UniProtKB - Q13322 (GRB10_HUMAN)
Growth factor receptor-bound protein 10
GRB10
Functioni
Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways. Binds to, and suppress signals from, activated receptors tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. The inhibitory effect can be achieved by 2 mechanisms: interference with the signaling pathway and increased receptor degradation. Delays and reduces AKT1 phosphorylation in response to insulin stimulation. Blocks association between INSR and IRS1 and IRS2 and prevents insulin-stimulated IRS1 and IRS2 tyrosine phosphorylation. Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization and degradation by both the proteasomal and lysosomal pathways. May play a role in mediating insulin-stimulated ubiquitination of INSR, leading to proteasomal degradation. Negatively regulates Wnt signaling by interacting with LRP6 intracellular portion and interfering with the binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-2.
4 PublicationsMiscellaneous
Activity regulationi
GO - Molecular functioni
- identical protein binding Source: IntAct
- insulin receptor binding Source: BHF-UCL
- signaling receptor complex adaptor activity Source: Ensembl
GO - Biological processi
- ERK1 and ERK2 cascade Source: Ensembl
- gene expression Source: Ensembl
- insulin-like growth factor receptor signaling pathway Source: Ensembl
- insulin receptor signaling pathway Source: BHF-UCL
- negative regulation of glucose import Source: BHF-UCL
- negative regulation of glycogen biosynthetic process Source: BHF-UCL
- negative regulation of insulin receptor signaling pathway Source: BHF-UCL
- negative regulation of phosphorylation Source: Ensembl
- negative regulation of Wnt signaling pathway Source: UniProtKB
- positive regulation of cold-induced thermogenesis Source: YuBioLab
- positive regulation of phosphorylation Source: BHF-UCL
- positive regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
- response to insulin Source: BHF-UCL
- vascular associated smooth muscle cell migration Source: Ensembl
Enzyme and pathway databases
PathwayCommonsi | Q13322 |
Reactomei | R-HSA-1433557, Signaling by SCF-KIT R-HSA-74713, IRS activation R-HSA-74749, Signal attenuation R-HSA-74751, Insulin receptor signalling cascade R-HSA-8853659, RET signaling R-HSA-9607240, FLT3 Signaling R-HSA-9648895, Response of EIF2AK1 (HRI) to heme deficiency |
SignaLinki | Q13322 |
SIGNORi | Q13322 |
Names & Taxonomyi
Protein namesi | Recommended name: Growth factor receptor-bound protein 10Alternative name(s): GRB10 adapter protein Insulin receptor-binding protein Grb-IR |
Gene namesi | Name:GRB10 Synonyms:GRBIR, KIAA0207 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4564, GRB10 |
MIMi | 601523, gene |
neXtProti | NX_Q13322 |
VEuPathDBi | HostDB:ENSG00000106070 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Note: When complexed with NEDD4 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R-containing endosomes before the sorting of the receptor to the lysosomal compartment (By similarity).By similarity
Cytosol
- cytosol Source: Reactome
Plasma Membrane
- plasma membrane Source: ProtInc
Other locations
- cytoplasm Source: ProtInc
- protein-containing complex Source: UniProtKB
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 104 | S → G: No effect on phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 134 | S → A: No effect on YWHAE-binding. 1 Publication | 1 | |
Mutagenesisi | 136 | P → A: No effect on NEDD4-binding; when associated with A-139 and A-141. 1 Publication | 1 | |
Mutagenesisi | 139 | P → A: No effect on NEDD4-binding; when associated with A-136 and A-141. 1 Publication | 1 | |
Mutagenesisi | 141 | P → S: No effect on NEDD4-binding; when associated with A-136 and A-139. 1 Publication | 1 | |
