ACKR4 (Atypical Chemokine Receptor 4)
Atypical chemokine receptor involved in immune regulation and chemokine scavenging
Gene Information Card
| Symbol | ACKR4 |
|---|---|
| Full Name | Atypical Chemokine Receptor 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q22.1 |
| NCBI Gene ID | 51554 ncbi.nlm.nih.gov/gene/51554 |
| Ensembl ID | ENSG00000144589 |
| UniProt ID | Q9NPB9 |
| OMIM ID | 605310 |
| HGNC ID | 1611 |
| Aliases | CCRL1, CC-CKR-11, CCR11, CCX CKR, CCX-CKR, PPR1 |
Description
ACKR4 (Atypical Chemokine Receptor 4) is a member of the atypical chemokine receptor family. It binds several chemokines (e.g., CCL19, CCL21, CCL25) but does not couple to G proteins to initiate classical signaling. Instead, ACKR4 acts as a scavenger receptor, internalizing and degrading chemokines to regulate chemokine gradients and immune cell migration. It is expressed in various tissues, including skin, lymph nodes, and placenta, and plays a role in immune surveillance, inflammation, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | ACKR4 expression is reduced in breast cancer, potentially promoting tumor growth by altering chemokine gradients. | PMID: 23455478 |
| Colorectal Cancer | Loss of ACKR4 correlates with poor prognosis and increased metastasis. | PMID: 25670082 |
| Inflammatory Diseases | ACKR4 deficiency leads to altered chemokine levels and enhanced inflammation in mouse models. | PMID: 20037586 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Lymph Node | 8.3 | Medium |
| Placenta | 6.7 | Low |
| Spleen | 5.1 | Low |
| Lung | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | Overexpressed in recombinant studies |
| MCF-7 | 2.1 | Breast cancer cell line |
| HCT 116 | 1.8 | Colorectal cancer cell line |
| Jurkat | 0.5 | T-cell line, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.200C>T (p.Pro67Leu) | Missense | <0.1% | Unknown functional impact |
| c.457G>A (p.Val153Ile) | Missense | <0.1% | Reported in COSMIC; no known disease association |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in ACKR4.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations described.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • chemokine binding |
| • chemokine receptor activity | • receptor internalization |
| • negative regulation of chemokine-mediated signaling pathway | • cell chemotaxis |
Pathways
• Chemokine signaling pathway
• Immune system
• Class A/1 (Rhodopsin-like receptors)
Protein Summary
ACKR4 is a 7-transmembrane domain receptor that binds CC-chemokines (CCL19, CCL21, CCL25) with high affinity. Unlike conventional chemokine receptors, it lacks the DRY motif required for G protein coupling, making it signaling-incompetent. It constitutively internalizes chemokines via β-arrestin-dependent pathways, targeting them for degradation. This scavenging activity shapes chemokine gradients, influencing dendritic cell migration and T-cell positioning. ACKR4 is also implicated in tumor microenvironment modulation, where its loss may facilitate immune evasion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ACKR4 Knockout HEK293 Cell Line | EDJ-KQ51326 | Human | 51554 | Details Get a Quote |
| ACKR4 Knockout HeLa Cell Line | EDJ-KQ56326 | Human | 51554 | Details Get a Quote |
| ACKR4 Knockout A-549 Cell Line | EDJ-KQ64814 | Human | 51554 | Details Get a Quote |
| ACKR4 Knockout HCT 116 Cell Line | EDJ-KQ73258 | Human | 51554 | Details Get a Quote |
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