ACKR3_HUMAN
ID ACKR3_HUMAN Reviewed; 362 AA.
AC P25106; A8K6J4; Q53RV4; Q8NE10; Q92938; Q92986;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 205.
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 159;
DE AltName: Full=G-protein coupled receptor RDC1 homolog;
DE Short=RDC-1;
GN Name=ACKR3 {ECO:0000312|HGNC:HGNC:23692};
GN Synonyms=CMKOR1, CXCR7 {ECO:0000303|PubMed:17804806}, GPR159,
GN RDC1 {ECO:0000303|PubMed:16107333};
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 [GENOMIC DNA / MRNA].
RX PubMed=1675791; DOI=10.1073/pnas.88.11.4986;
RA Sreedharan S.P., Robichon A., Peterson K.E., Goetzl E.J.;
RT "Cloning and expression of the human vasoactive intestinal peptide
RT receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:4986-4990(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Oates E.L., Roos B.A., Howard G.A.;
RT "Coding and 3'-noncoding sequence of human RDC1, an orphan G protein-
RT coupled receptor.";
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Bi A., Yu L., Zhang Q., Tu Q., Xing Y., Zheng L.;
RT "Human RDC1 gene.";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Martin A.L., Kaighin V.A., Aronstam R.S.;
RT "Isolation of cDNA coding for Homo sapiens chemokine orphan receptor 1
RT (CMKOR1).";
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [9]
RP DOUBTS ON THE ORIGINAL FUNCTION.
RX PubMed=1315461; DOI=10.1016/0165-6147(92)90037-7;
RA Nagata S., Ishihara T., Robberecht P., Libert F., Parmentier M.,
RA Christophe J., Vassart G.;
RT "RDC1 may not be VIP receptor.";
RL Trends Pharmacol. Sci. 13:102-103(1992).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16107333; DOI=10.1074/jbc.m508234200;
RA Balabanian K., Lagane B., Infantino S., Chow K.Y., Harriague J., Moepps B.,
RA Arenzana-Seisdedos F., Thelen M., Bachelerie F.;
RT "The chemokine SDF-1/CXCL12 binds to and signals through the orphan
RT receptor RDC1 in T lymphocytes.";
RL J. Biol. Chem. 280:35760-35766(2005).
RN [11]
RP FUNCTION.
RX PubMed=16940167; DOI=10.1084/jem.20052144;
RA Burns J.M., Summers B.C., Wang Y., Melikian A., Berahovich R., Miao Z.,
RA Penfold M.E., Sunshine M.J., Littman D.R., Kuo C.J., Wei K., McMaster B.E.,
RA Wright K., Howard M.C., Schall T.J.;
RT "A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival,
RT cell adhesion, and tumor development.";
RL J. Exp. Med. 203:2201-2213(2006).
RN [12]
RP TISSUE SPECIFICITY.
RX PubMed=16455976; DOI=10.4049/jimmunol.176.4.2197;
RA Infantino S., Moepps B., Thelen M.;
RT "Expression and regulation of the orphan receptor RDC1 and its putative
RT ligand in human dendritic and B cells.";
RL J. Immunol. 176:2197-2207(2006).
RN [13]
RP FUNCTION, AND HETERODIMERIZATION.
RX PubMed=17804806; DOI=10.1073/pnas.0702229104;
RA Sierro F., Biben C., Martinez-Munoz L., Mellado M., Ransohoff R.M., Li M.,
RA Woehl B., Leung H., Groom J., Batten M., Harvey R.P., Martinez-A C.,
RA Mackay C.R., Mackay F.;
RT "Disrupted cardiac development but normal hematopoiesis in mice deficient
RT in the second CXCL12/SDF-1 receptor, CXCR7.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:14759-14764(2007).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18653785; DOI=10.1189/jlb.0208088;
RA Hartmann T.N., Grabovsky V., Pasvolsky R., Shulman Z., Buss E.C.,
RA Spiegel A., Nagler A., Lapidot T., Thelen M., Alon R.;
RT "A crosstalk between intracellular CXCR7 and CXCR4 involved in rapid
RT CXCL12-triggered integrin activation but not in chemokine-triggered
RT motility of human T lymphocytes and CD34+ cells.";
RL J. Leukoc. Biol. 84:1130-1140(2008).
RN [15]
RP FUNCTION, AND SUBUNIT.
