ID ACKR3_RAT Reviewed; 362 AA. AC O89039; Q9JLZ0; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 25-JAN-2012, sequence version 2. DT 24-JAN-2024, entry version 158. DE RecName: Full=Atypical chemokine receptor 3 {ECO:0000305}; DE AltName: Full=C-X-C chemokine receptor type 7; DE Short=CXC-R7; DE Short=CXCR-7; DE AltName: Full=Chemokine orphan receptor 1; DE AltName: Full=G-protein coupled receptor RDC1 homolog; DE Short=RDC-1; GN Name=Ackr3 {ECO:0000312|RGD:620601}; Synonyms=Cmkor1, Cxcr7, Rdc1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Sprague-Dawley; TISSUE=Lung; RA Mirtella A., Lowe S.R., Bartlett T.J., Drake W., Clark A.J.; RT "Investigation of the role of rat RDC-1 as a putative calcitonin gene- RT related peptide receptor."; RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Muscle; RA Xie P., Fu A.K.Y., Ip N.Y.; RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=18615560; DOI=10.1002/cne.21780; RA Schonemeier B., Kolodziej A., Schulz S., Jacobs S., Hoellt V., Stumm R.; RT "Regional and cellular localization of the CXCl12/SDF-1 chemokine receptor RT CXCR7 in the developing and adult rat brain."; RL J. Comp. Neurol. 510:207-220(2008). RN [5] RP TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=18513805; DOI=10.1016/j.jneuroim.2008.04.010; RA Schonemeier B., Schulz S., Hoellt V., Stumm R.; RT "Enhanced expression of the CXCl12/SDF-1 chemokine receptor CXCR7 after RT cerebral ischemia in the rat brain."; RL J. Neuroimmunol. 198:39-45(2008). RN [6] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=20018651; DOI=10.1073/pnas.0912852107; RA Rajagopal S., Kim J., Ahn S., Craig S., Lam C.M., Gerard N.P., Gerard C., RA Lefkowitz R.J.; RT "Beta-arrestin- but not G protein-mediated signaling by the 'decoy' RT receptor CXCR7."; RL Proc. Natl. Acad. Sci. U.S.A. 107:628-632(2010). RN [7] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=21655198; DOI=10.1371/journal.pone.0020680; RA Shimizu S., Brown M., Sengupta R., Penfold M.E., Meucci O.; RT "CXCR7 protein expression in human adult brain and differentiated RT neurons."; RL PLoS ONE 6:E20680-E20680(2011). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). 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 CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein- CC mediated signal transduction but instead induces beta-arrestin CC recruitment, leading to ligand internalization and activation of MAPK CC signaling pathway. Required for regulation of CXCR4 protein levels in CC migrating interneurons, thereby adapting their chemokine CC responsiveness. In glioma cells, transduces signals via MEK/ERK CC pathway, mediating resistance to apoptosis. Promotes cell growth and CC survival. Not involved in cell migration, adhesion or proliferation of CC normal hematopoietic progenitors but activated by CXCL11 in malignant CC hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) CC and enhanced cell adhesion and migration. Plays a regulatory role in CC CXCR4-mediated activation of cell surface integrins by CXCL12. Required CC for heart valve development. {ECO:0000269|PubMed:20018651}. 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 CXCL11 and CXCL12/SDF1 (By similarity). Chemokine binding does not CC activate G-protein-mediated signal transduction but instead induces CC beta-arrestin recruitment, leading to ligand internalization and CC activation of MAPK signaling pathway (PubMed:20018651). Required for CC regulation of CXCR4 protein levels in migrating interneurons, thereby CC adapting their chemokine responsiveness. In glioma cells, transduces CC signals via MEK/ERK pathway, mediating resistance to apoptosis. CC Promotes cell growth and survival. Not involved in cell migration, CC adhesion or proliferation of normal hematopoietic progenitors but CC activated by CXCL11 in malignant hemapoietic cells, leading to CC phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and CC migration. Plays a regulatory role in CXCR4-mediated activation of cell CC surface integrins by CXCL12. Required for heart valve development. CC Regulates axon guidance in the oculomotor system through the regulation CC of CXCL12 levels (By similarity). {ECO:0000250|UniProtKB:P25106, CC ECO:0000269|PubMed:20018651}. CC -!