Human Gene GRB10 (ENST00000401949.6_11) from GENCODE V45lift37
  Description: Homo sapiens growth factor receptor bound protein 10 (GRB10), transcript variant 1, mRNA. (from RefSeq NM_001350814)
RefSeq Summary (NM_001350814): The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor receptors. Overexpression of some isoforms of the encoded protein inhibits tyrosine kinase activity and results in growth suppression. This gene is imprinted in a highly isoform- and tissue-specific manner, with expression observed from the paternal allele in the brain, and from the maternal allele in the placental trophoblasts. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010].
Gencode Transcript: ENST00000401949.6_11
Gencode Gene: ENSG00000106070.20_14
Transcript (Including UTRs)
   Position: hg19 chr7:50,657,765-50,850,593 Size: 192,829 Total Exon Count: 19 Strand: -
Coding Region
   Position: hg19 chr7:50,660,649-50,800,019 Size: 139,371 Coding Exon Count: 16 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
GO AnnotationsmRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2024-04-24 11:59:55

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:50,657,765-50,850,593)mRNA (may differ from genome)Protein (594 aa)
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HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: GRB10_HUMAN
DESCRIPTION: RecName: Full=Growth factor receptor-bound protein 10; AltName: Full=GRB10 adapter protein; AltName: Full=Insulin receptor-binding protein Grb-IR;
FUNCTION: 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.
ACTIVITY REGULATION: Phosphorylation by mTORC1 stabilizes and activates GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR- dependent signaling.
SUBUNIT: 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.
INTERACTION: Q13322; P00533: EGFR; NbExp=3; IntAct=EBI-80275, EBI-297353; Q13322; P54762: EPHB1; NbExp=2; IntAct=EBI-80275, EBI-80252; Q13322; P36888: FLT3; NbExp=6; IntAct=EBI-80275, EBI-3946257; Q13322; P06213: INSR; NbExp=3; IntAct=EBI-80275, EBI-475899; Q13322; P27986: PIK3R1; NbExp=2; IntAct=EBI-80275, EBI-79464; Q13322; Q9UKA8: RCAN3; NbExp=3; IntAct=EBI-80275, EBI-9091952; Q13322; P31947: SFN; NbExp=2; IntAct=EBI-80275, EBI-476295; Q13322; P62258: YWHAE; NbExp=2; IntAct=EBI-80275, EBI-356498; Q13322-3; Q13322-3: GRB10; NbExp=2; IntAct=EBI-15796145, EBI-15796145; Q13322-4; Q16613: AANAT; NbExp=3; IntAct=EBI-12353035, EBI-7451846; Q13322-4; Q86V38: ATN1; NbExp=3; IntAct=EBI-12353035, EBI-11954292; Q13322-4; P51451: BLK; NbExp=3; IntAct=EBI-12353035, EBI-2105445; Q13322-4; P02489: CRYAA; NbExp=3; IntAct=EBI-12353035, EBI-6875961; Q13322-4; O95363: FARS2; NbExp=3; IntAct=EBI-12353035, EBI-2513774; Q13322-4; P01100: FOS; NbExp=3; IntAct=EBI-12353035, EBI-852851; Q13322-4; P50440: GATM; NbExp=3; IntAct=EBI-12353035, EBI-2552594; Q13322-4; P14136: GFAP; NbExp=3; IntAct=EBI-12353035, EBI-744302; Q13322-4; Q13322-4: GRB10; NbExp=3; IntAct=EBI-12353035, EBI-12353035; Q13322-4; P62993: GRB2; NbExp=3; IntAct=EBI-12353035, EBI-401755; Q13322-4; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-12353035, EBI-1055254; Q13322-4; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-12353035, EBI-2556193; Q13322-4; O00505: KPNA3; NbExp=3; IntAct=EBI-12353035, EBI-358297; Q13322-4; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-12353035, EBI-11742507; Q13322-4; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-12353035, EBI-10271199; Q13322-4; Q13153: PAK1; NbExp=3; IntAct=EBI-12353035, EBI-1307; Q13322-4; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-12353035, EBI-79165; Q13322-4; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-12353035, EBI-9090795; Q13322-4; P12931: SRC; NbExp=3; IntAct=EBI-12353035, EBI-621482; Q13322-4; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-12353035, EBI-750487; Q13322-4; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-12353035, EBI-11139477; Q13322-4; Q13470-2: TNK1; NbExp=3; IntAct=EBI-12353035, EBI-11018037; Q13322-4; P42681: TXK; NbExp=3; IntAct=EBI-12353035, EBI-7877438; Q13322-4; P61981: YWHAG; NbExp=3; IntAct=EBI-12353035, EBI-359832; Q13322-4; Q96E35: ZMYND19; NbExp=3; IntAct=EBI-12353035, EBI-746595;
SUBCELLULAR LOCATION: Cytoplasm 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).
TISSUE SPECIFICITY: Widely expressed in fetal and adult tissues, including fetal and postnatal liver, lung, kidney, skeletal muscle, heart, spleen, skin and brain.
DOMAIN: The PH domain binds relatively non-specifically to several phosphoinositides, including PI(5)P, PI(4,5)P2, PI(3,4)P2 and PI(3,4,5)P3, with modest affinities.
PTM: Phosphorylated on serine residues upon EGF, FGF and PDGF stimulation (By similarity). Phosphorylated at Tyr-67 by TEC.
MISCELLANEOUS: The GRB10 locus is imprinted. During embryonic development, the expression in the brain and spinal cord is from the paternal allele, while in placental villous trophoblasts and skeletal muscle, it is from the maternal one. Expression is biallelic in most other tissues. Paternal expression in the brain is maintained throughout adulthood. Imprinting often is isoform-specific.
MISCELLANEOUS: GRB10 is unlikely to be responsible for Silver-Russell syndrome (SRS).
SIMILARITY: Belongs to the GRB7/10/14 family.
SEQUENCE CAUTION: Sequence=BAA13198.2; Type=Erroneous initiation; Evidence=;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="https://atlasgeneticsoncology.org/gene/278/GRB10";

