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. This protein likely has an inhibitory effect on receptor tyrosine kinase si... See more...

Aliases for GRB14 Gene

Aliases for GRB14 Gene

  • Growth Factor Receptor Bound Protein 14 2 3 5
  • Growth Factor Receptor-Bound Protein 14 2 3 4
  • GRB14 Adapter Protein 3 4

External Ids for GRB14 Gene

Previous GeneCards Identifiers for GRB14 Gene

  • GC02M163404
  • GC02M163891
  • GC02M165313
  • GC02M165551
  • GC02M165174
  • GC02M165057
  • GC02M157231
  • GC02M165350

Summaries for GRB14 Gene

Entrez Gene Summary for GRB14 Gene

  • 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. This protein likely has an inhibitory effect on receptor tyrosine kinase signaling and, in particular, on insulin receptor signaling. This gene may play a role in signaling pathways that regulate growth and metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

GeneCards Summary for GRB14 Gene

GRB14 (Growth Factor Receptor Bound Protein 14) is a Protein Coding gene. Diseases associated with GRB14 include Diabetes Mellitus, Noninsulin-Dependent and Kabuki Syndrome 1. Among its related pathways are Cell surface interactions at the vascular wall and Insulin Pathway. Gene Ontology (GO) annotations related to this gene include SH3/SH2 adaptor activity. An important paralog of this gene is GRB10.

UniProtKB/Swiss-Prot Summary for GRB14 Gene

  • Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal.

Gene Wiki entry for GRB14 Gene

Additional gene information for GRB14 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GRB14 Gene

Genomics for GRB14 Gene

GeneHancer (GH) Regulatory Elements for GRB14 Gene

Promoters and enhancers for GRB14 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J164620 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 500.7 +0.6 649 2.4 MYC USF1 POLR2G PHF8 ZFX ZIC2 ZBTB26 ZBTB7A CTBP1 HDAC2 HSALNG0020110 GRB14 SLC38A11 ENSG00000277998
GH02J164622 Promoter 0.8 EPDnew 500.7 -0.6 -609 0.1 FOXA2 ZBTB33 JUND RAD21 RXRA HNF4A REST FOXA1 SRF SP1 HSALNG0020110 GRB14 lnc-SCN2A-9-001
GH02J164567 Enhancer 0.8 Ensembl ENCODE 16 +53.8 53842 1.6 TCF12 FOXA2 NR2F2 FOXA1 EHMT2 RXRA NR2F6 HNF4A MAFK GATA3 lnc-COBLL1-4 GRB14 lnc-COBLL1-5
GH02J164661 Enhancer 0.9 Ensembl ENCODE 10.5 -39.7 -39670 0.2 ZNF217 TCF12 CUX1 EP300 CTBP1 FOXA2 FOS CEBPG CEBPB ZBTB33 piR-32651-006 ENSG00000224331 SNORA70F GRB14 lnc-SCN2A-8 lnc-COBLL1-1 COBLL1
GH02J164560 Enhancer 0.5 Ensembl 15.5 +60.5 60450 1.6 CTCF ZBTB25 TRIM22 ZSCAN9 SMC3 ZGPAT GATAD2A ZNF157 RAD21 GRB14 lnc-COBLL1-4 lnc-COBLL1-5
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GRB14 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GRB14

Top Transcription factor binding sites by QIAGEN in the GRB14 gene promoter:
  • AML1a
  • AREB6
  • C/EBPalpha
  • Egr-2
  • FOXI1
  • FOXL1
  • HFH-3
  • Lmo2

Genomic Locations for GRB14 Gene

Genomic Locations for GRB14 Gene
chr2:164,492,406-164,621,850
(GRCh38/hg38)
Size:
129,445 bases
Orientation:
Minus strand
chr2:165,349,322-165,478,360
(GRCh37/hg19)
Size:
129,039 bases
Orientation:
Minus strand

Genomic View for GRB14 Gene

Genes around GRB14 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GRB14 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GRB14 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GRB14 Gene

Proteins for GRB14 Gene

  • Protein details for GRB14 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14449-GRB14_HUMAN
    Recommended name:
    Growth factor receptor-bound protein 14
    Protein Accession:
    Q14449
    Secondary Accessions:
    • B7Z7F9
    • Q7Z6I1

    Protein attributes for GRB14 Gene

    Size:
    540 amino acids
    Molecular mass:
    60988 Da
    Quaternary structure:
    • Interacts with the cytoplasmic domain of the autophosphorylated insulin receptor (INSR), through the SH2 domain (By similarity). Interacts with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop on INSR from dephosphorylation. Binds to the ankyrin repeat region of TNKS2 via its N-terminus. Interacts with activated NRAS. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated).

