ACKR3_RAT
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 03-AUG-2022, entry version 150.
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 (E14 to
CC P56). Strong expression detected in the cranial connective tissue
CC surrounding the brain at E14-E15. In the cortex, expressed mainly in
CC the marginal zone at preplate stage (E14), with expression increasing
CC strongly in the marginal zone/layer I between E15 and E18 and declining
CC rapidly in layer I after P0. Expression emerges in the lateral part of
CC cortical plate at E15 and increases in the medial and lateral parts
CC between E15 and E17. Expression not detected in the cortical
CC ventricular and subventricular zones at the early embryonic stages but
CC emerges at E18. Expressed in GABAergic precursors and in some reelin-
CC expressing Cajal-Ratzius cells, in neurons forming the cortical plate
CC and sparsely in the developing dentate gyrus and cerebellar external
CC germinal layer. In the ventral telencephalon, expressed in the
CC germinative zone of the ganglionic eminences and in GABAergic neurons
CC forming the caudate putamen between E14 and E18.
CC {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}.
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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 GlyGen; O89039; 2 sites.
DR iPTMnet; O89039; -.
DR PhosphoSitePlus; O89039; -.
DR PaxDb; O89039; -.
DR PRIDE; O89039; -.
DR Ensembl; ENSRNOT00000026558; ENSRNOP00000026558; ENSRNOG00000019622.
DR Ensembl; ENSRNOT00000098919; ENSRNOP00000091223; ENSRNOG00000019622.
DR Ensembl; ENSRNOT00000108608; ENSRNOP00000094961; ENSRNOG00000019622.
DR Ensembl; ENSRNOT00000113813; ENSRNOP00000088201; ENSRNOG00000019622.
DR Ensembl; ENSRNOT00000115723; ENSRNOP00000086994; ENSRNOG00000019622.
DR Ensembl; ENSRNOT00000116518; ENSRNOP00000083985; ENSRNOG00000019622.
DR GeneID; 84348; -.
DR KEGG; rno:84348; -.
DR UCSC; RGD:620601; rat.
DR CTD; 57007; -.
DR RGD; 620601; Ackr3.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244811; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; O89039; -.
DR OMA; HFIPFSC; -.
DR OrthoDB; 819032at2759; -.
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 tissues.
DR Genevisible; O89039; RN.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
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 InterPro; IPR001416; ACKR3.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR10489:SF931; PTHR10489:SF931; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00646; RDC1ORPHANR.
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 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
