FGFR3. [Q60631-1]
DR Reactome; R-MMU-5654712; FRS-mediated FGFR4 signaling. [Q60631-1]
DR Reactome; R-MMU-5654719; SHC-mediated cascade:FGFR4. [Q60631-1]
DR Reactome; R-MMU-5654720; PI-3K cascade:FGFR4. [Q60631-1]
DR Reactome; R-MMU-5654726; Negative regulation of FGFR1 signaling. [Q60631-1]
DR Reactome; R-MMU-5654727; Negative regulation of FGFR2 signaling. [Q60631-1]
DR Reactome; R-MMU-5654732; Negative regulation of FGFR3 signaling. [Q60631-1]
DR Reactome; R-MMU-5654733; Negative regulation of FGFR4 signaling. [Q60631-1]
DR Reactome; R-MMU-5663213; RHO GTPases Activate WASPs and WAVEs. [Q60631-1]
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade. [Q60631-1]
DR Reactome; R-MMU-6807004; Negative regulation of MET activity. [Q60631-1]
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. [Q60631-1]
DR Reactome; R-MMU-74749; Signal attenuation. [Q60631-1]
DR Reactome; R-MMU-74751; Insulin receptor signalling cascade. [Q60631-1]
DR Reactome; R-MMU-8851805; MET activates RAS signaling. [Q60631-1]
DR Reactome; R-MMU-8851907; MET activates PI3K/AKT signaling. [Q60631-1]
DR Reactome; R-MMU-8853659; RET signaling. [Q60631-1]
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis. [Q60631-1]
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis. [Q60631-1]
DR Reactome; R-MMU-8865999; MET activates PTPN11. [Q60631-1]
DR Reactome; R-MMU-8875555; MET activates RAP1 and RAC1. [Q60631-1]
DR Reactome; R-MMU-8875656; MET receptor recycling. [Q60631-1]
DR Reactome; R-MMU-8983432; Interleukin-15 signaling. [Q60631-1]
DR Reactome; R-MMU-9013420; RHOU GTPase cycle. [Q60631-1]
DR Reactome; R-MMU-9027284; Erythropoietin activates RAS. [Q60631-1]
DR Reactome; R-MMU-9028731; Activated NTRK2 signals through FRS2 and FRS3. [Q60631-1]
DR Reactome; R-MMU-912526; Interleukin receptor SHC signaling. [Q60631-1]
DR Reactome; R-MMU-912631; Regulation of signaling by CBL. [Q60631-1]
DR Reactome; R-MMU-9607240; FLT3 Signaling. [Q60631-1]
DR Reactome; R-MMU-9674555; Signaling by CSF3 (G-CSF). [Q60631-1]
DR Reactome; R-MMU-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. [Q60631-1]
DR BioGRID-ORCS; 14784; 17 hits in 71 CRISPR screens.
DR ChiTaRS; Grb2; mouse.
DR EvolutionaryTrace; Q60631; -.
DR PRO; PR:Q60631; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q60631; protein.
DR Bgee; ENSMUSG00000059923; Expressed in ectoplacental cone and 273 other tissues.
DR ExpressionAtlas; Q60631; baseline and differential.
DR Genevisible; Q60631; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0008180; C:COP9 signalosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0070436; C:Grb2-EGFR complex; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0012506; C:vesicle membrane; IDA:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0043560; F:insulin receptor substrate binding; ISO:MGI.
DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; ISO:MGI.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; IPI:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:MGI.
DR GO; GO:0017124; F:SH3 domain binding; ISS:UniProtKB.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IGI:MGI.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISO:MGI.
DR GO; GO:0007568; P:aging; ISO:MGI.
DR GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IMP:MGI.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IMP:MGI.
DR GO; GO:0071479; P:cellular response to ionizing radiation; ISO:MGI.
DR GO; GO:0035987; P:endodermal cell differentiation; IMP:MGI.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IGI:MGI.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IGI:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IGI:MGI.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; TAS:MGI.
DR GO; GO:0031623; P:receptor internalization; ISO:MGI.
DR GO; GO:0043408; P:regulation of MAPK cascade; IGI:MGI.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0042770; P:signal transduction in response to DNA damage; ISO:MGI.
DR CDD; cd11949; SH3_GRB2_C; 1.
DR CDD; cd11946; SH3_GRB2_N; 1.
DR Gene3D; 3.30.505.10; -; 1.
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; 1.
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; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; SH2 domain; SH3 domain.
FT CHAIN 1..217
FT /note="Growth factor receptor-bound protein 2"
FT /id="PRO_0000088199"
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:0000250|UniProtKB:P62993"
FT MOD_RES 6
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62993"
FT MOD_RES 50
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62993"
FT MOD_RES 109
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62993"
FT MOD_RES 211
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P62993"
FT VAR_SEQ 60..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_001841"
FT STRAND 2..7
FT /evidence="ECO:0007829|PDB:1GBQ"
FT STRAND 13..16
FT /evidence="ECO:0007829|PDB:2GBQ"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:1GBQ"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:1GBQ"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:1GBQ"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:1GBQ"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:1GBQ"
SQ SEQUENCE 217 AA; 25238 MW; 97F4A4FE4B248DDF CRC64;
MEAIAKYDFK ATADDELSFK RGDILKVLNE ECDQNWYKAE LNGKDGFIPK NYIEMKPHPW
FFGKIPRAKA EEMLSKQRHD GAFLIRESES APGDFSLSVK FGNDVQHFKV LRDGAGKYFL
WVVKFNSLNE LVDYHRSTSV SRNQQIFLRD IEQMPQQPTY VQALFDFDPQ EDGELGFRRG
DFIHVMDNSD PNWWKGACHG QTGMFPRNYV TPVNRNV