    Three dimensional structures from OCA and Proteopedia for GRB14 Gene

    Alternative splice isoforms for GRB14 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GRB14 Gene

Post-translational modifications for GRB14 Gene

  • Phosphorylated on serine residues. Phosphorylated on tyrosine residues by TEK/TIE2.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GRB14 Gene

No data available for DME Specific Peptides for GRB14 Gene

Domains & Families for GRB14 Gene

Gene Families for GRB14 Gene

Protein Domains for GRB14 Gene

Blocks:
  • Pleckstrin-like
  • SH2 domain signature
  • RA domain
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GRB14 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ51137, highly similar to Growth factor receptor-bound protein 14 (B7Z7F9_HUMAN)
  • GRB14 adapter protein (GRB14_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q14449

UniProtKB/Swiss-Prot:

GRB14_HUMAN :
  • The PH domain binds relatively non-specifically and with low affinity to several phosphoinositides, the best binder being PI(3,4,5)P3.
  • Belongs to the GRB7/10/14 family.
Domain:
  • The PH domain binds relatively non-specifically and with low affinity to several phosphoinositides, the best binder being PI(3,4,5)P3.
Family:
  • Belongs to the GRB7/10/14 family.
genes like me logo Genes that share domains with GRB14: view

Function for GRB14 Gene

Molecular function for GRB14 Gene

UniProtKB/Swiss-Prot Function:
Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal.
GENATLAS Biochemistry:
growth factor receptor bound protein 14,homolog to C elegans mig 10 gene,widely expressed,involved in signal transduction

Phenotypes From GWAS Catalog for GRB14 Gene

Gene Ontology (GO) - Molecular Function for GRB14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005070 SH3/SH2 adaptor activity IBA 21873635
GO:0030971 receptor tyrosine kinase binding IPI 16246733
GO:0042802 identical protein binding IMP 16246733
GO:0042803 protein homodimerization activity IMP 16246733
genes like me logo Genes that share ontologies with GRB14: view
genes like me logo Genes that share phenotypes with GRB14: view

Animal Models for GRB14 Gene

MGI Knock Outs for GRB14:

Animal Model Products

CRISPR Products

miRNA for GRB14 Gene

miRTarBase miRNAs that target GRB14

Clone Products

  • Addgene plasmids for GRB14

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GRB14 Gene

Localization for GRB14 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GRB14 Gene

Cytoplasm. Endosome membrane; Peripheral membrane protein. Note=Upon insulin stimulation, translocates to the plasma membrane. {ECO:0000269 PubMed:15210700, ECO:0000269 PubMed:19648926}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GRB14 gene
Compartment Confidence
cytosol 5
plasma membrane 4
nucleus 3
endosome 3
cytoskeleton 2
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for GRB14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA,IBA 11278563
GO:0005768 endosome IEA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IDA 11278563
GO:0010008 endosome membrane IEA --
genes like me logo Genes that share ontologies with GRB14: view

Pathways & Interactions for GRB14 Gene

PathCards logo

SuperPathways for GRB14 Gene

genes like me logo Genes that share pathways with GRB14: view

Pathways by source for GRB14 Gene

1 GeneGo (Thomson Reuters) pathway for GRB14 Gene
  • Development Angiopoietin - Tie2 signaling
3 Qiagen pathways for GRB14 Gene
  • Angiopoietin-TIE2 Signaling
  • Breast Cancer Regulation by Stathmin1
  • Caspase Cascade

Gene Ontology (GO) - Biological Process for GRB14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction IEA,TAS 8647858
GO:0008286 insulin receptor signaling pathway IBA 21873635
GO:0009967 positive regulation of signal transduction IEA --
GO:0046627 negative regulation of insulin receptor signaling pathway IMP 16246733
GO:0050900 leukocyte migration TAS --
genes like me logo Genes that share ontologies with GRB14: view

No data available for SIGNOR curated interactions for GRB14 Gene

Drugs & Compounds for GRB14 Gene

(1) Drugs for GRB14 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for GRB14 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with GRB14: view

Transcripts for GRB14 Gene

mRNA/cDNA for GRB14 Gene

2 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for GRB14

Alternative Splicing Database (ASD) splice patterns (SP) for GRB14 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3a · 3b · 3c · 3d ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16
SP1:
SP2:
SP3: - - - - - -
SP4: - -
SP5: - - - - -
SP6: -
SP7:
SP8: -
SP9: - - - - - -

Relevant External Links for GRB14 Gene

GeneLoc Exon Structure for
GRB14

Expression for GRB14 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GRB14 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GRB14 Gene

This gene is overexpressed in Liver (x12.2), Kidney - Cortex (x4.9), and Adrenal Gland (x4.6).