-  Primer design for this transcript
 

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-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): GRB10
CDC HuGE Published Literature: GRB10
Positive Disease Associations: Scleroderma, Systemic
Related Studies:
  1. Scleroderma, Systemic
    Olga Gorlova et al. PLoS genetics 2011, Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy., PLoS genetics. [PubMed 21779181]

-  MalaCards Disease Associations
  MalaCards Gene Search: GRB10
Diseases sorted by gene-association score: silver-russell syndrome (14), silver spastic paraplegia syndrome (8), adult syndrome (5), diabetes mellitus, transient neonatal, 1 (4)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D001564 Benzo(a)pyrene
  • D016572 Cyclosporine
  • D013749 Tetrachlorodibenzodioxin
  • C014175 pyrazolo(3,4-d)pyrimidine
  • C017947 sodium arsenite
  • C479799 (E)-4-((2-N-(4-methoxybenzenesulfonyl)amino)stilbazole)1-oxide
  • C111118 2',3,3',4',5-pentachloro-4-hydroxybiphenyl
  • C063002 2,3-dimethoxy-1,4-naphthoquinone
  • C009505 4,4'-diaminodiphenylmethane
  • C075773 4-phenylbutyric acid
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 22.93 RPKM in Pancreas
Total median expression: 482.86 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -392.50799-0.491 Picture PostScript Text
3' UTR -865.602884-0.300 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR015042 - BPS-dom
IPR039664 - GRB/APBB1IP
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

Pfam Domains:
PF08947 - BPS (Between PH and SH2)
PF00169 - PH domain
PF00788 - Ras association (RalGDS/AF-6) domain
PF00017 - SH2 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1NRV - X-ray 3HK0 - X-ray


ModBase Predicted Comparative 3D Structure on Q13322
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005070 SH3/SH2 adaptor activity
GO:0005158 insulin receptor binding
GO:0005515 protein binding
GO:0042802 identical protein binding

Biological Process:
GO:0007165 signal transduction
GO:0007411 axon guidance
GO:0008286 insulin receptor signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0030949 positive regulation of vascular endothelial growth factor receptor signaling pathway
GO:0032868 response to insulin
GO:0042327 positive regulation of phosphorylation
GO:0045719 negative regulation of glycogen biosynthetic process
GO:0046325 negative regulation of glucose import
GO:0046627 negative regulation of insulin receptor signaling pathway

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0032991 macromolecular complex


