ACKR3_CANLF
ID ACKR3_CANLF Reviewed; 362 AA.
AC P11613;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Atypical chemokine receptor 3;
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;
DE Short=RDC-1;
GN Name=ACKR3; Synonyms=CMKOR1, CXCR7, RDC1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Thyroid;
RX PubMed=2541503; DOI=10.1126/science.2541503;
RA Libert F., Parmentier M., Lefort A., Dinsart C., van Sande J., Maenhaut C.,
RA Simons M.-J., Dumont J.E., Vassart G.;
RT "Selective amplification and cloning of four new members of the G protein-
RT coupled receptor family.";
RL Science 244:569-572(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Thyroid;
RX PubMed=2159631; DOI=10.1093/nar/18.7.1917;
RA Libert F., Parmentier M., Lefort A., Dumont J.E., Vassart G.;
RT "Complete nucleotide sequence of a putative G protein coupled receptor:
RT RDC1.";
RL Nucleic Acids Res. 18:1917-1917(1990).
RN [3]
RP SHOWS THAT RDC1 IS NOT A VIP RECEPTOR.
RX PubMed=1373390; DOI=10.1016/0014-5793(92)80184-i;
RA Cook J.S., Wolsing D.H., Lameh J., Olson C.A., Correa P.E., Sadee W.,
RA Blumnthal E.M., Rosenbaum J.S.;
RT "Characterization of the RDC1 gene which encodes the canine homolog of a
RT proposed human VIP receptor. Expression does not correlate with an increase
RT in VIP binding sites.";
RL FEBS Lett. 300:149-152(1992).
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. Regulates axon guidance in the oculomotor
CC system through the regulation of CXCL12 levels.
CC {ECO:0000250|UniProtKB:P25106}.
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:0000250|UniProtKB:P25106};
CC Multi-pass membrane protein {ECO:0000255}. Early endosome
CC {ECO:0000250|UniProtKB:P25106}. Recycling endosome
CC {ECO:0000250|UniProtKB:P25106}. 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
CC membrane. {ECO:0000250|UniProtKB:P25106}.
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; X14048; CAA32206.1; -; mRNA.
DR PIR; A30341; A30341.
DR RefSeq; NP_001003281.1; NM_001003281.2.
DR RefSeq; XP_005635961.1; XM_005635904.2.
DR RefSeq; XP_005635962.1; XM_005635905.2.
DR RefSeq; XP_005635963.1; XM_005635906.2.
DR AlphaFoldDB; P11613; -.
DR SMR; P11613; -.
DR STRING; 9612.ENSCAFP00000017975; -.
DR BindingDB; P11613; -.
DR ChEMBL; CHEMBL4739676; -.
DR PaxDb; P11613; -.
DR Ensembl; ENSCAFT00845048801; ENSCAFP00845038289; ENSCAFG00845027671.
DR Ensembl; ENSCAFT00845048817; ENSCAFP00845038301; ENSCAFG00845027671.
DR GeneID; 403964; -.
DR KEGG; cfa:403964; -.
DR CTD; 57007; -.
DR VEuPathDB; HostDB:ENSCAFG00845027671; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244811; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; P11613; -.
DR OMA; HFIPFSC; -.
DR OrthoDB; 819032at2759; -.
DR TreeFam; TF333489; -.
DR Reactome; R-CFA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-CFA-418594; G alpha (i) signalling events.
DR Proteomes; UP000002254; Chromosome 25.
DR Bgee; ENSCAFG00000012206; Expressed in bone marrow and 48 other 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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IEA:Ensembl.
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:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
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: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 2: Evidence at transcript 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_0000070100"
FT TOPO_DOM 1..40
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 41..61
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 62..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:0000250|UniProtKB:P56485"
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 CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 117..196
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 362 AA; 41416 MW; AA1B288DB9674343 CRC64;
MDLHLFDYAE PGNFSDISWP CNSSDCIVVD TVLCPNMPNK SVLLYTLSFI YIFIFVIGMI
ANSVVVWVNI QAKTTGYDTH CYILNLAIAD LWVVVTIPVW VVSLVQHNQW PMGELTCKIT
HLIFSINLFG SIFFLTCMSV DRYLSITYFA STSSRRKKVV RRAVCVLVWL LAFCVSLPDT
YYLKTVTSAS NNETYCRSFY PEHSVKEWLI SMELVSVVLG FAIPFCVIAV FYCLLARAIS
ASSDQEKQSS RKIIFSYVVV FLVCWLPYHV VVLLDIFSIL HYIPFTCQLE NFLFTALHVT
QCLSLVHCCV NPVLYSFINR NYRYELMKAF IFKYSAKTGL TKLIDASRVS ETEYSALEQN
AK
