Full text data of GAB1
GAB1
[Confidence: low (only semi-automatic identification from reviews)]
GRB2-associated-binding protein 1 (GRB2-associated binder 1; Growth factor receptor bound protein 2-associated protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
GRB2-associated-binding protein 1 (GRB2-associated binder 1; Growth factor receptor bound protein 2-associated protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q13480
ID GAB1_HUMAN Reviewed; 694 AA.
AC Q13480; A8K152; Q4W5G2; Q6P1W2;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-FEB-2006, sequence version 2.
DT 22-JAN-2014, entry version 119.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8596638; DOI=10.1038/379560a0;
RA Holgado-Madruga M., Emlet D.R., Moscatello D.K., Godwin A.K.,
RA Wong A.J.;
RT "A Grb2-associated docking protein in EGF- and insulin-receptor
RT signalling.";
RL Nature 379:560-564(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-311.
RG NIEHS SNPs program;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH LAT2.
RX PubMed=12486104; DOI=10.1084/jem.20021405;
RA Brdicka T., Imrich M., Angelisova P., Brdickova N., Horvath O.,
RA Spicka J., Hilgert I., Luskova P., Draber P., Novak P., Engels N.,
RA Wienands J., Simeoni L., Oesterreicher J., Aguado E., Malissen M.,
RA Schraven B., 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 [8]
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
RT of the receptor protein-tyrosine phosphatase DEP-1.";
RL J. Biol. Chem. 278:5728-5735(2003).
RN [9]
RP PHOSPHORYLATION BY HCK, AND INTERACTION WITH HCK; CRKL PTPN11 AND
RP GRB2.
RX PubMed=15010462; DOI=10.1074/jbc.M305783200;
RA Podar K., Mostoslavsky G., Sattler M., Tai Y.T., Hayashi T.,
RA Catley L.P., Hideshima T., Mulligan R.C., Chauhan D., Anderson K.C.;
RT "Critical role for hematopoietic cell kinase (Hck)-mediated
RT phosphorylation of Gab1 and Gab2 docking proteins in interleukin 6-
RT induced proliferation and survival of multiple myeloma cells.";
RL J. Biol. Chem. 279:21658-21665(2004).
RN [10]
RP REVIEW ON ROLE IN FGFR1 SIGNALING; SUBUNIT AND PHOSPHORYLATION.
RX PubMed=15863030; DOI=10.1016/j.cytogfr.2005.01.001;
RA Eswarakumar V.P., Lax I., Schlessinger J.;
RT "Cellular signaling by fibroblast growth factor receptors.";
RL Cytokine Growth Factor Rev. 16:139-149(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-659, PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-547 (ISOFORM 2), AND MASS SPECTROMETRY.
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-627, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-83 AND ASN-387.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Adapter protein that plays a role in intracellular
CC signaling cascades triggered by activated receptor-type kinases.
CC Plays a role in FGFR1 signaling. Probably involved in signaling by
CC the epidermal growth factor receptor (EGFR) and the insulin
CC receptor (INSR).
CC -!- SUBUNIT: Interacts with GRB2 and with other SH2-containing
CC proteins. Interacts with phosphorylated LAT2. Interacts with
CC PTPRJ. Identified in a complex containing FRS2, GRB2, GAB1, PIK3R1
CC and SOS1. Interacts (phosphorylated) with PTPN11. Interacts with
CC HCK.
CC -!- INTERACTION:
CC P62993:GRB2; NbExp=5; IntAct=EBI-517684, EBI-401755;
CC P27986:PIK3R1; NbExp=9; IntAct=EBI-517684, EBI-79464;
CC Q06124:PTPN11; NbExp=21; IntAct=EBI-517684, EBI-297779;
CC Q12913:PTPRJ; NbExp=2; IntAct=EBI-517684, EBI-2264500;
CC P49023:PXN; NbExp=2; IntAct=EBI-517684, EBI-702209;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13480-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13480-2; Sequence=VSP_017137;
CC Note=Contains a phosphoserine at position 547;
CC -!- PTM: Phosphorylated in response to FGFR1 activation.
CC 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
CC that contain SH2 domains. Phosphorylated on tyrosine residues by
CC HCK upon IL6 signaling.
CC -!- SIMILARITY: Belongs to the GAB family.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gab1/";
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DR EMBL; U43885; AAC50380.1; -; mRNA.
