ID GRB7_BOVIN Reviewed; 532 AA.
AC Q1RMW5;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 1.
DT 24-JAN-2024, entry version 106.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Uterus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
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 (via SH2 domain) with TEK/TIE2 (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) (By similarity).
CC {ECO:0000250}.
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 -!- 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; BC114669; AAI14670.1; -; mRNA.
DR RefSeq; NP_001039479.1; NM_001046014.1.
DR RefSeq; XP_005220751.1; XM_005220694.3.
DR RefSeq; XP_005220752.1; XM_005220695.3.
DR RefSeq; XP_005220753.1; XM_005220696.3.
DR RefSeq; XP_005220754.1; XM_005220697.2.
DR RefSeq; XP_015314313.1; XM_015458827.1.
DR AlphaFoldDB; Q1RMW5; -.
DR SMR; Q1RMW5; -.
DR STRING; 9913.ENSBTAP00000023091; -.
DR PaxDb; 9913-ENSBTAP00000023091; -.
DR Ensembl; ENSBTAT00000023091.4; ENSBTAP00000023091.3; ENSBTAG00000017366.4.
DR GeneID; 508847; -.
DR KEGG; bta:508847; -.
DR CTD; 2886; -.
DR VEuPathDB; HostDB:ENSBTAG00000017366; -.
DR VGNC; VGNC:29632; GRB7.
DR eggNOG; KOG3751; Eukaryota.
DR GeneTree; ENSGT00940000158710; -.
DR HOGENOM; CLU_023207_0_1_1; -.
DR InParanoid; Q1RMW5; -.
DR OMA; RCFCFLR; -.
DR OrthoDB; 3144731at2759; -.
DR TreeFam; TF317511; -.
DR Reactome; R-BTA-1306955; GRB7 events in ERBB2 signaling.
DR Reactome; R-BTA-1433557; Signaling by SCF-KIT.
DR Reactome; R-BTA-186763; Downstream signal transduction.
DR Reactome; R-BTA-210993; Tie2 Signaling.
DR Reactome; R-BTA-8853659; RET signaling.
DR Reactome; R-BTA-9696273; RND1 GTPase cycle.
DR Proteomes; UP000009136; Chromosome 19.
DR Bgee; ENSBTAG00000017366; Expressed in placenta and 81 other cell types or tissues.
DR ExpressionAtlas; Q1RMW5; baseline and differential.
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:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
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 CDD; cd16140; RA_GRB7; 1.
DR CDD; cd10413; SH2_Grb7; 1.
DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR Gene3D; 3.30.505.10; SH2 domain; 1.
DR InterPro; IPR015042; BPS-dom.
DR InterPro; IPR039664; GRB/APBB1IP.
DR InterPro; IPR046986; GRB7_RA.
DR InterPro; IPR035032; Grb7_SH2.
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; GROWTH FACTOR RECEPTOR-BOUND PROTEIN; 1.
DR PANTHER; PTHR11243:SF25; GROWTH FACTOR RECEPTOR-BOUND PROTEIN 7; 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; SSF50729; PH domain-like; 1.
DR SUPFAM; SSF55550; SH2 domain; 1.
DR SUPFAM; SSF54236; Ubiquitin-like; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50200; RA; 1.
DR PROSITE; PS50001; SH2; 1.
PE 2: Evidence at transcript 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..532
FT /note="Growth factor receptor-bound protein 7"
FT /id="PRO_0000245330"
FT DOMAIN 100..186
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 229..338
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 431..527
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 59..87
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 239
FT /note="Important for lipid binding and for stimulation of
FT cell migration"
FT /evidence="ECO:0000250"
FT SITE 511
FT /note="Important for dimerization and for HRAS activation"
FT /evidence="ECO:0000250"
FT MOD_RES 188
FT /note="Phosphotyrosine; by FAK1"
FT /evidence="ECO:0000250|UniProtKB:Q14451"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14451"
SQ SEQUENCE 532 AA; 59653 MW; 8C8C23029FF717E0 CRC64;
MELGLSPLHL SSSPEDLYLA SGTPPGTPPP LDAPLSGEVK RSQPLPIPTS RKLLREEELQ
STSLPSIPNP FPELCSPSSQ SPILGGSSSA RGLLPRDTSC PHVIKVYSED GTCRSVEVAT
GATARYVCEM LVQRSHALSD ENWGLVECHP YLALERALED HESVAEVQAA WPIGGDSRIV
FRKNFAKYEL FKSTPHSLFP EKMVSSCLDA HTGMSHEDVI QNFLNAGSFP EIQGFLQLRG
SGRKLWKRFF CFLRRSGLYY STKGTSKDPR HLQYVADVNE SNVYVVTQGR KLYGMPTDFG
FCIKPNKLRN GHKGLRLFCT EDERSRSCWL AAFRLFKFGV QLYKNYQQTL CRHMCPPCGG
SPPSRSVSDD TLVAMDFSGH AGRVIENPRE ALSAALEEAQ AWRKKTNHRL SLPTPSSGTS
LSAAIHRTQP WFHGRISREE SQRLIRQQGL VDGLFLVRES QRNPQGFVLS LCHVQKVKHY
LILPSEEEGR LYFSMDDGLT RFTDLLQLVE FHQLNRGILP CLLRYCCTRV AL
//
