ACKR4_HUMAN
ID ACKR4_HUMAN Reviewed; 350 AA.
AC Q9NPB9; B2R9U7;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Atypical chemokine receptor 4;
DE AltName: Full=C-C chemokine receptor type 11;
DE Short=C-C CKR-11;
DE Short=CC-CKR-11;
DE Short=CCR-11;
DE AltName: Full=CC chemokine receptor-like 1;
DE Short=CCRL1;
DE AltName: Full=CCX CKR;
GN Name=ACKR4; Synonyms=CCBP2, CCR11, CCRL1, VSHK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=10767544; DOI=10.1016/s0378-1119(00)00076-7;
RA Khoja H., Wang G., Ng C.-T.L., Tucker J., Brown T., Shyamala V.;
RT "Cloning of CCRL1, an orphan seven transmembrane receptor related to
RT chemokine receptors, expressed abundantly in the heart.";
RL Gene 246:229-238(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=10734104; DOI=10.1074/jbc.275.13.9550;
RA Schweickart V.L., Epp A., Raport C.J., Gray P.W.;
RT "CCR11 is a functional receptor for the monocyte chemoattractant protein
RT family of chemokines.";
RL J. Biol. Chem. 275:9550-9556(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION IN CHEMOKINES BINDING.
RX PubMed=10706668; DOI=10.4049/jimmunol.164.6.2851;
RA Gosling J., Dairaghi D.J., Wang Y., Hanley M., Talbot D., Miao Z.,
RA Schall T.J.;
RT "Identification of a novel chemokine receptor that binds dendritic
RT cell- and T cell-active chemokines including ELC, SLC, and TECK.";
RL J. Immunol. 164:2851-2856(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=11981810;
RX DOI=10.1002/1521-4141(200205)32:5<1230::aid-immu1230>3.0.co;2-l;
RA Townson J.R., Nibbs R.J.;
RT "Characterization of mouse CCX-CKR, a receptor for the lymphocyte-
RT attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19:
RT comparison to human CCX-CKR.";
RL Eur. J. Immunol. 32:1230-1241(2002).
RN [8]
RP REVIEW.
RX PubMed=20373092; DOI=10.1007/82_2010_19;
RA Bonecchi R., Savino B., Borroni E.M., Mantovani A., Locati M.;
RT "Chemokine decoy receptors: structure-function and biological properties.";
RL Curr. Top. Microbiol. Immunol. 341:15-36(2010).
RN [9]
RP REVIEW.
RX PubMed=22698181; DOI=10.1016/j.imlet.2012.04.004;
RA Graham G.J., Locati M., Mantovani A., Rot A., Thelen M.;
RT "The biochemistry and biology of the atypical chemokine receptors.";
RL Immunol. Lett. 145:30-38(2012).
RN [10]
RP REVIEW.
RX PubMed=23356288; DOI=10.1042/bst20120246;
RA Cancellieri C., Vacchini A., Locati M., Bonecchi R., Borroni E.M.;
RT "Atypical chemokine receptors: from silence to sound.";
RL Biochem. Soc. Trans. 41:231-236(2013).
RN [11]
RP FUNCTION, AND SUBUNIT.
RX PubMed=23121557; DOI=10.1111/bph.12042;
RA Vinet J., van Zwam M., Dijkstra I.M., Brouwer N., van Weering H.R.,
RA Watts A., Meijer M., Fokkens M.R., Kannan V., Verzijl D., Vischer H.F.,
RA Smit M.J., Leurs R., Biber K., Boddeke H.W.;
RT "Inhibition of CXCR3-mediated chemotaxis by the human chemokine receptor-
RT like protein CCX-CKR.";
RL Br. J. Pharmacol. 168:1375-1387(2013).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ARRB1 AND ARRB2.
RX PubMed=23341447; DOI=10.1074/jbc.m112.406108;
RA Watts A.O., Verkaar F., van der Lee M.M., Timmerman C.A., Kuijer M.,
RA van Offenbeek J., van Lith L.H., Smit M.J., Leurs R., Zaman G.J.,
RA Vischer H.F.;
RT "Beta-arrestin recruitment and G protein signaling by the atypical human
RT chemokine decoy receptor CCX-CKR.";
RL J. Biol. Chem. 288:7169-7181(2013).
CC -!- FUNCTION: Atypical chemokine receptor that controls chemokine levels
CC and localization via high-affinity chemokine binding that is uncoupled
CC from classic ligand-driven signal transduction cascades, resulting
CC instead in chemokine sequestration, degradation, or transcytosis. Also
CC known as interceptor (internalizing receptor) or chemokine-scavenging
CC receptor or chemokine decoy receptor. Acts as a receptor for chemokines
CC CCL2, CCL8, CCL13, CCL19, CCL21 and CCL25. Chemokine-binding does not
CC activate G-protein-mediated signal transduction but instead induces
CC beta-arrestin recruitment, leading to ligand internalization. Plays an
CC important role in controlling the migration of immune and cancer cells
CC that express chemokine receptors CCR7 and CCR9, by reducing the
CC availability of CCL19, CCL21, and CCL25 through internalization.
CC Negatively regulates CXCR3-induced chemotaxis. Regulates T-cell
CC development in the thymus. {ECO:0000269|PubMed:10706668,
CC ECO:0000269|PubMed:23121557, ECO:0000269|PubMed:23341447}.