DR EMBL; DQ021880; AAY26398.1; -; Genomic_DNA.
DR EMBL; AK289767; BAF82456.1; -; mRNA.
DR EMBL; AC097658; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104685; AAY40964.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05072.1; -; Genomic_DNA.
DR EMBL; BC064848; AAH64848.1; -; mRNA.
DR PIR; S68442; S68442.
DR RefSeq; NP_002030.2; NM_002039.3.
DR RefSeq; NP_997006.1; NM_207123.2.
DR UniGene; Hs.618456; -.
DR UniGene; Hs.80720; -.
DR ProteinModelPortal; Q13480; -.
DR SMR; Q13480; 26-111.
DR IntAct; Q13480; 18.
DR MINT; MINT-140909; -.
DR STRING; 9606.ENSP00000262995; -.
DR PhosphoSite; Q13480; -.
DR DMDM; 90180201; -.
DR PaxDb; Q13480; -.
DR PRIDE; Q13480; -.
DR DNASU; 2549; -.
DR Ensembl; ENST00000262994; ENSP00000262994; ENSG00000109458.
DR Ensembl; ENST00000262995; ENSP00000262995; ENSG00000109458.
DR GeneID; 2549; -.
DR KEGG; hsa:2549; -.
DR UCSC; uc003ije.3; human.
DR CTD; 2549; -.
DR GeneCards; GC04P144257; -.
DR H-InvDB; HIX0004529; -.
DR HGNC; HGNC:4066; GAB1.
DR MIM; 604439; gene.
DR neXtProt; NX_Q13480; -.
DR PharmGKB; PA28477; -.
DR eggNOG; NOG80382; -.
DR HOGENOM; HOG000236270; -.
DR HOVERGEN; HBG051685; -.
DR KO; K09593; -.
DR OMA; ETDCNDN; -.
DR OrthoDB; EOG7T4MJJ; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q13480; -.
DR GeneWiki; GAB1; -.
DR GenomeRNAi; 2549; -.
DR NextBio; 10055; -.
DR PRO; PR:Q13480; -.
DR ArrayExpress; Q13480; -.
DR Bgee; Q13480; -.
DR CleanEx; HS_GAB1; -.
DR Genevestigator; Q13480; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0005070; F:SH3/SH2 adaptor activity; TAS:ProtInc.
DR GO; GO:0004871; F:signal transducer activity; IEA:Ensembl.
DR GO; GO:0007257; P:activation of JUN kinase activity; IEA:Ensembl.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008544; P:epidermis development; IEA:Ensembl.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0060711; P:labyrinthine layer development; IEA:Ensembl.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030334; P:regulation of cell migration; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001849; Pleckstrin_homology.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT CHAIN 1 694 GRB2-associated-binding protein 1.
FT /FTId=PRO_0000050282.
FT DOMAIN 5 116 PH.
FT COMPBIAS 449 540 Pro-rich.
FT MOD_RES 627 627 Phosphotyrosine.
FT MOD_RES 659 659 Phosphotyrosine.
FT VAR_SEQ 528 528 K -> KGQSPKILRLKPHGLERTDSQTIGDFATRRK (in
FT isoform 2).
FT /FTId=VSP_017137.
FT VARIANT 83 83 Y -> C (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036132.
FT VARIANT 311 311 P -> L (in dbSNP:rs28925904).
FT /FTId=VAR_025261.
FT VARIANT 377 377 T -> I (in dbSNP:rs2229879).
FT /FTId=VAR_053096.
FT VARIANT 387 387 T -> N (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036133.
FT CONFLICT 204 204 A -> G (in Ref. 1; AAC50380).
FT CONFLICT 213 213 C -> S (in Ref. 1; AAC50380).