RX PubMed=19380869; DOI=10.1182/blood-2008-12-196618;
RA Levoye A., Balabanian K., Baleux F., Bachelerie F., Lagane B.;
RT "CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein
RT signaling.";
RL Blood 113:6085-6093(2009).
RN [16]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19641136; DOI=10.4049/jimmunol.0900269;
RA Zabel B.A., Wang Y., Lewen S., Berahovich R.D., Penfold M.E., Zhang P.,
RA Powers J., Summers B.C., Miao Z., Zhao B., Jalili A.,
RA Janowska-Wieczorek A., Jaen J.C., Schall T.J.;
RT "Elucidation of CXCR7-mediated signaling events and inhibition of CXCR4-
RT mediated tumor cell transendothelial migration by CXCR7 ligands.";
RL J. Immunol. 183:3204-3211(2009).
RN [17]
RP FUNCTION, AND SUBUNIT.
RX PubMed=19255243; DOI=10.1124/mol.108.053389;
RA Kalatskaya I., Berchiche Y.A., Gravel S., Limberg B.J., Rosenbaum J.S.,
RA Heveker N.;
RT "AMD3100 is a CXCR7 ligand with allosteric agonist properties.";
RL Mol. Pharmacol. 75:1240-1247(2009).
RN [18]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=20388803; DOI=10.1158/0008-5472.can-09-3642;
RA Hattermann K., Held-Feindt J., Lucius R., Muerkoster S.S., Penfold M.E.,
RA Schall T.J., Mentlein R.;
RT "The chemokine receptor CXCR7 is highly expressed in human glioma cells and
RT mediates antiapoptotic effects.";
RL Cancer Res. 70:3299-3308(2010).
RN [19]
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 [20]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=20887389; DOI=10.1111/j.1600-0609.2010.01531.x;
RA Tarnowski M., Liu R., Wysoczynski M., Ratajczak J., Kucia M.,
RA Ratajczak M.Z.;
RT "CXCR7: a new SDF-1-binding receptor in contrast to normal CD34(+)
RT progenitors is functional and is expressed at higher level in human
RT malignant hematopoietic cells.";
RL Eur. J. Haematol. 85:472-483(2010).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-145 AND THR-147.
RX PubMed=20161793; DOI=10.1371/journal.pone.0009175;
RA Naumann U., Cameroni E., Pruenster M., Mahabaleshwar H., Raz E.,
RA Zerwes H.G., Rot A., Thelen M.;
RT "CXCR7 functions as a scavenger for CXCL12 and CXCL11.";
RL PLoS ONE 5:E9175-E9175(2010).
RN [22]
RP FUNCTION.
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 [23]
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 [24]
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 [25]
RP FUNCTION, SUBCELLULAR LOCATION, C-TERMINAL CYTOPLASMIC TAIL, AND
RP INTERACTION WITH ARRB2.
RX PubMed=22300987; DOI=10.1016/j.biocel.2012.01.007;
RA Ray P., Mihalko L.A., Coggins N.L., Moudgil P., Ehrlich A., Luker K.E.,
RA Luker G.D.;
RT "Carboxy-terminus of CXCR7 regulates receptor localization and function.";
RL Int. J. Biochem. Cell Biol. 44:669-678(2012).
RN [26]
RP UBIQUITINATION, C-TERMINAL CYTOPLASMIC TAIL, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH ARRB1 AND ARRB2.
RX PubMed=22457824; DOI=10.1371/journal.pone.0034192;
RA Canals M., Scholten D.J., de Munnik S., Han M.K., Smit M.J., Leurs R.;
RT "Ubiquitination of CXCR7 controls receptor trafficking.";
RL PLoS ONE 7:E34192-E34192(2012).
RN [27]
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 [28]
RP REVIEW.
RX PubMed=23153575; DOI=10.1016/j.molmed.2012.10.004;
RA Sanchez-Martin L., Sanchez-Mateos P., Cabanas C.;
RT "CXCR7 impact on CXCL12 biology and disease.";
RL Trends Mol. Med. 19:12-22(2013).