Mutagenesisi | 150 | S → I: Loss of phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 300 | K → A: 2-fold loss of inositide-binding. 1 Publication | 1 | |
Mutagenesisi | 305 | K → A: 5-fold loss of inositide-binding. 1 Publication | 1 | |
Mutagenesisi | 308 | K → A: 5-fold loss of inositide-binding. 1 Publication | 1 | |
Mutagenesisi | 355 | N → G: 5-fold loss of inositide-binding. 1 Publication | 1 | |
Mutagenesisi | 418 | S → A: No net loss of phosphorylation, this may be due to a compensatory phosphorylation of T-422 in vitro. 1 Publication | 1 | |
Mutagenesisi | 428 | S → A: Impairs YWHAE-binding. 1 Publication | 1 | |
Mutagenesisi | 476 | S → A: Loss of phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 520 | R → K: No effect on NEDD4-binding. No effect on the disruption of the interaction between INSR and IRS1 and IRS2. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 2887 |
OpenTargetsi | ENSG00000106070 |
PharmGKBi | PA28960 |
Miscellaneous databases
Pharosi | Q13322, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3621028 |
Genetic variation databases
BioMutai | GRB10 |
DMDMi | 6166186 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000150346 | 1 – 594 | Growth factor receptor-bound protein 10Add BLAST | 594 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 67 | Phosphotyrosine; by TEC1 Publication | 1 | |
Modified residuei | 104 | PhosphoserineCombined sources | 1 | |
Modified residuei | 150 | Phosphoserine; by MTOR, MAPK1 and MAPK32 Publications | 1 | |
Modified residuei | 418 | Phosphoserine; by MAPK1 and MAPK3; in vitroCombined sources1 Publication | 1 | |
Modified residuei | 428 | Phosphoserine; by MTOR and PKB/AKT12 Publications | 1 | |
Modified residuei | 431 | PhosphoserineBy similarity | 1 | |
Modified residuei | 476 | Phosphoserine; by MTOR, MAPK1 and MAPK32 Publications | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
CPTACi | CPTAC-1247 |
EPDi | Q13322 |
jPOSTi | Q13322 |
MassIVEi | Q13322 |
MaxQBi | Q13322 |
PaxDbi | Q13322 |
PeptideAtlasi | Q13322 |
PRIDEi | Q13322 |
ProteomicsDBi | 59307 [Q13322-1] 59308 [Q13322-2] 59309 [Q13322-3] 59310 [Q13322-4] |
PTM databases
GlyGeni | Q13322, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q13322 |
PhosphoSitePlusi | Q13322 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000106070, Expressed in body of pancreas and 243 other tissues |
ExpressionAtlasi | Q13322, baseline and differential |
Genevisiblei | Q13322, HS |
Organism-specific databases
HPAi | ENSG00000106070, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with ligand-activated tyrosine kinase receptors, including FGFR1, INSR, IGF1R, MET and PDGFRB in a phosphotyrosine-dependent manner through the SH2 domain (By similarity). Poorly binds to the EGFR (By similarity). Directly interacts with MAP3K14/NIK and is recruited to the EGFR-ERBB2 complex.
Interacts with GIGYF1/PERQ1 and GIGYF2/TNRC15 (By similarity). When unphosphorylated, interacts with AKT1 and when phosphorylated with YWHAE/14-3-3 epsilon.
Interacts with NEDD4.
Interacts with LRP6, thus interfering with the binding of AXIN1 to LRP6 (By similarity). Binds to activated NRAS.
By similarity5 PublicationsBinary interactionsi
Q13322
GRB10 - isoform 2 [Q13322-3]
With | #Exp. | IntAct |
---|---|---|
itself | 2 | EBI-15796145,EBI-15796145 |
GRB10 - isoform 4 [Q13322-4]
GO - Molecular functioni
- identical protein binding Source: IntAct
- insulin receptor binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 109144, 149 interactors |
DIPi | DIP-31657N |
ELMi | Q13322 |
IntActi | Q13322, 123 interactors |
MINTi | Q13322 |
STRINGi | 9606.ENSP00000381793 |
Chemistry databases
BindingDBi | Q13322 |
Miscellaneous databases
RNActi | Q13322, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q13322 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q13322 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 166 – 250 | Ras-associatingPROSITE-ProRule annotationAdd BLAST | 85 | |
