GAB1_MOUSE
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 03-AUG-2022, entry version 164.
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.ENSMUSP00000034150; -.
DR iPTMnet; Q9QYY0; -.
DR PhosphoSitePlus; Q9QYY0; -.
DR MaxQB; Q9QYY0; -.
DR PaxDb; Q9QYY0; -.
DR PRIDE; Q9QYY0; -.
DR ProteomicsDB; 268834; -.
DR Antibodypedia; 3614; 389 antibodies from 42 providers.
DR DNASU; 14388; -.
DR Ensembl; ENSMUST00000034150; ENSMUSP00000034150; ENSMUSG00000031714.
DR GeneID; 14388; -.
DR KEGG; mmu:14388; -.
DR UCSC; uc009mjb.2; mouse.
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; 1153633at2759; -.
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 72 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 258 other tissues.
DR ExpressionAtlas; Q9QYY0; baseline and differential.
DR Genevisible; Q9QYY0; MM.
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:0031532; P:actin cytoskeleton reorganization; ISO: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:0043406; P:positive regulation of MAP kinase activity; IMP:MGI.
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: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 Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR046355; Gab1-4-like.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR45960; PTHR45960; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
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
