ITGA5 (Integrin Subunit Alpha 5): A Key Mediator of Cell Adhesion, Migration, and Cancer Progression
Comprehensive gene resource for ITGA5, covering genomic context, protein function, expression profiles, disease associations, and mutation landscape.
Gene Information Card
| Symbol | ITGA5 |
|---|---|
| Full Name | Integrin Subunit Alpha 5 |
| Gene Type | protein coding |
| Chromosomal Location | 12q13.13 |
| NCBI Gene ID | 3678 ncbi.nlm.nih.gov/gene/3678 |
| Ensembl ID | ENSG00000161638 |
| UniProt ID | P08648 |
| OMIM ID | 135620 |
| HGNC ID | 6141 |
| Aliases | CD49e, FNRA, VLA-5, VLA5A |
Description
ITGA5 encodes the alpha 5 subunit of the integrin receptor family. This protein non-covalently associates with the beta 1 subunit (ITGB1) to form the integrin alpha-5/beta-1 (VLA-5) heterodimer, a primary receptor for fibronectin and other extracellular matrix (ECM) proteins. VLA-5 mediates cell adhesion, migration, proliferation, and survival by linking the ECM to the intracellular cytoskeleton and activating intracellular signaling pathways. ITGA5 is crucial for embryonic development, angiogenesis, and tissue remodeling, and its dysregulation is implicated in cancer progression, fibrosis, and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Overexpression of ITGA5 enhances cell adhesion, migration, invasion, and survival, promoting tumor growth and metastasis. It also contributes to angiogenesis and drug resistance. | High expression is associated with poor prognosis in multiple cancers, including breast, lung, colon, and gastric cancers. Functional studies show that ITGA5 knockdown reduces tumorigenicity and metastasis in xenograft models. (Source: COSMIC, PubMed literature) |
| Idiopathic Pulmonary Fibrosis (IPF) | ITGA5 expression is upregulated in fibrotic lung tissue. It promotes fibroblast adhesion, migration, and differentiation into myofibroblasts, contributing to excessive ECM deposition and tissue scarring. | Single-cell RNA sequencing and immunohistochemistry show increased ITGA5 in myofibroblasts from IPF patients. In vitro and in vivo studies demonstrate that ITGA5 inhibition attenuates fibrosis. (Source: PubMed literature) |
| Rheumatoid Arthritis (RA) | ITGA5 is expressed on synovial fibroblasts and inflammatory cells. It facilitates leukocyte infiltration into the joint and promotes synovial hyperplasia and angiogenesis, contributing to joint destruction. | Elevated ITGA5 expression is found in the synovium of RA patients. Blocking antibodies against ITGA5 reduce inflammation and joint damage in animal models of arthritis. (Source: PubMed literature) |
| Atherosclerosis | ITGA5 on endothelial cells and macrophages mediates adhesion to fibronectin and promotes inflammatory cell recruitment, foam cell formation, and plaque progression. | ITGA5 expression is increased in atherosclerotic plaques. Studies in mouse models show that ITGA5 deletion in macrophages reduces atherosclerotic lesion size. (Source: PubMed literature) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 20.1 | High |
| Liver | 15.3 | Medium |
| Kidney | 12.8 | Medium |
| Spleen | 11.5 | Medium |
| Bone Marrow | 10.2 | Medium |
| Adipose Tissue | 8.9 | Low |
| Heart | 7.4 | Low |
| Brain | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung Carcinoma) | 25.4 | High expression; associated with invasive phenotype. |
| HepG2 (Hepatocellular Carcinoma) | 18.7 | Moderate-high expression; involved in cell adhesion and migration. |
| MCF7 (Breast Adenocarcinoma) | 12.3 | Moderate expression; expression increases with metastatic potential. |
| HUVEC (Endothelial) | 30.2 | Very high expression; critical for angiogenesis and cell survival. |
| K562 (Chronic Myelogenous Leukemia) | 5.6 | Low expression; can be induced upon differentiation. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1540G>A (p.Asp514Asn) | Missense | Rare (<0.01%) | Located in the extracellular domain; predicted to affect ligand binding affinity. |
| c.1973C>T (p.Thr658Met) | Missense | Rare (<0.01%) | Located in the extracellular domain; potential impact on protein stability. |
| c.2230G>A (p.Val744Ile) | Missense | Rare (<0.01%) | Located in the cytoplasmic tail; may affect intracellular signaling. |
| c.2452C>T (p.Arg818Cys) | Missense | Rare (<0.01%) | Located in the cytoplasmic tail; potential effect on integrin activation. |
Mutation functional classification
Loss of Function (LOF)
Complete loss-of-function mutations in ITGA5 are lethal in mice, indicating its essential role in development. In humans, no homozygous loss-of-function variants have been reported in healthy populations, suggesting strong selective pressure against such mutations. Partial loss-of-function variants, if they occur, would likely impair cell adhesion and migration.
