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ITGA4 integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor) [ Homo sapiens (human) ]

Gene ID: 3676, updated on 14-Apr-2014
Official Symbol
ITGA4provided by HGNC
Official Full Name
integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)provided by HGNC
Primary source
HGNC:6140
See related
Ensembl:ENSG00000115232; HPRD:01894; MIM:192975; Vega:OTTHUMG00000154212
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
IA4; CD49D
Summary
The product of this gene belongs to the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This gene encodes an alpha 4 chain. Unlike other integrin alpha chains, alpha 4 neither contains an I-domain, nor undergoes disulfide-linked cleavage. Alpha 4 chain associates with either beta 1 chain or beta 7 chain. [provided by RefSeq, Jul 2008]
Location :
2q31.3
Sequence :
Chromosome: 2; NC_000002.12 (181456892..181537747)
See ITGA4 in Epigenomics, MapViewer

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ubiquitin-conjugating enzyme E2E 3 Neighboring gene uncharacterized LOC101927156 Neighboring gene microRNA 4437 Neighboring gene ceramide kinase-like Neighboring gene Sin3A-associated protein, 18kDa pseudogene Neighboring gene neuronal differentiation 1

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

Description
Genetic variation associated with circulating monocyte count in the eMERGE Network.
NHGRI GWA Catalog
Identification of nine novel loci associated with white blood cell subtypes in a Japanese population.
NHGRI GWA Catalog
Multiple common variants for celiac disease influencing immune gene expression.
NHGRI GWA Catalog
Multiple loci are associated with white blood cell phenotypes.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120/41 Envelope proteins form a complex with integrin a47 and chemokine receptor CCR5 on the CD4-negative gamma-delta T cell membrane, which leads to activation of the p38-caspase pathway and induces the death of gamma-delta cells PubMed
env A mutant integrin alpha4beta7 carrying alpha4 K201/N/I/E reduces its binding to HIV-1 gp120 PubMed
env HIV-1 gp120 is identified to have a physical interaction with integrin, alpha 4 (ITGA4) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
env The gp120-integrin alpha4beta7 complex mediates LFA-1 activation on T cells and increases the efficiency of infection by promoting synapse formation PubMed
env Integrin alpha4beta 7 mediates HIV-1 gp120 binding to natural killer cells. The residues 182-184 in the V2 loop of gp120 is required for the binding between gp120 and integrin alpha4beta7 PubMed
env HIV-1 gp120 induces CD4 association with lymphocyte surface molecules CD3, CD11a, CD27, CD45RA, CD45RB, CD45RO, CD49d, CD38, CD26, CD59, CD95 and class I MHC molecules PubMed
env Increased integrin alpha4beta7 affinity is mediated by sequences encoded in gp120 V1/V2 and also influenced by N-linked glycosylation sites located in gp120 C3/V4 PubMed
Envelope transmembrane glycoprotein gp41 env HIV-1 gp120/41 Envelope proteins form a complex with integrin a47 and chemokine receptor CCR5 on the CD4-negative gamma-delta T cell membrane, which leads to activation of the p38-caspase pathway and induces the death of gamma-delta cells PubMed