SQ SEQUENCE 694 AA; 76616 MW; E0FAC78772B6677B CRC64;
MSGGEVVCSG WLRKSPPEKK LKRYAWKRRW FVLRSGRLTG DPDVLEYYKN DHAKKPIRII
DLNLCQQVDA GLTFNKKEFE NSYIFDINTI DRIFYLVADS EEEMNKWVRC ICDICGFNPT
EEDPVKPPGS SLQAPADLPL AINTAPPSTQ ADSSSATLPP PYQLINVPPH LETLGIQEDP
QDYLLLINCQ SKKPEPTRTH ADSAKSTSSE TDCNDNVPSH KNPASSQSKH GMNGFFQQQM
IYDSPPSRAP SASVDSSLYN LPRSYSHDVL PKVSPSSTEA DGELYVFNTP SGTSSVETQM
RHVSISYDIP PTPGNTYQIP RTFPEGTLGQ TSKLDTIPDI PPPRPPKPHP AHDRSPVETC
SIPRTASDTD SSYCIPTAGM SPSRSNTIST VDLNKLRKDA SSQDCYDIPR AFPSDRSSSL
EGFHNHFKVK NVLTVGSVSS EELDENYVPM NPNSPPRQHS SSFTEPIQEA NYVPMTPGTF
DFSSFGMQVP PPAHMGFRSS PKTPPRRPVP VADCEPPPVD RNLKPDRKVK PAPLEIKPLP
EWEELQAPVR SPITRSFARD SSRFPMSPRP DSVHSTTSSS DSHDSEENYV PMNPNLSSED
PNLFGSNSLD GGSSPMIKPK GDKQVEYLDL DLDSGKSTPP RKQKSSGSGS SVADERVDYV
VVDQQKTLAL KSTREAWTDG RQSTESETPA KSVK
//
ID GAB1_HUMAN Reviewed; 694 AA.
AC Q13480; A8K152; Q4W5G2; Q6P1W2;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-FEB-2006, sequence version 2.
DT 22-JAN-2014, entry version 119.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8596638; DOI=10.1038/379560a0;
RA Holgado-Madruga M., Emlet D.R., Moscatello D.K., Godwin A.K.,
RA Wong A.J.;
RT "A Grb2-associated docking protein in EGF- and insulin-receptor
RT signalling.";
RL Nature 379:560-564(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-311.
RG NIEHS SNPs program;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH LAT2.
RX PubMed=12486104; DOI=10.1084/jem.20021405;
RA Brdicka T., Imrich M., Angelisova P., Brdickova N., Horvath O.,
RA Spicka J., Hilgert I., Luskova P., Draber P., Novak P., Engels N.,
RA Wienands J., Simeoni L., Oesterreicher J., Aguado E., Malissen M.,
RA Schraven B., 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 [8]
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
RT of the receptor protein-tyrosine phosphatase DEP-1.";
RL J. Biol. Chem. 278:5728-5735(2003).
RN [9]
RP PHOSPHORYLATION BY HCK, AND INTERACTION WITH HCK; CRKL PTPN11 AND
RP GRB2.
RX PubMed=15010462; DOI=10.1074/jbc.M305783200;
RA Podar K., Mostoslavsky G., Sattler M., Tai Y.T., Hayashi T.,
RA Catley L.P., Hideshima T., Mulligan R.C., Chauhan D., Anderson K.C.;
RT "Critical role for hematopoietic cell kinase (Hck)-mediated
RT phosphorylation of Gab1 and Gab2 docking proteins in interleukin 6-
RT induced proliferation and survival of multiple myeloma cells.";
RL J. Biol. Chem. 279:21658-21665(2004).
RN [10]
RP REVIEW ON ROLE IN FGFR1 SIGNALING; SUBUNIT AND PHOSPHORYLATION.
RX PubMed=15863030; DOI=10.1016/j.cytogfr.2005.01.001;
RA Eswarakumar V.P., Lax I., Schlessinger J.;
RT "Cellular signaling by fibroblast growth factor receptors.";
RL Cytokine Growth Factor Rev. 16:139-149(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-659, PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-547 (ISOFORM 2), AND MASS SPECTROMETRY.
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-627, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-83 AND ASN-387.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Adapter protein that plays a role in intracellular
CC signaling cascades triggered by activated receptor-type kinases.
CC Plays a role in FGFR1 signaling. Probably involved in signaling by
CC the epidermal growth factor receptor (EGFR) and the insulin
CC receptor (INSR).
CC -!- SUBUNIT: Interacts with GRB2 and with other SH2-containing
CC proteins. Interacts with phosphorylated LAT2. Interacts with
CC PTPRJ. Identified in a complex containing FRS2, GRB2, GAB1, PIK3R1
CC and SOS1. Interacts (phosphorylated) with PTPN11. Interacts with
CC HCK.