Gain of Function (GOF)
Gain-of-function mutations or, more commonly, gene amplification and overexpression, are observed in cancer. These changes enhance integrin signaling, promoting cell survival, proliferation, and metastasis. Specific activating point mutations have not been well-characterized.
Dominant Negative (DN)
Dominant-negative effects are theoretically possible if a mutant ITGA5 subunit can dimerize with ITGB1 but fails to bind ligand or signal properly, thereby interfering with the function of the wild-type receptor. However, no such naturally occurring dominant-negative mutations have been definitively documented for ITGA5.
View complete mutation data：
Gene Ontology (GO)
| • integrin-mediated signaling pathway | • cell adhesion |
| • cell-matrix adhesion | • cell migration |
| • angiogenesis | • extracellular matrix organization |
| • positive regulation of cell proliferation | • positive regulation of cell migration |
| • receptor-mediated endocytosis | • signal transduction |
| • integrin complex | • plasma membrane |
| • external side of plasma membrane | • focal adhesion |
| • fibronectin binding | • protein binding |
| • metal ion binding |
Pathways
• Integrin Signaling Pathway
• ECM-receptor interaction
• Focal Adhesion
• PI3K-Akt signaling pathway
• Rap1 signaling pathway
• Regulation of actin cytoskeleton
• Pathways in cancer
Protein Summary
The ITGA5 protein is a 1,049 amino acid type I transmembrane glycoprotein. It is synthesized as a precursor that is cleaved into a heavy chain and a light chain, which remain linked by disulfide bonds. The extracellular domain contains seven homologous repeats that bind divalent cations (e.g., Ca2+, Mg2+) essential for ligand binding. ITGA5 pairs exclusively with ITGB1 to form the VLA-5 receptor. The primary ligand is fibronectin, but it also binds to other ECM proteins like osteopontin and fibrillin. Upon ligand binding, VLA-5 clusters and recruits intracellular proteins like talin and paxillin to form focal adhesions, activating downstream kinases such as FAK and Src. This signaling cascade regulates cell survival, proliferation, and cytoskeletal reorganization, driving cell migration and invasion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| Itga5 Knockout MOC2 Cell Line | EDJ-KQ59 | Mouse | 16402 | Details Get a Quote |
| Itga5 Knockout MC-38 Cell Line | EDJ-KQ92 | Mouse | 16402 | Details Get a Quote |
| ITGA5 Knockout HEK293 Cell Line | EDJ-KQ17703 | Human | 3678 | Details Get a Quote |
| ITGA5 Knockout A-549 Cell Line | EDJ-KQ18165 | Human | 3678 | Details Get a Quote |
| ITGA5 Knockout HCT 116 Cell Line | EDJ-KQ18289 | Human | 3678 | Details Get a Quote |
| ITGA5 Knockout HeLa Cell Line | EDJ-KQ19557 | Human | 3678 | Details Get a Quote |
| ITGA5 Knockout MDA-MB-231 Cell Line | EDJ-KQ78085 | Human | 3678 | Details Get a Quote |
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