GRB7_MOUSE
ID GRB7_MOUSE Reviewed; 535 AA.
AC Q03160; Q3TH55;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Growth factor receptor-bound protein 7;
DE AltName: Full=Epidermal growth factor receptor GRB-7;
DE AltName: Full=GRB7 adapter protein;
GN Name=Grb7;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo;
RX PubMed=1409582; DOI=10.1073/pnas.89.19.8894;
RA Margolis B., Silvennoinen O., Comoglio F., Roonprapunt C., Skolnik E.Y.,
RA Ullrich A., Schlessinger J.;
RT "High-efficiency expression/cloning of epidermal growth factor-receptor-
RT binding proteins with Src homology 2 domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8894-8898(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney, and Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH RET, AND TYROSINE PHOSPHORYLATION.
RX PubMed=8631863; DOI=10.1074/jbc.271.18.10607;
RA Pandey A., Liu X., Dixon J.E., Di Fiore P.P., Dixit V.M.;
RT "Direct association between the Ret receptor tyrosine kinase and the Src
RT homology 2-containing adapter protein Grb7.";
RL J. Biol. Chem. 271:10607-10610(1996).
RN [7]
RP INTERACTION WITH PDGFRA; PDGFRB AND SHC1.
RX PubMed=8940081; DOI=10.1074/jbc.271.48.30942;
RA Yokote K., Margolis B., Heldin C.H., Claesson-Welsh L.;
RT "Grb7 is a downstream signaling component of platelet-derived growth factor
RT alpha- and beta-receptors.";
RL J. Biol. Chem. 271:30942-30949(1996).
RN [8]
RP INTERACTION WITH KIT.
RX PubMed=10377264; DOI=10.1042/bj3410211;
RA Thommes K., Lennartsson J., Carlberg M., Ronnstrand L.;
RT "Identification of Tyr-703 and Tyr-936 as the primary association sites for
RT Grb2 and Grb7 in the c-Kit/stem cell factor receptor.";
RL Biochem. J. 341:211-216(1999).
RN [9]
RP INTERACTION WITH TEK/TIE2, AND PHOSPHORYLATION.
RX PubMed=10521483; DOI=10.1074/jbc.274.43.30896;
RA Jones N., Master Z., Jones J., Bouchard D., Gunji Y., Sasaki H., Daly R.,
RA Alitalo K., Dumont D.J.;
RT "Identification of Tek/Tie2 binding partners. Binding to a multifunctional
RT docking site mediates cell survival and migration.";
RL J. Biol. Chem. 274:30896-30905(1999).
RN [10]
RP FUNCTION, INTERACTION WITH PTK2/FAK1, PHOSPHORYLATION, RNA-BINDING, AND
RP MUTAGENESIS OF TYR-483 AND TYR-495.
RX PubMed=17318180; DOI=10.1038/sj.emboj.7601598;
RA Tsai N.P., Bi J., Wei L.N.;
RT "The adaptor Grb7 links netrin-1 signaling to regulation of mRNA
RT translation.";
RL EMBO J. 26:1522-1531(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH ELAVL1,
RP AND IDENTIFICATION IN A COMPLEX WITH PTK2/FAK1; ELAVL1 AND TIA1.
RX PubMed=18273060; DOI=10.1038/emboj.2008.19;
RA Tsai N.P., Ho P.C., Wei L.N.;
RT "Regulation of stress granule dynamics by Grb7 and FAK signalling
RT pathway.";
RL EMBO J. 27:715-726(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
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).
CC -!- FUNCTION: Adapter protein that interacts with the cytoplasmic domain of
CC numerous receptor kinases and modulates down-stream signaling. Promotes
CC activation of down-stream protein kinases, including STAT3, AKT1, MAPK1
CC and/or MAPK3. Promotes activation of HRAS. Plays a role in signal
CC transduction in response to EGF. Plays a role in the regulation of cell
CC proliferation and cell migration (By similarity). Plays a role in the
CC assembly and stability of RNA stress granules. Binds to the 5'UTR of
CC target mRNA molecules and represses translation of target mRNA species,
CC when not phosphorylated. Phosphorylation impairs RNA binding and
CC promotes stress granule disassembly during recovery after cellular
CC stress. {ECO:0000250, ECO:0000269|PubMed:17318180,
CC ECO:0000269|PubMed:18273060}.
CC -!- SUBUNIT: Homodimer. Interacts (via SH2 domain) with EGFR, ERBB2, ERBB3
CC (when phosphorylated), ERBB4 (when phosphorylated), EPHB1, INSR, FGFR1,
CC PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated).
