GRB2 growth factor receptor bound protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRB2provided by HGNC
Official Full Name: growth factor receptor bound protein 2provided by HGNC
Primary source: HGNC:HGNC:4566
See related: Ensembl:ENSG00000177885 MIM:108355; AllianceGenome:HGNC:4566
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
Also known as: ASH; Grb3-3; MST084; NCKAP2; MSTP084; EGFRBP-GRB2
Summary: The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in lymph node (RPKM 63.6), appendix (RPKM 60.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q25.1

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (75318076..75405678, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (76210297..76297898, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (73314157..73401759, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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?

DUS4L suppresses invasion and metastasis in LUAD via modulation of PI3K/AKT and ERK/MAPK signaling through GRB2.
Title: DUS4L suppresses invasion and metastasis in LUAD via modulation of PI3K/AKT and ERK/MAPK signaling through GRB2.
Targeting Grb2 SH3 Domains with Affimer Proteins Provides Novel Insights into Ras Signalling Modulation.
Title: Targeting Grb2 SH3 Domains with Affimer Proteins Provides Novel Insights into Ras Signalling Modulation.
CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche.
Title: CCDC6-RET fusion protein regulates Ras/MAPK signaling through the fusion- GRB2-SHC1 signal niche.
The binding selectivity of the C-terminal SH3 domain of Grb2, but not its folding pathway, is dictated by its contiguous SH2 domain.
Title: The binding selectivity of the C-terminal SH3 domain of Grb2, but not its folding pathway, is dictated by its contiguous SH2 domain.
GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer.
Title: GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer.
GRB2 is a BECN1 interacting protein that regulates autophagy.
Title: GRB2 is a BECN1 interacting protein that regulates autophagy.
Preosteoclast plays a pathogenic role in syndesmophyte formation of ankylosing spondylitis through the secreted PDGFB - GRB2/ERK/RUNX2 pathway.
Title: Preosteoclast plays a pathogenic role in syndesmophyte formation of ankylosing spondylitis through the secreted PDGFB - GRB2/ERK/RUNX2 pathway.
GRB2 serves as a viable target against skin fibrosis in systemic sclerosis by regulating endothelial cell apoptosis.
Title: GRB2 serves as a viable target against skin fibrosis in systemic sclerosis by regulating endothelial cell apoptosis.
RNF173 suppresses RAF/MEK/ERK signaling to regulate invasion and metastasis via GRB2 ubiquitination in Hepatocellular Carcinoma.
Title: RNF173 suppresses RAF/MEK/ERK signaling to regulate invasion and metastasis via GRB2 ubiquitination in Hepatocellular Carcinoma.
The Role of the LINC01234/miR-433-3p/GRB2 ceRNA Network in NSCLC Cell Malignant Proliferation.
Title: The Role of the LINC01234/miR-433-3p/GRB2 ceRNA Network in NSCLC Cell Malignant Proliferation.

Submit: New GeneRIF Correction See all GeneRIFs (164)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	Grb3-3, an isoform of Grb2, is upregulated by HIV-1 Nef protein and potentiates HIV-1 LTR promoter activity	PubMed
Pol	gag-pol	HIV-1 Pol is identified to have a physical interaction with growth factor receptor-bound protein 2 (GRB2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed
Tat	tat	Grb3-3, an isoform of Grb2, is upregulated by HIV-1 Tat protein and potentiates HIV-1 LTR promoter activity	PubMed
	tat	The binding between HIV-1 Tat and Grb2 is mediated by the proline-rich sequence (residues 1-18) of Tat and the SH3 domain (residues 160-212) of Grb2, which impairs activation of the Raf/MAPK pathway and increases the PKA/Raf inhibitory pathway	PubMed
	tat	HIV-1 Tat-induced small GTPase Ras activation is mediated by tyrosine phosphorylation of Shc and recruitment of Grb2 in human endothelial cells	PubMed
reverse transcriptase	gag-pol	HIV-1 RT is identified to have a physical interaction with growth factor receptor-bound protein 2 (GRB2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D17S820E (e-PCR)
- UniSTS:18221

