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GRAP GRB2 related adaptor protein [ Homo sapiens (human) ]

Gene ID: 10750, updated on 3-Apr-2024

Summary

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Official Symbol
GRAPprovided by HGNC
Official Full Name
GRB2 related adaptor proteinprovided by HGNC
Primary source
HGNC:HGNC:4562
See related
Ensembl:ENSG00000154016 MIM:604330; AllianceGenome:HGNC:4562
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
DFNB114
Summary
This gene encodes a member of the GRB2/Sem5/Drk family and functions as a cytoplasmic signaling protein which contains an SH2 domain flanked by two SH3 domains. The SH2 domain interacts with ligand-activated receptors for stem cell factor and erythropoietin, and facilitates the formation of a stable complex with the BCR-ABL oncoprotein. This protein also associates with the Ras guanine nucleotide exchange factor SOS1 (son of sevenless homolog 1) through its N-terminal SH3 domain. In general, it couples signals from receptor and cytoplasmic tyrosine kinases to the Ras signaling pathway. [provided by RefSeq, Jul 2012]
Expression
Broad expression in lymph node (RPKM 19.4), spleen (RPKM 17.2) and 19 other tissues See more
Orthologs
all
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Genomic context

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See GRAP in Genome Data Viewer
Location:
17p11.2
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (19020656..19051373, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (18968549..18999272, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (18923969..18950270, complement)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene small nucleolar RNA MBII-202 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:18850561-18851174 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18851175-18851788 Neighboring gene solute carrier family 5 member 10 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8281 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18864393-18865390 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18866439-18866973 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18866974-18867507 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:18871247-18872190 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18874077-18875018 Neighboring gene family with sequence similarity 83 member G Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18883844-18884799 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18884800-18885754 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18885755-18886709 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8282 Neighboring gene Sharpr-MPRA regulatory region 2479 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_47104 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18917397-18918386 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11848 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:18934086-18934883 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18935718-18936468 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18936469-18937218 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18954567-18955068 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:18955069-18955568 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:18966649-18967243 Neighboring gene small nucleolar RNA, C/D box 3B-1 Neighboring gene small nucleolar RNA, C/D box 3B-2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. m(6)A Modification-mediated GRAP Regulates Vascular Remodeling in Hypoxic Pulmonary Hypertension. Liu P, et al. Am J Respir Cell Mol Biol, 2022 Nov. PMID 35972996
  2. miR-654-5p Targets GRAP to Promote Proliferation, Metastasis, and Chemoresistance of Oral Squamous Cell Carcinoma Through Ras/MAPK Signaling. Lu M, et al. DNA Cell Biol, 2018 Apr. PMID 29364705
  3. Quantitative mass spectrometry of diabetic kidney tubules identifies GRAP as a novel regulator of TGF-beta signaling. Cummins TD, et al. Biochim Biophys Acta, 2010 Apr. PMID 19836472, Free PMC Article
  4. Detection of Grb-2-related adaptor protein gene (GRAP) and peptide molecule in salivary glands of MRL/lpr mice and patients with Sjögren's syndrome. Shiraiwa H, et al. J Int Med Res, 2004 May-Jun. PMID 15174222
  5. Polymorphisms of four bone mineral density candidate genes in Chinese populations and comparison with other populations of different ethnicity. Lei SF, et al. J Bone Miner Metab, 2003. PMID 12491092