Domaini | 290 – 399 | PHPROSITE-ProRule annotationAdd BLAST | 110 | |
Domaini | 493 – 574 | SH2PROSITE-ProRule annotationAdd BLAST | 82 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 18 – 41 | DisorderedSequence analysisAdd BLAST | 24 | |
Regioni | 82 – 113 | DisorderedSequence analysisAdd BLAST | 32 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 82 – 111 | Polar residuesSequence analysisAdd BLAST | 30 |
Domaini
Sequence similaritiesi
Keywords - Domaini
SH2 domainPhylogenomic databases
eggNOGi | KOG3751, Eukaryota |
GeneTreei | ENSGT00940000155909 |
HOGENOMi | CLU_023207_0_1_1 |
InParanoidi | Q13322 |
OMAi | QNGQHTR |
OrthoDBi | 497681at2759 |
PhylomeDBi | Q13322 |
TreeFami | TF317511 |
Family and domain databases
CDDi | cd01259, PH_APBB1IP, 1 hit cd10415, SH2_Grb10, 1 hit |
Gene3Di | 2.30.29.30, 1 hit 3.30.505.10, 1 hit |
InterProi | View protein in InterPro IPR015042, BPS-dom IPR039664, GRB/APBB1IP IPR035036, Grb10 IPR035037, Grb10_SH2 IPR011993, PH-like_dom_sf IPR039665, PH_APBB1IP IPR001849, PH_domain IPR000159, RA_dom IPR000980, SH2 IPR036860, SH2_dom_sf IPR029071, Ubiquitin-like_domsf |
PANTHERi | PTHR11243, PTHR11243, 1 hit PTHR11243:SF4, PTHR11243:SF4, 1 hit |
Pfami | View protein in Pfam PF08947, BPS, 1 hit PF00169, PH, 1 hit PF00788, RA, 1 hit PF00017, SH2, 1 hit |
PRINTSi | PR00401, SH2DOMAIN |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00314, RA, 1 hit SM00252, SH2, 1 hit |
SUPFAMi | SSF54236, SSF54236, 1 hit SSF55550, SSF55550, 1 hit |
PROSITEi | View protein in PROSITE PS50003, PH_DOMAIN, 1 hit PS50200, RA, 1 hit PS50001, SH2, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MALAGCPDSF LHHPYYQDKV EQTPRSQQDP AGPGLPAQSD RLANHQEDDV
60 70 80 90 100
DLEALVNDMN ASLESLYSAC SMQSDTVPLL QNGQHARSQP RASGPPRSIQ
110 120 130 140 150
PQVSPRQRVQ RSQPVHILAV RRLQEEDQQF RTSSLPAIPN PFPELCGPGS
160 170 180 190 200
PPVLTPGSLP PSQAAAKQDV KVFSEDGTSK VVEILADMTA RDLCQLLVYK
210 220 230 240 250
SHCVDDNSWT LVEHHPHLGL ERCLEDHELV VQVESTMASE SKFLFRKNYA
260 270 280 290 300
KYEFFKNPMN FFPEQMVTWC QQSNGSQTQL LQNFLNSSSC PEIQGFLHVK
310 320 330 340 350
ELGKKSWKKL YVCLRRSGLY CSTKGTSKEP RHLQLLADLE DSNIFSLIAG
360 370 380 390 400
RKQYNAPTDH GLCIKPNKVR NETKELRLLC AEDEQTRTCW MTAFRLLKYG
410 420 430 440 450
MLLYQNYRIP QQRKALLSPF STPVRSVSEN SLVAMDFSGQ TGRVIENPAE
460 470 480 490 500
AQSAALEEGH AWRKRSTRMN ILGSQSPLHP STLSTVIHRT QHWFHGRISR
510 520 530 540 550
EESHRIIKQQ GLVDGLFLLR DSQSNPKAFV LTLCHHQKIK NFQILPCEDD
560 570 580 590
GQTFFSLDDG NTKFSDLIQL VDFYQLNKGV LPCKLKHHCI RVAL
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A2R8YCL1 | A0A2R8YCL1_HUMAN | Growth factor receptor-bound protei... | GRB10 | 632 | Annotation score: | ||
H7C3B9 | H7C3B9_HUMAN | Growth factor receptor-bound protei... | GRB10 | 108 | Annotation score: | ||
C9JTW6 | C9JTW6_HUMAN | Growth factor receptor-bound protei... | GRB10 | 55 | Annotation score: | ||
A0A2R8Y6Q4 | A0A2R8Y6Q4_HUMAN | Growth factor receptor-bound protei... | GRB10 | 94 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 152 | P → A in BAA13198 (PubMed:9039502).Curated | 1 | |
Sequence conflicti | 400 | G → E in AAB08431 (PubMed:9006901).Curated | 1 | |
Sequence conflicti | 428 | S → F in BAF82200 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 498 | I → F in AAB08431 (PubMed:9006901).Curated | 1 | |
Sequence conflicti | 541 | N → I in AAC50671 (PubMed:8798417).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_053112 | 36 | P → L. Corresponds to variant dbSNP:rs35647889EnsemblClinVar. | 1 | |
Natural variantiVAR_062864 | 95 | P → S1 PublicationCorresponds to variant dbSNP:rs80244589Ensembl. | 1 | |
Natural variantiVAR_053113 | 558 | D → H. Corresponds to variant dbSNP:rs11768472Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_001842 | 1 – 58 | Missing in isoform 2. 4 PublicationsAdd BLAST | 58 | |