CC -!- SUBUNIT: Forms heteromers with CXCR3. Interacts with ARRB1 and ARRB2.
CC {ECO:0000269|PubMed:23121557, ECO:0000269|PubMed:23341447}.
CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000269|PubMed:23341447}.
CC Recycling endosome {ECO:0000269|PubMed:23341447}. Cell membrane
CC {ECO:0000269|PubMed:23341447}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:23341447}. Note=Predominantly localizes to
CC endocytic vesicles, and upon stimulation by the ligand is internalized
CC via caveolae. Once internalized, the ligand dissociates from the
CC receptor, and is targeted to degradation while the receptor is recycled
CC back to the cell membrane.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in heart. Lower expression
CC in lung, pancreas, spleen, colon, skeletal muscle and small intestine.
CC {ECO:0000269|PubMed:10734104, ECO:0000269|PubMed:10767544,
CC ECO:0000269|PubMed:11981810}.
CC -!- PTM: The Ser/Thr residues in the C-terminal cytoplasmic tail may be
CC phosphorylated.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC Atypical chemokine receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00521}.
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DR EMBL; AF110640; AAF59827.1; -; mRNA.
DR EMBL; AF193507; AAF61299.1; -; Genomic_DNA.
DR EMBL; AF233281; AAF44751.1; -; Genomic_DNA.
DR EMBL; AY221094; AAO65972.1; -; Genomic_DNA.
DR EMBL; AK313923; BAG36644.1; -; mRNA.
DR EMBL; BC069438; AAH69438.1; -; mRNA.
DR CCDS; CCDS3075.1; -.
DR RefSeq; NP_057641.1; NM_016557.3.
DR RefSeq; NP_848540.1; NM_178445.2.
DR AlphaFoldDB; Q9NPB9; -.
DR SMR; Q9NPB9; -.
DR BioGRID; 119606; 8.
DR DIP; DIP-5918N; -.
DR IntAct; Q9NPB9; 2.
DR STRING; 9606.ENSP00000249887; -.
DR GuidetoPHARMACOLOGY; 315; -.
DR GlyGen; Q9NPB9; 2 sites.
DR iPTMnet; Q9NPB9; -.
DR PhosphoSitePlus; Q9NPB9; -.
DR BioMuta; ACKR4; -.
DR DMDM; 14285406; -.
DR MassIVE; Q9NPB9; -.
DR PaxDb; Q9NPB9; -.
DR PeptideAtlas; Q9NPB9; -.
DR PRIDE; Q9NPB9; -.
DR ProteomicsDB; 81962; -.
DR Antibodypedia; 17718; 249 antibodies from 28 providers.
DR DNASU; 51554; -.
DR Ensembl; ENST00000249887.3; ENSP00000249887.2; ENSG00000129048.7.
DR GeneID; 51554; -.
DR KEGG; hsa:51554; -.
DR MANE-Select; ENST00000249887.3; ENSP00000249887.2; NM_016557.4; NP_057641.1.
DR UCSC; uc003eow.5; human.
DR CTD; 51554; -.
DR DisGeNET; 51554; -.
DR GeneCards; ACKR4; -.
DR HGNC; HGNC:1611; ACKR4.
DR HPA; ENSG00000129048; Tissue enhanced (intestine).
DR MIM; 606065; gene.
DR neXtProt; NX_Q9NPB9; -.
DR OpenTargets; ENSG00000129048; -.
DR PharmGKB; PA35036; -.
DR VEuPathDB; HostDB:ENSG00000129048; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234667; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; Q9NPB9; -.
DR OMA; YNVVKLC; -.
DR OrthoDB; 839817at2759; -.
DR PhylomeDB; Q9NPB9; -.
DR TreeFam; TF330966; -.
DR PathwayCommons; Q9NPB9; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR SignaLink; Q9NPB9; -.
DR SIGNOR; Q9NPB9; -.
DR BioGRID-ORCS; 51554; 19 hits in 1034 CRISPR screens.
DR ChiTaRS; ACKR4; human.
DR GeneWiki; CCRL1; -.
DR GenomeRNAi; 51554; -.
DR Pharos; Q9NPB9; Tbio.
DR PRO; PR:Q9NPB9; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NPB9; protein.
DR Bgee; ENSG00000129048; Expressed in duodenum and 103 other tissues.
DR ExpressionAtlas; Q9NPB9; baseline and differential.
DR Genevisible; Q9NPB9; HS.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0019957; F:C-C chemokine binding; IBA:GO_Central.
DR GO; GO:0016493; F:C-C chemokine receptor activity; IBA:GO_Central.
DR GO; GO:0004950; F:chemokine receptor activity; IDA:UniProtKB.
DR GO; GO:0005044; F:scavenger receptor activity; IEA:InterPro.
DR GO; GO:0019722; P:calcium-mediated signaling; IBA:GO_Central.
DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR InterPro; IPR005383; ACKR4.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR01558; CHEMOKINER11.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Endosome; G-protein coupled receptor;
KW Glycoprotein; Membrane; Phosphoprotein; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..350
FT /note="Atypical chemokine receptor 4"
FT /id="PRO_0000069296"
FT TOPO_DOM 1..42
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..63
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 64..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..108
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 109..113
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..134
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..175
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 176..201
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..240
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..261
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 262..289
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 290..310
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 311..350
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 6
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 112..184
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ 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
