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

Gene ID: 9402, updated on 18-May-2019

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
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

Genomic context

See GRAP2 in Genome Data Viewer
Location:
22q13.1
Exon count:
9
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 22 NC_000022.11 (39901073..39973343)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (40297086..40369347)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene ENTH domain containing 1 Neighboring gene RN7SK pseudogene 210 Neighboring gene ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 pseudogene 1 Neighboring gene translation machinery-associated protein 7 pseudogene Neighboring gene family with sequence similarity 83 member F Neighboring gene family with sequence similarity 83 member F

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Pathways from BioSystems

  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • CD28 co-stimulation, organism-specific biosystem (from REACTOME)
    CD28 co-stimulation, organism-specific biosystemIn naive T cells, CD28 costimulation enhances cell cycle entry, potently stimulates expression of both the mitogenic lymphokine interleukin-2 (IL-2) and its receptor, and stimulates the activation o...
  • Costimulation by the CD28 family, organism-specific biosystem (from REACTOME)
    Costimulation by the CD28 family, organism-specific biosystemOptimal activation of T-lymphocytes requires at least two signals. A primary one is delivered by the T-cell receptor (TCR) complex after antigen recognition and additional costimulatory signals are d...
  • DAP12 interactions, organism-specific biosystem (from REACTOME)
    DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
  • DAP12 signaling, organism-specific biosystem (from REACTOME)
    DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
  • FCERI mediated Ca+2 mobilization, organism-specific biosystem (from REACTOME)
    FCERI mediated Ca+2 mobilization, organism-specific biosystemIncrease of intracellular calcium in mast cells is most crucial for mast cell degranulation. Elevation of intracellular calcium is achieved by activation of PLC-gamma. Mast cells express both PLC-gam...
  • FCERI mediated MAPK activation, organism-specific biosystem (from REACTOME)
    FCERI mediated MAPK activation, organism-specific biosystemFormation of the LAT signaling complex leads to activation of MAPK and production of cytokines. The sequence of events that leads from LAT to cytokine production has not been as clearly defined as th...
  • Fc epsilon receptor (FCERI) signaling, organism-specific biosystem (from REACTOME)
    Fc epsilon receptor (FCERI) signaling, organism-specific biosystemMast cells (MC) are distributed in tissues throughout the human body and have long been recognized as key cells of type I hypersensitivity reactions. They also play important roles in inflammatory an...
  • Generation of second messenger molecules, organism-specific biosystem (from REACTOME)
    Generation of second messenger molecules, organism-specific biosystemIn addition to serving as a scaffold via auto-phosphorylation, ZAP-70 also phosphorylates a restricted set of substrates following TCR stimulation - including LAT and SLP-76. These substrates have be...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • JNK signaling in the CD4+ TCR pathway, organism-specific biosystem (from Pathway Interaction Database)
    JNK signaling in the CD4+ TCR pathway, organism-specific biosystem
    JNK signaling in the CD4+ TCR pathway
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
    Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
  • Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem
    Signaling events mediated by Stem cell factor receptor (c-Kit)
  • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
    T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
  • T cell receptor signaling pathway, conserved biosystem (from KEGG)
    T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
  • T-Cell antigen Receptor (TCR) Signaling Pathway, organism-specific biosystem (from WikiPathways)
    T-Cell antigen Receptor (TCR) Signaling Pathway, organism-specific biosystemThe T-cell antigen receptor (TCR) complex is composed of a ligand-binding subunit, the ? and ? chains, and a signaling subunit, namely the CD3?, ? and ? chains and the TCR? chain. This complex partic...
  • T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection, organism-specific biosystem (from WikiPathways)
    T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection, organism-specific biosystemThis pathway is based on Figure 4 of "A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus au...
  • TCR signaling, organism-specific biosystem (from REACTOME)
    TCR signaling, organism-specific biosystemThe TCR is a multisubunit complex that consists of clonotypic alpha/beta chains noncovalently associated with the invariant CD3 delta/epsilon/gamma and TCR zeta chains. T cell activation by antigen p...
  • TCR signaling in naive CD4+ T cells, organism-specific biosystem (from Pathway Interaction Database)
    TCR signaling in naive CD4+ T cells, organism-specific biosystem
    TCR signaling in naive CD4+ T cells
  • TCR signaling in naive CD8+ T cells, organism-specific biosystem (from Pathway Interaction Database)
    TCR signaling in naive CD8+ T cells, organism-specific biosystem
    TCR signaling in naive CD8+ T cells

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
SH3/SH2 adaptor activity TAS
Traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
 
Ras protein signal transduction TAS
Traceable Author Statement
more info
PubMed 
T cell costimulation TAS
Traceable Author Statement
more info
 
T cell receptor signaling pathway TAS
Traceable Author Statement
more info
 
cell-cell signaling TAS
Traceable Author Statement
more info
PubMed 
positive regulation of signal transduction IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
endosome IDA
Inferred from Direct Assay
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

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)

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)

  1. NM_001291824.1NP_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, Z82206
    Consensus CDS
    CCDS13999.1
    UniProtKB/Swiss-Prot
    O75791
    UniProtKB/TrEMBL
    Q6FI14
    Conserved Domains (3) summary
    cd09941
    Location:54147
    SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins
    cd11947
    Location:253
    SH3_GRAP2_N; N-terminal Src homology 3 domain of GRB2-related adaptor protein 2
    cd11950
    Location:275327
    SH3_GRAP2_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein 2
  2. NM_001291825.1NP_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
    O75791
    UniProtKB/TrEMBL
    Q6FI14
    Related
    ENSP00000385607.3, ENST00000407075.3
    Conserved Domains (3) summary
    cd09941
    Location:54147
    SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins
    cd11947
    Location:253
    SH3_GRAP2_N; N-terminal Src homology 3 domain of GRB2-related adaptor protein 2
    cd11950
    Location:275327
    SH3_GRAP2_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein 2
  3. NM_001291826.1NP_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, Z82206
    UniProtKB/TrEMBL
    B7Z8E3
    Conserved Domains (2) summary
    cd09941
    Location:375
    SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins
    cd11950
    Location:203255
    SH3_GRAP2_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein 2
  4. NM_001291828.1NP_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, Z82206
    UniProtKB/Swiss-Prot
    O75791
    Conserved Domains (1) summary
    cd11950
    Location:162214
    SH3_GRAP2_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein 2
  5. NM_004810.4NP_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
    O75791
    UniProtKB/TrEMBL
    Q6FI14
    Related
    ENSP00000339186.4, ENST00000344138.8
    Conserved Domains (3) summary
    cd09941
    Location:54147
    SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins
    cd11947
    Location:253
    SH3_GRAP2_N; N-terminal Src homology 3 domain of GRB2-related adaptor protein 2
    cd11950
    Location:275327
    SH3_GRAP2_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein 2

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p12 Primary Assembly

    Range
    39901073..39973343
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006724376.3XP_006724439.1  GRB2-related adapter protein 2 isoform X1

    See identical proteins and their annotated locations for XP_006724439.1

    UniProtKB/TrEMBL
    B7Z8E3
    Conserved Domains (2) summary
    cd09941
    Location:375
    SH2_Grb2_like; Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins
    cd11950
    Location:203255
    SH3_GRAP2_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein 2
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