CC Interacts with SHC1. Interacts with RND1. Interacts (when tyrosine
CC phosphorylated) with FHL2 and HAX1 (By similarity). Interacts (via SH2
CC domain) with RET and PTK2/FAK1. Interacts (when not phosphorylated)
CC with ELAVL1. In stressed cells, but not in normal cells, part of a
CC complex that contains at least GRB7, PTK2/FAK1, STAU1, ELAVL1 and TIA1.
CC Interacts (via SH2 domain) with KIT (phosphorylated). Interacts (via
CC SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). {ECO:0000250,
CC ECO:0000269|PubMed:10377264, ECO:0000269|PubMed:10521483,
CC ECO:0000269|PubMed:17318180, ECO:0000269|PubMed:18273060,
CC ECO:0000269|PubMed:8631863, ECO:0000269|PubMed:8940081}.
CC -!- INTERACTION:
CC Q03160; P70372: Elavl1; NbExp=7; IntAct=EBI-7100053, EBI-6877056;
CC Q03160; Q02858: Tek; NbExp=3; IntAct=EBI-7100053, EBI-7099626;
CC Q03160; Q80ZW7: Tia1; NbExp=4; IntAct=EBI-7100053, EBI-7809240;
CC Q03160; Q03135: CAV1; Xeno; NbExp=3; IntAct=EBI-7100053, EBI-603614;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18273060}. Cell
CC projection {ECO:0000250|UniProtKB:Q14451}. Cell junction, focal
CC adhesion {ECO:0000250|UniProtKB:Q14451}. Cell membrane
CC {ECO:0000250|UniProtKB:Q14451}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q14451}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q14451}. Cytoplasmic granule
CC {ECO:0000269|PubMed:18273060}. Note=Predominantly cytoplasmic. Detected
CC in stress granules where mRNA is stored under stress conditions.
CC {ECO:0000269|PubMed:18273060}.
CC -!- DOMAIN: The PH domain mediates interaction with membranes containing
CC phosphoinositides. {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine and threonine residues in response to
CC activation of receptor kinases. Phosphorylated on tyrosine residues by
CC TEK/TIE2. Phosphorylated on tyrosine residues by PTK2/FAK1, and
CC possibly also other kinases. Phosphorylation is enhanced by activation
CC of receptor kinases. Tyrosine phosphorylation is essential for
CC activation of down-stream protein kinases (By similarity).
CC Phosphorylated on tyrosine residues in response to NTN1 signaling.
CC Phosphorylation promotes stress granule disassembly during recovery
CC after cellular stress. {ECO:0000250, ECO:0000269|PubMed:10521483,
CC ECO:0000269|PubMed:17318180, ECO:0000269|PubMed:18273060}.
CC -!- SIMILARITY: Belongs to the GRB7/10/14 family. {ECO:0000305}.
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DR EMBL; M94450; AAA37733.1; -; mRNA.
DR EMBL; AK145996; BAE26817.1; -; mRNA.
DR EMBL; AK168438; BAE40343.1; -; mRNA.
DR EMBL; AL591390; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466556; EDL16144.1; -; Genomic_DNA.
DR EMBL; BC003295; AAH03295.1; -; mRNA.
DR CCDS; CCDS25351.1; -.
DR PIR; C46243; C46243.
DR RefSeq; NP_034476.1; NM_010346.2.
DR RefSeq; XP_006532296.1; XM_006532233.1.
DR AlphaFoldDB; Q03160; -.
DR SMR; Q03160; -.
DR BioGRID; 200047; 2.
DR CORUM; Q03160; -.
DR DIP; DIP-43965N; -.
DR IntAct; Q03160; 7.
DR MINT; Q03160; -.
DR STRING; 10090.ENSMUSP00000019456; -.
DR iPTMnet; Q03160; -.
DR PhosphoSitePlus; Q03160; -.
DR EPD; Q03160; -.
DR MaxQB; Q03160; -.
DR PaxDb; Q03160; -.
DR PeptideAtlas; Q03160; -.
DR PRIDE; Q03160; -.
DR ProteomicsDB; 271327; -.
DR Antibodypedia; 3928; 370 antibodies from 38 providers.
DR DNASU; 14786; -.
DR Ensembl; ENSMUST00000019456; ENSMUSP00000019456; ENSMUSG00000019312.
DR GeneID; 14786; -.
DR KEGG; mmu:14786; -.
DR UCSC; uc007lgk.1; mouse.
DR CTD; 2886; -.
DR MGI; MGI:102683; Grb7.
