CML2_HUMAN
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 03-AUG-2022, entry version 169.
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}.
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; 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 GlyGen; P46091; 1 site.
DR iPTMnet; P46091; -.
DR PhosphoSitePlus; P46091; -.
DR BioMuta; GPR1; -.
DR DMDM; 82654939; -.
DR PaxDb; P46091; -.
DR PeptideAtlas; P46091; -.
DR PRIDE; P46091; -.
DR Antibodypedia; 1410; 242 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 CTD; 2825; -.
DR DisGeNET; 2825; -.
DR GeneCards; GPR1; -.
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; 910274at2759; -.
DR PhylomeDB; P46091; -.
DR TreeFam; TF330976; -.
DR PathwayCommons; P46091; -.
DR SignaLink; P46091; -.
DR BioGRID-ORCS; 2825; 8 hits in 1060 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 92 other tissues.
DR ExpressionAtlas; P46091; baseline and differential.
DR Genevisible; P46091; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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:0042277; F:peptide 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 InterPro; IPR002275; CML2.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01146; GPR1ORPHANR.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
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