ID   GAB1_MOUSE              Reviewed;         695 AA.
AC   Q9QYY0; Q91VW7;
DT   13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT   13-APR-2004, sequence version 2.
DT   24-JAN-2024, entry version 172.
DE   RecName: Full=GRB2-associated-binding protein 1;
DE   AltName: Full=GRB2-associated binder 1;
DE   AltName: Full=Growth factor receptor bound protein 2-associated protein 1;
GN   Name=Gab1;
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].
RA   Sachs M.;
RL   Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Mammary tumor;
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   [3]
RP   PHOSPHORYLATION IN RESPONSE TO FGFR1 SIGNALING, AND IDENTIFICATION IN A
RP   COMPLEX WITH FRS2; GRB2; PIK3R1 AND SOS1.
RX   PubMed=11353842; DOI=10.1073/pnas.111114298;
RA   Ong S.H., Hadari Y.R., Gotoh N., Guy G.R., Schlessinger J., Lax I.;
RT   "Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor
RT   receptors is mediated by coordinated recruitment of multiple docking
RT   proteins.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:6074-6079(2001).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Heart, Lung, 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   [5]
RP   REVIEW ON FUNCTION IN FGF SIGNALING.
RX   PubMed=20094046; DOI=10.1038/nrc2780;
RA   Turner N., Grose R.;
RT   "Fibroblast growth factor signalling: from development to cancer.";
RL   Nat. Rev. Cancer 10:116-129(2010).
RN   [6]
RP   TISSUE SPECIFICITY.
RX   PubMed=29408807; DOI=10.1172/jci97350;
RA   Yousaf R., Ahmed Z.M., Giese A.P., Morell R.J., Lagziel A., Dabdoub A.,
RA   Wilcox E.R., Riazuddin S., Friedman T.B., Riazuddin S.;
RT   "Modifier variant of METTL13 suppresses human GAB1-associated profound
RT   deafness.";
RL   J. Clin. Invest. 128:1509-1522(2018).
CC   -!- FUNCTION: Adapter protein that plays a role in intracellular signaling
CC       cascades triggered by activated receptor-type kinases. Plays a role in
CC       FGFR1 signaling. Probably involved in signaling by the epidermal growth
CC       factor receptor (EGFR) and the insulin receptor (INSR). Involved in the
CC       MET/HGF-signaling pathway. {ECO:0000250|UniProtKB:Q13480}.
CC   -!- SUBUNIT: Identified in a complex containing FRS2, GRB2, GAB1, PIK3R1
CC       and SOS1 (PubMed:11353842). Forms a tripartite complex containing GAB1,
CC       METTL13 and SPRY2 (By similarity). Within the complex interacts with
CC       METTL13 (By similarity). Interacts with GRB2 and with other SH2-
CC       containing proteins (PubMed:11353842). Interacts with phosphorylated
CC       LAT2 (By similarity). Interacts with PTPRJ (By similarity). Interacts
CC       (phosphorylated) with PTPN11 (By similarity). Interacts with HCK (By
CC       similarity). {ECO:0000250|UniProtKB:Q13480,
CC       ECO:0000269|PubMed:11353842}.
CC   -!- INTERACTION:
CC       Q9QYY0; Q60631: Grb2; NbExp=8; IntAct=EBI-644784, EBI-1688;
CC   -!- TISSUE SPECIFICITY: Expressed in the inner ear (at protein level)
CC       (PubMed:29408807). Expression is detected in the cochlear duct, spiral
CC       limbus region, efferent and afferent nerves, and in spiral ganglion
CC       neurons (at protein level) (PubMed:29408807).
CC       {ECO:0000269|PubMed:29408807}.
CC   -!- PTM: Phosphorylated on tyrosine residue(s) by the epidermal growth
CC       factor receptor (EGFR) and the insulin receptor (INSR). Tyrosine
CC       phosphorylation of GAB1 mediates interaction with several proteins that
CC       contain SH2 domains. Phosphorylated on tyrosine residues by HCK upon
CC       IL6 signaling (By similarity). Phosphorylated in response to FGFR1
CC       activation. {ECO:0000250, ECO:0000269|PubMed:11353842}.