RN [29]
RP VARIANT OCABSN MET-258, CHARACTERIZATION OF VARIANT OCABSN MET-258,
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=31211835; DOI=10.1093/hmg/ddz137;
RA Whitman M.C., Miyake N., Nguyen E.H., Bell J.L., Matos Ruiz P.M.,
RA Chan W.M., Di Gioia S.A., Mukherjee N., Barry B.J., Bosley T.M., Khan A.O.,
RA Engle E.C.;
RT "Decreased ACKR3 (CXCR7) function causes oculomotor synkinesis in mice and
RT humans.";
RL Hum. Mol. Genet. 28:3113-3125(2019).
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 (PubMed:16107333, PubMed:19255243,
CC PubMed:19380869, PubMed:20161793, PubMed:22300987). Chemokine binding
CC does not activate G-protein-mediated signal transduction but instead
CC induces beta-arrestin recruitment, leading to ligand internalization
CC and activation of MAPK signaling pathway (PubMed:16940167,
CC PubMed:18653785, PubMed:20018651). Required for regulation of CXCR4
CC protein levels in migrating interneurons, thereby adapting their
CC chemokine responsiveness (PubMed:16940167, PubMed:18653785). In glioma
CC cells, transduces signals via MEK/ERK pathway, mediating resistance to
CC apoptosis. Promotes cell growth and survival (PubMed:16940167,
CC PubMed:20388803). Not involved in cell migration, adhesion or
CC proliferation of normal hematopoietic progenitors but activated by
CC CXCL11 in malignant hemapoietic cells, leading to phosphorylation of
CC ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration
CC (PubMed:17804806, PubMed:18653785, PubMed:19641136, PubMed:20887389).
CC Plays a regulatory role in CXCR4-mediated activation of cell surface
CC integrins by CXCL12 (PubMed:18653785). Required for heart valve
CC development (PubMed:17804806). Regulates axon guidance in the
CC oculomotor system through the regulation of CXCL12 levels
CC (PubMed:31211835). {ECO:0000269|PubMed:16107333,
CC ECO:0000269|PubMed:16940167, ECO:0000269|PubMed:17804806,
CC ECO:0000269|PubMed:18653785, ECO:0000269|PubMed:19255243,
CC ECO:0000269|PubMed:19380869, ECO:0000269|PubMed:19641136,
CC ECO:0000269|PubMed:20018651, ECO:0000269|PubMed:20161793,
CC ECO:0000269|PubMed:20388803, ECO:0000269|PubMed:20887389,
CC ECO:0000269|PubMed:22300987, ECO:0000269|PubMed:31211835}.
CC -!- FUNCTION: (Microbial infection) Acts as coreceptor with CXCR4 for a
CC restricted number of HIV isolates. {ECO:0000305|PubMed:23153575}.
CC -!- SUBUNIT: Homodimer. Can form heterodimers with CXCR4;
CC heterodimerization may regulate CXCR4 signaling activity. Interacts
CC with ARRB1 and ARRB2. {ECO:0000269|PubMed:19255243,
CC ECO:0000269|PubMed:19380869, ECO:0000269|PubMed:22300987,
CC ECO:0000269|PubMed:22457824}.
CC -!- INTERACTION:
CC P25106; P37288: AVPR1A; NbExp=7; IntAct=EBI-1965291, EBI-6656842;
CC P25106; P61073: CXCR4; NbExp=18; IntAct=EBI-1965291, EBI-489411;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31211835};
CC Multi-pass membrane protein {ECO:0000255}. Early endosome
CC {ECO:0000269|PubMed:22457824}. Recycling endosome
CC {ECO:0000269|PubMed:22457824}. 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:0000269|PubMed:22457824}.
CC -!- TISSUE SPECIFICITY: Expressed in monocytes, basophils, B-cells,
CC umbilical vein endothelial cells (HUVEC) and B-lymphoblastoid cells.
CC Lower expression detected in CD4+ T-lymphocytes and natural killer
CC cells. In the brain, detected in endothelial cells and capillaries, and
CC in mature neurons of the frontal cortex and hippocampus. Expressed in
CC tubular formation in the kidney. Highly expressed in astroglial tumor
CC endothelial, microglial and glioma cells. Expressed at low levels in
CC normal CD34+ progenitor cells, but at very high levels in several
CC myeloid malignant cell lines. Expressed in breast carcinomas but not in
CC normal breast tissue (at protein level). {ECO:0000269|PubMed:16107333,
CC ECO:0000269|PubMed:16455976, ECO:0000269|PubMed:19641136,
CC ECO:0000269|PubMed:20388803, ECO:0000269|PubMed:20887389,
CC ECO:0000269|PubMed:21655198}.
