CCL5 (C-C Motif Chemokine Ligand 5): Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the CCL5 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | CCL5 |
|---|---|
| Full Name | C-C Motif Chemokine Ligand 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q12 |
| NCBI Gene ID | 6352 ncbi.nlm.nih.gov/gene/6352 |
| Ensembl ID | ENSG00000271503 |
| UniProt ID | P13501 |
| OMIM ID | 187011 |
| HGNC ID | 10632 |
| Aliases | RANTES, SCYA5, SIS-delta, TCP228, D17S136E |
Description
CCL5 (C-C Motif Chemokine Ligand 5), also known as RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted), is a chemokine gene located on chromosome 17q12. It encodes a small secreted protein that functions as a chemoattractant for immune cells, including T cells, eosinophils, and basophils. CCL5 plays a critical role in inflammatory and immune responses, and is involved in various diseases including HIV infection, cancer, and inflammatory disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| HIV infection | CCL5 acts as a ligand for the CCR5 receptor, which is a co-receptor for HIV entry. CCL5 can block HIV entry by competing with the virus for CCR5 binding. | Multiple studies, including those in NCBI and OMIM, demonstrate that CCL5 inhibits HIV-1 infection in vitro. |
| Inflammatory diseases (e.g., rheumatoid arthritis, atherosclerosis) | CCL5 promotes leukocyte recruitment to inflamed tissues, contributing to chronic inflammation. | Elevated CCL5 levels found in synovial fluid and atherosclerotic plaques; evidence from OMIM and literature. |
| Cancer (e.g., breast, ovarian, prostate) | CCL5 can promote tumor growth, angiogenesis, and metastasis by recruiting immune cells that create a tumor-supportive microenvironment. | Studies in COSMIC and literature show altered CCL5 expression in various cancers; mechanistic evidence from cell and animal models. |
| Allergic asthma | CCL5 attracts eosinophils and Th2 cells to airways, exacerbating allergic inflammation. | Clinical and experimental evidence from NCBI and OMIM. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.3 | Medium |
| Spleen | 10.1 | Medium |
| Appendix | 8.5 | Low |
| Bone marrow | 7.2 | Low |
| Lung | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression; inducible by PMA |
| Jurkat (T cell) | 8.7 | Moderate; upregulated upon activation |
| HeLa (cervical) | 3.1 | Low basal expression |
| A549 (lung) | 2.4 | Low; inducible by cytokines |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2107538 (promoter) | SNP | ~20% allele frequency | May affect CCL5 expression levels; associated with altered disease susceptibility. |
| rs2280788 (intronic) | SNP | ~15% allele frequency | Potential regulatory effect; linked to inflammatory conditions. |
| c.64G>A (p.Gly22Ser) | Missense | Rare | Alters protein function; not well characterized. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CCL5 are rare and not well documented. Reduced CCL5 expression may impair immune cell recruitment, potentially leading to immunodeficiency or altered inflammatory responses.
Gain of Function (GOF)
Gain-of-function mutations are not commonly reported. Overexpression of CCL5 is often observed in cancer and inflammatory diseases, but this is typically due to transcriptional regulation rather than mutations.
Dominant Negative (DN)
No dominant-negative mutations have been described for CCL5.
View complete mutation data：
Gene Ontology (GO)
| • chemokine activity | • CCR5 chemokine receptor binding |
| • protein binding | • extracellular space |
| • immune response | • cell chemotaxis |
| • inflammatory response | • signal transduction |
Pathways
• Chemokine signaling pathway (KEGG hsa04062)
• Cytokine-cytokine receptor interaction (KEGG hsa04060)
• Toll-like receptor signaling pathway (KEGG hsa04620)
• T cell receptor signaling pathway (KEGG hsa04660)
Protein Summary
The CCL5 protein is a 91-amino-acid precursor that is processed to a mature 68-amino-acid secreted chemokine. It belongs to the CC chemokine family, characterized by two adjacent cysteines. CCL5 binds to several receptors, including CCR1, CCR3, and CCR5, and exerts its effects through G-protein-coupled receptor signaling. It is involved in leukocyte migration, inflammation, and immune regulation. Post-translational modifications include signal peptide cleavage and possible glycosylation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CCL5 Knockout HEK293 Cell Line | EDJ-KQ1123 | Human | 6352 | Details Get a Quote |
| CCL5 Knockout HeLa Cell Line | EDJ-KQ54415 | Human | 6352 | Details Get a Quote |
| CCL5 Knockout A-549 Cell Line | EDJ-KQ62904 | Human | 6352 | Details Get a Quote |
| CCL5 Knockout HCT 116 Cell Line | EDJ-KQ71372 | Human | 6352 | Details Get a Quote |
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