CC   -!- SIMILARITY: Belongs to the GAB family. {ECO:0000305}.
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DR   EMBL; AJ250669; CAB59832.1; -; mRNA.
DR   EMBL; BC007483; AAH07483.1; -; mRNA.
DR   CCDS; CCDS22443.1; -.
DR   RefSeq; NP_067331.2; NM_021356.2.
DR   AlphaFoldDB; Q9QYY0; -.
DR   SMR; Q9QYY0; -.
DR   BioGRID; 199793; 18.
DR   DIP; DIP-39377N; -.
DR   IntAct; Q9QYY0; 11.
DR   MINT; Q9QYY0; -.
DR   STRING; 10090.ENSMUSP00000147784; -.
DR   GlyGen; Q9QYY0; 12 sites, 1 O-linked glycan (12 sites).
DR   iPTMnet; Q9QYY0; -.
DR   PhosphoSitePlus; Q9QYY0; -.
DR   MaxQB; Q9QYY0; -.
DR   PaxDb; 10090-ENSMUSP00000034150; -.
DR   ProteomicsDB; 268834; -.
DR   Pumba; Q9QYY0; -.
DR   Antibodypedia; 3614; 486 antibodies from 42 providers.
DR   DNASU; 14388; -.
DR   Ensembl; ENSMUST00000034150.10; ENSMUSP00000034150.9; ENSMUSG00000031714.10.
DR   GeneID; 14388; -.
DR   KEGG; mmu:14388; -.
DR   UCSC; uc009mjb.2; mouse.
DR   AGR; MGI:108088; -.
DR   CTD; 2549; -.
DR   MGI; MGI:108088; Gab1.
DR   VEuPathDB; HostDB:ENSMUSG00000031714; -.
DR   eggNOG; KOG3751; Eukaryota.
DR   GeneTree; ENSGT00940000156801; -.
DR   HOGENOM; CLU_028652_0_0_1; -.
DR   InParanoid; Q9QYY0; -.
DR   OrthoDB; 2904117at2759; -.
DR   PhylomeDB; Q9QYY0; -.
DR   TreeFam; TF329487; -.
DR   Reactome; R-MMU-109704; PI3K Cascade.
DR   Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-MMU-180292; GAB1 signalosome.
DR   Reactome; R-MMU-1963642; PI3K events in ERBB2 signaling.
DR   Reactome; R-MMU-5654689; PI-3K cascade:FGFR1.
DR   Reactome; R-MMU-5654695; PI-3K cascade:FGFR2.
DR   Reactome; R-MMU-5654710; PI-3K cascade:FGFR3.
DR   Reactome; R-MMU-5654720; PI-3K cascade:FGFR4.
DR   Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-MMU-8851907; MET activates PI3K/AKT signaling.
DR   Reactome; R-MMU-8853659; RET signaling.
DR   Reactome; R-MMU-8865999; MET activates PTPN11.
DR   Reactome; R-MMU-8875555; MET activates RAP1 and RAC1.
DR   Reactome; R-MMU-8875656; MET receptor recycling.
DR   Reactome; R-MMU-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR   BioGRID-ORCS; 14388; 2 hits in 77 CRISPR screens.
DR   ChiTaRS; Gab1; mouse.
DR   PRO; PR:Q9QYY0; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; Q9QYY0; Protein.
DR   Bgee; ENSMUSG00000031714; Expressed in vestibular membrane of cochlear duct and 262 other cell types or tissues.
DR   ExpressionAtlas; Q9QYY0; baseline and differential.
DR   GO; GO:0005938; C:cell cortex; IGI:MGI.
DR   GO; GO:0005911; C:cell-cell junction; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0035591; F:signaling adaptor activity; IDA:MGI.
DR   GO; GO:0001525; P:angiogenesis; ISO:MGI.
DR   GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:BHF-UCL.