-  Descriptions from all associated GenBank mRNAs
  BX649028 - Homo sapiens mRNA; cDNA DKFZp686P1694 (from clone DKFZp686P1694).
D86962 - Homo sapiens mRNA for KIAA0207 gene, partial cds.
U69276 - Human hGrbIRbeta/hGrb10 (GRBIRbeta/GRB10) mRNA, complete cds.
U34355 - Human skeletal muscle insulin receptor binding protein (Grb-IR) mRNA, complete cds.
BC024285 - Homo sapiens growth factor receptor-bound protein 10, mRNA (cDNA clone MGC:39227 IMAGE:4590330), complete cds.
AJ271366 - Homo sapiens mRNA for putative adaptor protein (GRB10 gene).
U66065 - Human Grb10- and Grb-IR-related splice variant 1 mRNA, complete cds.
AK289511 - Homo sapiens cDNA FLJ76730 complete cds, highly similar to Homo sapiens growth factor receptor-bound protein 10 (GRB10), transcript variant 3, mRNA.
AF000017 - Homo sapiens adapter protein (hGrb10zeta) mRNA, complete cds.
AF001534 - Homo sapiens insulin receptor binding protein (Grb-IR/hGrb10) mRNA, complete cds.
AB000731 - Homo sapiens mRNA for Grb-10, complete cds.
DQ891700 - Synthetic construct clone IMAGE:100004330; FLH183443.01X; RZPDo839C07142D growth factor receptor-bound protein 10 (GRB10) gene, encodes complete protein.
DQ896846 - Synthetic construct Homo sapiens clone IMAGE:100011306; FLH183439.01L; RZPDo839C07141D growth factor receptor-bound protein 10 (GRB10) gene, encodes complete protein.
AB383799 - Synthetic construct DNA, clone: pF1KSDA0207, Homo sapiens GRB10 gene for growth factor receptor-bound protein 10, complete cds, without stop codon, in Flexi system.
JD304377 - Sequence 285401 from Patent EP1572962.
JD360681 - Sequence 341705 from Patent EP1572962.
JD507900 - Sequence 488924 from Patent EP1572962.
JD137086 - Sequence 118110 from Patent EP1572962.
JD443805 - Sequence 424829 from Patent EP1572962.
JD279945 - Sequence 260969 from Patent EP1572962.
JD469656 - Sequence 450680 from Patent EP1572962.
JD117659 - Sequence 98683 from Patent EP1572962.
JD531103 - Sequence 512127 from Patent EP1572962.
JD116477 - Sequence 97501 from Patent EP1572962.
JD135496 - Sequence 116520 from Patent EP1572962.
JD181890 - Sequence 162914 from Patent EP1572962.
JD258226 - Sequence 239250 from Patent EP1572962.
JD145637 - Sequence 126661 from Patent EP1572962.
JD126333 - Sequence 107357 from Patent EP1572962.
JD386662 - Sequence 367686 from Patent EP1572962.
JD285986 - Sequence 267010 from Patent EP1572962.
JD181115 - Sequence 162139 from Patent EP1572962.
JD354972 - Sequence 335996 from Patent EP1572962.
JD316924 - Sequence 297948 from Patent EP1572962.
JD127210 - Sequence 108234 from Patent EP1572962.
JD167467 - Sequence 148491 from Patent EP1572962.
JD164432 - Sequence 145456 from Patent EP1572962.
JD435123 - Sequence 416147 from Patent EP1572962.
JD196680 - Sequence 177704 from Patent EP1572962.
JD274168 - Sequence 255192 from Patent EP1572962.
JD521672 - Sequence 502696 from Patent EP1572962.
JD091771 - Sequence 72795 from Patent EP1572962.
JD446105 - Sequence 427129 from Patent EP1572962.
JD473033 - Sequence 454057 from Patent EP1572962.
AF000018 - Homo sapiens adapter protein mRNA, partial cds.
JD452124 - Sequence 433148 from Patent EP1572962.
JD155723 - Sequence 136747 from Patent EP1572962.
JD290690 - Sequence 271714 from Patent EP1572962.
JD177785 - Sequence 158809 from Patent EP1572962.
AK021643 - Homo sapiens cDNA FLJ11581 fis, clone HEMBA1003598.
JD455603 - Sequence 436627 from Patent EP1572962.
JD384548 - Sequence 365572 from Patent EP1572962.
JD200016 - Sequence 181040 from Patent EP1572962.
JD068251 - Sequence 49275 from Patent EP1572962.
JD363372 - Sequence 344396 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q13322 (Reactome details) participates in the following event(s):

R-HSA-110011 Binding of Grb10 to the insulin receptor
R-HSA-1433501 Interaction of other adapter proteins with p-KIT
R-HSA-8853753 2x p-5Y-RET:GDNF:GFRA complexes bind GRB7,10
R-HSA-74749 Signal attenuation
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-8853659 RET signaling
R-HSA-74751 Insulin receptor signalling cascade
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-422475 Axon guidance
R-HSA-74752 Signaling by Insulin receptor
R-HSA-162582 Signal Transduction
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: A4D258, A7VJ95, A8K0E6, D3DVM9, ENST00000401949.1, ENST00000401949.2, ENST00000401949.3, ENST00000401949.4, ENST00000401949.5, GRB10_HUMAN, GRBIR, KIAA0207, NM_001350814, O00427, O00701, O75222, Q13322, Q92606, Q92907, Q92948, uc319bpa.1
UCSC ID: ENST00000401949.6_11
RefSeq Accession: NM_001350814
Protein: Q13322 (aka GRB10_HUMAN)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.