CC -!- INTERACTION:
CC P62993:GRB2; NbExp=5; IntAct=EBI-517684, EBI-401755;
CC P27986:PIK3R1; NbExp=9; IntAct=EBI-517684, EBI-79464;
CC Q06124:PTPN11; NbExp=21; IntAct=EBI-517684, EBI-297779;
CC Q12913:PTPRJ; NbExp=2; IntAct=EBI-517684, EBI-2264500;
CC P49023:PXN; NbExp=2; IntAct=EBI-517684, EBI-702209;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13480-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13480-2; Sequence=VSP_017137;
CC Note=Contains a phosphoserine at position 547;
CC -!- PTM: Phosphorylated in response to FGFR1 activation.
CC 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
CC that contain SH2 domains. Phosphorylated on tyrosine residues by
CC HCK upon IL6 signaling.
CC -!- SIMILARITY: Belongs to the GAB family.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gab1/";
CC -----------------------------------------------------------------------
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DR EMBL; U43885; AAC50380.1; -; mRNA.
DR EMBL; DQ021880; AAY26398.1; -; Genomic_DNA.
DR EMBL; AK289767; BAF82456.1; -; mRNA.
DR EMBL; AC097658; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104685; AAY40964.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX05072.1; -; Genomic_DNA.
DR EMBL; BC064848; AAH64848.1; -; mRNA.
DR PIR; S68442; S68442.
DR RefSeq; NP_002030.2; NM_002039.3.
DR RefSeq; NP_997006.1; NM_207123.2.
DR UniGene; Hs.618456; -.
DR UniGene; Hs.80720; -.
DR ProteinModelPortal; Q13480; -.
DR SMR; Q13480; 26-111.
DR IntAct; Q13480; 18.
DR MINT; MINT-140909; -.
DR STRING; 9606.ENSP00000262995; -.
DR PhosphoSite; Q13480; -.
DR DMDM; 90180201; -.
DR PaxDb; Q13480; -.
DR PRIDE; Q13480; -.
DR DNASU; 2549; -.
DR Ensembl; ENST00000262994; ENSP00000262994; ENSG00000109458.
DR Ensembl; ENST00000262995; ENSP00000262995; ENSG00000109458.
DR GeneID; 2549; -.
DR KEGG; hsa:2549; -.
DR UCSC; uc003ije.3; human.
DR CTD; 2549; -.
DR GeneCards; GC04P144257; -.
DR H-InvDB; HIX0004529; -.
DR HGNC; HGNC:4066; GAB1.
DR MIM; 604439; gene.
DR neXtProt; NX_Q13480; -.
DR PharmGKB; PA28477; -.
DR eggNOG; NOG80382; -.
DR HOGENOM; HOG000236270; -.
DR HOVERGEN; HBG051685; -.
DR KO; K09593; -.
DR OMA; ETDCNDN; -.
DR OrthoDB; EOG7T4MJJ; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q13480; -.
DR GeneWiki; GAB1; -.
DR GenomeRNAi; 2549; -.
DR NextBio; 10055; -.
DR PRO; PR:Q13480; -.
DR ArrayExpress; Q13480; -.
DR Bgee; Q13480; -.
DR CleanEx; HS_GAB1; -.
DR Genevestigator; Q13480; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0005070; F:SH3/SH2 adaptor activity; TAS:ProtInc.
DR GO; GO:0004871; F:signal transducer activity; IEA:Ensembl.
DR GO; GO:0007257; P:activation of JUN kinase activity; IEA:Ensembl.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008544; P:epidermis development; IEA:Ensembl.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0060711; P:labyrinthine layer development; IEA:Ensembl.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030334; P:regulation of cell migration; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001849; Pleckstrin_homology.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Phosphoprotein; Polymorphism;
KW Reference proteome.
FT CHAIN 1 694 GRB2-associated-binding protein 1.
FT /FTId=PRO_0000050282.
FT DOMAIN 5 116 PH.
FT COMPBIAS 449 540 Pro-rich.
FT MOD_RES 627 627 Phosphotyrosine.
FT MOD_RES 659 659 Phosphotyrosine.
FT VAR_SEQ 528 528 K -> KGQSPKILRLKPHGLERTDSQTIGDFATRRK (in
FT isoform 2).
FT /FTId=VSP_017137.
FT VARIANT 83 83 Y -> C (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036132.
