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Q16570 (ACKR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (9) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Duffy antigen/chemokine receptor
Alternative name(s):
Atypical chemokine receptor 1
Fy glycoprotein
Short name=GpFy
Glycoprotein D
Plasmodium vivax receptor
CD_antigen=CD234
Gene names
Name:DARC
Synonyms:ACKR1, FY, GPD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length336 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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.

Subcellular 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.

Polymorphism

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.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 2 (identifier: Q16570-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 1 (identifier: Q16570-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: MGNCLHR → MASSGYVLQ

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 336336Duffy antigen/chemokine receptor
PRO_0000152585

Regions

Topological domain1 – 6363Extracellular Potential
Transmembrane64 – 8421Helical; Name=1; Potential
Topological domain85 – 9511Cytoplasmic Potential
Transmembrane96 – 11621Helical; Name=2; Potential
Topological domain117 – 12913Extracellular Potential
Transmembrane130 – 15324Helical; Name=3; Potential
Topological domain154 – 16613Cytoplasmic Potential
Transmembrane167 – 18721Helical; Name=4; Potential
Topological domain188 – 20720Extracellular Potential
Transmembrane208 – 22821Helical; Name=5; Potential
Topological domain229 – 24416Cytoplasmic Potential
Transmembrane245 – 26521Helical; Name=6; Potential
Topological domain266 – 28722Extracellular Potential
Transmembrane288 – 30821Helical; Name=7; Potential
Topological domain309 – 33628Cytoplasmic Potential

Amino acid modifications

Glycosylation161N-linked (GlcNAc...) Ref.10
Glycosylation331N-linked (GlcNAc...) Potential
Disulfide bond51 ↔ 276 Ref.10
Disulfide bond129 ↔ 195 Ref.10

Natural variations

Alternative sequence1 – 77MGNCLHR → MASSGYVLQ in isoform 1.
VSP_001323
Natural variant421G → D Antigen Fy(b). Ref.1 Ref.2 Ref.4 Ref.5 Ref.16
Corresponds to variant rs12075 [ dbSNP | Ensembl ].
VAR_003480
Natural variant891R → C Antigen Fy(x). Ref.4 Ref.5 Ref.17
Corresponds to variant rs34599082 [ dbSNP | Ensembl ].
VAR_015068
Natural variant1001A → T. Ref.4 Ref.5
Corresponds to variant rs13962 [ dbSNP | Ensembl ].
VAR_015069
Natural variant2031L → Q.
Corresponds to variant rs3027020 [ dbSNP | Ensembl ].
VAR_044116
Natural variant3261S → F. Ref.6 Ref.8
Corresponds to variant rs17851570 [ dbSNP | Ensembl ].
VAR_044117

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified June 7, 2005. Version 3.
Checksum: C3F2A3E71D972E2D

FASTA33635,553
        10         20         30         40         50         60 
MGNCLHRAEL SPSTENSSQL DFEDVWNSSY GVNDSFPDGD YGANLEAAAP CHSCNLLDDS 

        70         80         90        100        110        120 
ALPFFILTSV LGILASSTVL FMLFRPLFRW QLCPGWPVLA QLAVGSALFS IVVPVLAPGL 

       130        140        150        160        170        180 
GSTRSSALCS LGYCVWYGSA FAQALLLGCH ASLGHRLGAG QVPGLTLGLT VGIWGVAALL 

       190        200        210        220        230        240 
TLPVTLASGA SGGLCTLIYS TELKALQATH TVACLAIFVL LPLGLFGAKG LKKALGMGPG 

       250        260        270        280        290        300 
PWMNILWAWF IFWWPHGVVL GLDFLVRSKL LLLSTCLAQQ ALDLLLNLAE ALAILHCVAT 

       310        320        330 
PLLLALFCHQ ATRTLLPSLP LPEGWSSHLD TLGSKS 

« Hide

Isoform 1 [UniParc].

