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Atypical chemokine receptor 4 (C-C chemokine receptor type 11) (C-C CKR-11) (CC-CKR-11) (CCR-11) (CC chemokine receptor-like 1) (CCRL1) (CCX CKR)

 ACKR4_HUMAN             Reviewed;         350 AA.
Q9NPB9; B2R9U7;
01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
01-OCT-2000, sequence version 1.
20-JUN-2018, entry version 147.
RecName: Full=Atypical chemokine receptor 4;
AltName: Full=C-C chemokine receptor type 11;
Short=C-C CKR-11;
Short=CC-CKR-11;
Short=CCR-11;
AltName: Full=CC chemokine receptor-like 1;
Short=CCRL1;
AltName: Full=CCX CKR;
Name=ACKR4; Synonyms=CCBP2, CCR11, CCRL1, VSHK1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
PubMed=10767544; DOI=10.1016/S0378-1119(00)00076-7;
Khoja H., Wang G., Ng C.-T.L., Tucker J., Brown T., Shyamala V.;
"Cloning of CCRL1, an orphan seven transmembrane receptor related to
chemokine receptors, expressed abundantly in the heart.";
Gene 246:229-238(2000).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
PubMed=10734104; DOI=10.1074/jbc.275.13.9550;
Schweickart V.L., Epp A., Raport C.J., Gray P.W.;
"CCR11 is a functional receptor for the monocyte chemoattractant
protein family of chemokines.";
J. Biol. Chem. 275:9550-9556(2000).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION IN CHEMOKINES BINDING.
PubMed=10706668; DOI=10.4049/jimmunol.164.6.2851;
Gosling J., Dairaghi D.J., Wang Y., Hanley M., Talbot D., Miao Z.,
Schall T.J.;
"Identification of a novel chemokine receptor that binds dendritic
cell- and T cell-active chemokines including ELC, SLC, and TECK.";
J. Immunol. 164:2851-2856(2000).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Kopatz S.A., Aronstam R.S., Sharma S.V.;
"cDNA clones of human proteins involved in signal transduction
sequenced by the Guthrie cDNA resource center (www.cdna.org).";
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
TISSUE SPECIFICITY.
PubMed=11981810;
DOI=10.1002/1521-4141(200205)32:5<1230::AID-IMMU1230>3.0.CO;2-L;
Townson J.R., Nibbs R.J.;
"Characterization of mouse CCX-CKR, a receptor for the lymphocyte-
attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19:
comparison to human CCX-CKR.";
Eur. J. Immunol. 32:1230-1241(2002).
[8]
REVIEW.
PubMed=20373092; DOI=10.1007/82_2010_19;
Bonecchi R., Savino B., Borroni E.M., Mantovani A., Locati M.;
"Chemokine decoy receptors: structure-function and biological
properties.";
Curr. Top. Microbiol. Immunol. 341:15-36(2010).
[9]
REVIEW.
PubMed=22698181; DOI=10.1016/j.imlet.2012.04.004;
Graham G.J., Locati M., Mantovani A., Rot A., Thelen M.;
"The biochemistry and biology of the atypical chemokine receptors.";
Immunol. Lett. 145:30-38(2012).
[10]
REVIEW.
PubMed=23356288; DOI=10.1042/BST20120246;
Cancellieri C., Vacchini A., Locati M., Bonecchi R., Borroni E.M.;
"Atypical chemokine receptors: from silence to sound.";
Biochem. Soc. Trans. 41:231-236(2013).
[11]
FUNCTION, AND SUBUNIT.
PubMed=23121557; DOI=10.1111/bph.12042;
Vinet J., van Zwam M., Dijkstra I.M., Brouwer N., van Weering H.R.,
Watts A., Meijer M., Fokkens M.R., Kannan V., Verzijl D.,
Vischer H.F., Smit M.J., Leurs R., Biber K., Boddeke H.W.;
"Inhibition of CXCR3-mediated chemotaxis by the human chemokine
receptor-like protein CCX-CKR.";
Br. J. Pharmacol. 168:1375-1387(2013).
