ACKR4
ACKR4 (atypical chemokine receptor 4, also known as CCR11, CCBP2, VSHK1, CCX-CKR, PPR1 and CCRL1) is a G protein-coupled receptor family member that binds C-C chemokines with high affinity. Rather than triggering classic signalling, it controls chemokine levels and localisation by sequestering, degrading or transcytosing its ligands. Browse Assay Genie's current range of ACKR4 research reagents below, or read on for the biology behind the target.
ACKR4 is an atypical chemokine receptor that regulates chemokine levels and localisation through high-affinity binding that is uncoupled from ligand-driven signal transduction. Ligand binding does not activate G protein-mediated signalling. Instead it induces beta-arrestin recruitment, which leads to internalisation of the chemokine. The outcome is chemokine sequestration, degradation or transcytosis, which is why the receptor is also described as an interceptor (internalising receptor), a chemokine-scavenging receptor or a chemokine decoy receptor.
The receptor binds the chemokines CCL2, CCL8, CCL13, CCL19, CCL21 and CCL25. By internalising CCL19, CCL21 and CCL25, ACKR4 reduces their availability and so helps control the migration of immune and cancer cells that express the chemokine receptors CCR7 and CCR9. It also negatively regulates CXCR3-induced chemotaxis and plays a role in T-cell development in the thymus. The ACKR4 protein localises to early endosomes, recycling endosomes and the cell membrane.
The ACKR4 gene encodes a member of the G protein-coupled receptor 1 family, placed in the atypical chemokine receptor subfamily and the HGNC gene group of the same name. Its previous HGNC name was chemokine (C-C motif) receptor-like 1, reflected in the alias CCRL1. RefSeq notes that alternatively spliced transcript variants encode the same protein, and that a pseudogene of the gene lies on chromosome 6. Mouse Ackr4 is the corresponding ortholog. Related family members include ACKR1 and ACKR3.
ACKR4 shapes chemokine gradients by binding and internalising ligands such as CCL19, CCL21 and CCL25 without activating G protein signalling.
It limits chemokine availability for CCR7- and CCR9-expressing cells and negatively regulates CXCR3-induced chemotaxis, making it relevant to leukocyte trafficking.
ACKR4 regulates T-cell development in the thymus, linking chemokine scavenging to lymphocyte maturation.
By reducing ligand availability, ACKR4 helps control the migration of cancer cells that express chemokine receptors such as CCR7 and CCR9.
ACKR4 is a chemokine-scavenging receptor. It binds chemokines including CCL19, CCL21 and CCL25 with high affinity but does not signal through G proteins. Ligand binding recruits beta-arrestin and drives internalisation, which removes chemokines and shapes the migration of CCR7- and CCR9-expressing cells.
The gene was first named chemokine (C-C motif) receptor-like 1, giving CCRL1. Other names include CCR11, CCBP2, VSHK1, CCX-CKR and PPR1. The current HGNC symbol ACKR4 reflects its place among the atypical chemokine receptors, which do not signal in the classic way.
Yes, the mouse ortholog is Ackr4. Human ACKR4 belongs to the G protein-coupled receptor 1 family, atypical chemokine receptor subfamily. Check the datasheet of any product for its validated reactivity.
Other atypical chemokine receptors with research products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9NPB9; product specifications from Assay Genie datasheets.