FT VARIANT 311 311 P -> L (in dbSNP:rs28925904).
FT /FTId=VAR_025261.
FT VARIANT 377 377 T -> I (in dbSNP:rs2229879).
FT /FTId=VAR_053096.
FT VARIANT 387 387 T -> N (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036133.
FT CONFLICT 204 204 A -> G (in Ref. 1; AAC50380).
FT CONFLICT 213 213 C -> S (in Ref. 1; AAC50380).
SQ SEQUENCE 694 AA; 76616 MW; E0FAC78772B6677B CRC64;
MSGGEVVCSG WLRKSPPEKK LKRYAWKRRW FVLRSGRLTG DPDVLEYYKN DHAKKPIRII
DLNLCQQVDA GLTFNKKEFE NSYIFDINTI DRIFYLVADS EEEMNKWVRC ICDICGFNPT
EEDPVKPPGS SLQAPADLPL AINTAPPSTQ ADSSSATLPP PYQLINVPPH LETLGIQEDP
QDYLLLINCQ SKKPEPTRTH ADSAKSTSSE TDCNDNVPSH KNPASSQSKH GMNGFFQQQM
IYDSPPSRAP SASVDSSLYN LPRSYSHDVL PKVSPSSTEA DGELYVFNTP SGTSSVETQM
RHVSISYDIP PTPGNTYQIP RTFPEGTLGQ TSKLDTIPDI PPPRPPKPHP AHDRSPVETC
SIPRTASDTD SSYCIPTAGM SPSRSNTIST VDLNKLRKDA SSQDCYDIPR AFPSDRSSSL
EGFHNHFKVK NVLTVGSVSS EELDENYVPM NPNSPPRQHS SSFTEPIQEA NYVPMTPGTF
DFSSFGMQVP PPAHMGFRSS PKTPPRRPVP VADCEPPPVD RNLKPDRKVK PAPLEIKPLP
EWEELQAPVR SPITRSFARD SSRFPMSPRP DSVHSTTSSS DSHDSEENYV PMNPNLSSED
PNLFGSNSLD GGSSPMIKPK GDKQVEYLDL DLDSGKSTPP RKQKSSGSGS SVADERVDYV
VVDQQKTLAL KSTREAWTDG RQSTESETPA KSVK
//
MIM
604439
*RECORD*
*FIELD* NO
604439
*FIELD* TI
*604439 GRB2-ASSOCIATED BINDING PROTEIN 1; GAB1
*FIELD* TX
DESCRIPTION
GAB1 is a member of the GAB/DOS ('Daughter of Sevenless') family of
read moreadaptor molecules, which contain a pleckstrin homology domain and
potential binding sites for SH2 and SH3 domains.
CLONING
Using a radioactively labeled GRB2 (108355) fusion protein to screen an
expression glial tumor cDNA library, Holgado-Madruga et al. (1996)
identified a cDNA encoding a deduced 694-amino acid protein, which they
termed GAB1, with a molecular mass of 77 kD. The GAB1 protein shares
amino acid sequence homology and several structural features with the
IRS1 protein (147545). The greatest homology (31% identity and 44%
similarity) is in the pleckstrin homology domain in the N terminus of
both proteins. The distal two-thirds of both proteins have numerous
predicted serine/threonine phosphorylation sites and several potential
phosphotyrosine sites, suggesting that, like IRS1, GAB1 is a docking
protein. Northern blot analysis revealed 2 GAB1 transcripts of 4.2 and 7
kb in all tissues examined except liver, lung, and kidney. The authors
suggested that the larger transcript may represent alternative splicing
or a related gene. They found that GAB1 transcripts were more easily
detected than those of IRS1, suggesting that GAB1 is more prevalent than
IRS1.
GENE FUNCTION
By Far Western blot analysis, Holgado-Madruga et al. (1996) showed that
GRB2 bound to a 100-kD protein from bacterial cells transformed with the
proline/serine-rich fragment of GAB1. In vitro kinase assays
demonstrated that GAB1 is a direct substrate of the epidermal growth
factor receptor (EGFR; 131550) and the insulin receptor (INSR; 147670).
Tyrosine phosphorylation of GAB1 mediates interaction with several
proteins that contain SH2 domains.
