Tclin ITGA4 Integrin alpha-4

Protein Summary

Description

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). 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]

Uniprot Accession IDs

• P13612
• D3DPG4
• Q7Z4L6

Gene Name

• ITGA4

Ensembl ID

• ENST00000339307
• ENSP00000340149
• ENSG00000115232
• ENST00000397033
• ENSP00000380227

Symbol

• CD49D
• IA4
• CD49D

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
gene perturbation	0.94
interacting protein	0.92
cellular component	0.79
biological term	0.77
transcription factor perturbation	0.74

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 419.14   (req: < 5)

Gene RIFs: 187   (req: <= 3)

Antibodies: 1835   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 419.14   (req: >= 5)

Gene RIFs: 187   (req: > 3)

Antibodies: 1835   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 28

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 128

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (2)

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1 – 2 of 2

natalizumab

ITGA4Tclin

ANTIBODY BINDING :

vedolizumab

ITGA4Tclin

ANTIBODY BINDING pIC50 : 8.3

Active Ligands (128)

Explore Active Ligands

1 – 10 of 128

CHEMBL296804

ITGA4Tclin

pIC50 : 10.15

CHEMBL502641

ITGA4Tclin

pIC50 : 10.1

CHEMBL601470

ITGA4Tclin

pIC50 : 10.1

CHEMBL601683

ITGA4Tclin

pIC50 : 10.1

CHEMBL448863

ITGA4Tclin

pIC50 : 10.05

CHEMBL507665

ITGA4Tclin

pIC50 : 10.05

CHEMBL275603

ITGA4Tclin

pIC50 : 10

CHEMBL445303

ITGA4Tclin

pIC50 : 10

CHEMBL505992

ITGA4Tclin

pIC50 : 10

CHEMBL506449

ITGA4Tclin

pIC50 : 9.96

Protein-Protein Interactions (260)

Explore Interacting Targets

1 – 10 of 260

• See Interactions on String-DB

LGALS8

Tchem

Novelty:  0.00623836

p_int:  0.999347776

p_ni:  0.000652224

Score:  0.406

Data Source:  BioPlex,STRINGDB

CST9

Tbio

Novelty:  0.08129086

p_int:  0.998446921

p_ni:  0.001553079

Score:  0.237

Data Source:  BioPlex,STRINGDB

BTNL8

Tdark

Novelty:  0.40339869

p_int:  0.99581156

p_ni:  0.004187797

p_wrong:  6.43e-7

Data Source:  BioPlex

LGALS9

Tchem

Novelty:  0.00381766

p_int:  0.995172481

p_ni:  0.004827519

Score:  0.226

Data Source:  BioPlex,STRINGDB

PTCH1

Tbio

Novelty:  0.00077635

p_int:  0.99456638

p_ni:  0.005215166

p_wrong:  0.000218454

Data Source:  BioPlex

PON2

Tbio

Family:  Enzyme

Novelty:  0.00414855

p_int:  0.983720088

p_ni:  0.016279912

Data Source:  BioPlex

HYOU1

Tbio

Novelty:  0.00833649

p_int:  0.979569996

p_ni:  0.020425941

p_wrong:  0.000004064

Data Source:  BioPlex

FAM19A2

Tbio

Novelty:  0.28999346

p_int:  0.974015755

p_ni:  0.023807286

p_wrong:  0.002176959

Data Source:  BioPlex

NAAA

Tchem

Family:  Enzyme

Novelty:  0.00368876

p_int:  0.969295775

p_ni:  0.030703748

p_wrong:  4.77e-7

Data Source:  BioPlex

PRSS2

Tchem

Family:  Enzyme

Novelty:  0.00959404

p_int:  0.957084011

p_ni:  0.042682596

p_wrong:  0.000233392

Score:  0.178

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (44)

Reactome (12)

KEGG (14)

PathwayCommons (10)

WikiPathways (8)

Adaptive Immune System (R-HSA-1280218)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Cell surface interactions at the vascular wall	211 targets	R-HSA-202733
Reactome	Extracellular matrix organization	297 targets	R-HSA-1474244
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Generic Transcription Pathway	1195 targets	R-HSA-212436

Name	Explore in Pharos	Explore in Source
Adaptive Immune System	894 targets	R-HSA-1280218
Cell surface interactions at the vascular wall	211 targets	R-HSA-202733
Extracellular matrix organization	297 targets	R-HSA-1474244
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (36)

Functions (5)

Components (8)

Processes (23)

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GO Term	Evidence	Assigned by
cell adhesion molecule binding	Inferred from Mutant Phenotype (IMP)	UniProtKB
coreceptor activity	Traceable Author Statement (TAS)	UniProtKB
fibronectin binding	Inferred from Electronic Annotation (IEA)	Ensembl
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
protein antigen binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (20)

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5

1 – 5 of 20

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
monocyte count	EFO_0005091	9	9	11		99.8
monocyte percentage of leukocytes	EFO_0007989	2	3	4		98.2
leukocyte count	EFO_0004308	5	4	5		95.8
myeloid white cell count	EFO_0007988	3	3	3		94.8
reticulocyte measurement	EFO_0010700	3	3	4		94.8

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
monocyte count	EFO_0005091	11		99.8
monocyte percentage of leukocytes	EFO_0007989	4		98.2
leukocyte count	EFO_0004308	5		95.8
myeloid white cell count	EFO_0007988	3		94.8
reticulocyte measurement	EFO_0010700	4		94.8

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Calcium
Cell adhesion
Complete proteome
Direct protein sequencing
Disulfide bond
Glycoprotein
Integrin
Membrane

GWAS Trait Find Similar Targets

No Header	No Header
basophil count
eosinophil count
granulocyte count
granulocyte percentage of myeloid white cells
inflammatory bowel disease
leukocyte count
lymphocyte count
lymphocyte percentage of leukocytes
mean corpuscular volume
mean reticulocyte volume

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
embryo phenotype
hematopoietic system phenotype
immune system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	integrin subunit alpha 4	VGNC:2704	470596
Macaque	integrin subunit alpha 4		704745
Mouse	integrin alpha 4	MGI:96603	16401
Rat	integrin subunit alpha 4	RGD:1593249	311144
Dog	integrin subunit alpha 4	VGNC:42126	488429

Species	Name	OMA	EggNOG	Inparanoid
Chimp	integrin subunit alpha 4
Macaque	integrin subunit alpha 4
Mouse	integrin alpha 4
Rat	integrin subunit alpha 4
Dog	integrin subunit alpha 4

Publication Statistics

PubMed Score 419.14

PubMed score by year

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PubTator Score 248.43

PubTator score by year

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Related Publications

Text Mined References (230)

GeneRif Annotations (187)

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PMID	Year	Title