CC -!- INDUCTION: Up-regulated during cell differentiation in glioma cells.
CC {ECO:0000269|PubMed:20388803}.
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:0000269|PubMed:22457824}.
CC -!- PTM: The Ser/Thr residues in the C-terminal cytoplasmic tail may be
CC phosphorylated. {ECO:0000269|PubMed:22457824}.
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:0000269|PubMed:22457824}.
CC -!- DISEASE: Oculomotor-abducens synkinesis (OCABSN) [MIM:619215]: An
CC autosomal recessive disorder characterized by ptosis and elevation of
CC the eyelid on ipsilateral abduction. OCABSN features are consistent
CC with abnormal innervation of the levator palpebrae superioris muscle,
CC which raises the eyelid, and the lateral rectus muscle, which controls
CC lateral eye movement. {ECO:0000269|PubMed:31211835}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC Atypical chemokine receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00521}.
CC -!- CAUTION: Was originally thought to be the receptor for VIP.
CC {ECO:0000305|PubMed:1675791}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CMKOR1ID40108ch2q37.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CXC chemokine receptors entry;
CC URL="https://en.wikipedia.org/wiki/CXC_chemokine_receptors";
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DR EMBL; M64749; AAA62370.1; -; mRNA.
DR EMBL; U73141; AAB18130.1; -; Genomic_DNA.
DR EMBL; U67784; AAB16913.1; -; mRNA.
DR EMBL; AF030297; AAB94130.1; -; mRNA.
DR EMBL; DQ822477; ABH01258.1; -; mRNA.
DR EMBL; AK291659; BAF84348.1; -; mRNA.
DR EMBL; AC079611; AAX93086.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW71092.1; -; Genomic_DNA.
DR EMBL; BC036661; AAH36661.1; -; mRNA.
DR CCDS; CCDS2516.1; -.
DR PIR; A39714; A39714.
DR RefSeq; NP_064707.1; NM_020311.2.
DR RefSeq; XP_005246154.1; XM_005246097.2.
DR RefSeq; XP_005246155.1; XM_005246098.3.
DR RefSeq; XP_016860005.1; XM_017004516.1.
DR PDB; 6K3F; X-ray; 2.30 A; U/V/W/X/Y/Z=331-345.
DR PDBsum; 6K3F; -.
DR AlphaFoldDB; P25106; -.
DR SMR; P25106; -.
DR BioGRID; 121321; 53.
DR IntAct; P25106; 31.
DR MINT; P25106; -.
DR STRING; 9606.ENSP00000272928; -.
DR BindingDB; P25106; -.
DR ChEMBL; CHEMBL2010631; -.
DR DrugCentral; P25106; -.
DR GuidetoPHARMACOLOGY; 80; -.
DR GlyGen; P25106; 3 sites.
DR iPTMnet; P25106; -.
DR PhosphoSitePlus; P25106; -.
DR BioMuta; ACKR3; -.
DR DMDM; 115502380; -.
DR MassIVE; P25106; -.
DR MaxQB; P25106; -.
DR PaxDb; P25106; -.
DR PeptideAtlas; P25106; -.
DR PRIDE; P25106; -.
DR ProteomicsDB; 54262; -.
DR ABCD; P25106; 9 sequenced antibodies.
DR Antibodypedia; 47699; 824 antibodies from 39 providers.
DR DNASU; 57007; -.
DR Ensembl; ENST00000272928.4; ENSP00000272928.3; ENSG00000144476.6.
DR GeneID; 57007; -.
DR KEGG; hsa:57007; -.
DR MANE-Select; ENST00000272928.4; ENSP00000272928.3; NM_020311.3; NP_064707.1.
DR UCSC; uc002vwd.4; human.
DR CTD; 57007; -.
DR DisGeNET; 57007; -.
DR GeneCards; ACKR3; -.
DR HGNC; HGNC:23692; ACKR3.
DR HPA; ENSG00000144476; Low tissue specificity.
DR MalaCards; ACKR3; -.
DR MIM; 610376; gene.
DR MIM; 619215; phenotype.
DR neXtProt; NX_P25106; -.
DR OpenTargets; ENSG00000144476; -.
DR PharmGKB; PA162383053; -.
DR VEuPathDB; HostDB:ENSG00000144476; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244811; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; P25106; -.