GAB1 is tyrosine phosphorylated upon stimulation of various cytokines,
growth factors, and antigen receptors in cell lines and interacts with
signaling molecules such as SHP2 (176876) and phosphatidylinositol
3-kinase (e.g., 171833) (Holgado-Madruga et al., 1996, 1997).
Nakaoka et al. (2003) investigated the role of GAB1 in gp130-mediated
cardiac hypertrophy. Stimulation with leukemia inhibitory factor (LIF;
159540) induced tyrosine phosphorylation of GAB1, and phosphorylated
GAB1 interacted with SHP2 and p85 in cultured cardiomyocytes. Using 3
adenovirus vectors (carrying wildtype GAB1, mutated GAB1 lacking the
SHP2-binding site, and beta-galactosidase), they showed that GAB1 plays
a critical role in elongation of cardiomyocytes induced by LIF through
interaction with SHP2, and that the interaction of GAB1 with SHP2 is
involved not only in the regulation of brain natriuretic polypeptide
(NPPB; 600295) and skeletal alpha-actin (ACTA1; 102610) gene expression
but also in the activation of ERK5 (MAPK7; 602521) after stimulation
with LIF in cardiomyocytes. Coinfection of adenovirus vectors carrying
wildtype GAB1 and dominant-negative ERK5 abrogated the LIF-induced
cardiomyocyte elongation. Nakaoka et al. (2003) concluded that GAB1-SHP2
interaction plays a crucial role in gp130-dependent longitudinal
elongation of cardiomyocytes through activation of ERK5.
MAPPING
By FISH, Yamada et al. (2001) mapped the GAB1 gene to human chromosome
4q13.1 and mouse chromosome 8C3.
ANIMAL MODEL
To reveal the functions of Gab1 in vivo, Itoh et al. (2000) generated
mice lacking Gab1 by gene targeting. Gab1-deficient embryos died in
utero and displayed developmental defects in the heart, placenta, and
skin, which were similar to phenotypes observed in mice lacking signals
of the hepatocyte growth factor (142409), platelet-derived growth factor
(e.g., 173430), and epidermal growth factor (131530) pathways.
Consistent with these observations, extracellular signal-regulated
kinase mitogen-activated protein kinases (ERK MAPKs) were activated at
much lower levels in cells from Gab1-deficient embryos in response to
these growth factors or to stimulation of the cytokine receptor gp130
(IL6ST; 600694). Itoh et al. (2000) concluded that Gab1 is a common
player in a broad range of growth factor and cytokine signaling pathways
linking ERK MAP kinase activation.
Vasyutina et al. (2005) found that Cxcr4 (162643)-positive muscle
progenitor cells reach the anlage of the tongue in Gab1-null or
Cxcr4-null mouse embryos, but not in Cxcr4/Gab1 double mutants,
suggesting that these proteins interact during progenitor cell
migration.
*FIELD* RF
1. Holgado-Madruga, M.; Emlet, D. R.; Moscatello, D. K.; Godwin, A.
K.; Wong, A. J.: A Grb2-associated docking protein in EGF- and insulin-receptor
signalling. Nature 379: 560-564, 1996.
2. Holgado-Madruga, M.; Moscatello, D. K.; Emlet, D. R.; Dieterich,
R.; Wong, A. J.: Grb2-associated binder-1 mediates phosphatidylinositol
3-kinase activation and the promotion of cell survival by nerve growth
factor. Proc. Nat. Acad. Sci. 94: 12419-12424, 1997.
3. Itoh, M.; Yoshida, Y.; Nishida, K.; Narimatsu, M.; Hibi, M.; Hirano,
T.: Role of Gab1 in heart, placenta, and skin development and growth
factor- and cytokine-induced extracellular signal-regulated kinase
mitogen-activated protein kinase activation. Molec. Cell. Biol. 20:
3695-3704, 2000.
4. Nakaoka, Y.; Nishida, K.; Fujio, Y.; Izumi, M.; Terai, K.; Oshima,
Y.; Sugiyama, S.; Matsuda, S.; Koyasu, S.; Yamauchi-Takihara, K.;
Hirano, T.; Kawase, I.; Hirota, H.: Activation of gp130 transduces
hypertrophic signal through interaction of scaffolding/docking protein
Gab1 with tyrosine phosphatase SHP2 in cardiomyocytes. Circ. Res. 93:
221-229, 2003.