- SUBUNIT: Homodimer. Can form heterodimers with CXCR4; CC heterodimerization may regulate CXCR4 signaling activity. Interacts CC with ARRB1 and ARRB2. {ECO:0000250|UniProtKB:P25106}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21655198}; CC Multi-pass membrane protein {ECO:0000269|PubMed:21655198}. Early CC endosome {ECO:0000305|PubMed:21655198}. Recycling endosome CC {ECO:0000305|PubMed:21655198}. Note=Predominantly localizes to CC endocytic vesicles, and upon stimulation by the ligand is internalized CC via clathrin-coated pits in a beta-arrestin -dependent manner. 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|UniProtKB:P25106}. CC -!- TISSUE SPECIFICITY: Expressed in vascular smooth muscle cells (at CC protein level). In brain, expressed in blood vessels, pyramidal cells CC in hippocampal subfield CA3, mature dentate gyrus granule cells, CC ventricle walls, olfactory bulb, accumbens shell, supraoptic, CC lateroanterior and ventromedial hypothalamic nuclei, medial region of CC thalamus, and motor nuclei, central gray and raphe magnus nucleus of CC brain stem. Detected in primary neurons, GABAergic neurons, astrocytes, CC cerebral cortex, ventral striatum and choroid plexus. Not detected in CC mesencephalon. {ECO:0000269|PubMed:18513805, CC ECO:0000269|PubMed:18615560, ECO:0000269|PubMed:20018651, CC ECO:0000269|PubMed:21655198}. CC -!- DEVELOPMENTAL STAGE: Expressed in the ventral and dorsal parts of CC telencephalon at all developmental stages of brain analyzed (14 dpc to CC P56). Strong expression detected in the cranial connective tissue CC surrounding the brain at 14 dpc to 15 dpc. In the cortex, expressed CC mainly in the marginal zone at preplate stage (14 dpc), with expression CC increasing strongly in the marginal zone/layer I between 15 dpc and 18 CC dpc and declining rapidly in layer I after P0. Expression emerges in CC the lateral part of cortical plate at 15 dpc and increases in the CC medial and lateral parts between 15 dpc and 17 dpc. Expression not CC detected in the cortical ventricular and subventricular zones at the CC early embryonic stages but emerges at 18 dpc. Expressed in GABAergic CC precursors and in some reelin-expressing Cajal-Ratzius cells, in CC neurons forming the cortical plate and sparsely in the developing CC dentate gyrus and cerebellar external germinal layer. In the ventral CC telencephalon, expressed in the germinative zone of the ganglionic CC eminences and in GABAergic neurons forming the caudate putamen between CC 14 dpc and 18 dpc. {ECO:0000269|PubMed:18615560}. CC -!- INDUCTION: By ischemia. Up-regulated in the cingulate, retrosplenial CC and frontal areas of the cortex ipsilateral to middle cerebral artery CC occlusion (MCAO) by 163% at 6 hours, 220% at 2 days and 89% at 4 days CC after ischemia-onset, with expression reduced back to control level at CC 10 days after MCAO. Expression is almost undetectable in the infarct CC area between days 2 and 10 after MCAO. {ECO:0000269|PubMed:18513805}. CC -!- DOMAIN: The C-terminal cytoplasmic tail, plays a key role in: correct CC trafficking to the cell membrane, recruitment of beta-arrestin, CC ubiquitination, and in chemokine scavenging and signaling functions. CC The Ser/Thr residues and the Lys residues in the C-terminal cytoplasmic CC tail are essential for beta-arrestin recruitment and ubiquitination CC respectively. {ECO:0000250|UniProtKB:P25106}. CC -!