See all (24) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. m(6)A Modification-mediated GRAP Regulates Vascular Remodeling in Hypoxic Pulmonary Hypertension.
    Title: m(6)A Modification-mediated GRAP Regulates Vascular Remodeling in Hypoxic Pulmonary Hypertension.
  2. The function of the growth factor receptor-bound protein 2 (GRB2)-related adaptor protein (GRAP) in the auditory system is not known.
    Title: Dysfunction of GRAP, encoding the GRB2-related adaptor protein, is linked to sensorineural hearing loss.
  3. Findings suggest that the miR-654-5p/GRAP/Ras/Erk signaling pathway in OSCC cells might contribute to the underlying mechanism through which miR-654-5p participates in the regulation of OSCC progression.
    Title: miR-654-5p Targets GRAP to Promote Proliferation, Metastasis, and Chemoresistance of Oral Squamous Cell Carcinoma Through Ras/MAPK Signaling.
  4. Grb2-related adaptor protein (GRAP) was up-regulated in kidney tubules from fibrotic kidneys from diabetic patients, and subsequently confirmed as a novel component of TGF-beta signaling in cultured human renal tubule cells.
    Title: Quantitative mass spectrometry of diabetic kidney tubules identifies GRAP as a novel regulator of TGF-beta signaling.
  5. 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.
  6. Observational study of genotype prevalence. (HuGE Navigator)
    Title: Polymorphisms of four bone mineral density candidate genes in Chinese populations and comparison with other populations of different ethnicity.
  7. Results suggest that the GRAP gene might have a role in the pathogenesis of Sjogren's syndrome.
    Title: Detection of Grb-2-related adaptor protein gene (GRAP) and peptide molecule in salivary glands of MRL/lpr mice and patients with Sjögren's syndrome.
Submit: New GeneRIF Correction

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

Associated conditions

Description Tests
Hearing loss, autosomal recessive 114
MedGen: C5193107 OMIM: 618456 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Vif vif HIV-1 Vif downregulates the expression of GRB2-related adaptor protein (GRAP) in Vif-expression T cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC64880

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables epidermal growth factor receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
  
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 sensory perception of sound IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
part_of COP9 signalosome IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
is_active_in nucleoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in presynapse ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
GRB2-related adapter protein
Names
growth factor receptor-bound protein 2-related adaptor 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.

mRNA and Protein(s)

  1. NM_001330148.2 → NP_001317077.1  GRB2-related adapter protein isoform 2

    Status: REVIEWED

    Source sequence(s)
    AI362516, BC035856, BG684099, BI906472
    Consensus CDS
    CCDS82085.1
    UniProtKB/TrEMBL
    I3L2P9
    Related
    ENSP00000459833.1, ENST00000573099.5
    Conserved Domains (2) summary
    cd11948
    Location:2 → 55
    SH3_GRAP_N; N-terminal Src homology 3 domain of GRB2-related adaptor protein
    cl15255
    Location:56 → 101
    SH2; Src homology 2 (SH2) domain

  2. NM_006613.4 → NP_006604.1  GRB2-related adapter protein isoform 1

    See identical proteins and their annotated locations for NP_006604.1

    Status: REVIEWED

    Source sequence(s)
    AC003957, BC063035
    Consensus CDS
    CCDS11202.1
    UniProtKB/Swiss-Prot
    Q13588
    Related
    ENSP00000284154.5, ENST00000284154.10
    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
    cd11948
    Location:2 → 55
    SH3_GRAP_N; N-terminal Src homology 3 domain of GRB2-related adaptor protein
    cd11951
    Location:162 → 214
    SH3_GRAP_C; C-terminal Src homology 3 domain of GRB2-related adaptor protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    19020656..19051373 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047435154.1 → XP_047291110.1  GRB2-related adapter protein isoform X1

    UniProtKB/Swiss-Prot
    Q13588

  2. XM_047435155.1 → XP_047291111.1  GRB2-related adapter protein isoform X2

    UniProtKB/TrEMBL
    I3L2P9

  3. XM_047435156.1 → XP_047291112.1  GRB2-related adapter protein isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    18968549..18999272 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054314746.1 → XP_054170721.1  GRB2-related adapter protein isoform X1

    UniProtKB/Swiss-Prot
    Q13588

  2. XM_054314747.1 → XP_054170722.1  GRB2-related adapter protein isoform X2

    UniProtKB/TrEMBL
    I3L2P9

  3. XM_054314748.1 → XP_054170723.1  GRB2-related adapter protein isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13588.1 GenPept UniProtKB/Swiss-Prot:Q13588

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