GRB7_RAT
ID GRB7_RAT Reviewed; 535 AA.
AC Q9QZC5;
DT 21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 139.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH INSR; EGFR; FGFR1 AND RET,
RP MUTAGENESIS OF ARG-461, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=10803466; DOI=10.1038/sj.onc.1203469;
RA Kasus-Jacobi A., Bereziat V., Perdereau D., Girard J., Burnol A.F.;
RT "Evidence for an interaction between the insulin receptor and Grb7. A role
RT for two of its binding domains, PIR and SH2.";
RL Oncogene 19:2052-2059(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-364, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. Plays a role in the assembly and
CC stability of RNA stress granules. Binds to the 5'UTR of target mRNA
CC molecules and represses translation of target mRNA species, when not
CC phosphorylated. Phosphorylation impairs RNA binding and promotes stress
CC granule disassembly during recovery after cellular stress (By
CC similarity). {ECO:0000250}.
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) (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q9QZC5; P00533: EGFR; Xeno; NbExp=7; IntAct=EBI-22085551, EBI-297353;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14451}. 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:0000250|UniProtKB:Q03160}. Note=Predominantly cytoplasmic.
CC Detected in stress granules where mRNA is stored under stress
CC conditions. {ECO:0000250|UniProtKB:Q03160}.
CC -!- TISSUE SPECIFICITY: Detected in liver, kidney and placenta, and at
CC lower levels in lung. {ECO:0000269|PubMed:10803466}.
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 by a cognate ligand. Tyrosine phosphorylation is
CC essential for activation of down-stream protein kinases.
CC Phosphorylation decreases affinity for target mRNA molecules (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GRB7/10/14 family. {ECO:0000305}.
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DR EMBL; AF190121; AAF01776.1; -; mRNA.
DR EMBL; CH473948; EDM05933.1; -; Genomic_DNA.
DR EMBL; BC081757; AAH81757.1; -; mRNA.
DR RefSeq; NP_445855.1; NM_053403.2.
DR RefSeq; XP_006247494.1; XM_006247432.3.
DR RefSeq; XP_006247495.1; XM_006247433.3.
DR RefSeq; XP_008766347.1; XM_008768125.1.
DR RefSeq; XP_017453048.1; XM_017597559.1.
DR RefSeq; XP_017453049.1; XM_017597560.1.
DR RefSeq; XP_017453050.1; XM_017597561.1.
DR AlphaFoldDB; Q9QZC5; -.
DR SMR; Q9QZC5; -.
DR BioGRID; 249963; 8.
DR IntAct; Q9QZC5; 38.
DR STRING; 10116.ENSRNOP00000009299; -.
DR iPTMnet; Q9QZC5; -.
DR PhosphoSitePlus; Q9QZC5; -.
DR jPOST; Q9QZC5; -.
DR PaxDb; Q9QZC5; -.
DR PRIDE; Q9QZC5; -.
DR GeneID; 84427; -.
DR KEGG; rno:84427; -.
DR UCSC; RGD:619759; rat.
DR CTD; 2886; -.
DR RGD; 619759; Grb7.
DR VEuPathDB; HostDB:ENSRNOG00000006990; -.
DR eggNOG; KOG3751; Eukaryota.
DR HOGENOM; CLU_023207_0_1_1; -.
DR InParanoid; Q9QZC5; -.
DR OMA; RCFCFLR; -.
DR OrthoDB; 497681at2759; -.
DR PhylomeDB; Q9QZC5; -.
DR TreeFam; TF317511; -.
DR Reactome; R-RNO-1433557; Signaling by SCF-KIT.
DR Reactome; R-RNO-186763; Downstream signal transduction.
DR Reactome; R-RNO-210993; Tie2 Signaling.
DR Reactome; R-RNO-8853659; RET signaling.
DR Reactome; R-RNO-9696273; RND1 GTPase cycle.
DR PRO; PR:Q9QZC5; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Proteomes; UP000234681; Chromosome 10.
DR Bgee; ENSRNOG00000006990; Expressed in jejunum and 13 other tissues.
DR Genevisible; Q9QZC5; RN.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS: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:RGD.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0017148; P:negative regulation of translation; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR GO; GO:0034063; P:stress granule assembly; ISS: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_0000412210"
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..89
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 SITE 238
FT /note="Important for lipid binding and for stimulation of
FT cell migration"
FT /evidence="ECO:0000250"
FT SITE 514
FT /note="Important for dimerization and for HRAS activation"
FT /evidence="ECO:0000250"
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:0007744|PubMed:22673903"
FT MUTAGEN 461
FT /note="R->K: Reduces interaction with INSR."
FT /evidence="ECO:0000269|PubMed:10803466"
SQ SEQUENCE 535 AA; 59889 MW; 15DB67C4D19B89E4 CRC64;
MELDLSPSHL SSSPEDVCPT PGTPPETPPP PDNPPPGDVK RSQPLPIPSS RKLREEEFQA
TSLPSIPNPF PELCSPPSQK PILGGSSGAR GLLPRDSSRL CVVKVYSEDG ACRSVEVAAG
ATARHVCEML VQRAHALSDE NWGLVECHPY LALERGLEDH ESVVEVQEAW PVGGDSRFIF
RKNFAKYELF KSPPHTLFPE KMVSSCLDTP TGISHEDLIQ NFLNAGSFPE IQGFLQLRGS
GRGSGRKLWK RFFCFLRRSG LYYSTKGTSK DPRHLQYVAD INESNVYVVT QGRKLYGIPT
DFGFCVKPNK LRNGHKGLHI FCSEDEQSRT CWLSAFRLFK YGVQLYKNYQ QAQSRHLRLS
YLGSPPLRSV SDNTLVAMDF SGHAGRVIEN PQEALSAATE EAQAWRKKTN HRLSLPTPCS
GLSLSAAIHR TQPWFHGRIS REESQRLIGQ QGLVDGVFLV RESQRNPQGF VLSLCHLQKV
KHYLILPSED EGCLYFSMDD GQTRFTDLLQ LVEFHQLNRG ILPCLLRHCC ARVAL
