CCL3 (C-C Motif Chemokine Ligand 3) Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the CCL3 gene, its protein product, associated diseases, expression patterns, and mutations, based on authoritative genomic databases.
Gene Information Card
| Symbol | CCL3 |
|---|---|
| Full Name | C-C Motif Chemokine Ligand 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q12 (GRCh38: 17:36,088,256-36,090,143) |
| NCBI Gene ID | 6348 ncbi.nlm.nih.gov/gene/6348 |
| Ensembl ID | ENSG00000277632 |
| UniProt ID | P10147 |
| OMIM ID | 182283 |
| HGNC ID | 10627 |
| Aliases | MIP-1-alpha, MIP1A, SCYA3, G0S19-1, LD78ALPHA |
Description
CCL3 (C-C Motif Chemokine Ligand 3) encodes a secreted chemokine, also known as Macrophage Inflammatory Protein 1-alpha (MIP-1α). This protein is a member of the CC chemokine family and functions as a chemoattractant for monocytes, macrophages, T cells, and natural killer cells. It plays a critical role in inflammatory responses, immune cell recruitment, and hematopoiesis. CCL3 binds to chemokine receptors CCR1, CCR4, and CCR5, and is involved in various physiological and pathological processes, including infection, inflammation, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| HIV-1 Infection | CCL3 acts as a ligand for CCR5, a co-receptor for HIV-1 entry. High levels of CCL3 can compete with the virus for receptor binding, potentially inhibiting viral entry and slowing disease progression. | ClinVar: association with HIV-1 susceptibility; PMID: 10623786 |
| Inflammatory Diseases (e.g., Rheumatoid Arthritis) | CCL3 promotes recruitment of inflammatory cells to synovial tissue, contributing to chronic inflammation and joint destruction. | OMIM: 182283; PMID: 10780963 |
| Multiple Sclerosis | CCL3 is upregulated in active lesions and cerebrospinal fluid, attracting T cells and macrophages that mediate demyelination. | PMID: 10623786; OMIM: 182283 |
| Cancer (e.g., Breast, Lung) | CCL3 in the tumor microenvironment recruits immunosuppressive cells (e.g., Tregs, M2 macrophages), promoting tumor progression and metastasis. | COSMIC: CCL3 expression altered in various cancers; PMID: 24658396 |
| Hematopoietic Disorders | CCL3 inhibits proliferation of hematopoietic stem cells, potentially contributing to bone marrow suppression in certain conditions. | UniProt: P10147; PMID: 7688265 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 0.4 | Low |
| Lung | 0.3 | Low |
| Spleen | 0.2 | Low |
| Liver | 0.1 | Low |
| Blood | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | 0.2 | Low baseline; inducible by LPS |
| HeLa (cervical carcinoma) | 0.1 | Low baseline |
| A549 (lung carcinoma) | 0.1 | Low baseline; inducible by cytokines |
| MCF7 (breast carcinoma) | 0.1 | Low baseline |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1719134 (promoter variant) | SNP | Allele frequency: ~0.3 (global) | May affect CCL3 expression levels; associated with altered inflammatory response. |
| rs1063349 (3' UTR variant) | SNP | Allele frequency: ~0.2 (global) | Potential impact on mRNA stability; linked to HIV-1 susceptibility. |
| c.64C>T (p.Arg22Trp) | Missense | Rare (not in gnomAD) | May alter receptor binding affinity; functional impact not fully characterized. |
Mutation functional classification
Loss of Function (LOF)
No clear loss-of-function mutations have been reported for CCL3. Given its role in immune response, complete loss might be compensated by other chemokines.
Gain of Function (GOF)
Overexpression of CCL3 is observed in inflammatory diseases and tumors, leading to enhanced immune cell recruitment and inflammation. No gain-of-function mutations are documented.
Dominant Negative (DN)
No dominant-negative mutations have been described for CCL3.
View complete mutation data：
Gene Ontology (GO)
| • chemokine activity | • CCR1 chemokine receptor binding |
| • CCR5 chemokine receptor binding | • cytokine activity |
| • extracellular space | • immune response |
| • cell chemotaxis | • inflammatory response |
| • positive regulation of T cell migration | • signal transduction |
Pathways
• Cytokine-cytokine receptor interaction (KEGG hsa04060)
• Chemokine signaling pathway (KEGG hsa04062)
• Toll-like receptor signaling pathway (KEGG hsa04620)
• TNF signaling pathway (KEGG hsa04668)
• Hematopoietic cell lineage (KEGG hsa04640)
Protein Summary
The CCL3 protein (UniProt P10147) is a 92-amino-acid precursor with a 19-amino-acid signal peptide, yielding a mature secreted protein of 69 amino acids. It forms homodimers and higher-order oligomers. CCL3 binds to G-protein-coupled receptors CCR1, CCR4, and CCR5, activating downstream signaling pathways such as PI3K/AKT and MAPK. It is a potent chemoattractant for monocytes, T cells, and eosinophils, and also modulates hematopoiesis by inhibiting stem cell proliferation. Post-translational modifications include proteolytic processing and glycosylation, which can affect its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CCL3L3 Knockout HEK293 Cell Line | EDJ-KQ12815 | Human | 414062 | Details Get a Quote |
| CCL3 Knockout HEK293 Cell Line | EDJ-KQ50613 | Human | 6348 | Details Get a Quote |
| CCL3 Knockout HeLa Cell Line | EDJ-KQ54413 | Human | 6348 | Details Get a Quote |
| CCL3L3 Knockout HeLa Cell Line | EDJ-KQ60356 | Human | 414062 | Details Get a Quote |
| CCL3 Knockout A-549 Cell Line | EDJ-KQ62902 | Human | 6348 | Details Get a Quote |
| CCL3L3 Knockout A-549 Cell Line | EDJ-KQ68824 | Human | 414062 | Details Get a Quote |
| CCL3 Knockout HCT 116 Cell Line | EDJ-KQ71370 | Human | 6348 | Details Get a Quote |
| CCL3L3 Knockout HCT 116 Cell Line | EDJ-KQ77188 | Human | 414062 | Details Get a Quote |
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