ID ACKR4_MOUSE Reviewed; 350 AA.
AC Q924I3; Q8C0M1; Q8QZW9;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 27-MAR-2024, entry version 148.
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=Ccr11, Ccrl1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=11063828; DOI=10.1016/s0165-5728(00)00371-4;
RA Dorf M.E., Berman M.A., Tanabe S., Heesen M., Luo Y.;
RT "Astrocytes express functional chemokine receptors.";
RL J. Neuroimmunol. 111:109-121(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN CHEMOKINES BINDING, AND TISSUE
RP 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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RA Luo Y., Berman M.A., Fischer F.R., Abromson-Leeman S.R., Kuziel W.A.,
RA Gerard C., Dorf M.E.;
RT "RANTES and eotaxin stimulate chemotaxis, chemokine/cytokine synthesis, and
RT receptor modulation in murine astrocytes.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=23152546; DOI=10.1182/blood-2012-06-434886;
RA Bunting M.D., Comerford I., Seach N., Hammett M.V., Asquith D.L.,
RA Koerner H., Boyd R.L., Nibbs R.J., McColl S.R.;
RT "CCX-CKR deficiency alters thymic stroma impairing thymocyte development
RT and promoting autoimmunity.";
RL Blood 121:118-128(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 and inhibits spontaneous autoimmunity.
CC {ECO:0000269|PubMed:11981810, ECO:0000269|PubMed:23152546}.
CC -!- SUBUNIT: Forms heteromers with CXCR3. Interacts with ARRB1 and ARRB2
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000250}. Recycling endosome
CC {ECO:0000250}. Cell membrane {ECO:0000250}; Multi-pass membrane protein
CC {ECO:0000250}. Note=Predominantly localizes to endocytic vesicles, and
CC upon stimulation by the ligand is internalized via caveolae. Once
CC internalized, the ligand dissociates from the receptor, and is targeted
CC to degradation while the receptor is recycled back to the cell membrane
CC (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in lung, heart, spleen, skeletal muscle,
CC testis, astrocytes and microglia. Expressed by cortical thymic
CC epithelial cells. {ECO:0000269|PubMed:11063828,
CC ECO:0000269|PubMed:11981810, ECO:0000269|PubMed:23152546}.
CC -!- PTM: The Ser/Thr residues in the C-terminal cytoplasmic tail may be
CC phosphorylated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice have a larger thymus with relatively fewer
CC cortical thymic epithelial cells and this is associated with severe
CC reductions in cortical CCL25 distribution and accumulation of DN2
CC thymocyte precursor cells in the medulla. The downstream effects
CC materialize in reduced proportions of DN3 cells and significantly
CC reduced numbers of cortical DN3 cells. Aberrant thymocyte development
CC culminates in increased prevalence of spontaneous autoimmune-like
CC disease, characterized by lymphocytic infiltration of peripheral
CC organs. {ECO:0000269|PubMed:23152546}.
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; AF306532; AAK81712.1; -; mRNA.
DR EMBL; AY072796; AAL68400.1; -; mRNA.
DR EMBL; AY072938; AAL68962.1; -; mRNA.
DR EMBL; AK030643; BAC27061.1; -; mRNA.
DR EMBL; AK042430; BAC31258.1; -; mRNA.
DR CCDS; CCDS23459.1; -.
DR RefSeq; NP_663746.2; NM_145700.2.
DR RefSeq; XP_006511797.1; XM_006511734.3.
DR RefSeq; XP_006511798.1; XM_006511735.3.
DR AlphaFoldDB; Q924I3; -.
DR SMR; Q924I3; -.
DR STRING; 10090.ENSMUSP00000075507; -.
DR GlyCosmos; Q924I3; 2 sites, No reported glycans.
DR GlyGen; Q924I3; 2 sites.
DR PhosphoSitePlus; Q924I3; -.
DR PaxDb; 10090-ENSMUSP00000075507; -.
DR Antibodypedia; 17718; 272 antibodies from 28 providers.
DR DNASU; 252837; -.
DR Ensembl; ENSMUST00000076147.6; ENSMUSP00000075507.4; ENSMUSG00000079355.6.
DR Ensembl; ENSMUST00000188000.2; ENSMUSP00000140792.2; ENSMUSG00000079355.6.
DR Ensembl; ENSMUST00000219146.2; ENSMUSP00000152036.2; ENSMUSG00000079355.6.
DR GeneID; 252837; -.
DR KEGG; mmu:252837; -.
DR UCSC; uc009rhh.2; mouse.
DR AGR; MGI:2181676; -.
DR CTD; 51554; -.
DR MGI; MGI:2181676; Ackr4.
DR VEuPathDB; HostDB:ENSMUSG00000079355; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234667; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; Q924I3; -.
DR OMA; YGYWRRQ; -.
DR OrthoDB; 5311329at2759; -.
DR PhylomeDB; Q924I3; -.
DR TreeFam; TF330966; -.
DR Reactome; R-MMU-380108; Chemokine receptors bind chemokines.
DR BioGRID-ORCS; 252837; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Ccrl2; mouse.
DR PRO; PR:Q924I3; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q924I3; Protein.
DR Bgee; ENSMUSG00000079355; Expressed in lip and 85 other cell types or tissues.
DR Genevisible; Q924I3; MM.
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: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; ISS: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:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR CDD; cd15176; 7tmA_ACKR4_CCR11; 1.
DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR InterPro; IPR005383; ACKR4.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR10489:SF733; ATYPICAL CHEMOKINE RECEPTOR 4; 1.
DR PANTHER; PTHR10489; CELL ADHESION MOLECULE; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR01558; CHEMOKINER11.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
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; Endosome; G-protein coupled receptor; Glycoprotein;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..350
FT /note="Atypical chemokine receptor 4"
FT /id="PRO_0000069297"
FT TOPO_DOM 1..41
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 42..62
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 63..77
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 78..99
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 100..114
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..135
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 136..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..199
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 200..220
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 221..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 CONFLICT 50
FT /note="V -> M (in Ref. 4; BAC27061)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="V -> L (in Ref. 2; AAL68400/AAL68962)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 350 AA; 39531 MW; C5F7D9DC949CECCF CRC64;
MALELNQSAE YYYEENEMNY THDYSQYEVI CIKEEVRQFA KVFLPAFFTV AFVTGLAGNS
VVVAIYAYYK KQRTKTDVYI LNLAVADLLL LITLPFWAVN AVHGWILGKM MCKVTSALYT
VNFVSGMQFL ACISIDRYWA ITKAPSQSGA GRPCWIICCC VWMAAILLSI PQLVFYTVNQ
NARCTPIFPH HLGTSLKASI QMLEIGIGFV VPFLIMGVCY ASTARALIKM PNIKKSRPLR
VLLAVVVVFI VTQLPYNVVK FCQAIDAIYL LITSCDMSKR MDVAIQVTES IALFHSCLNP
ILYVFMGASF KNYIMKVAKK YGSWRRQRQN VEEIPFDSEG PTEPTSSFTI
//
