Atypical chemokine receptor 1 (ACKR1)

The protein contains 336 amino acids for an estimated molecular weight of 35553 Da.

 

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. (updated: Jan. 7, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  5. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 15%
Model score: 0
No model available.

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VariantDescription
Antigen Fy(b)
Antigen Fy(x)
dbSNP:rs13962
dbSNP:rs3027020
dbSNP:rs17851570

No binding partner found

The reference OMIM entry for this protein is 110700

Blood group, duffy system; fy
Duffy blood group system plasmodium vivax, resistance to, included

A number sign (#) is used with this entry because the Duffy blood group system is based on variation in the DARC gene (613665). Complete resistance to infection by the malarial parasite Plasmodium vivax (see 611162) is associated with the Duffy phenotype Fy(a-b-), which results from a polymorphism in the DARC promoter (613665.0002).

DESCRIPTION

The Duffy blood group system, which consists of 4 alleles, 5 phenotypes, and 5 antigens, is important in clinical medicine because of transfusion incompatibilities and hemolytic disease of the newborn. Duffy antigens are located on DARC (613665), an acidic glycoprotein found on erythrocytes and other cells throughout the body. The 2 principal antigens, Fy(a) and Fy(b), are produced by the FYA and FYB codominant alleles (see 613665.0001). Four phenotypes are defined by the corresponding antibodies, anti-Fy(a) and anti-Fy(b): Fy(a+b-), Fy(a-b+), Fy(a+b+), and Fy(a-b-). Fy(a-b-), or Duffy null, is the major phenotype in African and American blacks and is characterized by the presence of Fy(b) on nonerythroid cells, but an absence of Fy(b) on erythrocytes. The Fy(a-b-) phenotype is associated with complete resistance to infection by the malarial parasite Plasmodium vivax (see 611162). Individuals with the Fy(a-b-) phenotype have the FYB-erythroid silent (FYB-ES) allele with a mutation in the DARC promoter (613665.0002). A fifth phenotype, Fy(bwk), or Fy(x), is characterized by weak Fy(b) expression on erythrocytes due to a reduced amount of protein. Individuals with the Fy(bwk) phenotype have the FYB-weak (FYB-WK) allele, also called the FYX allele, with a missense mutation in DARC (613665.0003). Other Duffy antigens include Fy3, Fy4, Fy5, and Fy6 (reviews by Pogo and Chaudhuri (2000), Langhi and Bordin (2006), and Meny (2010)).

CLINICAL FEATURES

An association between sickle cell trait (603903) and Duffy-null blood group was demonstrated in Saudi Arabs (Gelpi and King, 1976). Neither linkage nor association of the usual type was the basis, but rather a protection against malaria provided by both traits.

BIOCHEMICAL FEATURES

Nichols et al. (1987) reported a new Duffy specificity, Fy6, defined by a murine monoclonal antibody. Fy6 is related to susceptibility to invasion of red cells by P. vivax.

DIAGNOSIS

Maternal allo-immunization to antigens of the Duffy blood group system can result in hemolytic disease of the newborn (HDN). Hessner et al. (1999) evaluated the use of allele-specific PCR for prenatal genotyping of the Duffy antigen system to identify pregnancies at risk for HDN. Oligonucleotide primers were designed for FYA, FYB, and null-FY alleles. The authors found a perfect match between results of serotyping and detection by molecular methods. They suggested that this assay is particularly useful for rapid genotyping of fetal amniotic cells to identify pregnancies at risk for HDN due to maternal-fetal incompatibilities within the Duffy blood group system.

MAPPING

The Duffy system enjoys the distinction of being the first blood group whose genetic locus was assigned to a specific autosome, i.e., chromosome 1 (Donahue et al., 1968). Duffy and the locus for a form of hereditary cataract (116200) are closely linked. From extensive family studies, Robson et al. (1973) arrived at a tentative map of chromosome 1. Palmer et al. (1977) studied a parent with transposition of segment 1q31-1q32 from the long arm to the short arm of chromosome 1 and a c ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for ACKR1

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 110700 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed

Sept. 16, 2015: Protein entry updated
Automatic update: model status changed