- PTM: The Ser/Thr residues in the C-terminal cytoplasmic tail may be CC phosphorylated. {ECO:0000250|UniProtKB:P25106}. CC -!- PTM: Ubiquitinated at the Lys residues in its C-terminal cytoplasmic CC tail and is essential for correct trafficking from and to the cell CC membrane. Deubiquitinated by CXCL12-stimulation in a reversible manner. CC {ECO:0000250|UniProtKB:P25106}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC Atypical chemokine receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00521}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ010828; CAA09370.1; -; mRNA. DR EMBL; AF118816; AAF34338.1; -; mRNA. DR EMBL; CH473997; EDL92073.1; -; Genomic_DNA. DR EMBL; CH473997; EDL92074.1; -; Genomic_DNA. DR RefSeq; NP_445804.1; NM_053352.1. DR RefSeq; XP_006245541.1; XM_006245479.3. DR AlphaFoldDB; O89039; -. DR SMR; O89039; -. DR IntAct; O89039; 2. DR STRING; 10116.ENSRNOP00000026558; -. DR BindingDB; O89039; -. DR ChEMBL; CHEMBL4739671; -. DR GuidetoPHARMACOLOGY; 80; -. DR GlyCosmos; O89039; 2 sites, No reported glycans. DR GlyGen; O89039; 2 sites. DR iPTMnet; O89039; -. DR PhosphoSitePlus; O89039; -. DR PaxDb; 10116-ENSRNOP00000026558; -. DR Ensembl; ENSRNOT00000026558.4; ENSRNOP00000026558.2; ENSRNOG00000019622.4. DR Ensembl; ENSRNOT00000098919.1; ENSRNOP00000091223.1; ENSRNOG00000019622.4. DR Ensembl; ENSRNOT00000108608.1; ENSRNOP00000094961.1; ENSRNOG00000019622.4. DR Ensembl; ENSRNOT00000113813.1; ENSRNOP00000088201.1; ENSRNOG00000019622.4. DR Ensembl; ENSRNOT00000115723.1; ENSRNOP00000086994.1; ENSRNOG00000019622.4. DR Ensembl; ENSRNOT00000116518.1; ENSRNOP00000083985.1; ENSRNOG00000019622.4. DR Ensembl; ENSRNOT00055017132; ENSRNOP00055013784; ENSRNOG00055010155. DR Ensembl; ENSRNOT00055017135; ENSRNOP00055013787; ENSRNOG00055010155. DR Ensembl; ENSRNOT00055017137; ENSRNOP00055013789; ENSRNOG00055010155. DR Ensembl; ENSRNOT00055017144; ENSRNOP00055013796; ENSRNOG00055010155. DR Ensembl; ENSRNOT00055017145; ENSRNOP00055013797; ENSRNOG00055010155. DR Ensembl; ENSRNOT00060017945; ENSRNOP00060013949; ENSRNOG00060010605. DR Ensembl; ENSRNOT00060017948; ENSRNOP00060013953; ENSRNOG00060010605. DR Ensembl; ENSRNOT00060017956; ENSRNOP00060013961; ENSRNOG00060010605. DR Ensembl; ENSRNOT00060017958; ENSRNOP00060013963; ENSRNOG00060010605. DR Ensembl; ENSRNOT00060017959; ENSRNOP00060013964; ENSRNOG00060010605. DR Ensembl; ENSRNOT00065033508; ENSRNOP00065026799; ENSRNOG00065019894. DR Ensembl; ENSRNOT00065033514; ENSRNOP00065026806; ENSRNOG00065019894. DR Ensembl; ENSRNOT00065033517; ENSRNOP00065026809; ENSRNOG00065019894. DR Ensembl; ENSRNOT00065033532; ENSRNOP00065026824; ENSRNOG00065019894. DR Ensembl; ENSRNOT00065033543; ENSRNOP00065026833; ENSRNOG00065019894. DR GeneID; 84348; -. DR KEGG; rno:84348; -. DR UCSC; RGD:620601; rat. DR AGR; RGD:620601; -. DR CTD; 57007; -. DR RGD; 620601; Ackr3. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT01090000260051; -. DR HOGENOM; CLU_009579_8_3_1; -. DR InParanoid; O89039; -. DR OMA; SLVHCCI; -. DR OrthoDB; 5353045at2759; -. DR TreeFam; TF333489; -. DR Reactome; R-RNO-380108; Chemokine receptors bind chemokines. DR Reactome; R-RNO-418594; G alpha (i) signalling events. DR PRO; PR:O89039; -. DR Proteomes; UP000002494; Chromosome 9. DR Proteomes; UP000234681; Chromosome 9. DR Bgee; ENSRNOG00000019622; Expressed in esophagus and 20 other cell types or tissues. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:0005905; C:clathrin-coated pit; ISS:UniProtKB. DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; ISS:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. 