Grb2 growth factor receptor bound protein 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Grb2provided by MGI
Official Full Name: growth factor receptor bound protein 2provided by MGI
Primary source: MGI:MGI:95805
See related: Ensembl:ENSMUSG00000059923 AllianceGenome:MGI:95805
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Ash
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. Three alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2015]
Expression: Ubiquitous expression in CNS E18 (RPKM 40.7), frontal lobe adult (RPKM 37.9) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 E2; 11 80.91 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
109	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (115534871..115599423, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (115644045..115708597, complement)

Chromosome 11 - NC_000077.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MicroRNA-27a-3p aggravates renal ischemia/reperfusion injury by promoting oxidative stress via targeting growth factor receptor-bound protein 2.
Title: MicroRNA-27a-3p aggravates renal ischemia/reperfusion injury by promoting oxidative stress via targeting growth factor receptor-bound protein 2.
Long noncoding RNA AC092171.4 promotes hepatocellular carcinoma progression by sponging microRNA-1271 and upregulating GRB2.
Title: Long noncoding RNA AC092171.4 promotes hepatocellular carcinoma progression by sponging microRNA-1271 and upregulating GRB2.
Role of long noncoding RNA MEG3/miR-378/GRB2 axis in neuronal autophagy and neurological functional impairment in ischemic stroke.
Title: Role of long noncoding RNA MEG3/miR-378/GRB2 axis in neuronal autophagy and neurological functional impairment in ischemic stroke.
we have demonstrated that Grb2 directly interacts with phosphorylated HGAL, collaborating in cSMAC formation while oppositely regulating BCR-induced intracellular biochemical signaling. These interactions may play an important function in regulating the magnitude of BCR signaling and antigen presentation.
Title: Interplay between HGAL and Grb2 proteins regulates B-cell receptor signaling.
Gab1 enhances interleukin-6-induced MAPK-pathway activation in an SHP2-, Grb2-, and time-dependent manner
Title: The multi-site docking protein Grb2-associated binder 1 (Gab1) enhances interleukin-6-induced MAPK-pathway activation in an SHP2-, Grb2-, and time-dependent manner.
the study identifies a novel pro-fibrotic lncRNA, PCFL, and the mechanism involves the direct interaction of PCFL with miR-378, which in turn relieves the inhibition effect of miR-378 on GRB2 and promotes cardiac fibrosis.
Title: LncRNA PCFL promotes cardiac fibrosis via miR-378/GRB2 pathway following myocardial infarction.
GRB2 inhibitors may have the potential to dampen tissue eosinophilia in various eosinophil-associated diseases.
Title: Murine eosinophil development and allergic lung eosinophilia are largely dependent on the signaling adaptor GRB2.
Study shows that growth factor receptor binding protein 2 carboxyl-terminal SH3 domain can bivalently associate with two ligands, in an SH3 dependent manner. Extrapolating the results of this study to the in vivo conditions, Grb2 should bind the SLP65 transducer module first, and then Vav should associate.
Title: Grb2 carboxyl-terminal SH3 domain can bivalently associate with two ligands, in an SH3 dependent manner.
Our findings position Grb2 as a key adaptor that integrates various cytokines response in cycling Hematopoietic Stem and Progenitor Cell .
Title: Grb2 regulates the proliferation of hematopoietic stem and progenitors cells.
Themis1 acts as a positive regulator of TCR signaling during thymocyte development by promoting Vav1 activity and Grb2 stability
Title: Themis1 enhances T cell receptor signaling during thymocyte development by promoting Vav1 activity and Grb2 stability.

