ID GAB2_HUMAN Reviewed; 676 AA. AC Q9UQC2; A2RRM2; A6NEW9; A7MD36; O60317; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 184. DE RecName: Full=GRB2-associated-binding protein 2; DE AltName: Full=GRB2-associated binder 2; DE AltName: Full=Growth factor receptor bound protein 2-associated protein 2; DE AltName: Full=pp100; GN Name=GAB2; Synonyms=KIAA0571; 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), AND INTERACTION WITH PTPN11. RC TISSUE=Myeloma; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=9628581; DOI=10.1093/dnares/5.1.31; RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. IX. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 5:31-39(1998). RN [3] RP SEQUENCE REVISION. RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). 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 [7] RP PHOSPHORYLATION BY HCK, AND INTERACTION WITH HCK; CRKL PTPN11 AND GRB2. RX PubMed=15010462; DOI=10.1074/jbc.m305783200; RA Podar K., Mostoslavsky G., Sattler M., Tai Y.T., Hayashi T., Catley L.P., RA Hideshima T., Mulligan R.C., Chauhan D., Anderson K.C.; RT "Critical role for hematopoietic cell kinase (Hck)-mediated phosphorylation RT of Gab1 and Gab2 docking proteins in interleukin 6-induced proliferation RT and survival of multiple myeloma cells."; RL J. Biol. Chem. 279:21658-21665(2004). RN [8] RP FUNCTION, AND INTERACTION WITH TNFRSF11A. RX PubMed=15750601; DOI=10.1038/nm1203; RA Wada T., Nakashima T., Oliveira-dos-Santos A.J., Gasser J., Hara H., RA Schett G., Penninger J.M.; RT "The molecular scaffold Gab2 is a crucial component of RANK signaling and RT osteoclastogenesis."; RL Nat. Med. 11:394-399(2005). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EGFR; GRB2; PTPN11; PI-3 RP KINASE; SFN; SHC1; YWHAB; YWHAE; YWHAG; YWHAH; YWHAQ AND YWHAZ, MUTAGENESIS RP OF SER-210 AND THR-391, AND PHOSPHORYLATION AT SER-133; SER-140; SER-141; RP SER-148; SER-149; SER-159; SER-164; SER-210; SER-218; SER-223; SER-264; RP THR-278; SER-281; THR-287; TYR-293; THR-331; THR-385; THR-391; SER-405; RP SER-480; SER-543; SER-622 AND SER-623. RX PubMed=19172738; DOI=10.1038/emboj.2008.159; RA Brummer T., Larance M., Herrera Abreu M.T., Lyons R.J., Timpson P., RA Emmerich C.H., Fleuren E.D.G., Lehrbach G.M., Schramek D., Guilhaus M., RA James D.E., Daly R.J.; RT "Phosphorylation-dependent binding of 14-3-3 terminates signalling by the RT Gab2 docking protein."; RL EMBO J. 27:2305-2316(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-543, 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 [11] 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 [12] 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 [13] RP IDENTIFICATION IN A COMPLEX WITH EEIG1; TNFRSF11A; PLCG2; TEC AND BTK. RX PubMed=23478294; DOI=10.1038/cr.2013.33; RA Choi H.K., Kang H.R., Jung E., Kim T.E., Lin J.J., Lee S.Y.; RT "Early estrogen-induced gene 1, a novel RANK signaling component, is RT essential for osteoclastogenesis."; RL Cell Res. 23:524-536(2013). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-148; SER-149; SER-223; RP SER-264; SER-285; THR-287; SER-368; THR-391; SER-422; SER-425; SER-543 AND RP TYR-643, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 350-358 IN COMPLEX WITH GRB2, AND RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 508-522 IN COMPLEX WITH GRB2. 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). CC -!- FUNCTION: Adapter protein which acts downstream of several membrane CC receptors including cytokine, antigen, hormone, cell matrix and growth CC factor receptors to regulate multiple signaling pathways. Regulates CC osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In CC allergic response, it plays a role in mast cells activation and CC degranulation through PI-3-kinase regulation. Also involved in the CC regulation of cell proliferation and hematopoiesis. CC {ECO:0000269|PubMed:15750601, ECO:0000269|PubMed:19172738}. CC -!