ITGA4 integrin subunit alpha 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ITGA4provided by HGNC
Official Full Name: integrin subunit alpha 4provided by HGNC
Primary source: HGNC:HGNC:6140
See related: Ensembl:ENSG00000115232 MIM:192975; AllianceGenome:HGNC:6140
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 gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 4 subunit. This subunit associates with a beta 1 or beta 7 subunit to form an integrin that may play a role in cell motility and migration. This integrin is a therapeutic target for the treatment of multiple sclerosis, Crohn's disease and inflammatory bowel disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
Expression: Broad expression in spleen (RPKM 22.7), appendix (RPKM 22.2) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q31.3

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (181457205..181538940)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (181947690..182029083)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (182321932..182403667)

Chromosome 2 - NC_000002.12 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
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?

[Association of ITGA4 and ICAM-1 gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease].
Title: [Association of ITGA4 and ICAM-1 gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease].
LRP12 is an endogenous transmembrane inactivator of alpha4 integrins.
Title: LRP12 is an endogenous transmembrane inactivator of α4 integrins.
Low CD49d expression in newly diagnosed chronic lymphocytic leukaemia may be associated with high-risk features and reduced treatment-free-intervals.
Title: Low CD49d expression in newly diagnosed chronic lymphocytic leukaemia may be associated with high-risk features and reduced treatment-free-intervals.
[The correlation of CD49d expression pattern with molecular genetics and hotspot gene mutants in patients with chronic lymphocytic leukemia].
Title: [The correlation of CD49d expression pattern with molecular genetics and hotspot gene mutants in patients with chronic lymphocytic leukemia].
Increased Levels of VCAM-1 in Sera and VLA-4 Expression on Neutrophils in Dermatomyositis with Interstitial Lung Disease.
Title: Increased Levels of VCAM-1 in Sera and VLA-4 Expression on Neutrophils in Dermatomyositis with Interstitial Lung Disease.
Elastin MIcrofibriL INterfacer1 (EMILIN-1) is an alternative prosurvival VLA-4 ligand in chronic lymphocytic leukemia.
Title: Elastin MIcrofibriL INterfacer1 (EMILIN-1) is an alternative prosurvival VLA-4 ligand in chronic lymphocytic leukemia.
Enhanced Migratory Capacity of T Lymphocytes in Severe Chagasic Patients Is Correlated With VLA-4 and TNF-alpha Expression.
Title: Enhanced Migratory Capacity of T Lymphocytes in Severe Chagasic Patients Is Correlated With VLA-4 and TNF-α Expression.
CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity.
Title: CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity.
[Value of combined detection of ITGA4 and SFRP2 gene methylation in stool DNA in diagnosis and prognostic evaluation of colorectal tumors].
Title: [Value of combined detection of ITGA4 and SFRP2 gene methylation in stool DNA in diagnosis and prognostic evaluation of colorectal tumors].
The association of alpha4beta7 expression with HIV acquisition and disease progression in people who inject drugs and men who have sex with men: Case control studies.
Title: The association of α4β7 expression with HIV acquisition and disease progression in people who inject drugs and men who have sex with men: Case control studies.

Submit: New GeneRIF Correction See all GeneRIFs (204)

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

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 infected patients exhibit an upregulation of ITGA4/ITGB7 positive lymphocytes in peripheral blood of immunological nonresponder clinical samples	PubMed
Knockdown of integrin alpha 4 protein by shRNA inhibits HIV-1 infection in primary lymphocytes	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 Env gp120 amino acids from position 158 to 192 bind alpha-4/beta-7 integrin (ITGA4/ITGB7)	PubMed
	env	HIV-1 Env (gp120) V2/V3 loops bind to ITGA4 and ITGB7 (a4b7), which can be inhibited by anti-V2 peptide or integrin or anti-V3 antibodies	PubMed
	env	HIV-1 Env gp120/41 (JRFL Env in the contaxt of HIV-Gag-GFP VLP) binds to ITGA4 on the surface of basophils	PubMed
	env	HIV-1 Env gp120 with P/SDI/V-ITGA4/ITGB7 binding motifs interact more with ITGA4/ITGB7	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
	env	Integrin alpha4beta7 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	Little or no integrin alpha4beta7 binding is detected with multiple HIV-1 gp120s and gp140s, including gp120s from transmitted/founder strains, or when gp120 is produced in CHO, 293T, and 293S/GnT1(-/-) cells	PubMed
	env	The peptide segment at positions 166-178 of the V2 loop of HIV-1 gp120 appears to harbor a cryptic determinant of integrin alpha4beta7 binding on primary human T cells	PubMed
	env	Treatment of B cells with HIV-1 gp120 upregulates the expression of FCRL4 and limits the proliferative expansion of B cells in an integrin alpha 4/beta 7-dependent manner	PubMed
	env	HIV-1 gp120 binds to human B cells through integrin alpha 4/beta 7	PubMed
	env	HIV-1 gp120/41 Envelope proteins form a complex with integrin alpha4beta7 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	The gp120-integrin alpha4beta7 complex mediates LFA-1 activation on T cells and increases the efficiency of infection by promoting synapse formation	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	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
Envelope surface glycoprotein gp160, precursor	env	Little or no integrin alpha4beta7 binding is detected with multiple HIV-1 gp140s in human cells	PubMed
Envelope transmembrane glycoprotein gp41	env	HIV-1 gp120/41 Envelope proteins form a complex with integrin alpha4beta7 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 Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH68735 (e-PCR)
- UniSTS:25089