Go to the HIV-1, Human Protein Interaction Database

  • 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...
  • Arrhythmogenic right ventricular cardiomyopathy, organism-specific biosystem (from WikiPathways)
    Arrhythmogenic right ventricular cardiomyopathy, organism-specific biosystemAdapted from KEGG: http://www.genome.jp/kegg/pathway/hsa/hsa05412.html
  • Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystem (from KEGG)
    Arrhythmogenic right ventricular cardiomyopathy (ARVC), organism-specific biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
  • Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystem (from KEGG)
    Arrhythmogenic right ventricular cardiomyopathy (ARVC), conserved biosystemArrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are prog...
  • Cell adhesion molecules (CAMs), organism-specific biosystem (from KEGG)
    Cell adhesion molecules (CAMs), organism-specific biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
  • Cell adhesion molecules (CAMs), conserved biosystem (from KEGG)
    Cell adhesion molecules (CAMs), conserved biosystemCell adhesion molecules are (glyco)proteins expressed on the cell surface and play a critical role in a wide array of biologic processes that include hemostasis, the immune response, inflammation, em...
  • Cell surface interactions at the vascular wall, organism-specific biosystem (from REACTOME)
    Cell surface interactions at the vascular wall, organism-specific biosystemLeukocyte extravasation is a rigorously controlled process that guides white cell movement from the vascular lumen to sites of tissue inflammation. The powerful adhesive interactions that are require...
  • Dilated cardiomyopathy, organism-specific biosystem (from KEGG)
    Dilated cardiomyopathy, organism-specific biosystemDilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac d...
  • Dilated cardiomyopathy, conserved biosystem (from KEGG)
    Dilated cardiomyopathy, conserved biosystemDilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac d...
  • ECM-receptor interaction, organism-specific biosystem (from KEGG)
    ECM-receptor interaction, organism-specific biosystemThe extracellular matrix (ECM) consists of a complex mixture of structural and functional macromolecules and serves an important role in tissue and organ morphogenesis and in the maintenance of cell ...
  • ECM-receptor interaction, conserved biosystem (from KEGG)
    ECM-receptor interaction, conserved biosystemThe extracellular matrix (ECM) consists of a complex mixture of structural and functional macromolecules and serves an important role in tissue and organ morphogenesis and in the maintenance of cell ...
  • Extracellular matrix organization, organism-specific biosystem (from REACTOME)
    Extracellular matrix organization, organism-specific biosystemThe extracellular matrix is a component of all mammalian tissues, a network consisting largely of the fibrous proteins collagen, elastin and associated-microfibrils, fibronectin and laminins embedded...
  • Focal Adhesion, organism-specific biosystem (from WikiPathways)
    Focal Adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
  • Focal adhesion, organism-specific biosystem (from KEGG)
    Focal adhesion, organism-specific biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
  • Focal adhesion, conserved biosystem (from KEGG)
    Focal adhesion, conserved biosystemCell-matrix adhesions play essential roles in important biological processes including cell motility, cell proliferation, cell differentiation, regulation of gene expression and cell survival. At the...
  • Hematopoietic cell lineage, organism-specific biosystem (from KEGG)
    Hematopoietic cell lineage, organism-specific biosystemBlood-cell development progresses from a hematopoietic stem cell (HSC), which can undergo either self-renewal or differentiation into a multilineage committed progenitor cell: a common lymphoid proge...
  • Hematopoietic cell lineage, conserved biosystem (from KEGG)
    Hematopoietic cell lineage, conserved biosystemBlood-cell development progresses from a hematopoietic stem cell (HSC), which can undergo either self-renewal or differentiation into a multilineage committed progenitor cell: a common lymphoid proge...
  • Hemostasis, organism-specific biosystem (from REACTOME)
    Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
  • Hypertrophic cardiomyopathy (HCM), organism-specific biosystem (from KEGG)
    Hypertrophic cardiomyopathy (HCM), organism-specific biosystemHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological feat...
  • Hypertrophic cardiomyopathy (HCM), conserved biosystem (from KEGG)
    Hypertrophic cardiomyopathy (HCM), conserved biosystemHypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological feat...
  • 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...
  • Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystem (from REACTOME)
    Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell, organism-specific biosystemA number of receptors and cell adhesion molecules play a key role in modifying the response of cells of lymphoid origin (such as B-, T- and NK cells) to self and tumor antigens, as well as to pathoge...
  • Integrin cell surface interactions, organism-specific biosystem (from REACTOME)
    Integrin cell surface interactions, organism-specific biosystemThe extracellular matrix (ECM) is a network of macro-molecules that underlies all epithelia and endothelia and that surrounds all connective tissue cells. This matrix provides the mechanical strength...
  • Integrin-mediated cell adhesion, organism-specific biosystem (from WikiPathways)
    Integrin-mediated cell adhesion, organism-specific biosystemIntegrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and ...
  • Intestinal immune network for IgA production, organism-specific biosystem (from KEGG)
    Intestinal immune network for IgA production, organism-specific biosystemThe intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies tha...
  • Intestinal immune network for IgA production, conserved biosystem (from KEGG)
    Intestinal immune network for IgA production, conserved biosystemThe intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies tha...
  • Leishmaniasis, organism-specific biosystem (from KEGG)
    Leishmaniasis, organism-specific biosystemLeishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and prol...
  • Leishmaniasis, conserved biosystem (from KEGG)
    Leishmaniasis, conserved biosystemLeishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and prol...
  • Leukocyte transendothelial migration, organism-specific biosystem (from KEGG)
    Leukocyte transendothelial migration, organism-specific biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
  • Leukocyte transendothelial migration, conserved biosystem (from KEGG)
    Leukocyte transendothelial migration, conserved biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
  • PI3K-Akt signaling pathway, organism-specific biosystem (from KEGG)
    PI3K-Akt signaling pathway, organism-specific biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
  • PI3K-Akt signaling pathway, conserved biosystem (from KEGG)
    PI3K-Akt signaling pathway, conserved biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
  • Paxillin-dependent events mediated by a4b1, organism-specific biosystem (from Pathway Interaction Database)
    Paxillin-dependent events mediated by a4b1, organism-specific biosystem
    Paxillin-dependent events mediated by a4b1
  • Paxillin-independent events mediated by a4b1 and a4b7, organism-specific biosystem (from Pathway Interaction Database)
    Paxillin-independent events mediated by a4b1 and a4b7, organism-specific biosystem
    Paxillin-independent events mediated by a4b1 and a4b7
  • Regulation of actin cytoskeleton, organism-specific biosystem (from KEGG)
    Regulation of actin cytoskeleton, organism-specific biosystem
    Regulation of actin cytoskeleton
  • Regulation of actin cytoskeleton, conserved biosystem (from KEGG)
    Regulation of actin cytoskeleton, conserved biosystem
    Regulation of actin cytoskeleton
  • a4b1 and a4b7 Integrin signaling, organism-specific biosystem (from Pathway Interaction Database)
    a4b1 and a4b7 Integrin signaling, organism-specific biosystem
    a4b1 and a4b7 Integrin signaling
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
cell adhesion molecule binding IPI
Inferred from Physical Interaction
more info
PubMed 
fibronectin binding IEA
Inferred from Electronic Annotation
more info
 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
B cell differentiation IC
Inferred by Curator
more info
PubMed 
blood coagulation TAS
Traceable Author Statement
more info
 