DR   GO; GO:0090668; P:endothelial cell chemotaxis to vascular endothelial growth factor; ISO:MGI.
DR   GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IMP:MGI.
DR   GO; GO:0008544; P:epidermis development; IMP:MGI.
DR   GO; GO:0007507; P:heart development; IMP:MGI.
DR   GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IMP:MGI.
DR   GO; GO:0060711; P:labyrinthine layer development; IMP:MGI.
DR   GO; GO:0000165; P:MAPK cascade; IMP:MGI.
DR   GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IMP:MGI.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
DR   GO; GO:0038089; P:positive regulation of cell migration by vascular endothelial growth factor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:MGI.
DR   GO; GO:0030334; P:regulation of cell migration; IGI:MGI.
DR   GO; GO:0035728; P:response to hepatocyte growth factor; ISO:MGI.
DR   GO; GO:0006979; P:response to oxidative stress; IDA:MGI.
DR   GO; GO:0007165; P:signal transduction; IDA:MGI.
DR   GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; ISO:MGI.
DR   CDD; cd01266; PH_Gab1_Gab2; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
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:SF5; GRB2-ASSOCIATED-BINDING PROTEIN 1; 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; Q9QYY0; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Phosphoprotein; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   CHAIN           2..695
FT                   /note="GRB2-associated-binding protein 1"
FT                   /id="PRO_0000050284"
FT   DOMAIN          5..116
FT                   /note="PH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT   REGION          204..229
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          306..387
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          453..659
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          671..695
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        309..334
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        453..470
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        520..535
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        569..593
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        600..615
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        623..639
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   MOD_RES         251
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   MOD_RES         253
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   MOD_RES         266
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   MOD_RES         304
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   MOD_RES         388
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   MOD_RES         403
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   MOD_RES         455
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         628
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   MOD_RES         639
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   MOD_RES         652
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   MOD_RES         660
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   MOD_RES         684
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q13480"
FT   CONFLICT        236
FT                   /note="F -> L (in Ref. 1; CAB59832)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        351
FT                   /note="T -> S (in Ref. 1; CAB59832)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        379
FT                   /note="A -> V (in Ref. 1; CAB59832)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   695 AA;  76812 MW;  F0A567896E058C58 CRC64;
     MSGGEVVCSG WLRKSPPEKK LKRYAWKRRW FVLRSGRLTG DPDVLEYYKN DHAKKPIRII
     DLNLCQQVDA GLTFNKKEFE NSYIFDINTI DRIFYLVADS EEDMNKWVRC ICDICGFNPT
     EEDPVKPLTG SSQAPVDSPF AISTAPASSQ MEASSVALPP PYQVISLPPH PDTLGLQDDP
     QDYLLLINCQ SKKPEPNRTL FDSAKPTFSE TDCNDNVPSH QTPASSQSKH GMNGFFQQQM
     MYDCPPSRLT SVSGESSLYN LPRSYSHDVL PKESPSSTEA DGELYTFNTP SGTAGVETQM
     RHVSISYDIP PTPGNTYQIP RTFPESTLGQ SSKLDTIPDI PPPRPPKPHP THDRSPVETC
     GVPRTASDTD SSYCIPPPAG MTPSRSNTIS TVDLNKLRKD ASSQDCYDIP RTFPSDRSSS
     LEGFHSQYKI KSVLTAGGVS GEELDENYVP MNPNSPPRQH SGSFTEPIQE PNYVPMTPGT
     FDFSSFGMQV PPPAHMGFRS SPKTPPRRPV PVADCEPPPV DRNLKPDRKV KPAPLDIKPL
     SEWEELQAPV RSPITRSFAR DSSRFPMSPR PDSVHSTTSS SDSHDSEENY VPMNPNLSGE
     DPNLFASNSL DGGSSPMNKP KGDKQVEYLD LDLDSGKSTP PRKQKSSGSG SSMADERVDY
     VVVDQQKTLA LKSTREAWTD GRQSTESETP TKNVK
//