Browse ITGA4

Summary
SymbolITGA4
Nameintegrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
Aliases CD49d; 269C wild type; CD49 antigen-like family member D; VLA-4 subunit alpha; antigen CD49D, alpha-4 subuni ......
Chromosomal Location2q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Membrane; Single-pass type I membrane protein.
Domain PF01839 FG-GAP repeat
PF08441 Integrin alpha
Function

Integrins 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).

> Gene Ontology
 
Biological Process GO:0001667 ameboidal-type cell migration
GO:0001704 formation of primary germ layer
GO:0001706 endoderm formation
GO:0002521 leukocyte differentiation
GO:0002685 regulation of leukocyte migration
GO:0002687 positive regulation of leukocyte migration
GO:0002691 regulation of cellular extravasation
GO:0002693 positive regulation of cellular extravasation
GO:0003366 cell-matrix adhesion involved in ameboidal cell migration
GO:0006898 receptor-mediated endocytosis
GO:0007159 leukocyte cell-cell adhesion
GO:0007160 cell-matrix adhesion
GO:0007229 integrin-mediated signaling pathway
GO:0007369 gastrulation
GO:0007492 endoderm development
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030098 lymphocyte differentiation
GO:0030183 B cell differentiation
GO:0030198 extracellular matrix organization
GO:0030335 positive regulation of cell migration
GO:0031589 cell-substrate adhesion
GO:0032091 negative regulation of protein binding
GO:0034113 heterotypic cell-cell adhesion
GO:0034446 substrate adhesion-dependent cell spreading
GO:0035987 endodermal cell differentiation
GO:0040017 positive regulation of locomotion
GO:0042113 B cell activation
GO:0043062 extracellular structure organization
GO:0043113 receptor clustering
GO:0043393 regulation of protein binding
GO:0043496 regulation of protein homodimerization activity
GO:0045123 cellular extravasation
GO:0045785 positive regulation of cell adhesion
GO:0050900 leukocyte migration
GO:0050901 leukocyte tethering or rolling
GO:0050904 diapedesis
GO:0051098 regulation of binding
GO:0051100 negative regulation of binding
GO:0051272 positive regulation of cellular component movement
GO:0051640 organelle localization
GO:0051648 vesicle localization
GO:0051650 establishment of vesicle localization
GO:0051656 establishment of organelle localization
GO:0051668 localization within membrane
GO:0061756 leukocyte adhesion to vascular endothelial cell
GO:0072583 clathrin-dependent endocytosis
GO:0072657 protein localization to membrane
GO:0072676 lymphocyte migration
GO:0072678 T cell migration
GO:0090074 negative regulation of protein homodimerization activity
GO:0098657 import into cell
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1903236 regulation of leukocyte tethering or rolling
GO:1903238 positive regulation of leukocyte tethering or rolling
GO:1904994 regulation of leukocyte adhesion to vascular endothelial cell
GO:1904996 positive regulation of leukocyte adhesion to vascular endothelial cell
GO:1990771 clathrin-dependent extracellular exosome endocytosis
GO:2000147 positive regulation of cell motility
GO:2000401 regulation of lymphocyte migration
GO:2000403 positive regulation of lymphocyte migration
GO:2000404 regulation of T cell migration
GO:2000406 positive regulation of T cell migration
Molecular Function GO:0001968 fibronectin binding
GO:0003823 antigen binding
GO:0015026 coreceptor activity
GO:0019955 cytokine binding
GO:0019956 chemokine binding
GO:0019960 C-X3-C chemokine binding
GO:0050839 cell adhesion molecule binding
GO:1990405 protein antigen binding
Cellular Component GO:0005924 cell-substrate adherens junction
GO:0005925 focal adhesion
GO:0008305 integrin complex
GO:0030055 cell-substrate junction
GO:0034669 integrin alpha4-beta7 complex
GO:0043235 receptor complex
GO:0098636 protein complex involved in cell adhesion
GO:0098802 plasma membrane receptor complex
> KEGG and Reactome Pathway
 
