GRB10_RAT
ID GRB10_RAT Reviewed; 599 AA.
AC P0CE43;
DT 02-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 1.
DT 25-MAY-2022, entry version 76.
DE RecName: Full=Growth factor receptor-bound protein 10;
DE AltName: Full=GRB10 adapter protein;
GN Name=Grb10;
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 [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Adapter protein which modulates coupling of a number of cell
CC surface receptor kinases with specific signaling pathways. Binds to,
CC and suppress signals from, activated receptors tyrosine kinases,
CC including the insulin (INSR) and insulin-like growth factor (IGF1R)
CC receptors. The inhibitory effect can be achieved by 2 mechanisms:
CC interference with the signaling pathway and increased receptor
CC degradation. Delays and reduces AKT1 phosphorylation in response to
CC insulin stimulation. Blocks association between INSR and IRS1 and IRS2
CC and prevents insulin-stimulated IRS1 and IRS2 tyrosine phosphorylation.
CC Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased
CC internalization and degradation by both the proteasomal and lysosomal
CC pathways. A similar role in the mediation of ubiquitination has also
CC been suggested with INSR. Negatively regulates Wnt signaling by
CC interacting with LRP6 intracellular portion and interfering with the
CC binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2
CC signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-
CC 2 (By similarity). {ECO:0000250}.
CC -!- ACTIVITY REGULATION: Phosphorylation by mTORC1 stabilizes and activates
CC GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-
CC dependent signaling. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with ligand-activated tyrosine kinase receptors,
CC including FGFR1, INSR, IGF1R, MET and PDGFRB in a phosphotyrosine-
CC dependent manner through the SH2 domain. Poorly binds to the EGFR.
CC Directly interacts with MAP3K14/NIK and is recruited to the EGFR-ERBB2
CC complex. Interacts with GIGYF1/PERQ1 and GIGYF2/TNRC15. When
CC unphosphorylated, interacts with AKT1 and when phosphorylated with
CC YWHAE/14-3-3 epsilon. Interacts with NEDD4. Interacts with LRP6, thus
CC interfering with the binding of AXIN1 to LRP6. Binds relatively non-
CC specifically to several phosphoinositides, including PI(5)P, PI(4,5)P2,
CC PI(3,4)P2 and PI(3,4,5)P3, with modest affinities through the PH
CC domain. Binds to activated NRAS (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Note=When complexed with
CC NEDD4 and IGF1R, follows IGF1R internalization, remaining associated
CC with early endosomes. Uncouples from IGF1R-containing endosomes before
CC the sorting of the receptor to the lysosomal compartment (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine residues upon EGF, FGF and PDGF
CC stimulation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GRB7/10/14 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EDL76070.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; CH474055; EDL76070.1; ALT_INIT; Genomic_DNA.
DR RefSeq; XP_017454822.1; XM_017599333.1.
DR AlphaFoldDB; P0CE43; -.
DR SMR; P0CE43; -.
DR IntAct; P0CE43; 4.
DR STRING; 10116.ENSRNOP00000048487; -.
DR iPTMnet; P0CE43; -.
DR PhosphoSitePlus; P0CE43; -.
DR PaxDb; P0CE43; -.
DR GeneID; 498416; -.
DR UCSC; RGD:1566234; rat.
DR CTD; 2887; -.
DR RGD; 1566234; Grb10.
DR eggNOG; KOG3751; Eukaryota.
DR InParanoid; P0CE43; -.
DR OrthoDB; 497681at2759; -.
DR PhylomeDB; P0CE43; -.
DR Reactome; R-RNO-1433557; Signaling by SCF-KIT.
DR Reactome; R-RNO-74713; IRS activation.
DR Reactome; R-RNO-74749; Signal attenuation.
DR Reactome; R-RNO-74751; Insulin receptor signalling cascade.
DR Reactome; R-RNO-8853659; RET signaling.
DR Reactome; R-RNO-9607240; FLT3 Signaling.
DR PRO; PR:P0CE43; -.
DR Proteomes; UP000002494; Unplaced.
DR Proteomes; UP000234681; Chromosome 14.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0005158; F:insulin receptor binding; IDA:BHF-UCL.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:RGD.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; ISO:RGD.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0046325; P:negative regulation of glucose import; ISO:RGD.
DR GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0042326; P:negative regulation of phosphorylation; ISO:RGD.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:BHF-UCL.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032868; P:response to insulin; IDA:BHF-UCL.
DR GO; GO:1904738; P:vascular associated smooth muscle cell migration; ISO:RGD.
DR CDD; cd01259; PH_APBB1IP; 1.
DR CDD; cd10415; SH2_Grb10; 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; IPR035036; Grb10.
DR InterPro; IPR035037; Grb10_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:SF4; PTHR11243:SF4; 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 3: Inferred from homology;
KW Cytoplasm; Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..599
FT /note="Growth factor receptor-bound protein 10"
FT /id="PRO_0000392072"
FT DOMAIN 171..255
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 295..404
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 498..594
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..60
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 101..118
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13322"
FT MOD_RES 98
FT /note="Phosphoserine; by MTOR, MAPK1 and MAPK3"
FT /evidence="ECO:0000250|UniProtKB:Q13322"
FT MOD_RES 433
FT /note="Phosphoserine; by MTOR and PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q13322"
FT MOD_RES 436
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60760"
FT MOD_RES 481
FT /note="Phosphoserine; by MTOR, MAPK1 and MAPK3"
FT /evidence="ECO:0000250|UniProtKB:Q13322"
SQ SEQUENCE 599 AA; 67882 MW; 958392BFC94DE64D CRC64;
MNNDINSSVE SLNSACNMQS DTDTVPLLEN GQSASNQPSA SSSRGQPQAS PRQKMQRSQP
VHIQPLRRLQ EEDQQLRTSS LPAIPNPFPE LAGGAPGSPP SVAPSSLPPP PSQPPAKHFP
PGFQLAKLTR PGLWTKTTAR FSKRQPKNQC QTDTANAVSR IPTSQMEKLR LRKDVKVFSE
DGTSKVVEIL TDMTARDLCQ LLVYKSHCVD DNSWTLVEHH PQLGLERCLE DHEIVVQVES
TMPSESKFLF RKNYAKYEFF KNPVNFFPDQ MVTWCQQSNG GQAQLLQNFL NSSSCPEIQG
FLQVKEVGRK SWKKLYVCLR RSGLYYSTKG TSKEPRHLQL LADLEESSIF YLIAGKKQYN
APNEHGMCIK PNKAKIEMKE LRLLCAEDEQ IRTCWMTAFR LLKYGMLLYQ NYRIPQQRKG
LAPPFNAPMR SVSENSLVAM DFSGQIGRVI DNPAEAQSAA LEEGHAWRKR STRMNILSSQ
SPLHPSTLNS VIHRTQHWFH GRISREESHR IIKQQGLVDG LFLLRDSQSN PKAFVLTLCH
QQKIRNFQIL PCEDDGQTFF TLDDGNTKFS DLIQLVDFYQ LNKGVLPCKL KHHCIRVAL
