UniProt Summary: Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES and SCYA7/MCP-3. Upon active ligand stimulation, activates a beta-arrestin 1 (ARRB1)-dependent, G protein- independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1- LIMK1 signaling pathway. Activation of this pathway results in up- regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. By scavenging chemokines in tissues, on the surfaces of lymphatic vessels, and in placenta, plays an essential role in the resolution (termination) of the inflammatory response and in the regulation of adaptive immune responses. Plays a major role in the immune silencing of macrophages during the resolution of inflammation. Acts as a regulator of inflammatory leukocyte interactions with lymphatic endothelial cells (LECs) and is required for immature/mature dendritic cells discrimination by LECs. {ECO:0000269|PubMed:23479571, ECO:0000269|PubMed:23633677}.
Pfam DomainsGO Terms
Pfam Domains
7tm 1
GO Terms
chemokine receptor activity
C-C chemokine receptor activity
C-C chemokine binding
chemokine binding
scavenger receptor activity
chemokine-mediated signaling pathway
actin filament
response to chemokine
cellular response to chemokine
recycling endosome
calcium-mediated signaling
cell chemotaxis
nuclear membrane
early endosome
positive regulation of cytosolic calcium ion concentration
regulation of cytosolic calcium ion concentration
second-messenger-mediated signaling
external side of plasma membrane
cellular calcium ion homeostasis
calcium ion homeostasis
cellular divalent inorganic cation homeostasis
divalent inorganic cation homeostasis
inflammatory response
chemotaxis
taxis
endocytosis
cellular metal ion homeostasis
metal ion homeostasis
cellular cation homeostasis
cellular ion homeostasis
cytokine-mediated signaling pathway
import into cell
intracellular membrane-bounded organelle
cation homeostasis
inorganic ion homeostasis
cellular chemical homeostasis
ion homeostasis
cellular homeostasis
cell migration
cellular response to cytokine stimulus
cell motility
localization of cell
response to cytokine
chemical homeostasis
locomotion
G protein-coupled receptor signaling pathway
defense response
integral component of plasma membrane
movement of cell or subcellular component
homeostatic process
intracellular signal transduction
immune response
vesicle-mediated transport
CRISPR Data
Compound HitMost Correlated Genes in ChemogenomicsTissues where Essential in the Avana Dataset (DepMap 20Q1)