GRB10_PIG
ID GRB10_PIG Reviewed; 589 AA.
AC B5KFD7; B5KFD3; B5KFD4; B5KFD6;
DT 02-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Growth factor receptor-bound protein 10;
DE AltName: Full=GRB10 adapter protein;
GN Name=Grb10;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).
RA Nielsen A.L.;
RT "Pig Grb10 is bi-alleic expressed.";
RL Submitted (DEC-2006) 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}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=B5KFD7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=B5KFD7-2; Sequence=VSP_038785;
CC Name=3;
CC IsoId=B5KFD7-3; Sequence=VSP_038785, VSP_038786, VSP_038787;
CC Name=4;
CC IsoId=B5KFD7-4; Sequence=VSP_038786, VSP_038787;
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 ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; EF174191; ABO93312.1; -; mRNA.
DR EMBL; EF174192; ABO93313.1; -; mRNA.
DR EMBL; EF174193; ABO93314.1; -; mRNA.
DR EMBL; EF174194; ABO93315.1; -; mRNA.
DR EMBL; EF174195; ABO93316.1; -; mRNA.
DR EMBL; EF174196; ABO93317.1; -; mRNA.
DR EMBL; EF174197; ABO93318.1; -; mRNA.
DR EMBL; EF174198; ABO93319.1; -; mRNA.
DR EMBL; EF174199; ABO93320.1; -; mRNA.
DR RefSeq; NP_001128437.1; NM_001134965.1. [B5KFD7-1]
DR AlphaFoldDB; B5KFD7; -.
DR SMR; B5KFD7; -.
DR STRING; 9823.ENSSSCP00000020573; -.
DR PaxDb; B5KFD7; -.
DR PRIDE; B5KFD7; -.
DR Ensembl; ENSSSCT00000057201; ENSSSCP00000057939; ENSSSCG00000015631. [B5KFD7-4]
DR Ensembl; ENSSSCT00000060494; ENSSSCP00000031279; ENSSSCG00000015631. [B5KFD7-1]
DR Ensembl; ENSSSCT00015098893; ENSSSCP00015040822; ENSSSCG00015069263. [B5KFD7-2]
DR Ensembl; ENSSSCT00025030811; ENSSSCP00025013000; ENSSSCG00025021300. [B5KFD7-1]
DR Ensembl; ENSSSCT00025030952; ENSSSCP00025013047; ENSSSCG00025021300. [B5KFD7-3]
DR Ensembl; ENSSSCT00030019333; ENSSSCP00030008610; ENSSSCG00030013785. [B5KFD7-1]
DR Ensembl; ENSSSCT00030019392; ENSSSCP00030008631; ENSSSCG00030013785. [B5KFD7-3]
DR Ensembl; ENSSSCT00035047394; ENSSSCP00035018961; ENSSSCG00035035590. [B5KFD7-1]
DR Ensembl; ENSSSCT00035047412; ENSSSCP00035018970; ENSSSCG00035035590. [B5KFD7-3]
DR Ensembl; ENSSSCT00045013453; ENSSSCP00045009288; ENSSSCG00045007886. [B5KFD7-1]
DR Ensembl; ENSSSCT00045013635; ENSSSCP00045009423; ENSSSCG00045007886. [B5KFD7-3]
DR Ensembl; ENSSSCT00050088371; ENSSSCP00050037878; ENSSSCG00050064694. [B5KFD7-1]
DR Ensembl; ENSSSCT00050088439; ENSSSCP00050037911; ENSSSCG00050064694. [B5KFD7-3]
DR Ensembl; ENSSSCT00055016172; ENSSSCP00055012722; ENSSSCG00055008083. [B5KFD7-1]
DR Ensembl; ENSSSCT00055016340; ENSSSCP00055012872; ENSSSCG00055008083. [B5KFD7-3]
DR Ensembl; ENSSSCT00060014480; ENSSSCP00060005616; ENSSSCG00060010913. [B5KFD7-1]
DR Ensembl; ENSSSCT00065006754; ENSSSCP00065002952; ENSSSCG00065004787. [B5KFD7-1]
DR Ensembl; ENSSSCT00065006762; ENSSSCP00065002957; ENSSSCG00065004787. [B5KFD7-3]
DR Ensembl; ENSSSCT00070014564; ENSSSCP00070012027; ENSSSCG00070007353. [B5KFD7-1]
DR Ensembl; ENSSSCT00070014581; ENSSSCP00070012040; ENSSSCG00070007353. [B5KFD7-1]
DR Ensembl; ENSSSCT00070014664; ENSSSCP00070012115; ENSSSCG00070007353. [B5KFD7-3]
DR GeneID; 100188977; -.
