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Protein

Atypical chemokine receptor 4

Gene

ACKR4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Acts as a receptor for chemokines CCL2, CCL8, CCL13, CCL19, CCL21 and CCL25. Chemokine-binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization. Plays an important role in controlling the migration of immune and cancer cells that express chemokine receptors CCR7 and CCR9, by reducing the availability of CCL19, CCL21, and CCL25 through internalization. Negatively regulates CXCR3-induced chemotaxis. Regulates T-cell development in the thymus.3 Publications

GO - Molecular functioni

  • chemokine receptor activity Source: UniProtKB
  • scavenger receptor activity Source: InterPro

GO - Biological processi

  • chemotaxis Source: ProtInc
  • G-protein coupled receptor signaling pathway Source: ProtInc
  • immune response Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.

Names & Taxonomyi

Protein namesi
Recommended name:
Atypical chemokine receptor 4
Alternative name(s):
C-C chemokine receptor type 11
Short name:
C-C CKR-11
Short name:
CC-CKR-11
Short name:
CCR-11
CC chemokine receptor-like 1
Short name:
CCRL1
CCX CKR
Gene namesi
Name:ACKR4
Synonyms:CCBP2, CCR11, CCRL1, VSHK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:1611. ACKR4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4242ExtracellularSequence analysisAdd
BLAST
Transmembranei43 – 6321Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini64 – 8724CytoplasmicSequence analysisAdd
BLAST
Transmembranei88 – 10821Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini109 – 1135ExtracellularSequence analysis
Transmembranei114 – 13421Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini135 – 15420CytoplasmicSequence analysisAdd
BLAST
Transmembranei155 – 17521Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini176 – 20126ExtracellularSequence analysisAdd
BLAST
Transmembranei202 – 22221Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini223 – 24018CytoplasmicSequence analysisAdd
BLAST
Transmembranei241 – 26121Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini262 – 28928ExtracellularSequence analysisAdd
BLAST
Transmembranei290 – 31021Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini311 – 35040CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • early endosome Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
  • recycling endosome Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35036.

Chemistry

GuidetoPHARMACOLOGYi315.

Polymorphism and mutation databases

DMDMi14285406.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 350350Atypical chemokine receptor 4PRO_0000069296Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi6 – 61N-linked (GlcNAc...)Sequence analysis
Glycosylationi19 – 191N-linked (GlcNAc...)Sequence analysis
Disulfide bondi112 ↔ 184PROSITE-ProRule annotation

Post-translational modificationi

The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9NPB9.
PRIDEiQ9NPB9.

PTM databases

iPTMnetiQ9NPB9.
PhosphoSiteiQ9NPB9.

Expressioni

Tissue specificityi

Predominantly expressed in heart. Lower expression in lung, pancreas, spleen, colon, skeletal muscle and small intestine.3 Publications

Gene expression databases

BgeeiENSG00000129048.
CleanExiHS_CCBP2.
HS_CCRL1.
ExpressionAtlasiQ9NPB9. baseline and differential.
GenevisibleiQ9NPB9. HS.

Organism-specific databases

HPAiCAB011569.

Interactioni

Subunit structurei

Forms heteromers with CXCR3. Interacts with ARRB1 and ARRB2.2 Publications

Protein-protein interaction databases

BioGridi119606. 5 interactions.
DIPiDIP-5906N.
IntActiQ9NPB9. 1 interaction.
MINTiMINT-123820.
STRINGi9606.ENSP00000249887.

Structurei

3D structure databases

ProteinModelPortaliQ9NPB9.
SMRiQ9NPB9. Positions 39-322.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFS2. Eukaryota.
ENOG4111EXQ. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiQ9NPB9.
KOiK04186.
OMAiLEICIGF.
OrthoDBiEOG091G0BMA.
PhylomeDBiQ9NPB9.
TreeFamiTF330966.