- SUBUNIT: Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, CC GAB2, TEC and BTK; complex formation increases in the presence of CC TNFSF11/RANKL (PubMed:23478294). Interacts with SHC1; may mediate CC interaction with receptors (By similarity). Interacts with SYK (By CC similarity). Interacts with PI-3 kinase. Interacts with GRB2 (via SH3 2 CC domain). Interacts (phosphorylated) with PTPN11. Interacts with CC TNFRSF11A (via cytoplasmic domain). Interacts (phosphorylated) with 14- CC 3-3 family proteins SFN, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and YWHAZ; CC prevents interaction with GRB2 and attenuates GAB2 signaling. Interacts CC with HCK. {ECO:0000250, ECO:0000269|PubMed:10068651, CC ECO:0000269|PubMed:15010462, ECO:0000269|PubMed:15750601, CC ECO:0000269|PubMed:19172738, ECO:0000269|PubMed:19523899, CC ECO:0000269|PubMed:23478294}. CC -!- INTERACTION: CC Q9UQC2; P11117: ACP2; NbExp=3; IntAct=EBI-975200, EBI-2907070; CC Q9UQC2; P00533: EGFR; NbExp=3; IntAct=EBI-975200, EBI-297353; CC Q9UQC2; O75791: GRAP2; NbExp=3; IntAct=EBI-975200, EBI-740418; CC Q9UQC2; P62993: GRB2; NbExp=14; IntAct=EBI-975200, EBI-401755; CC Q9UQC2; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-975200, EBI-14103818; CC Q9UQC2; P42858: HTT; NbExp=3; IntAct=EBI-975200, EBI-466029; CC Q9UQC2; Q06124: PTPN11; NbExp=4; IntAct=EBI-975200, EBI-297779; CC Q9UQC2; Q8WZ73-3: RFFL; NbExp=3; IntAct=EBI-975200, EBI-25839575; CC Q9UQC2; P08865: RPSA; NbExp=3; IntAct=EBI-975200, EBI-354112; CC Q9UQC2; P31946: YWHAB; NbExp=6; IntAct=EBI-975200, EBI-359815; CC Q9UQC2-1; P62993-1: GRB2; NbExp=3; IntAct=EBI-15787947, EBI-15787932; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19172738}. Cell CC membrane {ECO:0000269|PubMed:19172738}. Membrane raft CC {ECO:0000250|UniProtKB:Q9Z1S8}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UQC2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UQC2-2; Sequence=VSP_038520; CC -!- DOMAIN: The SH3-binding motifs mediate interaction with SHC1 and GRB2. CC {ECO:0000250}. CC -!- DOMAIN: The PH domain mediates phosphatidylinositol 3,4,5-trisphosphate CC and phosphatidylinositol 3,4-bisphosphate binding. {ECO:0000250}. CC -!- PTM: Phosphorylated on tyrosine residue(s) by the thrombopoietin CC receptor (TPOR), stem cell factor receptor (SCFR), and T-cell and B- CC cell antigen receptors, gp130, IL-2R and IL-3R (By similarity). CC Phosphorylated upon stimulation of TNFRSF11A/RANK by TNFSF11/RANKL (By CC similarity). Phosphorylated upon EGF stimulation. Phosphorylated on CC tyrosine residues by HCK upon IL6 signaling. {ECO:0000250, CC ECO:0000269|PubMed:15010462, ECO:0000269|PubMed:19172738}. CC -!- PTM: Dephosphorylated by PTPN11. CC -!- SIMILARITY: Belongs to the GAB family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA25497.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40664/GAB2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB018413; BAA76737.1; -; mRNA. DR EMBL; AB011143; BAA25497.2; ALT_INIT; mRNA. DR EMBL; AP002985; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW75057.1; -; Genomic_DNA. DR EMBL; CH471076; EAW75058.1; -; Genomic_DNA. DR EMBL; BC131711; AAI31712.1; -; mRNA. DR EMBL; BC152459; AAI52460.1; -; mRNA. DR CCDS; CCDS8259.1; -. [Q9UQC2-1] DR CCDS; CCDS8260.1; -. [Q9UQC2-2] DR RefSeq; NP_036428.1; NM_012296.3. [Q9UQC2-2] DR RefSeq; NP_536739.1; NM_080491.2. [Q9UQC2-1] DR RefSeq; XP_006718816.1; XM_006718753.2. DR PDB; 2VWF; X-ray; 1.58 A; B=508-522. DR PDB; 2W0Z; X-ray; 1.70 A; B=350-358. DR PDB; 5EWZ; X-ray; 2.34 A; C=387-395, D=207-212. DR PDB; 5EXA; X-ray; 1.95 A; C/D=387-396. DR PDB; 6Y3R; X-ray; 1.50 A; P=387-398. DR PDB; 6Y3S; X-ray; 1.95 A; P=205-214. DR PDB; 6ZVB; X-ray; 2.51 A; P=386-398. DR PDB; 6ZVC; X-ray; 2.51 A; P=386-398. DR PDB; 6ZVD; X-ray; 2.50 A; P=386-398. DR PDB; 6ZVE; X-ray; 2.51 A; P=386-398. DR PDBsum; 2VWF; -. DR PDBsum; 2W0Z; -. DR PDBsum; 5EWZ; -. DR PDBsum; 5EXA; -. DR PDBsum; 6Y3R; -. DR PDBsum; 6Y3S; -. DR PDBsum; 6ZVB; -. DR PDBsum; 6ZVC; -. DR PDBsum; 6ZVD; -. DR PDBsum; 6ZVE; -. DR AlphaFoldDB; Q9UQC2; -. DR SMR; Q9UQC2; -. DR BioGRID; 115181; 120. DR DIP; DIP-36653N; -. DR IntAct; Q9UQC2; 63. DR MINT; Q9UQC2; -. DR