Reviewed, UniProtKB/Swiss-Prot Q16570 (DUFFY_HUMAN)

Names and origin

Protein names

Recommended name:
    Duffy antigen/chemokine receptor
Alternative name(s):
    Fy glycoprotein
      Short name=GpFy
    Glycoprotein D
    Plasmodium vivax receptor
    CD_antigen=CD234

Gene names

Name:	DARC
Synonyms:	FY, GPD

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	336 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Non-specific receptor for many chemokines such as IL-8, GRO, RANTES, MCP-1 and TARC. It is also the receptor for the human malaria parasites Plasmodium vivax and Plasmodium knowlesi.
Subcellular location	Membrane; Multi-pass membrane protein.
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. 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 vivax malaria. This allele is found predominantly in population of African origin. Genetic variation in DARC is associated with white blood cell count quantitative trait locus type 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 Duffy family.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane
Molecular function	Blood group antigen G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW defense response Ref.9 Non-traceable author statement. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Traceable author statement. Source: ProtInc
Molecular function	chemokine receptor activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 336	336	Duffy antigen/chemokine receptor		PRO_0000152585
Regions
	Topological domain	1 – 63	63	Extracellular Potential
	Transmembrane	64 – 84	21	1 Potential
	Topological domain	85 – 95	11	Cytoplasmic Potential
	Transmembrane	96 – 116	21	2 Potential
	Topological domain	117 – 129	13	Extracellular Potential
	Transmembrane	130 – 153	24	3 Potential
	Topological domain	154 – 166	13	Cytoplasmic Potential
	Transmembrane	167 – 187	21	4 Potential
	Topological domain	188 – 207	20	Extracellular Potential
	Transmembrane	208 – 228	21	5 Potential
	Topological domain	229 – 244	16	Cytoplasmic Potential
	Transmembrane	245 – 265	21	6 Potential
	Topological domain	266 – 287	22	Extracellular Potential
	Transmembrane	288 – 308	21	7 Potential
	Topological domain	309 – 336	28	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	16	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	33	1	N-linked (GlcNAc...) Potential
	Disulfide bond	51 ↔ 276		Ref.10
	Disulfide bond	129 ↔ 195		Ref.10
Natural variations
	Alternative sequence	1 – 7	7	MGNCLHR → MASSGYVLQ in isoform 1.		VSP_001323
	Natural variant	42	1	G → D Antigen Fy(b). dbSNP rs12075. Ref.1 Ref.2 Ref.4 Ref.5 Ref.11		VAR_003480
	Natural variant	89	1	R → C Antigen Fy(x). dbSNP rs34599082. Ref.4 Ref.5 Ref.12		VAR_015068
	Natural variant	100	1	A → T: dbSNP rs13962. Ref.4 Ref.5		VAR_015069
	Natural variant	203	1	L → Q: dbSNP rs3027020.		VAR_044116
	Natural variant	326	1	S → F: dbSNP rs17851570. Ref.6 Ref.8		VAR_044117

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified June 7, 2005. Version 3. Checksum: C3F2A3E71D972E2D	FASTA	336	35,553
	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
	Isoform 1. Checksum: 5AC412B001F07F5B	FASTA	338	35,678
	10 20 30 40 50 60 MASSGYVLQA ELSPSTENSS QLDFEDVWNS SYGVNDSFPD GDYGANLEAA APCHSCNLLD 70 80 90 100 110 120 DSALPFFILT SVLGILASST VLFMLFRPLF RWQLCPGWPV LAQLAVGSAL FSIVVPVLAP 130 140 150 160 170 180 GLGSTRSSAL CSLGYCVWYG SAFAQALLLG CHASLGHRLG AGQVPGLTLG LTVGIWGVAA 190 200 210 220 230 240 LLTLPVTLAS GASGGLCTLI YSTELKALQA THTVACLAIF VLLPLGLFGA KGLKKALGMG 250 260 270 280 290 300 PGPWMNILWA WFIFWWPHGV VLGLDFLVRS KLLLLSTCLA QQALDLLLNL AEALAILHCV 310 320 330 ATPLLLALFC HQATRTLLPS LPLPEGWSSH LDTLGSKS

References

	« Hide 'large scale' referencesShow '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: 8248172] [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: 7663520] [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: 7833467] [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: 9731074] [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: 9886340] [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. , 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: 16710414] [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: 15489334] [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: 10570183] [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: 12956774] [Abstract] Cited for: DISULFIDE BONDS, GLYCOSYLATION AT ASN-16.
[11]	"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: 7705836] [Abstract] Cited for: VARIANT ASP-42. Tissue: Peripheral blood.
[12]	"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: 9746760] [Abstract] Cited for: VARIANT CYS-89.
[13]	"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: 18179887] [Abstract] Cited for: INVOLVEMENT IN WBCQ1.
[14]	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.
IPI	IPI00002940. IPI00215964.
PIR	I52608.
RefSeq	NP_001116423.1. NP_002027.2.
UniGene	Hs.153381
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-3783N.
STRING	Q16570.
Protein family/group databases
GPCRDB	Search...
Proteomic databases
PRIDE	Q16570.
Genome annotation databases
Ensembl	ENST00000359381; ENSP00000352341; ENSG00000213088; Homo sapiens. [Genome view] ENST00000368122; ENSP00000357104; ENSG00000213088; Homo sapiens. [Genome view]
GeneID	2532.
KEGG	hsa:2532.
UCSC	uc001fto.1. human.
Organism-specific databases
CTD	2532.
GeneCards	GC01P157440.
HGNC	HGNC:4035. DARC.
HPA	HPA016421. HPA017672.
MIM	110700. gene+phenotype. 611862. phenotype.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG09338.
HOVERGEN	Q16570.
OMA	HCVATPL.
OrthoDB	EOG91K1ZS.
PhylomeDB	Q16570.
Enzyme and pathway databases
Reactome	REACT_14797. Signaling by GPCR.
Gene expression databases
ArrayExpress	Q16570.
Bgee	Q16570.
CleanEx	HS_DARC.
Genevestigator	Q16570.
GermOnline	ENSG00000162706. Homo sapiens.
Family and domain databases
InterPro	IPR005384. Duffy_cmk_rcpt. [Graphical view]
PANTHER	PTHR14181. Duffy_cmk_rcpt. 1 hit.
PRINTS	PR01559. DUFFYANTIGEN.
ProtoNet	Search...
Other Resources
NextBio	9987.
SOURCE	Search...

Entry information

Entry name

DUFFY_HUMAN

Accession

Primary (citable) accession number: Q16570
Secondary accession number(s): A8YPG5 , 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:	January 19, 2010
This is version 97 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.