DR OMA; HFIPFSC; -.
DR OrthoDB; 819032at2759; -.
DR PhylomeDB; P25106; -.
DR TreeFam; TF333489; -.
DR PathwayCommons; P25106; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P25106; -.
DR SIGNOR; P25106; -.
DR BioGRID-ORCS; 57007; 9 hits in 1050 CRISPR screens.
DR ChiTaRS; ACKR3; human.
DR GeneWiki; CXCR7; -.
DR GenomeRNAi; 57007; -.
DR Pharos; P25106; Tchem.
DR PRO; PR:P25106; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P25106; protein.
DR Bgee; ENSG00000144476; Expressed in synovial joint and 192 other tissues.
DR ExpressionAtlas; P25106; baseline and differential.
DR Genevisible; P25106; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA: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:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA: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; IMP:UniProtKB.
DR GO; GO:0016494; F:C-X-C chemokine receptor activity; IMP:BHF-UCL.
DR GO; GO:0015026; F:coreceptor activity; IEA:InterPro.
DR GO; GO:0005044; F:scavenger receptor activity; IMP: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; IMP:BHF-UCL.
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; IMP:BHF-UCL.
DR GO; GO:0021557; P:oculomotor nerve development; IMP: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; IMP:UniProtKB.
DR GO; GO:1905322; P:positive regulation of mesenchymal stem cell migration; IEA:Ensembl.
DR GO; GO:0031623; P:receptor internalization; IMP: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 3D-structure; Cell adhesion; Cell membrane; Developmental protein;
KW Disease variant; Disulfide bond; Endosome; G-protein coupled receptor;
KW Glycoprotein; Host-virus interaction; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..362
FT /note="Atypical chemokine receptor 3"
FT /id="PRO_0000070101"
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 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"
FT VARIANT 219
FT /note="L -> W (in dbSNP:rs10183641)"
FT /id="VAR_027477"
FT VARIANT 258
FT /note="V -> M (in OCABSN; no effect on protein levels and
FT cell membrane location; lower binding affinity for CXCL12;
FT dbSNP:rs200582844)"
FT /evidence="ECO:0000269|PubMed:31211835"
FT /id="VAR_085335"
FT MUTAGEN 145
FT /note="S->A: Does not result in CXCL12-inducible
FT chemotaxis, calcium mobilization or ERK activation, and has
FT no effect on CXCR7-mediated CXCL12 degradation; when
FT associated with V-147."
FT /evidence="ECO:0000269|PubMed:20161793"
FT MUTAGEN 147
FT /note="T->V: Does not result in CXCL12-inducible
FT chemotaxis, calcium mobilization or ERK activation, and has
FT no effect on CXCR7-mediated CXCL12 degradation; when
FT associated with A-145."
FT /evidence="ECO:0000269|PubMed:20161793"
FT CONFLICT 9
FT /note="S -> A (in Ref. 1; AAA62370)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="G -> S (in Ref. 1; AAA62370, 2; AAB16913 and 3;
FT AAB94130)"
FT /evidence="ECO:0000305"
FT CONFLICT 131
FT /note="S -> G (in Ref. 1; AAA62370)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="I -> V (in Ref. 8; AAH36661)"
FT /evidence="ECO:0000305"
FT CONFLICT 360..361
FT /note="ST -> NA (in Ref. 1; AAA62370)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 362 AA; 41493 MW; A863EC1AFB5B158B CRC64;
MDLHLFDYSE PGNFSDISWP CNSSDCIVVD TVMCPNMPNK SVLLYTLSFI YIFIFVIGMI
ANSVVVWVNI QAKTTGYDTH CYILNLAIAD LWVVLTIPVW VVSLVQHNQW PMGELTCKVT
HLIFSINLFG SIFFLTCMSV DRYLSITYFT NTPSSRKKMV RRVVCILVWL LAFCVSLPDT
YYLKTVTSAS NNETYCRSFY PEHSIKEWLI GMELVSVVLG FAVPFSIIAV FYFLLARAIS
ASSDQEKHSS RKIIFSYVVV FLVCWLPYHV AVLLDIFSIL HYIPFTCRLE HALFTALHVT
QCLSLVHCCV NPVLYSFINR NYRYELMKAF IFKYSAKTGL TKLIDASRVS ETEYSALEQS
TK
