GRB14_RAT
ID GRB14_RAT Reviewed; 538 AA.
AC O88900;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 25-MAY-2022, entry version 153.
DE RecName: Full=Growth factor receptor-bound protein 14;
DE AltName: Full=GRB14 adapter protein;
GN Name=Grb14;
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].
RC STRAIN=Wistar;
RX PubMed=9748281; DOI=10.1074/jbc.273.40.26026;
RA Kasus-Jacobi A., Perdereau D., Auzan C., Clauser E., van Obberghen E.,
RA Mauvais-Jarvis F., Girard J., Burnol A.-F.;
RT "Identification of the rat adapter Grb14 as an inhibitor of insulin
RT actions.";
RL J. Biol. Chem. 273:26026-26035(1998).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370 AND SER-373, AND
RP IDENTIFICATION BY 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 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 O88900; P11362: FGFR1; Xeno; NbExp=3; IntAct=EBI-7639197, EBI-1028277;
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.
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; AF076619; AAC61478.1; -; mRNA.
DR RefSeq; NP_113811.1; NM_031623.1.
DR AlphaFoldDB; O88900; -.
DR SMR; O88900; -.
DR BioGRID; 248645; 2.
DR IntAct; O88900; 3.
DR MINT; O88900; -.
DR STRING; 10116.ENSRNOP00000046233; -.
DR iPTMnet; O88900; -.
DR PhosphoSitePlus; O88900; -.
DR PaxDb; O88900; -.
DR GeneID; 58844; -.
DR KEGG; rno:58844; -.
DR UCSC; RGD:61869; rat.
DR CTD; 2888; -.
DR RGD; 61869; Grb14.
DR eggNOG; KOG3751; Eukaryota.
DR InParanoid; O88900; -.
DR OrthoDB; 497681at2759; -.
DR PhylomeDB; O88900; -.
DR Reactome; R-RNO-210993; Tie2 Signaling.
DR PRO; PR:O88900; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005768; C:endosome; IDA:RGD.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:RGD.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:RGD.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IMP:CAFA.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IEP:RGD.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:RGD.
DR GO; GO:1904145; P:negative regulation of meiotic cell cycle process involved in oocyte maturation; IMP:CAFA.
DR CDD; cd01259; PH_APBB1IP; 1.
DR CDD; cd10414; SH2_Grb14; 1.
DR DisProt; DP00490; -.
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; IPR035035; Grb14.
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; PTHR11243; 1.
DR PANTHER; PTHR11243:SF22; PTHR11243:SF22; 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 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..538
FT /note="Growth factor receptor-bound protein 14"
FT /id="PRO_0000150350"
FT DOMAIN 104..190
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 232..340
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 437..533
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..70
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14449"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 538 AA; 60593 MW; CEBC9037E7868EEF CRC64;
MTTSLQDGQS AAGRAGAQDS PLAVQVCRVA QGKGDAQDPA QVPGLHALSP ASDATRRGAM
DRRKAKDLEV QETPSIPNPF PELCCSPLTS VLSAGLFPRS NSRKKQVIKV YSEDETSRAL
EVPSDVTARD VCQLLILKNH YVDDNSWTLF EHLSHTGVER TVEDHELLTE VLSHWVMEED
NKLYLRKNYA KYEFFKNPMY FFPEHMVSFA TEMNGDRSLT QIPQVFLSSN TYPEIHGFLH
AKEQGKKSWK KAYFFLRRSG LYFSTKGTSK EPRHLQFFSE FSTSNVYMSL AGKKKHGAPT
PYGFCFKPTK AGGPRDLKML CAEEDQSRMC WVTAIRLLKY GMQLYQNYMH PSQARSACSS
QSVSPMRSVS ENSLVAMDFS GQKTRVIDNP TEALSVAVEE GLAWRKKGCL RLGNHGSPTA
PSQSSAVNMA LHRSQPWFHH RISRDEAQQL ITRQGPVDGV FLVRDSQSNP RTFVLSMSHG
QKIKHFQIIP VEDDGEVFHT LDDGHTKFTD LIQLVEFYQL NKGVLPCKLK HYCARMAV