D8S2279 (e-PCR)
- UniSTS:473907

RH17761 (e-PCR)
- UniSTS:10093

D11S3114 (e-PCR)
- UniSTS:152207

D17S853E (e-PCR)
- UniSTS:472980

D17S820E (e-PCR)
- UniSTS:147406

RH16251 (e-PCR)
- UniSTS:66043

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables SH3 domain binding	IDA Inferred from Direct Assay more info	PubMed
enables ephrin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables epidermal growth factor receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables epidermal growth factor receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables guanyl-nucleotide exchange factor adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables insulin receptor substrate binding	IPI Inferred from Physical Interaction more info	PubMed
enables neurotrophin TRKA receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphotyrosine residue binding	IBA Inferred from Biological aspect of Ancestor more info
enables phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase binding	IEA Inferred from Electronic Annotation more info
enables protein-macromolecule adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane receptor protein tyrosine kinase adaptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in B cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in Ras protein signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in Schwann cell development	IEA Inferred from Electronic Annotation more info
involved_in T cell activation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within actin cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in branching involved in labyrinthine layer morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in cellular response to ionizing radiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endodermal cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in epidermal growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in epidermal growth factor receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in fibroblast growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in insulin receptor signaling pathway	IPI Inferred from Physical Interaction more info	PubMed
involved_in insulin-like growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in myelination	IEA Inferred from Electronic Annotation more info
involved_in natural killer cell mediated cytotoxicity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of actin filament polymerization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of reactive oxygen species metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in receptor internalization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction in response to DNA damage	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of COP9 signalosome	IBA Inferred from Biological aspect of Ancestor more info
part_of COP9 signalosome	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
part_of Grb2-EGFR complex	IDA Inferred from Direct Assay more info	PubMed
located_in cell cortex	IEA Inferred from Electronic Annotation more info
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
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	PubMed
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in nucleolus	IDA Inferred from Direct Assay more info
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	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	TAS Traceable Author Statement more info
located_in vesicle membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: growth factor receptor-bound protein 2

Names: HT027; SH2/SH3 adapter GRB2; abundant SRC homology; epidermal growth factor receptor-binding protein GRB2; epididymis secretory sperm binding protein; growth factor receptor-bound protein 3; protein Ash

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_029556.1 RefSeqGene

Range

5032..92634

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002086.5 → NP_002077.1 growth factor receptor-bound protein 2 isoform 1

See identical proteins and their annotated locations for NP_002077.1

Status: REVIEWED

Description

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

Source sequence(s)

AC011933

Consensus CDS

CCDS11721.1

UniProtKB/Swiss-Prot

P29354, P62993, Q14450, Q63057, Q63059

UniProtKB/TrEMBL

B0LPF3, B3KR50, Q6ICN0

Related

ENSP00000339007.4, ENST00000316804.10

Conserved Domains (3) summary

cd09941
Location:56 → 150

SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins

cd11946
Location:1 → 56

SH3_GRB2_N; N-terminal Src homology 3 domain of Growth factor receptor-bound protein 2

cd11949
Location:160 → 212

SH3_GRB2_C; C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2
NM_203506.3 → NP_987102.1 growth factor receptor-bound protein 2 isoform 2

See identical proteins and their annotated locations for NP_987102.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the 3' coding region, as compared to variant 1. It encodes the shorter isoform (2) that lacks an internal segment, as compared to isoform 1.

Source sequence(s)

AC011933, BC000631, DA458680

Consensus CDS

CCDS11722.1

UniProtKB/TrEMBL

B3KR50, Q6ICN0

Related

ENSP00000317360.5, ENST00000316615.9

Conserved Domains (2) summary

cd09941
Location:15 → 109

SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins

cd11949
Location:119 → 171

SH3_GRB2_C; C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2