G35017 (e-PCR)
- UniSTS:17199

SHGC-78143 (e-PCR)
- UniSTS:96059

RH18091 (e-PCR)
- UniSTS:48965

RH47596 (e-PCR)
- UniSTS:44168

ITGA4 (e-PCR)
- UniSTS:505484

ITGA4_1403 (e-PCR)
- UniSTS:277393

ITGA4_v453 (e-PCR)
- UniSTS:277393

SHGC-78758 (e-PCR)
- UniSTS:95636

D2S1872 (e-PCR)
- UniSTS:153564

D2S2637 (e-PCR)
- UniSTS:65521

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to C-X3-C chemokine binding	IDA Inferred from Direct Assay more info	PubMed
enables cell adhesion molecule binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables cell adhesion molecule binding	IPI Inferred from Physical Interaction more info	PubMed
enables coreceptor activity	TAS Traceable Author Statement more info	PubMed
enables fibronectin binding	IEA Inferred from Electronic Annotation more info
enables integrin binding	IBA Inferred from Biological aspect of Ancestor more info
enables integrin binding	TAS Traceable Author Statement more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein antigen binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell differentiation	IC Inferred by Curator more info	PubMed
involved_in axonogenesis involved in innervation	IEA Inferred from Electronic Annotation more info
involved_in cell adhesion mediated by integrin	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell adhesion in response to extracellular stimulus	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cell-cell adhesion mediated by integrin	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cell-matrix adhesion	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-matrix adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in cell-matrix adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell-matrix adhesion involved in ameboidal cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to amyloid-beta	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cellular response to cytokine stimulus	IEA Inferred from Electronic Annotation more info
involved_in clathrin-dependent extracellular exosome endocytosis	IEA Inferred from Electronic Annotation more info
involved_in diapedesis	IEA Inferred from Electronic Annotation more info
involved_in endodermal cell differentiation	IEP Inferred from Expression Pattern more info	PubMed
involved_in heterotypic cell-cell adhesion	IGI Inferred from Genetic Interaction more info	PubMed
involved_in heterotypic cell-cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in immune response in gut-associated lymphoid tissue	NAS Non-traceable Author Statement more info	PubMed
involved_in integrin-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in integrin-mediated signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in leukocyte cell-cell adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in leukocyte tethering or rolling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of vasoconstriction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron projection extension	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of leukocyte tethering or rolling	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of vascular endothelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in receptor clustering	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in substrate adhesion-dependent cell spreading	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular exosome	HDA more info	PubMed
located_in focal adhesion	HDA more info	PubMed
located_in growth cone	IEA Inferred from Electronic Annotation more info
part_of integrin alpha4-beta1 complex	TAS Traceable Author Statement more info	PubMed
part_of integrin alpha4-beta7 complex	IDA Inferred from Direct Assay more info	PubMed
part_of integrin alpha4-beta7 complex	IPI Inferred from Physical Interaction more info	PubMed
part_of integrin complex	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	HDA more info	PubMed
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: integrin alpha-4

Names: 269C wild type; CD49 antigen-like family member D; VLA-4 subunit alpha; alpha 4 subunit of VLA-4 receptor; antigen CD49D, alpha-4 subunit of VLA-4 receptor; integrin alpha-IV; very late activation protein 4 receptor, alpha 4 subunit

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.

Genomic

NG_050623.2 RefSeqGene

Range

5183..86737

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000885.6 → NP_000876.3 integrin alpha-4 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_000876.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC020595

Consensus CDS

CCDS42788.1

UniProtKB/Swiss-Prot

D3DPG4, P13612, Q7Z4L6

UniProtKB/TrEMBL

Q59H74

Related

ENSP00000380227.2, ENST00000397033.7

Conserved Domains (2) summary

smart00191
Location:366 → 418

Int_alpha; Integrin alpha (beta-propellor repeats)

pfam08441
Location:463 → 902

Integrin_alpha2; Integrin alpha
NM_001316312.2 → NP_001303241.1 integrin alpha-4 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 3' terminal exon, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus compared to isoform 1.

Source sequence(s)

AC020595, BC055419, DB114726

Consensus CDS

CCDS82540.1

UniProtKB/Swiss-Prot

P13612

Related

ENSP00000340149.4, ENST00000339307.8

Conserved Domains (1) summary

smart00191
Location:48 → 105

Int_alpha; Integrin alpha (beta-propellor repeats)