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:0019958; F:C-X-C chemokine binding; ISS:UniProtKB. DR GO; GO:0016494; F:C-X-C chemokine receptor activity; ISO:RGD. DR GO; GO:0015026; F:coreceptor activity; IEA:InterPro. DR GO; GO:0005044; F:scavenger receptor activity; ISS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:InterPro. DR GO; GO:0019722; P:calcium-mediated signaling; IBA:GO_Central. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central. DR GO; GO:0070098; P:chemokine-mediated signaling pathway; ISO:RGD. DR GO; GO:0006955; P:immune response; IBA:GO_Central. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD. DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; ISO:RGD. DR GO; GO:0021557; P:oculomotor nerve development; ISS:UniProtKB. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:1905322; P:positive regulation of mesenchymal stem cell migration; IMP:RGD. DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB. DR GO; GO:0001570; P:vasculogenesis; IEA:InterPro. DR CDD; cd14987; 7tmA_ACKR3_CXCR7; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR001416; ACKR3. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR047143; GPER1-like. DR PANTHER; PTHR24226; G-PROTEIN COUPLED RECEPTOR 182 AND ESTROGEN RECEPTOR 1; 1. DR PANTHER; PTHR24226:SF4; G_PROTEIN_RECEP_F1_2 DOMAIN-CONTAINING PROTEIN; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR00646; RDC1ORPHANR. 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. DR Genevisible; O89039; RN. PE 1: Evidence at protein level; KW Cell adhesion; Cell membrane; Developmental protein; Disulfide bond; KW Endosome; G-protein coupled receptor; Glycoprotein; Membrane; KW Phosphoprotein; Receptor; Reference proteome; Transducer; Transmembrane; KW Transmembrane helix; Ubl conjugation. FT CHAIN 1..362 FT /note="Atypical chemokine receptor 3" FT /id="PRO_0000070103" FT TOPO_DOM 1..47 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 48..68 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 69..81 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 82..102 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 103..118 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 119..139 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 140..162 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 163..183 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 184..213 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 214..234 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 235..252 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 253..273 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 274..296 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 297..319 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 320..362 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 324..362 FT /note="C-terminal cytoplasmic tail" FT /evidence="ECO:0000250" FT MOD_RES 347 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P56485" FT MOD_RES 350 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 355 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P56485" FT CARBOHYD 13 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 22 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 117..196 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT CONFLICT 17 FT /note="I -> S (in Ref. 1; CAA09370)" FT /evidence="ECO:0000305" FT CONFLICT 161 FT /note="R -> L (in Ref. 1; CAA09370)" FT /evidence="ECO:0000305" FT CONFLICT 361 FT /note="T -> A (in Ref. 1; CAA09370)" FT /evidence="ECO:0000305" SQ SEQUENCE 362 AA; 41650 MW; C47D1DD678697CFD CRC64; MDVHLFDYVE PGNYSDINWP CNSSDCIVVD TVQCPAMPNK NVLLYTLSFI YIFIFVIGMI ANSVVVWVNI QAKTTGYDTH CYILNLAIAD LWVVITIPVW VVSLVQHNQW PMGELTCKIT HLIFSINLFG SIFFLACMSV DRYLSITYFT STSSYKKKMV RRVVCVLVWL LAFFVSLPDT YYLKTVTSAS NNETYCRSFY PEHSIKEWLI GMELVSVILG FAVPFTIIAI FYFLLARAMS ASGDQEKHSS RKIIFSYVVV FLVCWLPYHF VVLLDIFSIL HYIPFTCQLE NVLFTALHVT QCLSLVHCCV NPVLYSFINR NYRYELMKAF IFKYSAKTGL TKLIDASRVS ETEYSALEQN TK //