GRAP2 GRB2 related adaptor protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRAP2provided by HGNC
Official Full Name: GRB2 related adaptor protein 2provided by HGNC
Primary source: HGNC:HGNC:4563
See related: Ensembl:ENSG00000100351 MIM:604518; AllianceGenome:HGNC:4563
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: P38; GADS; GRID; GRPL; GrbX; Mona; GRB2L; GRBLG; Grf40; GRAP-2
Summary: This gene encodes a member of the GRB2/Sem5/Drk family. This member is an adaptor-like protein involved in leukocyte-specific protein-tyrosine kinase signaling. Like its related family member, GRB2-related adaptor protein (GRAP), this protein contains an SH2 domain flanked by two SH3 domains. This protein interacts with other proteins, such as GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein (LCP2), through its SH3 domains. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]
Expression: Broad expression in lymph node (RPKM 6.7), spleen (RPKM 4.1) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q13.1

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (39893820..39973721)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (40364806..40444710)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (40297088..40369725)

Chromosome 22 - NC_000022.11 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?

These data are consistent with a model in which bivalent recruitment of a GADS/SLP-76 complex is required for costimulation by CD6.
Title: T Cell Costimulation by CD6 Is Dependent on Bivalent Binding of a GADS/SLP-76 Complex.
Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. These three adaptor proteins bind to the same site on CD28 with variable affinity
Title: Crystal Structures and Thermodynamic Analysis Reveal Distinct Mechanisms of CD28 Phosphopeptide Binding to the Src Homology 2 (SH2) Domains of Three Adaptor Proteins.
GADS deficient T cells displayed similar levels of T cell receptor -induced SLP-76 and PLC-gamma1 phosphorylation but exhibited substantial decrease in TCR-induced IL-2 and IFN-gamma release.
Title: GADS is required for TCR-mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells.
Gads was dispensable for TCR-induced phosphorylation of SLP-76, but was a dose-dependent amplifier of TCR-induced CD69 expression.
Title: Modulation of TCR responsiveness by the Grb2-family adaptor, Gads.
GADS mediates lymphoid disease downstream of BCR-ABL through the recruitment of specific signaling intermediates.
Title: Gads (Grb2-related adaptor downstream of Shc) is required for BCR-ABL-mediated lymphoid leukemia.
Histidine domain-protein tyrosine phosphatase interacts with Grb2 and GrpL
Title: Histidine domain-protein tyrosine phosphatase interacts with Grb2 and GrpL.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
The results show that Bcr-Abl regulates the actin cytoskeleton and non-apoptotic membrane blebbing via a GADS/Slp-76/Nck1 adaptor protein pathway.
Title: The Bcr-Abl kinase regulates the actin cytoskeleton via a GADS/Slp-76/Nck1 adaptor protein pathway.
Consistent Grap-2 expression suggests a specific role for this adaptor in human medullary thyroid carcinoma, while qualitative alterations do not appear to influence RET signaling
Title: Expression of the Grb2-related RET adapter protein Grap-2 in human medullary thyroid carcinoma.
Our findings define a pathway involving CD28 binding to Grb-2 and its co-operativity with Vav1 in the regulation of T-cell co-stimulation.
Title: CD28 and Grb-2, relative to Gads or Grap, preferentially co-operate with Vav1 in the activation of NFAT/AP-1 transcription.

Submit: New GeneRIF Correction See all GeneRIFs (17)

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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G65389 (e-PCR)
- UniSTS:166522

A008B01 (e-PCR)
- UniSTS:56196

SHGC-112304 (e-PCR)
- UniSTS:168604

SHGC-52589 (e-PCR)
- UniSTS:9181

D22S284 (e-PCR), detects polymorphism
- UniSTS:19937

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables phosphotyrosine residue binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Ras protein signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in cell-cell signaling	TAS Traceable Author Statement 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

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	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: GRB2-related adapter protein 2

Names: GRB-2-like protein; GRB2-related protein with insert domain; SH3-SH2-SH3 adapter Mona; SH3-SH2-SH3 adaptor molecule; adapter protein GRID; grf-40; grf40 adapter protein; growth factor receptor-binding protein; growth factor receptor-bound protein 2-related adaptor protein 2; hematopoietic cell-associated adapter protein GrpL; hematopoietic cell-associated adaptor protein GRPL

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_001291824.2 → NP_001278753.1 GRB2-related adapter protein 2 isoform 1

See identical proteins and their annotated locations for NP_001278753.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1, 2 and 3 encode the same isoform.