5. Vasyutina, E.; Stebler, J.; Brand-Saberi, B.; Schulz, S.; Raz,
E.; Birchmeier, C.: CXCR4 and Gab1 cooperate to control the development
of migrating muscle progenitor cells. Genes Dev. 19: 2187-2198,
2005.
6. Yamada, K.; Nishida, K.; Hibi, M.; Hirano, T.; Matsuda, Y.: Comparative
FISH mapping of Gab1 and Gab2 genes in human, mouse and rat. Cytogenet.
Cell Genet. 94: 39-42, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 9/3/2007
Marla J. F. O'Neill - updated: 2/27/2004
Carol A. Bocchini - updated: 2/7/2002
Patti M. Sherman - updated: 7/21/2000
*FIELD* CD
Paul J. Converse: 1/18/2000
*FIELD* ED
carol: 09/07/2007
terry: 9/3/2007
carol: 3/3/2004
terry: 2/27/2004
terry: 2/7/2002
carol: 9/13/2001
mcapotos: 8/3/2000
mcapotos: 7/31/2000
psherman: 7/21/2000
carol: 1/19/2000
*RECORD*
*FIELD* NO
604439
*FIELD* TI
*604439 GRB2-ASSOCIATED BINDING PROTEIN 1; GAB1
*FIELD* TX
DESCRIPTION
GAB1 is a member of the GAB/DOS ('Daughter of Sevenless') family of
read moreadaptor molecules, which contain a pleckstrin homology domain and
potential binding sites for SH2 and SH3 domains.
CLONING
Using a radioactively labeled GRB2 (108355) fusion protein to screen an
expression glial tumor cDNA library, Holgado-Madruga et al. (1996)
identified a cDNA encoding a deduced 694-amino acid protein, which they
termed GAB1, with a molecular mass of 77 kD. The GAB1 protein shares
amino acid sequence homology and several structural features with the
IRS1 protein (147545). The greatest homology (31% identity and 44%
similarity) is in the pleckstrin homology domain in the N terminus of
both proteins. The distal two-thirds of both proteins have numerous
predicted serine/threonine phosphorylation sites and several potential
phosphotyrosine sites, suggesting that, like IRS1, GAB1 is a docking
protein. Northern blot analysis revealed 2 GAB1 transcripts of 4.2 and 7
kb in all tissues examined except liver, lung, and kidney. The authors
suggested that the larger transcript may represent alternative splicing
or a related gene. They found that GAB1 transcripts were more easily
detected than those of IRS1, suggesting that GAB1 is more prevalent than
IRS1.
GENE FUNCTION
By Far Western blot analysis, Holgado-Madruga et al. (1996) showed that
GRB2 bound to a 100-kD protein from bacterial cells transformed with the
proline/serine-rich fragment of GAB1. In vitro kinase assays
demonstrated that GAB1 is a direct substrate of the epidermal growth
factor receptor (EGFR; 131550) and the insulin receptor (INSR; 147670).
Tyrosine phosphorylation of GAB1 mediates interaction with several
proteins that contain SH2 domains.
GAB1 is tyrosine phosphorylated upon stimulation of various cytokines,
growth factors, and antigen receptors in cell lines and interacts with
signaling molecules such as SHP2 (176876) and phosphatidylinositol
3-kinase (e.g., 171833) (Holgado-Madruga et al., 1996, 1997).
Nakaoka et al. (2003) investigated the role of GAB1 in gp130-mediated
cardiac hypertrophy. Stimulation with leukemia inhibitory factor (LIF;
159540) induced tyrosine phosphorylation of GAB1, and phosphorylated
GAB1 interacted with SHP2 and p85 in cultured cardiomyocytes. Using 3
adenovirus vectors (carrying wildtype GAB1, mutated GAB1 lacking the
SHP2-binding site, and beta-galactosidase), they showed that GAB1 plays
a critical role in elongation of cardiomyocytes induced by LIF through
interaction with SHP2, and that the interaction of GAB1 with SHP2 is
involved not only in the regulation of brain natriuretic polypeptide
(NPPB; 600295) and skeletal alpha-actin (ACTA1; 102610) gene expression
but also in the activation of ERK5 (MAPK7; 602521) after stimulation
with LIF in cardiomyocytes. Coinfection of adenovirus vectors carrying
wildtype GAB1 and dominant-negative ERK5 abrogated the LIF-induced
cardiomyocyte elongation. Nakaoka et al. (2003) concluded that GAB1-SHP2
interaction plays a crucial role in gp130-dependent longitudinal
elongation of cardiomyocytes through activation of ERK5.