DR KEGG; ssc:100188977; -.
DR CTD; 2887; -.
DR eggNOG; KOG3751; Eukaryota.
DR GeneTree; ENSGT00940000155909; -.
DR HOGENOM; CLU_023207_0_1_1; -.
DR InParanoid; B5KFD7; -.
DR OMA; QXRCLED; -.
DR OrthoDB; 497681at2759; -.
DR TreeFam; TF317511; -.
DR Reactome; R-SSC-1433557; Signaling by SCF-KIT.
DR Reactome; R-SSC-8853659; RET signaling.
DR Reactome; R-SSC-9607240; FLT3 Signaling.
DR Proteomes; UP000008227; Chromosome 9.
DR Proteomes; UP000314985; Chromosome 9.
DR Bgee; ENSSSCG00000015631; Expressed in muscle tissue and 41 other tissues.
DR ExpressionAtlas; B5KFD7; baseline.
DR Genevisible; B5KFD7; SS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0005158; F:insulin receptor binding; IBA:GO_Central.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IEA:Ensembl.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0046325; P:negative regulation of glucose import; IEA:Ensembl.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0042326; P:negative regulation of phosphorylation; IEA:Ensembl.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IEA:Ensembl.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:1904738; P:vascular associated smooth muscle cell migration; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Alternative splicing; Cytoplasm; Phosphoprotein; Reference proteome;
KW SH2 domain.
FT CHAIN 1..589
FT /note="Growth factor receptor-bound protein 10"
FT /id="PRO_0000392073"
FT DOMAIN 161..245
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 285..394
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 488..584
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 77..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13322"
FT MOD_RES 145
FT /note="Phosphoserine; by MTOR, MAPK1 and MAPK3"
FT /evidence="ECO:0000250|UniProtKB:Q13322"
FT MOD_RES 413
FT /note="Phosphoserine; by MAPK1 and MAPK3; in vitro"
FT /evidence="ECO:0000250|UniProtKB:Q13322"
FT MOD_RES 423
FT /note="Phosphoserine; by MTOR and PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q13322"
FT MOD_RES 426
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60760"
FT MOD_RES 471
FT /note="Phosphoserine; by MTOR, MAPK1 and MAPK3"
FT /evidence="ECO:0000250|UniProtKB:Q13322"
FT VAR_SEQ 1..59
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_038785"
FT VAR_SEQ 511..548
FT /note="LFLLRDSQSNPKAFVLTLCHHQKIKNFQILPCEDDGQT -> RCTRLQWPSS
FT KSLQTISAGEGVEKKEPYDPVGGIAYSI (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_038786"
FT VAR_SEQ 549..589
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_038787"
SQ SEQUENCE 589 AA; 66386 MW; 7F7F32CC84042B4D CRC64;
MALAGGPDSF LHHPYYQDQV EQTSPHHPRD LAGPGFPAQP DRLAPHQEDD VDLEALVNDM
DASLESLCSA SETAPLLHNG QHARGPPPPG ARPLRPQASP RHRVPRSQPL HILAARRLQE
EDQQFRTSSL PAIPNPFPEL CGPGSPPVLS PGSLPPGQAA AKQDVKVFSE DGTCKVVEIL
ADMTARDLCQ LLVYRSHCVD DNSWTLVEHH PHLGLERGLE DHERVTQVQH TLASESKFLF
RKNYAKYEFF KNPTNFFPEQ MVTWCQQSNG SQTQLLQNFL NSSSCPEIQG FLHVKELGRK
SWKKLYVCLR RSGLYCSTKG ASKEPRHLQL LADLEDSSIF SLIAGRKQYG APTDYGFCIK
PNRVRTEAKE LRLLCAEDEQ SRTCWMTAFR LLKYGMLLYQ NYRVPQQRKA VLSPFSAPVR
SVSENSLVAM DFSGQTGRVI ENPAEAQSAA LEEGHAWRKR STRMNILGSQ SPLHPSTLST
VIHRTQHWFH GRISREESHR IIKQQGLVDG LFLLRDSQSN PKAFVLTLCH HQKIKNFQIL
PCEDDGQTFF SLDDGNTKFS DLIQLVDFYQ LNKGVLPCKL KHHCIRVAL