Alternative sequenceiVSP_038784 | 1 – 17 | MALAG…HPYYQ → MQAAGPLFRSK in isoform 4. 1 PublicationAdd BLAST | 17 | |
Alternative sequenceiVSP_001843 | 283 – 328 | Missing in isoform 1. 2 PublicationsAdd BLAST | 46 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1NRV | X-ray | 1.65 | A/B | 487-591 | [»] | |
3HK0 | X-ray | 2.60 | A/B | 164-415 | [»] | |
SMRi | Q13322 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109144, 149 interactors |
DIPi | DIP-31657N |
ELMi | Q13322 |
IntActi | Q13322, 123 interactors |
MINTi | Q13322 |
STRINGi | 9606.ENSP00000381793 |
Chemistry databases
BindingDBi | Q13322 |
ChEMBLi | CHEMBL3621028 |
PTM databases
GlyGeni | Q13322, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q13322 |
PhosphoSitePlusi | Q13322 |
Genetic variation databases
BioMutai | GRB10 |
DMDMi | 6166186 |
Proteomic databases
CPTACi | CPTAC-1247 |
EPDi | Q13322 |
jPOSTi | Q13322 |
MassIVEi | Q13322 |
MaxQBi | Q13322 |
PaxDbi | Q13322 |
PeptideAtlasi | Q13322 |
PRIDEi | Q13322 |
ProteomicsDBi | 59307 [Q13322-1] 59308 [Q13322-2] 59309 [Q13322-3] 59310 [Q13322-4] |
Protocols and materials databases
Antibodypediai | 27751, 480 antibodies from 37 providers |
DNASUi | 2887 |
Genome annotation databases
Organism-specific databases
CTDi | 2887 |
DisGeNETi | 2887 |
GeneCardsi | GRB10 |
HGNCi | HGNC:4564, GRB10 |
HPAi | ENSG00000106070, Low tissue specificity |
MIMi | 601523, gene |
neXtProti | NX_Q13322 |
OpenTargetsi | ENSG00000106070 |
PharmGKBi | PA28960 |
VEuPathDBi | HostDB:ENSG00000106070 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3751, Eukaryota |
GeneTreei | ENSGT00940000155909 |
HOGENOMi | CLU_023207_0_1_1 |
InParanoidi | Q13322 |
OMAi | QNGQHTR |
OrthoDBi | 497681at2759 |
PhylomeDBi | Q13322 |
TreeFami | TF317511 |
Enzyme and pathway databases
PathwayCommonsi | Q13322 |
Reactomei | R-HSA-1433557, Signaling by SCF-KIT R-HSA-74713, IRS activation R-HSA-74749, Signal attenuation R-HSA-74751, Insulin receptor signalling cascade R-HSA-8853659, RET signaling R-HSA-9607240, FLT3 Signaling R-HSA-9648895, Response of EIF2AK1 (HRI) to heme deficiency |
SignaLinki | Q13322 |
SIGNORi | Q13322 |
Miscellaneous databases
BioGRID-ORCSi | 2887, 9 hits in 1048 CRISPR screens |
ChiTaRSi | GRB10, human |
EvolutionaryTracei | Q13322 |
GeneWikii | GRB10 |
GenomeRNAii | 2887 |
Pharosi | Q13322, Tbio |
PROi | PR:Q13322 |
RNActi | Q13322, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000106070, Expressed in body of pancreas and 243 other tissues |
ExpressionAtlasi | Q13322, baseline and differential |
Genevisiblei | Q13322, HS |
Family and domain databases
CDDi | cd01259, PH_APBB1IP, 1 hit cd10415, SH2_Grb10, 1 hit |
Gene3Di | 2.30.29.30, 1 hit 3.30.505.10, 1 hit |
InterProi | View protein in InterPro IPR015042, BPS-dom IPR039664, GRB/APBB1IP IPR035036, Grb10 IPR035037, Grb10_SH2 IPR011993, PH-like_dom_sf IPR039665, PH_APBB1IP IPR001849, PH_domain IPR000159, RA_dom IPR000980, SH2 IPR036860, SH2_dom_sf IPR029071, Ubiquitin-like_domsf |
PANTHERi | PTHR11243, PTHR11243, 1 hit PTHR11243:SF4, PTHR11243:SF4, 1 hit |
Pfami | View protein in Pfam PF08947, BPS, 1 hit PF00169, PH, 1 hit PF00788, RA, 1 hit PF00017, SH2, 1 hit |
PRINTSi | PR00401, SH2DOMAIN |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00314, RA, 1 hit SM00252, SH2, 1 hit |
SUPFAMi | SSF54236, SSF54236, 1 hit SSF55550, SSF55550, 1 hit |
PROSITEi | View protein in PROSITE PS50003, PH_DOMAIN, 1 hit PS50200, RA, 1 hit PS50001, SH2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | GRB10_HUMAN | |
Accessioni | Q13322Primary (citable) accession number: Q13322 Secondary accession number(s): A4D258 Q92948 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
Last sequence update: | July 15, 1999 | |
Last modified: | February 23, 2022 | |
This is version 217 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families