Submit: New GeneRIF Correction See all GeneRIFs (52)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (9) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH133824 (e-PCR)
- UniSTS:217107

Grb2 (e-PCR), detects polymorphism
- UniSTS:143250

RH125419 (e-PCR)
- UniSTS:162241

RH124678 (e-PCR)
- UniSTS:161500

Homology

Orthologs from Annotation Pipeline: 350 organisms have orthologs with human gene Grb2
Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables SH3 domain binding	ISO Inferred from Sequence Orthology more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables ephrin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables ephrin receptor binding	ISO Inferred from Sequence Orthology more info
enables epidermal growth factor receptor binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables epidermal growth factor receptor binding	ISO Inferred from Sequence Orthology more info
enables guanyl-nucleotide exchange factor adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor adaptor activity	ISO Inferred from Sequence Orthology more info	PubMed
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables insulin receptor substrate binding	ISO Inferred from Sequence Orthology more info
enables molecular function activator activity	IDA Inferred from Direct Assay more info	PubMed
enables molecular function activator activity	ISO Inferred from Sequence Orthology more info	PubMed
enables neurotrophin TRKA receptor binding	ISO Inferred from Sequence Orthology more info
enables phosphoprotein binding	ISO Inferred from Sequence Orthology more info
enables phosphotyrosine residue binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables phosphotyrosine residue binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	ISO Inferred from Sequence Orthology more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables protein-macromolecule adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane receptor protein tyrosine kinase adaptor activity	IGI Inferred from Genetic Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within Ras protein signal transduction	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within actin cytoskeleton reorganization	ISO Inferred from Sequence Orthology more info
involved_in aging	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within anatomical structure formation involved in morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within branching involved in labyrinthine layer morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to ionizing radiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within endodermal cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in epidermal growth factor receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in epidermal growth factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within fibroblast growth factor receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in insulin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in insulin receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in insulin-like growth factor receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of actin filament polymerization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of reactive oxygen species metabolic process	ISO Inferred from Sequence Orthology more info
involved_in receptor internalization	ISO Inferred from Sequence Orthology more info
involved_in regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info	PubMed
acts_upstream_of_or_within regulation of MAPK cascade	IGI Inferred from Genetic Interaction more info	PubMed
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in signal transduction in response to DNA damage	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
part_of COP9 signalosome	IBA Inferred from Biological aspect of Ancestor more info	PubMed
part_of COP9 signalosome	IDA Inferred from Direct Assay more info	PubMed
part_of COP9 signalosome	ISO Inferred from Sequence Orthology more info
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
part_of Grb2-EGFR complex	ISO Inferred from Sequence Orthology more info
located_in cell-cell junction	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endosome	ISO Inferred from Sequence Orthology more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in nucleolus	ISO Inferred from Sequence Orthology more info
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
located_in vesicle membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: growth factor receptor-bound protein 2

Names: SH2/SH3 adapter GRB2; adapter protein GRB2

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.

mRNA and Protein(s)

NM_001313936.1 → NP_001300865.1 growth factor receptor-bound protein 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. All three variants encode the same protein.

Source sequence(s)

AK155800, BC052377, BQ174314, BY292622

Consensus CDS

CCDS25645.1

UniProtKB/Swiss-Prot

Q60631, Q61240

UniProtKB/TrEMBL

A0A6P5QTC6, A0A8C6N416, Q3U1Q4, Q3U5I5

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_001313937.1 → NP_001300866.1 growth factor receptor-bound protein 2

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. All three variants encode the same protein.

Source sequence(s)

AK155800, BC052377, BQ174314, BY266228

Consensus CDS

CCDS25645.1

UniProtKB/Swiss-Prot

Q60631, Q61240

UniProtKB/TrEMBL

A0A6P5QTC6, A0A8C6N416, Q3U1Q4, Q3U5I5

Related

ENSMUSP00000102106.2, ENSMUST00000106497.8

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_008163.4 → NP_032189.1 growth factor receptor-bound protein 2

See identical proteins and their annotated locations for NP_032189.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. All three variants encode the same protein.

Source sequence(s)

AK155800, BC052377, BQ174314

Consensus CDS

CCDS25645.1

UniProtKB/Swiss-Prot

Q60631, Q61240

UniProtKB/TrEMBL

A0A6P5QTC6, A0A8C6N416, Q3U1Q4, Q3U5I5

Related

ENSMUSP00000021090.8, ENSMUST00000021090.14

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