Checksum: 5AC412B001F07F5B
Show »

FASTA33835,678

References

« Hide 'large scale' references
[1]"Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and the receptor for the Plasmodium vivax malaria parasite."
Chaudhuri A., Polyakova J., Zbrzezna V., Williams K., Gulati S., Pogo A.
Proc. Natl. Acad. Sci. U.S.A. 90:10793-10797(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANT ASP-42.
Tissue: Bone marrow.
[2]"Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals."
Tournamille C., Colin Y., Cartron J.-P., Le van Kim C.
Nat. Genet. 10:224-228(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASP-42.
Tissue: Blood.
[3]"Genomic organization of the glycoprotein D gene: Duffy blood group Fya/Fyb alloantigen system is associated with a polymorphism at the 44-amino acid residue."
Iwamoto S., Omi T., Kajii E., Ikemoto S.
Blood 85:622-626(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Blood.
[4]"Arg89Cys substitution results in very low membrane expression of the Duffy antigen/receptor for chemokines in Fy(x) individuals."
Tournamille C., Le Van Kim C., Gane P., Le Pennec P.Y., Roubinet F., Babinet J., Cartron J.-P., Colin Y.
Blood 92:2147-2156(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), VARIANTS ASP-42; CYS-89 AND THR-100.
Tissue: Blood.
[5]"The Fy(x) phenotype is associated with a missense mutation in the Fy(b) allele predicting Arg89Cys in the Duffy glycoprotein."
Olsson M.L., Smythe J.S., Hansson C., Poole J., Mallinson G., Jones J., Avent N.D., Daniels G.
Br. J. Haematol. 103:1184-1191(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ASP-42; CYS-89 AND THR-100.
[6]"New polymorphisms in DARC."
Doescher A.
Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PHE-326.
Tissue: Peripheral blood.
[7]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT PHE-326.
Tissue: Lung.
[9]"Emergence of FY*A(null) in a Plasmodium vivax-endemic region of Papua New Guinea."
Zimmerman P.A., Woolley I., Masinde G.L., Miller S.M., McNamara D.T., Hazlett F., Mgone C.S., Alpers M.P., Genton B., Boatin B.A., Kazura J.W.
Proc. Natl. Acad. Sci. U.S.A. 96:13973-13977(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-117 (ISOFORMS 1 AND 2).
[10]"Structure-function analysis of the extracellular domains of the Duffy antigen/receptor for chemokines: characterization of antibody and chemokine binding sites."
Tournamille C., Filipe A., Wasniowska K., Gane P., Lisowska E., Cartron J.-P., Colin Y., Le Van Kim C.
Br. J. Haematol. 122:1014-1023(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS, GLYCOSYLATION AT ASN-16.
[11]"Reduced Plasmodium vivax erythrocyte infection in PNG Duffy-negative heterozygotes."
Kasehagen L.J., Mueller I., Kiniboro B., Bockarie M.J., Reeder J.C., Kazura J.W., Kastens W., McNamara D.T., King C.H., Whalen C.C., Zimmerman P.A.
PLoS ONE 2:E336-E336(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: POLYMORPHISM, INVOLVEMENT IN RESISTANCE TO MALARIA.
[12]"Chemokine decoy receptors: structure-function and biological properties."
Bonecchi R., Savino B., Borroni E.M., Mantovani A., Locati M.
Curr. Top. Microbiol. Immunol. 341:15-36(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[13]"Duffy antigen receptor for chemokines and its involvement in patterning and control of inflammatory chemokines."
Novitzky-Basso I., Rot A.
Front. Immunol. 3:266-266(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[14]"The biochemistry and biology of the atypical chemokine receptors."
Graham G.J., Locati M., Mantovani A., Rot A., Thelen M.
Immunol. Lett. 145:30-38(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[15]"Atypical chemokine receptors: from silence to sound."
Cancellieri C., Vacchini A., Locati M., Bonecchi R., Borroni E.M.
Biochem. Soc. Trans. 41:231-236(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[16]"Molecular basis and PCR-DNA typing of the Fya/fyb blood group polymorphism."
Tournamille C., Le van Kim C., Gane P., Cartron J.-P., Colin Y.
Hum. Genet. 95:407-410(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASP-42.
Tissue: Peripheral blood.
[17]"A novel mutation in the coding sequence of the FY*B allele of the Duffy chemokine receptor gene is associated with an altered erythrocyte phenotype."
Parasol N., Reid M., Rios M., Castilho L., Harari I., Kosower N.S.
Blood 92:2237-2243(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CYS-89.
[18]"Admixture mapping of white cell count: genetic locus responsible for lower white blood cell count in the Health ABC and Jackson Heart Studies."
Nalls M.A., Wilson J.G., Patterson N.J., Tandon A., Zmuda J.M., Huntsman S., Garcia M., Hu D., Li R., Beamer B.A., Patel K.V., Akylbekova E.L., Files J.C., Hardy C.L., Buxbaum S.G., Taylor H.A., Reich D., Harris T.B., Ziv E.
Am. J. Hum. Genet. 82:81-87(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN WBCQ1.
[19]Erratum
Nalls M.A., Wilson J.G., Patterson N.J., Tandon A., Zmuda J.M., Huntsman S., Garcia M., Hu D., Li R., Beamer B.A., Patel K.V., Akylbekova E.L., Files J.C., Hardy C.L., Buxbaum S.G., Taylor H.A., Reich D., Harris T.B., Ziv E.
Am. J. Hum. Genet. 82:532-532(2008)
+Additional computationally mapped references.

