ID GRB14_BOVIN Reviewed; 540 AA.
AC Q5ICW4;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 08-NOV-2023, entry version 110.
DE RecName: Full=Growth factor receptor-bound protein 14;
DE AltName: Full=GRB14 adapter protein;
GN Name=GRB14;
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 [MRNA].
RC TISSUE=Retina;
RA Rajala R.V.S.;
RT "Retinal GRB14 in insulin receptor signaling.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Adapter protein which modulates coupling of cell surface
CC receptor kinases with specific signaling pathways. Binds to, and
CC suppresses signals from, the activated insulin receptor (INSR). Potent
CC inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical
CC role regulating PDPK1 membrane translocation in response to insulin
CC stimulation and serves as an adapter protein to recruit PDPK1 to
CC activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and
CC transduction of the insulin signal (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with the cytoplasmic domain of the
CC autophosphorylated insulin receptor, through the SH2 domain. Interacts
CC with GRB14 (via BPS domain); this interaction protects the tyrosines in
CC the activation loop on INSR from dephosphorylation (By similarity).
CC Binds to the ankyrin repeat region of TNKS2 via its N-terminus.
CC Interacts with activated NRAS. Interacts (via SH2 domain) with TEK/TIE2
CC (tyrosine phosphorylated) (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q5ICW4; P29973: CNGA1; Xeno; NbExp=4; IntAct=EBI-7639273, EBI-8417095;
CC Q5ICW4; Q14028: CNGB1; Xeno; NbExp=2; IntAct=EBI-7639273, EBI-7959609;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14449}.
CC Endosome membrane {ECO:0000250|UniProtKB:Q14449}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q14449}. Note=Upon insulin stimulation,
CC translocates to the plasma membrane. {ECO:0000250|UniProtKB:Q14449}.
CC -!- DOMAIN: The PH domain binds relatively non-specifically and with low
CC affinity to several phosphoinositides, the best binder being
CC PI(3,4,5)P3. {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine residues. Phosphorylated on tyrosine
CC residues by TEK/TIE2 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GRB7/10/14 family. {ECO:0000305}.
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DR EMBL; AY772475; AAW47246.1; -; mRNA.
DR RefSeq; NP_001011681.2; NM_001011681.3.
DR AlphaFoldDB; Q5ICW4; -.
DR SMR; Q5ICW4; -.
DR IntAct; Q5ICW4; 2.
DR MINT; Q5ICW4; -.
DR STRING; 9913.ENSBTAP00000025686; -.
DR PaxDb; 9913-ENSBTAP00000025686; -.
DR GeneID; 497029; -.
DR KEGG; bta:497029; -.
DR CTD; 2888; -.
DR eggNOG; KOG3751; Eukaryota.
DR InParanoid; Q5ICW4; -.
DR OrthoDB; 3144731at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IBA:GO_Central.
DR CDD; cd01259; PH_APBB1IP; 1.
DR CDD; cd16139; RA_GRB14; 1.
DR CDD; cd10414; SH2_Grb14; 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; IPR035034; Grb14_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:SF22; GROWTH FACTOR RECEPTOR-BOUND PROTEIN 14; 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 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Endosome; Membrane; Phosphoprotein;
KW Reference proteome; SH2 domain.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q14449"
FT CHAIN 2..540
FT /note="Growth factor receptor-bound protein 14"
FT /id="PRO_0000253502"
FT DOMAIN 106..192
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 234..342
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 439..535
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14449"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88900"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JLM9"
SQ SEQUENCE 540 AA; 61040 MW; 886BE74B11F1D062 CRC64;
MTTSLQDGQS AAGRAAARDS PLAAQVCGAA QGRGDARDLA PAPWLHARAL LPPPDATRGC
AADRRKKKDL DVLEMPSIPN PFPELCCSPF TSVLSAGLFP KANSRKKQVI KVYSEDETSR
ALEVPSDITA RDVCQLLILK NHYIDDHSWT LFEHLPHVGL ERTIEDHELV IEVLSNWGME
EENKLYFRKN YAKYEFFKNP MYFFPEHMVS FATETNGEIS PTQILQMFLS SSTYPEIHGF
LHAKEQGKKS WKKIYFLLRR SGLYFSTKGT SKEPRHLQFF SEFGNSDIYV SLAGKKKHGA
PTNYGFCFKP NKAGGPRDLK MLCAEEEQSR TCWVTAIRLL KYGMQLYQNY MHPYQGRSGY
SSQSISPMRS ISENSRVAMD FSGQKTRVIE NPTEALSVAV EEGLAWRKKG CLRLGSHGSP
TASSQSSATS MAIHRSQPWF HHKMSREEAQ RLIIQQGLVD GVFLVRDSQS NPKTFVLSMS
HGQKIKHFQI IPVEDDGEMF HTLDDGHTRF TDLIQLVEFY QLNKGVLPCK LKHYCARIAL
//
