ID   CML2_HUMAN              Reviewed;         355 AA.
AC   P46091; A5JUU6; A8K4L1; Q53TR9; Q6NVX4;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   22-NOV-2005, sequence version 2.
DT   27-MAR-2024, entry version 178.
DE   RecName: Full=Chemerin-like receptor 2 {ECO:0000303|PubMed:29279348};
DE   AltName: Full=Chemerin chemokine-like receptor 2 {ECO:0000312|HGNC:HGNC:4463};
DE   AltName: Full=Chemokine-like receptor 2;
DE   AltName: Full=G-protein coupled receptor 1 {ECO:0000303|PubMed:10233994};
GN   Name=CMKLR2 {ECO:0000312|HGNC:HGNC:4463};
GN   Synonyms=GPR1 {ECO:0000303|PubMed:10233994};
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].
RX   PubMed=7851889; DOI=10.1006/geno.1994.1549;
RA   Marchese A., Docherty J.M., Nguyen T., Heiber M., Cheng R., Heng H.H.Q.,
RA   Tsui L.-C., Shi X., George S.R., O'Dowd B.F.;
RT   "Cloning of human genes encoding novel G protein-coupled receptors.";
RL   Genomics 23:609-618(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Hippocampus;
RA   Martin A.L., Kaighin V.A., Aronstam R.S.;
RL   Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-307.
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-307.
RC   TISSUE=Placenta;
RX   PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA   Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA   Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA   Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA   Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA   Isogai T.;
RT   "Signal sequence and keyword trap in silico for selection of full-length
RT   human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT   libraries.";
RL   DNA Res. 12:117-126(2005).
RN   [5]
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   [6]
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-307.
RC   TISSUE=Placenta;
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   [8]
RP   FUNCTION (MICROBIAL INFECTION).
RX   PubMed=10233994; DOI=10.1128/jvi.73.6.5231-5239.1999;
RA   Shimizu N., Soda Y., Kanbe K., Liu H.Y., Jinno A., Kitamura T., Hoshino H.;
RT   "An orphan G protein-coupled receptor, GPR1, acts as a coreceptor to allow
RT   replication of human immunodeficiency virus types 1 and 2 in brain-derived
RT   cells.";
RL   J. Virol. 73:5231-5239(1999).
RN   [9]
RP   LIGAND-BINDING, AND FUNCTION.
RX   PubMed=18165312; DOI=10.1073/pnas.0710487105;
RA   Barnea G., Strapps W., Herrada G., Berman Y., Ong J., Kloss B., Axel R.,
RA   Lee K.J.;
RT   "The genetic design of signaling cascades to record receptor activation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:64-69(2008).
RN   [10]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=27716822; DOI=10.1371/journal.pone.0164179;
RA   De Henau O., Degroot G.N., Imbault V., Robert V., De Poorter C., Mcheik S.,
RA   Gales C., Parmentier M., Springael J.Y.;
RT   "Signaling properties of chemerin receptors CMKLR1, GPR1 and CCRL2.";
RL   PLoS ONE 11:e0164179-e0164179(2016).
RN   [11]
RP   NOMENCLATURE.
RX   PubMed=29279348; DOI=10.1124/pr.116.013177;
RA   Kennedy A.J., Davenport A.P.;
RT   "International Union of Basic and Clinical Pharmacology CIII: Chemerin
RT   Receptors CMKLR1 (Chemerin1) and GPR1 (Chemerin2) Nomenclature,
RT   Pharmacology, and Function.";
RL   Pharmacol. Rev. 70:174-196(2018).
CC   -!- FUNCTION: Receptor for chemoattractant adipokine chemerin/RARRES2
CC       suggesting a role for this receptor in the regulation of inflammation
CC       and energy homesotasis (PubMed:18165312, PubMed:27716822). Signals
CC       mainly via beta-arrestin pathway. Binding of RARRES2 activates weakly G
CC       proteins, calcium mobilization and MAPK1/MAPK3 (ERK1/2) phosphorylation
CC       too (PubMed:27716822). Acts also as a receptor for TAFA1, mediates its
CC       effects on neuronal stem-cell proliferation and differentiation via the
CC       activation of ROCK/ERK and ROCK/STAT3 signaling pathway (By
CC       similarity). {ECO:0000250|UniProtKB:Q8K087,
CC       ECO:0000269|PubMed:18165312, ECO:0000269|PubMed:27716822}.