blood vessel remodeling IEA
Inferred from Electronic Annotation
more info
 
chorio-allantoic fusion IEA
Inferred from Electronic Annotation
more info
 
extracellular matrix organization TAS
Traceable Author Statement
more info
 
face development IEA
Inferred from Electronic Annotation
more info
 
heart development IEA
Inferred from Electronic Annotation
more info
 
heterophilic cell-cell adhesion IEA
Inferred from Electronic Annotation
more info
 
integrin-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
 
leukocyte cell-cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
leukocyte migration TAS
Traceable Author Statement
more info
 
negative regulation of protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
regulation of immune response TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
external side of plasma membrane IEA
Inferred from Electronic Annotation
more info
 
extracellular vesicular exosome IDA
Inferred from Direct Assay
more info
PubMed 
integrin complex IEA
Inferred from Electronic Annotation
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
Preferred Names
integrin alpha-4
Names
integrin alpha-4
269C wild type
integrin alpha 4
integrin alpha-IV
VLA-4 subunit alpha
integrin alpha-4 subunit
CD49 antigen-like family member D
antigen CD49D, alpha-4 subunit of VLA-4 receptor
very late activation protein 4 receptor, alpha 4 subunit

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_000885.4NP_000876.3  integrin alpha-4 precursor

    See proteins identical to NP_000876.3

    Status: REVIEWED

    Source sequence(s)
    AC020595, X16983
    Consensus CDS
    CCDS42788.1
    UniProtKB/Swiss-Prot
    P13612
    Conserved Domains (2) summary
    smart00191
    Location:366418
    Blast Score: 168
    Int_alpha; Integrin alpha (beta-propellor repeats)
    pfam08441
    Location:463902
    Blast Score: 910
    Integrin_alpha2; Integrin alpha

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38 Primary Assembly

    Range
    181456892..181537747
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

  1. AC_000134.1 Alternate HuRef

    Range
    174178675..174259339
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018913.2 Alternate CHM1_1.1

    Range
    182327169..182407679
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Supplemental Content

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