[12]
FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ARRB1 AND ARRB2.
PubMed=23341447; DOI=10.1074/jbc.M112.406108;
Watts A.O., Verkaar F., van der Lee M.M., Timmerman C.A., Kuijer M.,
van Offenbeek J., van Lith L.H., Smit M.J., Leurs R., Zaman G.J.,
Vischer H.F.;
"Beta-arrestin recruitment and G protein signaling by the atypical
human chemokine decoy receptor CCX-CKR.";
J. Biol. Chem. 288:7169-7181(2013).
-!- 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. 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. {ECO:0000269|PubMed:10706668, ECO:0000269|PubMed:23121557,
ECO:0000269|PubMed:23341447}.
-!- SUBUNIT: Forms heteromers with CXCR3. Interacts with ARRB1 and
ARRB2. {ECO:0000269|PubMed:23121557, ECO:0000269|PubMed:23341447}.
-!- SUBCELLULAR LOCATION: Early endosome
{ECO:0000269|PubMed:23341447}. Recycling endosome
{ECO:0000269|PubMed:23341447}. Cell membrane
{ECO:0000269|PubMed:23341447}; Multi-pass membrane protein
{ECO:0000269|PubMed:23341447}. 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: Predominantly expressed in heart. Lower
expression in lung, pancreas, spleen, colon, skeletal muscle and
small intestine. {ECO:0000269|PubMed:10734104,
ECO:0000269|PubMed:10767544, ECO:0000269|PubMed:11981810}.
-!- PTM: The Ser/Thr residues in the C-terminal cytoplasmic tail may
be phosphorylated.
-!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
Atypical chemokine receptor subfamily. {ECO:0000255|PROSITE-
ProRule:PRU00521}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; AF110640; AAF59827.1; -; mRNA.
EMBL; AF193507; AAF61299.1; -; Genomic_DNA.
EMBL; AF233281; AAF44751.1; -; Genomic_DNA.
EMBL; AY221094; AAO65972.1; -; Genomic_DNA.
EMBL; AK313923; BAG36644.1; -; mRNA.
EMBL; BC069438; AAH69438.1; -; mRNA.
CCDS; CCDS3075.1; -.
RefSeq; NP_057641.1; NM_016557.3.
RefSeq; NP_848540.1; NM_178445.2.
UniGene; Hs.310512; -.
UniGene; Hs.743547; -.
ProteinModelPortal; Q9NPB9; -.
SMR; Q9NPB9; -.
BioGrid; 119606; 5.
DIP; DIP-5918N; -.
IntAct; Q9NPB9; 1.
STRING; 9606.ENSP00000249887; -.
GuidetoPHARMACOLOGY; 315; -.
iPTMnet; Q9NPB9; -.
PhosphoSitePlus; Q9NPB9; -.
DMDM; 14285406; -.
PaxDb; Q9NPB9; -.
PRIDE; Q9NPB9; -.
ProteomicsDB; 81962; -.
Ensembl; ENST00000249887; ENSP00000249887; ENSG00000129048.
GeneID; 51554; -.
KEGG; hsa:51554; -.
UCSC; uc003eow.5; human.
CTD; 51554; -.
DisGeNET; 51554; -.
EuPathDB; HostDB:ENSG00000129048.6; -.
GeneCards; ACKR4; -.
H-InvDB; HIX0094990; -.
HGNC; HGNC:1611; ACKR4.
HPA; HPA054926; -.
MIM; 606065; gene.
neXtProt; NX_Q9NPB9; -.
OpenTargets; ENSG00000129048; -.
PharmGKB; PA35036; -.
eggNOG; ENOG410IFS2; Eukaryota.
eggNOG; ENOG4111EXQ; LUCA.
GeneTree; ENSGT00760000118785; -.
HOGENOM; HOG000234122; -.
HOVERGEN; HBG106917; -.
InParanoid; Q9NPB9; -.
KO; K04186; -.
