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Protein

Atypical chemokine receptor 1

Gene

ACKR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • C-C chemokine binding Source: BHF-UCL
  • G protein-coupled receptor activity Source: UniProtKB-KW
  • signaling receptor activity Source: ProtInc
  • transmembrane signaling receptor activity Source: ProtInc

GO - Biological processi

  • chemokine-mediated signaling pathway Source: InterPro
  • defense response Source: UniProtKB
  • inflammatory response Source: GO_Central
  • regulation of chemokine production Source: GO_Central

Keywordsi

Molecular functionBlood group antigen, G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-375276 Peptide ligand-binding receptors

Names & Taxonomyi

Protein namesi
Recommended name:
Atypical chemokine receptor 1
Alternative name(s):
Duffy antigen/chemokine receptor
Fy glycoprotein
Short name:
GpFy
Glycoprotein D
Plasmodium vivax receptor
CD_antigen: CD234
Gene namesi
Name:ACKR1
Synonyms:DARC, FY, GPD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000213088.9
HGNCiHGNC:4035 ACKR1
MIMi613665 gene
neXtProtiNX_Q16570

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 63ExtracellularSequence analysisAdd BLAST63
Transmembranei64 – 84Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini85 – 95CytoplasmicSequence analysisAdd BLAST11
Transmembranei96 – 116Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini117 – 129ExtracellularSequence analysisAdd BLAST13
Transmembranei130 – 153Helical; Name=3Sequence analysisAdd BLAST24
Topological domaini154 – 166CytoplasmicSequence analysisAdd BLAST13
Transmembranei167 – 187Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini188 – 207ExtracellularSequence analysisAdd BLAST20
Transmembranei208 – 228Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini229 – 244CytoplasmicSequence analysisAdd BLAST16
Transmembranei245 – 265Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini266 – 287ExtracellularSequence analysisAdd BLAST22
Transmembranei288 – 308Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini309 – 336CytoplasmicSequence analysisAdd BLAST28

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2532
MalaCardsiACKR1
MIMi110700 phenotype
611162 phenotype
611862 phenotype
OpenTargetsiENSG00000213088
PharmGKBiPA28451

Chemistry databases

ChEMBLiCHEMBL2321626

Polymorphism and mutation databases

BioMutaiDARC
DMDMi67476970

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001525851 – 336Atypical chemokine receptor 1Add BLAST336

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi16N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi33N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi51 ↔ 2761 Publication
Disulfide bondi129 ↔ 1951 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ16570
PeptideAtlasiQ16570
PRIDEiQ16570
ProteomicsDBi60923
60924 [Q16570-2]

PTM databases

iPTMnetiQ16570
PhosphoSitePlusiQ16570

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000213088 Expressed in 193 organ(s), highest expression level in ectocervix
CleanExiHS_DARC
ExpressionAtlasiQ16570 baseline and differential
GenevisibleiQ16570 HS

Organism-specific databases

HPAiHPA016421
HPA017672

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
PVDRP222903EBI-15935975,EBI-15935953From Plasmodium vivax (strain Salvador I).

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108808, 3 interactors
DIPiDIP-3783N
IntActiQ16570, 1 interactor
STRINGi9606.ENSP00000357103

Structurei

Secondary structure

1336
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ16570
SMRiQ16570
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IHK3 Eukaryota
ENOG41119V5 LUCA
GeneTreeiENSGT00390000006372
HOVERGENiHBG051419
InParanoidiQ16570
KOiK06574
OMAiHCVATPL
PhylomeDBiQ16570
TreeFamiTF105419

Family and domain databases

CDDicd15010 7tmA_ACKR1_DARC, 1 hit
InterProiView protein in InterPro
IPR005384 Duffy_chemokine_rcpt
PANTHERiPTHR14181 PTHR14181, 1 hit
PRINTSiPR01559 DUFFYANTIGEN

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 2 (identifier: Q16570-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MGNCLHRAEL SPSTENSSQL DFEDVWNSSY GVNDSFPDGD YGANLEAAAP
60 70 80 90 100
CHSCNLLDDS ALPFFILTSV LGILASSTVL FMLFRPLFRW QLCPGWPVLA
110 120 130 140 150
QLAVGSALFS IVVPVLAPGL GSTRSSALCS LGYCVWYGSA FAQALLLGCH
160 170 180 190 200
ASLGHRLGAG QVPGLTLGLT VGIWGVAALL TLPVTLASGA SGGLCTLIYS
210 220 230 240 250
TELKALQATH TVACLAIFVL LPLGLFGAKG LKKALGMGPG PWMNILWAWF
260 270 280 290 300
IFWWPHGVVL GLDFLVRSKL LLLSTCLAQQ ALDLLLNLAE ALAILHCVAT
310 320 330
PLLLALFCHQ ATRTLLPSLP LPEGWSSHLD TLGSKS
Length:336
Mass (Da):35,553
Last modified:June 7, 2005 - v3
Checksum:iC3F2A3E71D972E2D
GO
Isoform 1 (identifier: Q16570-2) [UniParc]FASTAAdd to basket

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

Show »
Length:338
Mass (Da):35,678
Checksum:i5AC412B001F07F5B
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5JY94Q5JY94_HUMAN
Atypical chemokine receptor 1
ACKR1
155Annotation score:

Polymorphismi

DARC is responsible for the Duffy blood group system (FY) [MIMi: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 [MIMi:611162].
Genetic variations in DARC define the white blood cell count quantitative trait locus 1 (WBCQ1) [MIMi:611862]. Peripheral white blood cell count (WBC) is a common clinical measurement, used to determine evidence of acute inflammation 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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00348042G → D Antigen Fy(b). 5 PublicationsCorresponds to variant dbSNP:rs12075EnsemblClinVar.1
Natural variantiVAR_01506889R → C Antigen Fy(x). 3 PublicationsCorresponds to variant dbSNP:rs34599082EnsemblClinVar.1
Natural variantiVAR_015069100A → T2 PublicationsCorresponds to variant dbSNP:rs13962Ensembl.1
Natural variantiVAR_044116203L → Q. Corresponds to variant dbSNP:rs3027020Ensembl.1
Natural variantiVAR_044117326S → F2 PublicationsCorresponds to variant dbSNP:rs17851570Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0013231 – 7MGNCLHR → MASSGYVLQ in isoform 1. 2 Publications7

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
BC017817 mRNA Translation: AAH17817.1
AF100634 Genomic DNA Translation: AAF02415.1
AF100634 Genomic DNA Translation: AAF02416.1
CCDSiCCDS1183.1 [Q16570-1]
CCDS44252.1 [Q16570-2]
PIRiI52608
RefSeqiNP_001116423.1, NM_001122951.2 [Q16570-2]
NP_002027.2, NM_002036.3 [Q16570-1]
UniGeneiHs.153381

Genome annotation databases

EnsembliENST00000368121; ENSP00000357103; ENSG00000213088 [Q16570-2]
ENST00000368122; ENSP00000357104; ENSG00000213088 [Q16570-1]
ENST00000537147; ENSP00000441985; ENSG00000213088 [Q16570-1]
GeneIDi2532
KEGGihsa:2532

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

dbRBC/BGMUT

Blood group antigen gene mutation database

Wikipedia

Duffy antigen entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
BC017817 mRNA Translation: AAH17817.1
AF100634 Genomic DNA Translation: AAF02415.1
AF100634 Genomic DNA Translation: AAF02416.1
CCDSiCCDS1183.1 [Q16570-1]
CCDS44252.1 [Q16570-2]
PIRiI52608
RefSeqiNP_001116423.1, NM_001122951.2 [Q16570-2]
NP_002027.2, NM_002036.3 [Q16570-1]
UniGeneiHs.153381

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4NUUX-ray1.95C16-43[»]
4NUVX-ray2.60C/D14-43[»]
ProteinModelPortaliQ16570
SMRiQ16570
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108808, 3 interactors
DIPiDIP-3783N
IntActiQ16570, 1 interactor
STRINGi9606.ENSP00000357103

Chemistry databases

ChEMBLiCHEMBL2321626

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ16570
PhosphoSitePlusiQ16570

Polymorphism and mutation databases

BioMutaiDARC
DMDMi67476970

Proteomic databases

PaxDbiQ16570
PeptideAtlasiQ16570
PRIDEiQ16570
ProteomicsDBi60923
60924 [Q16570-2]

Protocols and materials databases

DNASUi2532
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368121; ENSP00000357103; ENSG00000213088 [Q16570-2]
ENST00000368122; ENSP00000357104; ENSG00000213088 [Q16570-1]
ENST00000537147; ENSP00000441985; ENSG00000213088 [Q16570-1]
GeneIDi2532
KEGGihsa:2532

Organism-specific databases

CTDi2532
DisGeNETi2532
EuPathDBiHostDB:ENSG00000213088.9
GeneCardsiACKR1
HGNCiHGNC:4035 ACKR1
HPAiHPA016421
HPA017672
MalaCardsiACKR1
MIMi110700 phenotype
611162 phenotype
611862 phenotype
613665 gene
neXtProtiNX_Q16570
OpenTargetsiENSG00000213088
PharmGKBiPA28451
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHK3 Eukaryota
ENOG41119V5 LUCA
GeneTreeiENSGT00390000006372
HOVERGENiHBG051419
InParanoidiQ16570
KOiK06574
OMAiHCVATPL
PhylomeDBiQ16570
TreeFamiTF105419

Enzyme and pathway databases

ReactomeiR-HSA-375276 Peptide ligand-binding receptors

Miscellaneous databases

ChiTaRSiACKR1 human
GeneWikiiDuffy_antigen_system
GenomeRNAii2532
PROiPR:Q16570
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000213088 Expressed in 193 organ(s), highest expression level in ectocervix
CleanExiHS_DARC
ExpressionAtlasiQ16570 baseline and differential
GenevisibleiQ16570 HS

Family and domain databases

CDDicd15010 7tmA_ACKR1_DARC, 1 hit
InterProiView protein in InterPro
IPR005384 Duffy_chemokine_rcpt
PANTHERiPTHR14181 PTHR14181, 1 hit
PRINTSiPR01559 DUFFYANTIGEN
ProtoNetiSearch...

Entry informationi

Entry nameiACKR1_HUMAN
AccessioniPrimary (citable) accession number: Q16570
Secondary accession number(s): A8YPG5
, O75898, Q16300, Q8WWE3, Q9UJP0, Q9UKZ5, Q9UKZ6, Q9UQE1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: June 7, 2005
Last modified: November 7, 2018
This is version 166 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  8. Blood group antigen proteins
    Nomenclature of blood group antigens and list of entries
  9. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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Main funding by: National Institutes of Health

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