Source sequence(s)

AK312830, DC409651, KF457461, Z82206

Consensus CDS

CCDS13999.1

UniProtKB/Swiss-Prot

B7Z8I3, O43726, O75791, Q9NRB7

UniProtKB/TrEMBL

Q6FHA6, Q6FI14

Conserved Domains (3) summary

cd09941
Location:54 → 147

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

cd11947
Location:2 → 53

SH3_GRAP2_N; N-terminal Src homology 3 domain of GRB2-related adaptor protein 2

cd11950
Location:275 → 327

SH3_GRAP2_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein 2
NM_001291825.1 → NP_001278754.1 GRB2-related adapter protein 2 isoform 1

See identical proteins and their annotated locations for NP_001278754.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1, 2 and 3 encode the same isoform 1.

Source sequence(s)

AF236120, Z82206

Consensus CDS

CCDS13999.1

UniProtKB/Swiss-Prot

B7Z8I3, O43726, O75791, Q9NRB7

UniProtKB/TrEMBL

Q6FHA6, Q6FI14

Related

ENSP00000385607.3, ENST00000407075.3

Conserved Domains (3) summary

cd09941
Location:54 → 147

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

cd11947
Location:2 → 53

SH3_GRAP2_N; N-terminal Src homology 3 domain of GRB2-related adaptor protein 2

cd11950
Location:275 → 327

SH3_GRAP2_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein 2
NM_001291826.2 → NP_001278755.1 GRB2-related adapter protein 2 isoform 2

See identical proteins and their annotated locations for NP_001278755.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an internal exon, which results in a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AK303280, DC409651, KF457461, Z82206

UniProtKB/TrEMBL

B7Z8E3, B7Z8J2

Conserved Domains (2) summary

cd09941
Location:3 → 75

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

cd11950
Location:203 → 255

SH3_GRAP2_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein 2
NM_001291828.2 → NP_001278757.1 GRB2-related adapter protein 2 isoform 3

See identical proteins and their annotated locations for NP_001278757.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks three internal exons, which results in an alternate downstream start codon, compared to variant 1. The resulting isoform (3) has a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AK303470, HY091328, KF457461, Z82206

UniProtKB/Swiss-Prot

O75791

Conserved Domains (1) summary

cd11950
Location:162 → 214

SH3_GRAP2_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein 2
NM_004810.4 → NP_004801.1 GRB2-related adapter protein 2 isoform 1

See identical proteins and their annotated locations for NP_004801.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1, 2 and 3 encode the same isoform 1.

Source sequence(s)

AY069959, KF457461, Z82206

Consensus CDS

CCDS13999.1

UniProtKB/Swiss-Prot

B7Z8I3, O43726, O75791, Q9NRB7

UniProtKB/TrEMBL

Q6FHA6, Q6FI14

Related

ENSP00000339186.4, ENST00000344138.9

Conserved Domains (3) summary

cd09941
Location:54 → 147

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

cd11947
Location:2 → 53

SH3_GRAP2_N; N-terminal Src homology 3 domain of GRB2-related adaptor protein 2

cd11950
Location:275 → 327

SH3_GRAP2_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein 2

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_000022.11 Reference GRCh38.p14 Primary Assembly

Range

39893820..39973721

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047441607.1 → XP_047297563.1 GRB2-related adapter protein 2 isoform X1

UniProtKB/Swiss-Prot

B7Z8I3, O43726, O75791, Q9NRB7

UniProtKB/TrEMBL

Q6FI14
XM_047441608.1 → XP_047297564.1 GRB2-related adapter protein 2 isoform X2

UniProtKB/TrEMBL

B7Z8F8

RNA

XR_007067995.1 RNA Sequence
XR_007067996.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060946.1 Alternate T2T-CHM13v2.0

Range

40364806..40444710

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054326139.1 → XP_054182114.1 GRB2-related adapter protein 2 isoform X1

UniProtKB/Swiss-Prot

B7Z8I3, O43726, O75791, Q9NRB7

UniProtKB/TrEMBL

Q6FI14
XM_054326140.1 → XP_054182115.1 GRB2-related adapter protein 2 isoform X2

UniProtKB/TrEMBL

B7Z8F8