KEGG hsa04151 PI3K-Akt signaling pathway
hsa04510 Focal adhesion
hsa04512 ECM-receptor interaction
hsa04514 Cell adhesion molecules (CAMs)
hsa04640 Hematopoietic cell lineage
hsa04670 Leukocyte transendothelial migration
hsa04672 Intestinal immune network for IgA production
hsa04810 Regulation of actin cytoskeleton
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-202733: Cell surface interactions at the vascular wall
R-HSA-1474244: Extracellular matrix organization
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-216083: Integrin cell surface interactions
Summary
SymbolITGA4
Nameintegrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
Aliases CD49d; 269C wild type; CD49 antigen-like family member D; VLA-4 subunit alpha; antigen CD49D, alpha-4 subuni ......
Chromosomal Location2q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between ITGA4 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between ITGA4 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25600437MelanomaPromote immunity (infiltration)Importantly, we found that the α4(S988A) mice exhibited a marked increase in T-cell entry into and reduced growth of B16 melanomas, consistent with antitumor roles of infiltrating T cells and progrowth functions of tumor-associated macrophages.
Summary
SymbolITGA4
Nameintegrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
Aliases CD49d; 269C wild type; CD49 antigen-like family member D; VLA-4 subunit alpha; antigen CD49D, alpha-4 subuni ......
Chromosomal Location2q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of ITGA4 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolITGA4
Nameintegrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
Aliases CD49d; 269C wild type; CD49 antigen-like family member D; VLA-4 subunit alpha; antigen CD49D, alpha-4 subuni ......
Chromosomal Location2q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of ITGA4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.6450.243
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.7440.515
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.5890.593
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.030.936
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.1280.936
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2330.912
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2990.563
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.4940.761
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.1920.908
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.2260.231
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.8450.227
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1410.328
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of ITGA4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.15.91.21
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1031033.3-23.30.423
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.49.6-2.21
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.410.2-2.81
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211714.329.4-15.10.426
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.516.7-4.21
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131115.436.4-210.357
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38277.93.74.20.636
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161412.57.15.41
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolITGA4
Nameintegrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
Aliases CD49d; 269C wild type; CD49 antigen-like family member D; VLA-4 subunit alpha; antigen CD49D, alpha-4 subuni ......
Chromosomal Location2q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ITGA4. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolITGA4
Nameintegrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
Aliases CD49d; 269C wild type; CD49 antigen-like family member D; VLA-4 subunit alpha; antigen CD49D, alpha-4 subuni ......
Chromosomal Location2q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ITGA4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ITGA4.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolITGA4
Nameintegrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
Aliases CD49d; 269C wild type; CD49 antigen-like family member D; VLA-4 subunit alpha; antigen CD49D, alpha-4 subuni ......
Chromosomal Location2q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ITGA4. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolITGA4
Nameintegrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
Aliases CD49d; 269C wild type; CD49 antigen-like family member D; VLA-4 subunit alpha; antigen CD49D, alpha-4 subuni ......
Chromosomal Location2q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of ITGA4 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolITGA4
Nameintegrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
Aliases CD49d; 269C wild type; CD49 antigen-like family member D; VLA-4 subunit alpha; antigen CD49D, alpha-4 subuni ......
Chromosomal Location2q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between ITGA4 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolITGA4
Nameintegrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
Aliases CD49d; 269C wild type; CD49 antigen-like family member D; VLA-4 subunit alpha; antigen CD49D, alpha-4 subuni ......
Chromosomal Location2q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting ITGA4 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting ITGA4.
ID Name Drug Type Targets #Targets
DB00108NatalizumabBiotechC1QA, C1QB, C1QC, C1R, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCG ......12
DB04997ATL1102Small MoleculeITGA41
DB05092CDP323Small MoleculeITGA41
DB05122R1295Small MoleculeITGA4, ITGB4, ITGB73
DB05468R411Small MoleculeITGA41
DB06822TinzaparinSmall MoleculeCXCL12, ITGA4, SERPINC13
DB09033VedolizumabBiotechITGA4, ITGB72