Web resources

dbRBC/BGMUT

Blood group antigen gene mutation database

GeneReviews
Wikipedia

Duffy antigen entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U01839 mRNA. Translation: AAC50055.1.
X85785 Genomic DNA. Translation: CAA59770.1.
S76830 Genomic DNA. Translation: AAB33239.1.
AF055992 Genomic DNA. Translation: AAC72301.1.
AF030521 mRNA. Translation: AAD20435.1.
AM887935 Genomic DNA. Translation: CAP12644.1.
AL035403 Genomic DNA. Translation: CAB56228.1.
BC017817 mRNA. Translation: AAH17817.1.
AF100634 Genomic DNA. Translation: AAF02415.1.
AF100634 Genomic DNA. Translation: AAF02416.1.
PIRI52608.
RefSeqNP_001116423.1. NM_001122951.2.
NP_002027.2. NM_002036.3.
UniGeneHs.153381.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4NUUX-ray1.95C16-43[»]
4NUVX-ray2.60C/D14-43[»]
ProteinModelPortalQ16570.
SMRQ16570. Positions 60-91, 286-323.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108808. 2 interactions.
DIPDIP-3783N.

Chemistry

ChEMBLCHEMBL2321626.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ16570.

Polymorphism databases

DMDM67476970.

Proteomic databases

PRIDEQ16570.

Protocols and materials databases

DNASU2532.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368121; ENSP00000357103; ENSG00000213088. [Q16570-2]
ENST00000368122; ENSP00000357104; ENSG00000213088. [Q16570-1]
ENST00000537147; ENSP00000441985; ENSG00000213088. [Q16570-1]
GeneID2532.
KEGGhsa:2532.
UCSCuc001fto.3. human. [Q16570-1]

Organism-specific databases

CTD2532.
GeneCardsGC01P159173.
HGNCHGNC:4035. DARC.
HPAHPA016421.
HPA017672.
MIM110700. phenotype.
611162. phenotype.
611862. phenotype.
613665. gene.
neXtProtNX_Q16570.
PharmGKBPA28451.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG28176.
HOVERGENHBG051419.
KOK06574.
OMAHCVATPL.
OrthoDBEOG7RFTHW.
PhylomeDBQ16570.
TreeFamTF105419.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ16570.
BgeeQ16570.
CleanExHS_DARC.
GenevestigatorQ16570.

Family and domain databases

InterProIPR005384. Duffy_chemokine_rcpt.
[Graphical view]
PANTHERPTHR14181. PTHR14181. 1 hit.
PRINTSPR01559. DUFFYANTIGEN.
ProtoNetSearch...

Other

ChiTaRSDARC. human.
GeneWikiDuffy_antigen_system.
GenomeRNAi2532.
NextBio9987.
PROQ16570.
SOURCESearch...

Entry information

Entry nameACKR1_HUMAN
AccessionPrimary (citable) accession number: Q16570
Secondary accession number(s): A8YPG5 expand/collapse secondary AC list , O75898, Q16300, Q8WWE3, Q9UJP0, Q9UKZ5, Q9UKZ6, Q9UQE1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: June 7, 2005
Last modified: April 16, 2014
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

Blood group antigen proteins

Nomenclature of blood group antigens and list of entries

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries