Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001465
UniProt IDP13612
Primary gene name(s)ITGA4
Synonym gene name(s)CD49D
Protein nameIntegrin alpha-4
Protein functionIntegrins alpha-4/beta-1, VLA-4 and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells. ITGA4:ITGB1 binds to fractalkine, CX3CL1 and may act as its coreceptor in CX3CR1-dependent fractalkine signaling, PubMed:23125415. ITGA4:ITGB1 binds to PLA2G2A via a site, site 2 which is distinct from the classical ligand-binding site, site 1 and this induces integrin conformational changes and enhanced ligand binding to site 1, PubMed:18635536, PubMed:25398877. {ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:19064666, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:25398877}.
Subcellular locationMembrane;
Single-pass type I membrane protein.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P13612
Gene Ontology
(Biological Process)
Complete annatation
B cell differentiation [GO:0030183];
cell-matrix adhesion [GO:0007160];
cell-matrix adhesion involved in ameboidal cell migration [GO:0003366];
cellular response to cytokine stimulus [GO:0071345];
clathrin-dependent extracellular exosome endocytosis [GO:1990771];
diapedesis [GO:0050904];
endodermal cell differentiation [GO:0035987];
extracellular matrix organization [GO:0030198];
heterotypic cell-cell adhesion [GO:0034113];
import into cell [GO:0098657];
integrin-mediated signaling pathway [GO:0007229];
leukocyte cell-cell adhesion [GO:0007159];
leukocyte migration [GO:0050900];
leukocyte tethering or rolling [GO:0050901];
negative regulation of protein homodimerization activity [GO:0090074];
positive regulation of leukocyte tethering or rolling [GO:1903238];
positive regulation of T cell migration [GO:2000406];
receptor clustering [GO:0043113];
regulation of immune response [GO:0050776];
substrate adhesion-dependent cell spreading [GO:0034446]
Gene Ontology
(Molecular Function)
Complete annatation
antigen binding [GO:0003823];
cell adhesion molecule binding [GO:0050839];
coreceptor activity [GO:0015026];
metal ion binding [GO:0046872]
Gene Ontology
(Cellular Component)
Complete annatation
cell surface [GO:0009986];
extracellular exosome [GO:0070062];
focal adhesion [GO:0005925];
integrin alpha4-beta7 complex [GO:0034669];
membrane [GO:0016020];
plasma membrane [GO:0005886]
Protein-protein interaction109883
Phylogenetic treeP13612
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-1.774289323243981.49275313443553e-071.38114028497313e-06
AZA vs. DISU-0.4476436925134660.07670354103190910.590222266291186
AZA vs. IL70.3311045137034790.08426109800338780.796280583200667
AZA vs. SAHA-0.8472161637432240.0009242852142725690.0197512765176782
DISU vs. CD31.31516665373640.0003589845035745220.00171952094276528
DISU vs. IL70.7692578523097070.002336759184132010.0471574895592905
DISU vs. SAHA-0.3978624434911410.1764589633890310.540607837535191
DMSO vs. AZA-0.01862705262952950.9110632754190071
DMSO vs. CD31.748883243122951.10419082655078e-079.66006666782082e-07
DMSO vs. DISU0.4285663021050980.0788506093071430.523932399584941
DMSO vs. IL70.3563144470052650.04696379406939740.434343064782924
DMSO vs. SAHA-0.8357406226782210.002934932999580140.038197215230287
HIV vs. Mock in Activation0.1480061381860650.8129578322435270.999983755607037
HIV vs. Mock in Latency0.5075566614110090.002074301013858750.111671476724667
IL7 vs. CD32.11191930629662.70830580184622e-105.31540278010783e-09
SAHA vs. CD30.9035810375084110.01127610059224630.0284307906851516
SAHA vs. IL7-1.180845368104242.01976122704561e-068.25091618874948e-05
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change -1.095484291
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.283382 0.057586
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.912 1.438 0.938 0.751 1.513
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00108 Natalizumab approved, investigational yes antibody
DB04997 ATL1102 investigational unknown unknown
DB05092 CDP323 investigational unknown unknown
DB05122 R1295 investigational unknown unknown
DB05468 R411 investigational unknown unknown
DB05802 MLN-02 investigational unknown unknown
DB06822 Tinzaparin approved unknown inhibitor
DB09033 Vedolizumab approved yes antibody

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
3V4P X-ray 3.1Å A/C=34-620.
3V4V X-ray 3.1Å A/C=34-620.
4HKC X-ray 2.2Å B=1003-1032.
5C7Z X-ray 2.7Å B=1008-1015.
5FPI X-ray 2.7Å B=1008-1015.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Envelope transmembrane glycoprotein gp41 complexes with 21926353
Envelope surface glycoprotein gp160; precursor binds 25008916
Envelope surface glycoprotein gp120 complexes with 18264102
Envelope surface glycoprotein gp120 interacts with 21383973
Envelope surface glycoprotein gp120 binds 18264102
HIV-1 virus replication enhanced by expression of human gene 25527342

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04512 ECM-receptor interaction - Homo sapiens (human)
hsa04514 Cell adhesion molecules (CAMs) - Homo sapiens (human)
hsa04640 Hematopoietic cell lineage - Homo sapiens (human)
hsa04670 Leukocyte transendothelial migration - Homo sapiens (human)
hsa04672 Intestinal immune network for IgA production - Homo sapiens (human)
hsa04810 Regulation of actin cytoskeleton - Homo sapiens (human)
hsa05140 Leishmaniasis - Homo sapiens (human)
hsa05410 Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human)
hsa05412 Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human)
hsa05414 Dilated cardiomyopathy - Homo sapiens (human)