MAPPING
By FISH, Yamada et al. (2001) mapped the GAB1 gene to human chromosome
4q13.1 and mouse chromosome 8C3.
ANIMAL MODEL
To reveal the functions of Gab1 in vivo, Itoh et al. (2000) generated
mice lacking Gab1 by gene targeting. Gab1-deficient embryos died in
utero and displayed developmental defects in the heart, placenta, and
skin, which were similar to phenotypes observed in mice lacking signals
of the hepatocyte growth factor (142409), platelet-derived growth factor
(e.g., 173430), and epidermal growth factor (131530) pathways.
Consistent with these observations, extracellular signal-regulated
kinase mitogen-activated protein kinases (ERK MAPKs) were activated at
much lower levels in cells from Gab1-deficient embryos in response to
these growth factors or to stimulation of the cytokine receptor gp130
(IL6ST; 600694). Itoh et al. (2000) concluded that Gab1 is a common
player in a broad range of growth factor and cytokine signaling pathways
linking ERK MAP kinase activation.
Vasyutina et al. (2005) found that Cxcr4 (162643)-positive muscle
progenitor cells reach the anlage of the tongue in Gab1-null or
Cxcr4-null mouse embryos, but not in Cxcr4/Gab1 double mutants,
suggesting that these proteins interact during progenitor cell
migration.
*FIELD* RF
1. Holgado-Madruga, M.; Emlet, D. R.; Moscatello, D. K.; Godwin, A.
K.; Wong, A. J.: A Grb2-associated docking protein in EGF- and insulin-receptor
signalling. Nature 379: 560-564, 1996.
2. Holgado-Madruga, M.; Moscatello, D. K.; Emlet, D. R.; Dieterich,
R.; Wong, A. J.: Grb2-associated binder-1 mediates phosphatidylinositol
3-kinase activation and the promotion of cell survival by nerve growth
factor. Proc. Nat. Acad. Sci. 94: 12419-12424, 1997.
3. Itoh, M.; Yoshida, Y.; Nishida, K.; Narimatsu, M.; Hibi, M.; Hirano,
T.: Role of Gab1 in heart, placenta, and skin development and growth
factor- and cytokine-induced extracellular signal-regulated kinase
mitogen-activated protein kinase activation. Molec. Cell. Biol. 20:
3695-3704, 2000.
4. Nakaoka, Y.; Nishida, K.; Fujio, Y.; Izumi, M.; Terai, K.; Oshima,
Y.; Sugiyama, S.; Matsuda, S.; Koyasu, S.; Yamauchi-Takihara, K.;
Hirano, T.; Kawase, I.; Hirota, H.: Activation of gp130 transduces
hypertrophic signal through interaction of scaffolding/docking protein
Gab1 with tyrosine phosphatase SHP2 in cardiomyocytes. Circ. Res. 93:
221-229, 2003.
5. Vasyutina, E.; Stebler, J.; Brand-Saberi, B.; Schulz, S.; Raz,
E.; Birchmeier, C.: CXCR4 and Gab1 cooperate to control the development
of migrating muscle progenitor cells. Genes Dev. 19: 2187-2198,
2005.
6. Yamada, K.; Nishida, K.; Hibi, M.; Hirano, T.; Matsuda, Y.: Comparative
FISH mapping of Gab1 and Gab2 genes in human, mouse and rat. Cytogenet.
Cell Genet. 94: 39-42, 2001.
*FIELD* CN
Patricia A. Hartz - updated: 9/3/2007
Marla J. F. O'Neill - updated: 2/27/2004
Carol A. Bocchini - updated: 2/7/2002
Patti M. Sherman - updated: 7/21/2000
*FIELD* CD
Paul J. Converse: 1/18/2000
*FIELD* ED
carol: 09/07/2007
terry: 9/3/2007
carol: 3/3/2004
terry: 2/27/2004
terry: 2/7/2002
carol: 9/13/2001
mcapotos: 8/3/2000
mcapotos: 7/31/2000
psherman: 7/21/2000
carol: 1/19/2000