GRB14 growth factor receptor bound protein 14 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRB14provided by HGNC
Official Full Name: growth factor receptor bound protein 14provided by HGNC
Primary source: HGNC:HGNC:4565
See related: Ensembl:ENSG00000115290 MIM:601524; AllianceGenome:HGNC:4565
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: 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]
Expression: Biased expression in kidney (RPKM 7.9), liver (RPKM 7.8) and 12 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q24.3

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (164492417..164621482, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (164949755..165079884, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (165348927..165477992, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Metabolic Effects of the Waist-To-Hip Ratio Associated Locus GRB14/COBLL1 Are Related to GRB14 Expression in Adipose Tissue.
Title: Metabolic Effects of the Waist-To-Hip Ratio Associated Locus GRB14/COBLL1 Are Related to GRB14 Expression in Adipose Tissue.
Identification of low-dose radiation-induced exosomal circ-METRN and miR-4709-3p/GRB14/PDGFRalpha pathway as a key regulatory mechanism in Glioblastoma progression and radioresistance: Functional validation and clinical theranostic significance.
Title: Identification of low-dose radiation-induced exosomal circ-METRN and miR-4709-3p/GRB14/PDGFRα pathway as a key regulatory mechanism in Glioblastoma progression and radioresistance: Functional validation and clinical theranostic significance.
These findings suggested that phosphate groups on Ser(358) and Ser(362) in hGrb14 are dephosphorylated by PP1, and the dephosphorylation facilitates hGrb14-IR complex formation.
Title: Dephosphorylation of clustered phosphoserine residues in human Grb14 by protein phosphatase 1 and its effect on insulin receptor complex formation.
We investigated the modification of air pollution and diabetes association by a genetic risk score covering 63 T2D genes. Five single variants near GRB14, UBE2E2, PTPRD, VPS26A and KCNQ1 showed nominally significant interactions with PM10 (P<0.05). Our results suggest that genetic risk for T2D may modify susceptibility to air pollution through alterations in insulin sensitivity.
Title: Air pollution and diabetes association: Modification by type 2 diabetes genetic risk score.
The N-terminus of the BPS domain plays an important role in the regulation of human Grb14 and insulin receptor complex formation through phosphorylation, in addition to other domains.
Title: Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor.
Data suggest that GRB10 and GRB14 are both Ca2+-dependent CaM-binding proteins; more than one CaM-binding site and/or accessory CaM-binding sites appear to exist in GRB10 and GRB14, as compared to a single one present in GRB7. (GRB10 = growth factor receptor-bound protein 10; GRB14 = growth factor receptor-bound protein 14; CaM = calmodulin; GRB7 = growth factor receptor-bound protein 7)
Title: The adaptors Grb10 and Grb14 are calmodulin-binding proteins.
Colorectal cancer patients with high GRB14 levels had a shorter survival and GRB14 was upregulated at an advanced clinical stage with enhanced tumor invasion and lymph node metastasis.
Title: High expression of growth factor receptor-bound protein 14 predicts poor prognosis for colorectal cancer patients.
Phosphorylation of Grb14 BPS domain by GSK-3 correlates with complex forming of Grb14 and insulin receptor.
Title: Phosphorylation of Grb14 BPS domain by GSK-3 correlates with complex forming of Grb14 and insulin receptor.
Genes within recently identified loci associated with waist-hip ratio (WHR) exhibit fat depot-specific mRNA expression, which correlates with obesity-related traits. Adipose tissue (AT) mRNA expression of 6 genes (TBX15/WARS2, STAB1, PIGC, ZNRF3, GRB14
Title: Fat depot-specific mRNA expression of novel loci associated with waist-hip ratio.
Modulation of mouse rod photoreceptor responses by Grb14 protein.
Title: Modulation of mouse rod photoreceptor responses by Grb14 protein.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. EBI GWAS Catalog EBI GWAS CatalogPubMed
Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association of lipid-lowering response to statins in combined study populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. EBI GWAS Catalog EBI GWAS CatalogPubMed
Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-11831 (e-PCR)
- UniSTS:20026

GRB14 (e-PCR)
- UniSTS:505445

RH27221 (e-PCR)
- UniSTS:90229

RH69060 (e-PCR)
- UniSTS:3781

SHGC-111120 (e-PCR)
- UniSTS:168153

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables molecular adaptor activity	EXP Inferred from Experiment more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-macromolecule adaptor activity	IEA Inferred from Electronic Annotation more info
enables receptor tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in insulin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of insulin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of insulin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in endosome membrane	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: growth factor receptor-bound protein 14

Names: GRB14 adapter protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_052839.1 RefSeqGene

Range

5369..134434

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001303422.2 → NP_001290351.1 growth factor receptor-bound protein 14 isoform 2

See identical proteins and their annotated locations for NP_001290351.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AC107075, AK301961, CN266581, DB560753

Consensus CDS

CCDS92883.1

UniProtKB/TrEMBL

B2R7X4

Related

ENSP00000512640.1, ENST00000696453.2

Conserved Domains (4) summary

cd10414
Location:346 → 453

SH2_Grb14; Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins

cd01259
Location:143 → 264

PH_APBB1IP; Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin homology (PH) domain

cd16139
Location:20 → 104

RA_GRB14; Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 14

pfam08947
Location:283 → 327

BPS; BPS (Between PH and SH2)
NM_004490.3 → NP_004481.2 growth factor receptor-bound protein 14 isoform 1

See identical proteins and their annotated locations for NP_004481.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC107075, AC110086, BC053559

Consensus CDS

CCDS2222.1

UniProtKB/Swiss-Prot

B7Z7F9, Q14449, Q7Z6I1

UniProtKB/TrEMBL

B2R7X4

Related

ENSP00000263915.3, ENST00000263915.8

Conserved Domains (4) summary

cd10414
Location:433 → 540

SH2_Grb14; Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins

cd01259
Location:230 → 351

PH_APBB1IP; Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin homology (PH) domain

cd16139
Location:107 → 191

RA_GRB14; Ras-associating (RA) domain found in growth factor receptor-bound (Grb) protein 14

pfam08947
Location:370 → 414

BPS; BPS (Between PH and SH2)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

164492417..164621482 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047444013.1 → XP_047299969.1 growth factor receptor-bound protein 14 isoform X1
XM_047444014.1 → XP_047299970.1 growth factor receptor-bound protein 14 isoform X2
XM_011511022.2 → XP_011509324.1 growth factor receptor-bound protein 14 isoform X3

UniProtKB/TrEMBL

Q53QQ0

Conserved Domains (3) summary

cd01787
Location:106 → 190

GRB7_RA; RA (RAS-associated like) domain of Grb7

cd01259
Location:230 → 309

PH_APBB1IP; Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin homology (PH) domain

pfam00169
Location:235 → 310

PH; PH domain

RNA

XR_427085.4 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

164949755..165079884 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054341529.1 → XP_054197504.1 growth factor receptor-bound protein 14 isoform X4
XM_054341530.1 → XP_054197505.1 growth factor receptor-bound protein 14 isoform X1
XM_054341531.1 → XP_054197506.1 growth factor receptor-bound protein 14 isoform X2
XM_054341532.1 → XP_054197507.1 growth factor receptor-bound protein 14 isoform X3