DR VEuPathDB; HostDB:ENSMUSG00000019312; -.
DR eggNOG; KOG3751; Eukaryota.
DR GeneTree; ENSGT00940000158710; -.
DR HOGENOM; CLU_023207_0_1_1; -.
DR InParanoid; Q03160; -.
DR OMA; RCFCFLR; -.
DR OrthoDB; 497681at2759; -.
DR PhylomeDB; Q03160; -.
DR TreeFam; TF317511; -.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-186763; Downstream signal transduction.
DR Reactome; R-MMU-210993; Tie2 Signaling.
DR Reactome; R-MMU-8853659; RET signaling.
DR Reactome; R-MMU-9696273; RND1 GTPase cycle.
DR BioGRID-ORCS; 14786; 4 hits in 73 CRISPR screens.
DR PRO; PR:Q03160; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q03160; protein.
DR Bgee; ENSMUSG00000019312; Expressed in ileal epithelium and 157 other tissues.
DR ExpressionAtlas; Q03160; baseline and differential.
DR Genevisible; Q03160; MM.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0017148; P:negative regulation of translation; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:MGI.
DR GO; GO:0034063; P:stress granule assembly; IMP:UniProtKB.
DR CDD; cd01259; PH_APBB1IP; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR015042; BPS-dom.
DR InterPro; IPR039664; GRB/APBB1IP.
DR InterPro; IPR035032; Grb7.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR039665; PH_APBB1IP.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000159; RA_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR11243; PTHR11243; 1.
DR PANTHER; PTHR11243:SF25; PTHR11243:SF25; 1.
DR Pfam; PF08947; BPS; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00788; RA; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00233; PH; 1.
DR SMART; SM00314; RA; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50200; RA; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Cell projection; Cytoplasm; Lipid-binding;
KW Membrane; Phosphoprotein; Reference proteome; Repressor; RNA-binding;
KW SH2 domain.
FT CHAIN 1..535
FT /note="Growth factor receptor-bound protein 7"
FT /id="PRO_0000150345"
FT DOMAIN 99..185
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 228..341
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 434..530
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..42
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 187
FT /note="Phosphotyrosine; by FAK1"
FT /evidence="ECO:0000250|UniProtKB:Q14451"
FT MOD_RES 341
FT /note="Phosphotyrosine; by FAK1"
FT /evidence="ECO:0000250|UniProtKB:Q14451"
FT MOD_RES 364
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14451"
FT MUTAGEN 262
FT /note="Y->F: Abolishes interaction with FHL2."
FT MUTAGEN 263
FT /note="Y->F: Abolishes interaction with FHL2."
FT MUTAGEN 287
FT /note="Y->F: Abolishes interaction with FHL2."
FT MUTAGEN 483
FT /note="Y->F: Strongly reduced tyrosine phosphorylation.
FT Abolishes interaction with FHL2."
FT /evidence="ECO:0000269|PubMed:17318180"
FT MUTAGEN 495
FT /note="Y->F: Strongly reduced tyrosine phosphorylation.
FT Abolishes interaction with FHL2."
FT /evidence="ECO:0000269|PubMed:17318180"
SQ SEQUENCE 535 AA; 59959 MW; CD8C307864703645 CRC64;
MELDLSPTHL SSSPEDVCPT PATPPETPPP PDNPPPGDVK RSQPLPIPSS RKLREEEFQA
TSLPSIPNPF PELCSPPSQK PILGGSSGAR GLLPRDSSRL CVVKVYSEDG ACRSVEVAAG
ATARHVCEML VQRAHALSDE SWGLVESHPY LALERGLEDH EFVVEVQEAW PVGGDSRFIF
RKNFAKYELF KSPPHTLFPE KMVSSCLDAQ TGISHEDLIQ NFLNAGSFPE IQGFLQLRGS
GRGSGRKLWK RFFCFLRRSG LYYSTKGTSK DPRHLQYVAD VNESNVYVVT QGRKLYGMPT
DFGFCVKPNK LRNGHKGLHI FCSEDEQSRT CWLAAFRLFK YGVQLYKNYQ QAQSRHLRLS
YLGSPPLRSV SDNTLVAMDF SGHAGRVIDN PREALSAAME EAQAWRKKTN HRLSLPTTCS
GSSLSAAIHR TQPWFHGRIS REESQRLIGQ QGLVDGVFLV RESQRNPQGF VLSLCHLQKV
KHYLILPSED EGCLYFSMDE GQTRFTDLLQ LVEFHQLNRG ILPCLLRHCC ARVAL
