ACKR1_HUMAN

Source: hRBCD ; ID: IPI00002940
PM19886704
PM23856902
BGMUT ; ID: duffy
BSc_CH
Marked as 'Integral membrane protein'
Confidence: high (a blood group or CD marker) Search PubMed for
(RBC AND this entry)
Gene names: DARC , ACKR1, FY, GPD
Protein names and data: ACKR1_HUMAN , Duffy antigen/chemokine receptor , Atypical chemokine receptor 1; Fy glycoprotein; GpFy; Glycoprotein D; Plasmodium vivax receptor; CD234 Lenght: 336 a.a.
Mass: 35553 Da
fasta formatted sequence
Function: 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. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1, TARC and also for the malaria parasites P.vivax and P.knowlesi. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels.
Cellular location: Early endosome. Recycling endosome. Membrane; Multi-pass membrane protein. Note=Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via caveolae. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane.
Tissue specificity: Found in adult kidney, adult spleen, bone marrow and fetal liver. In particular, it is expressed along postcapillary venules throughout the body, except in the adult liver. Erythroid cells and postcapillary venule endothelium are the principle tissues expressing duffy. Fy(-A-B) individuals do not express duffy in the bone marrow, however they do, in postcapillary venule endothelium.

Genetic variants

DARC is responsible for the Duffy blood group system (FY) [MIM:110700]. The molecular basis of the Fy(A)=Fy1/Fy(B)=Fy2 blood group antigens is a single variation in position 42; Gly-42 corresponds to Fy(A) and Asp-42 to Fy(B). Individuals that do not produce the Duffy antigen (FY(A-B-)) are more resistant to infection by the malarial parasite Plasmodium vivax. This allele is found predominantly in population of African origin [MIM:611162]. Genetic variations in DARC define the white blood cell count quantitative trait locus 1 (WBCQ1) [MIM:611862]. Peripheral white blood cell count (WBC) is a common clinical measurement, used to determine evidence of acute infammation or infection. Peripheral WBC is the sum of several cell types including neutrophils and lymphocytes, which are the most common types of WBC, as well as less common cell types such as eosinophils, basophils, and monocytes. Elevated WBC has been associated with risk of coronary heart disease, cancer, and all- cause mortality. White blood cell levels have widespread clinical applications including assessment of patients undergoing chemotherapy and evaluation of infection.

Database cross-references

UniProt: Q16570
Ensembl: ENST00000368121
Ensembl: ENST00000368122
Ensembl: ENST00000537147
MIM: 110700
MIM: 611162
MIM: 611862
MIM: 613665
neXtProt: NX_Q16570
Antibodypedia: Q16570 (may not find the protein thus also not any antibody)
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