Protein differential expression in normal tissues from HIPED for GRB14 Gene

This gene is overexpressed in Testis (45.3) and Liver (9.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GRB14 Gene



Protein tissue co-expression partners for GRB14 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GRB14

SOURCE GeneReport for Unigene cluster for GRB14 Gene:

Hs.411881

mRNA Expression by UniProt/SwissProt for GRB14 Gene:

Q14449-GRB14_HUMAN
Tissue specificity: Expressed at high levels in the liver, kidney, pancreas, testis, ovary, heart and skeletal muscle.

Evidence on tissue expression from TISSUES for GRB14 Gene

  • Liver(4.4)
  • Skin(4)
genes like me logo Genes that share expression patterns with GRB14: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for GRB14 Gene

Orthologs for GRB14 Gene

This gene was present in the common ancestor of animals.

Orthologs for GRB14 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GRB14 31 30
  • 99.14 (n)
OneToOne
dog
(Canis familiaris)
Mammalia GRB14 31 30
  • 95.56 (n)
OneToOne
cow
(Bos Taurus)
Mammalia GRB14 31 30
  • 94.81 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GRB14 31
  • 86 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Grb14 17 31 30
  • 85.38 (n)
rat
(Rattus norvegicus)
Mammalia Grb14 30
  • 85.01 (n)
oppossum
(Monodelphis domestica)
Mammalia GRB14 31
  • 25 (a)
OneToOne
chicken
(Gallus gallus)
Aves GRB14 31 30
  • 79.84 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GRB14 31
  • 74 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia grb14 30
  • 69.36 (n)
zebrafish
(Danio rerio)
Actinopterygii LOC100334415 30
  • 65.81 (n)
CABZ01083696.1 31
  • 64 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta pico 31
  • 11 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea mig-10 31
  • 12 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.10684 31
  • 35 (a)
OneToMany
Species where no ortholog for GRB14 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GRB14 Gene

ENSEMBL:
Gene Tree for GRB14 (if available)
TreeFam:
Gene Tree for GRB14 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GRB14: view image

Paralogs for GRB14 Gene

Paralogs for GRB14 Gene

(4) SIMAP similar genes for GRB14 Gene using alignment to 6 proteins:

  • GRB14_HUMAN
  • B7Z7F9_HUMAN
  • C9JD37_HUMAN
  • C9JLT6_HUMAN
  • Q53QM9_HUMAN
  • Q53QQ0_HUMAN
genes like me logo Genes that share paralogs with GRB14: view

Variants for GRB14 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GRB14 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
rs747345020 Uncertain Significance: not specified 164,494,433(-) G/A MISSENSE_VARIANT
rs144301087 - p.His507Tyr
rs61748245 - p.Phe90Ile

Additional dbSNP identifiers (rs#s) for GRB14 Gene

Structural Variations from Database of Genomic Variants (DGV) for GRB14 Gene

Variant ID Type Subtype PubMed ID
esv3593219 CNV loss 21293372
nsv473323 CNV novel sequence insertion 20440878

Variation tolerance for GRB14 Gene

Residual Variation Intolerance Score: 57.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 13.08; 95.08% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GRB14 Gene

Human Gene Mutation Database (HGMD)
GRB14
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GRB14

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GRB14 Gene

Disorders for GRB14 Gene

MalaCards: The human disease database

(2) MalaCards diseases for GRB14 Gene - From: DISEASES and Novoseek

- elite association - COSMIC cancer census association via MalaCards
Search GRB14 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GRB14

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GRB14: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GRB14 Gene

Publications for GRB14 Gene

  1. Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14. (PMID: 19648926) Depetris RS … Hubbard SR (Nature structural & molecular biology 2009) 3 4 23 54
  2. Structural basis for inhibition of the insulin receptor by the adaptor protein Grb14. (PMID: 16246733) Depetris RS … Hubbard SR (Molecular cell 2005) 3 4 23 54
  3. The adaptor protein Grb14 regulates the localization of 3-phosphoinositide-dependent kinase-1. (PMID: 15210700) King CC … Newton AC (The Journal of biological chemistry 2004) 3 4 23 54
  4. Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. (PMID: 21874001) Kooner JS … Chambers JC (Nature genetics 2011) 3 41 54
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54

Products for GRB14 Gene

Sources for GRB14 Gene