CC   -!- FUNCTION: (Microbial infection) Coreceptor for HIV-1.
CC       {ECO:0000269|PubMed:10233994}.
CC   -!- INTERACTION:
CC       P46091; PRO_0000041304 [P08563]; Xeno; NbExp=2; IntAct=EBI-11477864, EBI-11477759;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27716822};
CC       Multi-pass membrane protein {ECO:0000255}. Note=Internalizes in
CC       presence of its ligand, TAFA1 (By similarity). Internalizes efficiently
CC       in response to RARRES2 (PubMed:27716822).
CC       {ECO:0000250|UniProtKB:Q8K087, ECO:0000269|PubMed:27716822}.
CC   -!- TISSUE SPECIFICITY: Expressed in hippocampus.
CC   -!- SIMILARITY: Belongs to the chemokine-like receptor (CMKLR) family.
CC       {ECO:0000305}.
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DR   EMBL; U13666; AAA64592.1; -; Genomic_DNA.
DR   EMBL; EF577403; ABQ52423.1; -; mRNA.
DR   EMBL; AK290976; BAF83665.1; -; mRNA.
DR   EMBL; AK075130; BAG52070.1; -; mRNA.
DR   EMBL; AC007383; AAY15063.1; -; Genomic_DNA.
DR   EMBL; CH471063; EAW70383.1; -; Genomic_DNA.
DR   EMBL; BC067833; AAH67833.1; -; mRNA.
DR   CCDS; CCDS2368.1; -.
DR   PIR; A55733; A55733.
DR   RefSeq; NP_001091669.1; NM_001098199.1.
DR   RefSeq; NP_001248381.1; NM_001261452.1.
DR   RefSeq; NP_001248382.1; NM_001261453.1.
DR   RefSeq; NP_001248383.1; NM_001261454.1.
DR   RefSeq; NP_001248384.1; NM_001261455.1.
DR   RefSeq; NP_005270.2; NM_005279.3.
DR   RefSeq; XP_005246528.1; XM_005246471.2.
DR   RefSeq; XP_016859321.1; XM_017003832.1.
DR   AlphaFoldDB; P46091; -.
DR   SMR; P46091; -.
DR   IntAct; P46091; 1.
DR   MINT; P46091; -.
DR   STRING; 9606.ENSP00000480405; -.
DR   ChEMBL; CHEMBL4523229; -.
DR   GuidetoPHARMACOLOGY; 82; -.
DR   GlyCosmos; P46091; 1 site, No reported glycans.
DR   GlyGen; P46091; 1 site.
DR   iPTMnet; P46091; -.
DR   PhosphoSitePlus; P46091; -.
DR   BioMuta; GPR1; -.
DR   DMDM; 82654939; -.
DR   PaxDb; 9606-ENSP00000480405; -.
DR   PeptideAtlas; P46091; -.
DR   ProteomicsDB; 55717; -.
DR   Antibodypedia; 1410; 257 antibodies from 31 providers.
DR   DNASU; 2825; -.
DR   Ensembl; ENST00000407325.6; ENSP00000384345.2; ENSG00000183671.13.
DR   Ensembl; ENST00000437420.5; ENSP00000397535.1; ENSG00000183671.13.
DR   Ensembl; ENST00000621141.5; ENSP00000483003.1; ENSG00000183671.13.
DR   Ensembl; ENST00000636848.1; ENSP00000490642.1; ENSG00000283448.1.
DR   Ensembl; ENST00000637075.1; ENSP00000490813.1; ENSG00000283448.1.
DR   Ensembl; ENST00000638097.1; ENSP00000490453.1; ENSG00000283448.1.
DR   Ensembl; ENST00000638116.1; ENSP00000489673.1; ENSG00000283448.1.