STRING; 9606.ENSP00000354952; -. DR iPTMnet; Q9UQC2; -. DR PhosphoSitePlus; Q9UQC2; -. DR BioMuta; GAB2; -. DR DMDM; 46396035; -. DR EPD; Q9UQC2; -. DR jPOST; Q9UQC2; -. DR MassIVE; Q9UQC2; -. DR MaxQB; Q9UQC2; -. DR PaxDb; 9606-ENSP00000354952; -. DR PeptideAtlas; Q9UQC2; -. DR ProteomicsDB; 85541; -. [Q9UQC2-1] DR ProteomicsDB; 85542; -. [Q9UQC2-2] DR Pumba; Q9UQC2; -. DR Antibodypedia; 600; 840 antibodies from 39 providers. DR DNASU; 9846; -. DR Ensembl; ENST00000340149.6; ENSP00000343959.2; ENSG00000033327.13. [Q9UQC2-2] DR Ensembl; ENST00000361507.5; ENSP00000354952.4; ENSG00000033327.13. [Q9UQC2-1] DR GeneID; 9846; -. DR KEGG; hsa:9846; -. DR MANE-Select; ENST00000361507.5; ENSP00000354952.4; NM_080491.3; NP_536739.1. DR UCSC; uc001ozg.4; human. [Q9UQC2-1] DR AGR; HGNC:14458; -. DR CTD; 9846; -. DR DisGeNET; 9846; -. DR GeneCards; GAB2; -. DR HGNC; HGNC:14458; GAB2. DR HPA; ENSG00000033327; Tissue enhanced (brain). DR MIM; 606203; gene. DR neXtProt; NX_Q9UQC2; -. DR OpenTargets; ENSG00000033327; -. DR PharmGKB; PA28478; -. DR VEuPathDB; HostDB:ENSG00000033327; -. DR eggNOG; ENOG502QTS1; Eukaryota. DR GeneTree; ENSGT00940000157792; -. DR HOGENOM; CLU_028652_0_0_1; -. DR InParanoid; Q9UQC2; -. DR OMA; MAQCHRR; -. DR OrthoDB; 2904117at2759; -. DR PhylomeDB; Q9UQC2; -. DR TreeFam; TF329487; -. DR PathwayCommons; Q9UQC2; -. DR Reactome; R-HSA-109704; PI3K Cascade. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-1839117; Signaling by cytosolic FGFR1 fusion mutants. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-8853659; RET signaling. DR Reactome; R-HSA-8983432; Interleukin-15 signaling. DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling. DR Reactome; R-HSA-9607240; FLT3 Signaling. DR Reactome; R-HSA-9645135; STAT5 Activation. DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF). DR Reactome; R-HSA-9680350; Signaling by CSF1 (M-CSF) in myeloid cells. DR Reactome; R-HSA-9702518; STAT5 activation downstream of FLT3 ITD mutants. DR Reactome; R-HSA-9703465; Signaling by FLT3 fusion proteins. DR Reactome; R-HSA-9703648; Signaling by FLT3 ITD and TKD mutants. DR SignaLink; Q9UQC2; -. DR SIGNOR; Q9UQC2; -. DR BioGRID-ORCS; 9846; 68 hits in 1165 CRISPR screens. DR ChiTaRS; GAB2; human. DR EvolutionaryTrace; Q9UQC2; -. DR GeneWiki; GAB2; -. DR GenomeRNAi; 9846; -. DR Pharos; Q9UQC2; Tbio. DR PRO; PR:Q9UQC2; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q9UQC2; Protein. DR Bgee; ENSG00000033327; Expressed in inferior vagus X ganglion and 189 other cell types or tissues. DR ExpressionAtlas; Q9UQC2; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISS:UniProtKB. DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; ISS:UniProtKB. DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IDA:UniProtKB. DR GO; GO:0030316; P:osteoclast differentiation; IMP:UniProtKB. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0043306; P:positive regulation of mast cell degranulation; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR DisProt; DP01507; -. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR IDEAL; IID00522; -. DR InterPro; IPR046355; Gab1-4-like. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR PANTHER; PTHR45960; GRB2-ASSOCIATED-BINDING PROTEIN; 1. DR PANTHER; PTHR45960:SF1; GRB2-ASSOCIATED-BINDING PROTEIN 2; 1. DR Pfam; PF00169; PH; 1. DR SMART; SM00233; PH; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR Genevisible; Q9UQC2; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Cytoplasm; Membrane; KW Phosphoprotein; Reference proteome. FT CHAIN 1..676 FT /note="GRB2-associated-binding protein 2" FT /id="PRO_0000050285" FT DOMAIN 6..117 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT REGION 127..178 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 341..430 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 492..531 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 556..643 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 656..676 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 351..358 FT /note="SH3-binding" FT