Family and domain databases

InterProiIPR005383. ACKR4.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR10489:SF733. PTHR10489:SF733. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR01558. CHEMOKINER11.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9NPB9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALEQNQSTD YYYEENEMNG TYDYSQYELI CIKEDVREFA KVFLPVFLTI
60 70 80 90 100
VFVIGLAGNS MVVAIYAYYK KQRTKTDVYI LNLAVADLLL LFTLPFWAVN
110 120 130 140 150
AVHGWVLGKI MCKITSALYT LNFVSGMQFL ACISIDRYVA VTKVPSQSGV
160 170 180 190 200
GKPCWIICFC VWMAAILLSI PQLVFYTVND NARCIPIFPR YLGTSMKALI
210 220 230 240 250
QMLEICIGFV VPFLIMGVCY FITARTLMKM PNIKISRPLK VLLTVVIVFI
260 270 280 290 300
VTQLPYNIVK FCRAIDIIYS LITSCNMSKR MDIAIQVTES IALFHSCLNP
310 320 330 340 350
ILYVFMGASF KNYVMKVAKK YGSWRRQRQS VEEFPFDSEG PTEPTSTFSI
Length:350
Mass (Da):39,914
Last modified:October 1, 2000 - v1
Checksum:i8E26049D2D5757C8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110640 mRNA. Translation: AAF59827.1.
AF193507 Genomic DNA. Translation: AAF61299.1.
AF233281 Genomic DNA. Translation: AAF44751.1.
AY221094 Genomic DNA. Translation: AAO65972.1.
AK313923 mRNA. Translation: BAG36644.1.
BC069438 mRNA. Translation: AAH69438.1.
CCDSiCCDS3075.1.
RefSeqiNP_057641.1. NM_016557.3.
NP_848540.1. NM_178445.2.
UniGeneiHs.310512.
Hs.743547.

Genome annotation databases

EnsembliENST00000249887; ENSP00000249887; ENSG00000129048.
GeneIDi51554.
KEGGihsa:51554.
UCSCiuc003eow.5. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF110640 mRNA. Translation: AAF59827.1.
AF193507 Genomic DNA. Translation: AAF61299.1.
AF233281 Genomic DNA. Translation: AAF44751.1.
AY221094 Genomic DNA. Translation: AAO65972.1.
AK313923 mRNA. Translation: BAG36644.1.
BC069438 mRNA. Translation: AAH69438.1.
CCDSiCCDS3075.1.
RefSeqiNP_057641.1. NM_016557.3.
NP_848540.1. NM_178445.2.
UniGeneiHs.310512.
Hs.743547.

3D structure databases

ProteinModelPortaliQ9NPB9.
SMRiQ9NPB9. Positions 39-322.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119606. 5 interactions.
DIPiDIP-5906N.
IntActiQ9NPB9. 1 interaction.
MINTiMINT-123820.
STRINGi9606.ENSP00000249887.

Chemistry

GuidetoPHARMACOLOGYi315.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ9NPB9.
PhosphoSiteiQ9NPB9.

Polymorphism and mutation databases

DMDMi14285406.

Proteomic databases

PaxDbiQ9NPB9.
PRIDEiQ9NPB9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000249887; ENSP00000249887; ENSG00000129048.
GeneIDi51554.
KEGGihsa:51554.
UCSCiuc003eow.5. human.

Organism-specific databases

CTDi51554.
GeneCardsiACKR4.
H-InvDBHIX0094990.
HGNCiHGNC:1611. ACKR4.
HPAiCAB011569.
MIMi606065. gene.
neXtProtiNX_Q9NPB9.
PharmGKBiPA35036.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFS2. Eukaryota.
ENOG4111EXQ. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiQ9NPB9.
KOiK04186.
OMAiLEICIGF.
OrthoDBiEOG091G0BMA.
PhylomeDBiQ9NPB9.
TreeFamiTF330966.

Enzyme and pathway databases

ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.

Miscellaneous databases

GeneWikiiCCRL1.
GenomeRNAii51554.
PROiQ9NPB9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129048.
CleanExiHS_CCBP2.
HS_CCRL1.
ExpressionAtlasiQ9NPB9. baseline and differential.
GenevisibleiQ9NPB9. HS.

Family and domain databases

InterProiIPR005383. ACKR4.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR10489:SF733. PTHR10489:SF733. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR01558. CHEMOKINER11.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiACKR4_HUMAN
AccessioniPrimary (citable) accession number: Q9NPB9
Secondary accession number(s): B2R9U7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: October 1, 2000
Last modified: September 7, 2016
This is version 134 of the entry and version 1 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.