DR   GeneID; 2825; -.
DR   KEGG; hsa:2825; -.
DR   MANE-Select; ENST00000621141.5; ENSP00000483003.1; NM_001389445.1; NP_001376374.1.
DR   UCSC; uc002vbl.6; human.
DR   AGR; HGNC:4463; -.
DR   CTD; 2825; -.
DR   DisGeNET; 2825; -.
DR   GeneCards; CMKLR2; -.
DR   HGNC; HGNC:4463; CMKLR2.
DR   HPA; ENSG00000183671; Tissue enhanced (choroid).
DR   MIM; 600239; gene.
DR   neXtProt; NX_P46091; -.
DR   OpenTargets; ENSG00000183671; -.
DR   PharmGKB; PA28846; -.
DR   VEuPathDB; HostDB:ENSG00000183671; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT00940000160642; -.
DR   HOGENOM; CLU_009579_8_0_1; -.
DR   InParanoid; P46091; -.
DR   OMA; ISSKHFW; -.
DR   OrthoDB; 5384006at2759; -.
DR   PhylomeDB; P46091; -.
DR   TreeFam; TF330976; -.
DR   PathwayCommons; P46091; -.
DR   SignaLink; P46091; -.
DR   BioGRID-ORCS; 2825; 9 hits in 1138 CRISPR screens.
DR   GeneWiki; GPR1; -.
DR   GenomeRNAi; 2825; -.
DR   Pharos; P46091; Tchem.
DR   PRO; PR:P46091; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; P46091; Protein.
DR   Bgee; ENSG00000183671; Expressed in placenta and 93 other cell types or tissues.
DR   ExpressionAtlas; P46091; baseline and differential.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0097004; F:adipokinetic hormone binding; IDA:UniProtKB.
DR   GO; GO:0097003; F:adipokinetic hormone receptor activity; IDA:UniProtKB.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR   GO; GO:0042923; F:neuropeptide binding; IBA:GO_Central.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR   CDD; cd15119; 7tmA_GPR1; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR002275; CML2.
DR   InterPro; IPR000826; Formyl_rcpt-rel.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   PANTHER; PTHR24225:SF51; CHEMERIN-LIKE RECEPTOR 1; 1.
DR   PANTHER; PTHR24225; CHEMOTACTIC RECEPTOR; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR01146; GPR1ORPHANR.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; P46091; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW   Membrane; Receptor; Reference proteome; Transducer; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..355
FT                   /note="Chemerin-like receptor 2"
FT                   /id="PRO_0000069505"
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..73
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        74..94
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        95..112
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        113..133
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        134..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..210
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        211..231
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        232..247
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        248..268
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        269..286
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        287..307
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        308..355
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        14
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        110..187
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   VARIANT         307
FT                   /note="I -> V (in dbSNP:rs3732083)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16303743"
FT                   /id="VAR_023839"
FT   CONFLICT        65
FT                   /note="F -> L (in Ref. 1; AAA64592)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        237..238
FT                   /note="SI -> TV (in Ref. 1; AAA64592)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   355 AA;  41431 MW;  E25D54CBA59F9C8F CRC64;
     MEDLEETLFE EFENYSYDLD YYSLESDLEE KVQLGVVHWV SLVLYCLAFV LGIPGNAIVI
     WFTGFKWKKT VTTLWFLNLA IADFIFLLFL PLYISYVAMN FHWPFGIWLC KANSFTAQLN
     MFASVFFLTV ISLDHYIHLI HPVLSHRHRT LKNSLIVIIF IWLLASLIGG PALYFRDTVE
     FNNHTLCYNN FQKHDPDLTL IRHHVLTWVK FIIGYLFPLL TMSICYLCLI FKVKKRSILI
     SSRHFWTILV VVVAFVVCWT PYHLFSIWEL TIHHNSYSHH VMQAGIPLST GLAFLNSCLN
     PILYVLISKK FQARFRSSVA EILKYTLWEV SCSGTVSEQL RNSETKNLCL LETAQ
//