MOTIF 510..519 FT /note="SH3-binding" FT COMPBIAS 348..362 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 363..386 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 556..608 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 624..640 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 133 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 140 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 141 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 148 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738, FT ECO:0007744|PubMed:23186163" FT MOD_RES 149 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738, FT ECO:0007744|PubMed:23186163" FT MOD_RES 159 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 164 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 210 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 218 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 223 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738, FT ECO:0007744|PubMed:23186163" FT MOD_RES 264 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738, FT ECO:0007744|PubMed:23186163" FT MOD_RES 265 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1S8" FT MOD_RES 266 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1S8" FT MOD_RES 278 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 281 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 285 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 287 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:19172738, FT ECO:0007744|PubMed:23186163" FT MOD_RES 293 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 331 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 368 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 385 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 391 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:19172738, FT ECO:0007744|PubMed:23186163" FT MOD_RES 405 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 408 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1S8" FT MOD_RES 422 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 425 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 452 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1S8" FT MOD_RES 480 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 543 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163" FT MOD_RES 622 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 623 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:19172738" FT MOD_RES 643 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..38 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9628581" FT /id="VSP_038520" FT VARIANT 320 FT /note="P -> L (in dbSNP:rs752597583)" FT /id="VAR_053097" FT VARIANT 344 FT /note="P -> L (in dbSNP:rs2279374)" FT /id="VAR_020407" FT MUTAGEN 210 FT /note="S->A,E: Impaired interaction with 14-3-3 proteins FT and increased EGF-independent cell proliferation; when FT associated with A-391." FT /evidence="ECO:0000269|PubMed:19172738" FT MUTAGEN 391 FT /note="T->A,E: Impaired interaction with 14-3-3 proteins FT and increased EGF-independent cell proliferation; when FT associated with A-210." FT /evidence="ECO:0000269|PubMed:19172738" FT HELIX 515..517 FT /evidence="ECO:0007829|PDB:2VWF" SQ SEQUENCE 676 AA; 74458 MW; 107623FD07D884C9 CRC64; MSGGGDVVCT GWLRKSPPEK KLRRYAWKKR WFILRSGRMS GDPDVLEYYK NDHSKKPLRI INLNFCEQVD AGLTFNKKEL QDSFVFDIKT SERTFYLVAE TEEDMNKWVQ SICQICGFNQ AEESTDSLRN VSSAGHGPRS SPAELSSSSQ HLLRERKSSA PSHSSQPTLF TFEPPVSNHM QPTLSTSAPQ EYLYLHQCIS RRAENARSAS FSQGTRASFL MRSDTAVQKL AQGNGHCVNG ISGQVHGFYS LPKPSRHNTE FRDSTYDLPR SLASHGHTKG SLTGSETDNE DVYTFKTPSN TLCREFGDLL VDNMDVPATP LSAYQIPRTF TLDKNHNAMT VATPGDSAIA PPPRPPKPSQ AETPRWGSPQ QRPPISENSR SVAATIPRRN TLPAMDNSRL HRASSCETYE YPQRGGESAG RSAESMSDGV GSFLPGKMIV GRSDSTNSED NYVPMNPGSS TLLAMERAGD NSQSVYIPMS PGAHHFDSLG YPSTTLPVHR GPSRGSEIQP PPVNRNLKPD RKAKPTPLDL RNNTVIDELP FKSPITKSWS RANHTFNSSS SQYCRPISTQ SITSTDSGDS EENYVPMQNP VSASPVPSGT NSPAPKKSTG SVDYLALDFQ PSSPSPHRKP STSSVTSDEK VDYVQVDKEK TQALQNTMQE WTDVRQSSEP SKGAKL //