OMA; PFWAVNA; -.
OrthoDB; EOG091G0BMA; -.
PhylomeDB; Q9NPB9; -.
TreeFam; TF330966; -.
Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
GeneWiki; CCRL1; -.
GenomeRNAi; 51554; -.
PRO; PR:Q9NPB9; -.
Proteomes; UP000005640; Chromosome 3.
Bgee; ENSG00000129048; -.
CleanEx; HS_CCBP2; -.
CleanEx; HS_CCRL1; -.
ExpressionAtlas; Q9NPB9; baseline and differential.
Genevisible; Q9NPB9; HS.
GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
GO; GO:0019956; F:chemokine binding; IEA:InterPro.
GO; GO:0004950; F:chemokine receptor activity; IDA:UniProtKB.
GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
GO; GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:ProtInc.
GO; GO:0006955; P:immune response; TAS:ProtInc.
CDD; cd15176; 7tmA_ACKR4_CCR11; 1.
InterPro; IPR005383; ACKR4.
InterPro; IPR000355; Chemokine_rcpt.
InterPro; IPR000276; GPCR_Rhodpsn.
InterPro; IPR017452; GPCR_Rhodpsn_7TM.
Pfam; PF00001; 7tm_1; 1.
PRINTS; PR00657; CCCHEMOKINER.
PRINTS; PR01558; CHEMOKINER11.
PRINTS; PR00237; GPCRRHODOPSN.
PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
1: Evidence at protein level;
Cell membrane; Complete proteome; Disulfide bond; Endosome;
G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein;
Receptor; Reference proteome; Transducer; Transmembrane;
Transmembrane helix.
CHAIN 1 350 Atypical chemokine receptor 4.
/FTId=PRO_0000069296.
TOPO_DOM 1 42 Extracellular. {ECO:0000255}.
TRANSMEM 43 63 Helical; Name=1. {ECO:0000255}.
TOPO_DOM 64 87 Cytoplasmic. {ECO:0000255}.
TRANSMEM 88 108 Helical; Name=2. {ECO:0000255}.
TOPO_DOM 109 113 Extracellular. {ECO:0000255}.
TRANSMEM 114 134 Helical; Name=3. {ECO:0000255}.
TOPO_DOM 135 154 Cytoplasmic. {ECO:0000255}.
TRANSMEM 155 175 Helical; Name=4. {ECO:0000255}.
TOPO_DOM 176 201 Extracellular. {ECO:0000255}.
TRANSMEM 202 222 Helical; Name=5. {ECO:0000255}.
TOPO_DOM 223 240 Cytoplasmic. {ECO:0000255}.
TRANSMEM 241 261 Helical; Name=6. {ECO:0000255}.
TOPO_DOM 262 289 Extracellular. {ECO:0000255}.
TRANSMEM 290 310 Helical; Name=7. {ECO:0000255}.
TOPO_DOM 311 350 Cytoplasmic. {ECO:0000255}.
CARBOHYD 6 6 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 19 19 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 112 184 {ECO:0000255|PROSITE-ProRule:PRU00521}.
SEQUENCE 350 AA; 39914 MW; 8E26049D2D5757C8 CRC64;
MALEQNQSTD YYYEENEMNG TYDYSQYELI CIKEDVREFA KVFLPVFLTI VFVIGLAGNS
MVVAIYAYYK KQRTKTDVYI LNLAVADLLL LFTLPFWAVN AVHGWVLGKI MCKITSALYT
LNFVSGMQFL ACISIDRYVA VTKVPSQSGV GKPCWIICFC VWMAAILLSI PQLVFYTVND
NARCIPIFPR YLGTSMKALI QMLEICIGFV VPFLIMGVCY FITARTLMKM PNIKISRPLK
VLLTVVIVFI VTQLPYNIVK FCRAIDIIYS LITSCNMSKR MDIAIQVTES IALFHSCLNP
ILYVFMGASF KNYVMKVAKK YGSWRRQRQS VEEFPFDSEG PTEPTSTFSI


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