ID KISSR_HUMAN Reviewed; 398 AA. AC Q969F8; A5D8U2; B2RTV1; Q96QG0; DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 06-FEB-2007, sequence version 2. DT 24-JAN-2024, entry version 175. DE RecName: Full=KiSS-1 receptor; DE Short=KiSS-1R; DE AltName: Full=G-protein coupled receptor 54; DE AltName: Full=G-protein coupled receptor OT7T175; DE Short=hOT7T175; DE AltName: Full=Hypogonadotropin-1; DE AltName: Full=Kisspeptins receptor; DE AltName: Full=Metastin receptor; GN Name=KISS1R; Synonyms=AXOR12, GPR54; 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 [MRNA], VARIANT HIS-364, AND TISSUE SPECIFICITY. RX PubMed=11385580; DOI=10.1038/35079135; RA Ohtaki T., Shintani Y., Honda S., Matsumoto H., Hori A., Kanehashi K., RA Terao Y., Kumano S., Takatsu Y., Masuda Y., Ishibashi Y., Watanabe T., RA Asada M., Yamada T., Suenaga M., Kitada C., Usuki S., Kurokawa T., Onda H., RA Nishimura O., Fujino M.; RT "Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein- RT coupled receptor."; RL Nature 411:613-617(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT HIS-364, AND TISSUE SPECIFICITY. RX PubMed=11414709; DOI=10.1006/bbrc.2001.5098; RA Clements M.K., McDonald T.P., Wang R., Xie G., O'Dowd B.F., George S.R., RA Austin C.P., Liu Q.; RT "FMRFamide-related neuropeptides are agonists of the orphan G-protein- RT coupled receptor GPR54."; RL Biochem. Biophys. Res. Commun. 284:1189-1193(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=11387329; DOI=10.1074/jbc.m102743200; RA Muir A.I., Chamberlain L., Elshourbagy N.A., Michalovich D., Moore D.J., RA Calamari A., Szekeres P.G., Sarau H.M., Chambers J.K., Murdock P., RA Steplewski K., Shabon U., Miller J.E., Middleton S.E., Darker J.G., RA Larminie C.G.C., Wilson S., Bergsma D.J., Emson P., Faull R., RA Philpott K.L., Harrison D.C.; RT "AXOR12, a novel human G protein-coupled receptor, activated by the peptide RT KiSS-1."; RL J. Biol. Chem. 276:28969-28975(2001). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT HIS-364, POSSIBLE FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Hypothalamus; RX PubMed=11457843; DOI=10.1074/jbc.m104847200; RA Kotani M., Detheux M., Vandenbogaerde A., Communi D., Vanderwinden J.-M., RA Le Poul E., Brezillon S., Tyldesley R., Suarez-Huerta N., Vandeput F., RA Blanpain C., Schiffmann S.N., Vassart G., Parmentier M.; RT "The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural RT ligands of the orphan G protein-coupled receptor GPR54."; RL J. Biol. Chem. 276:34631-34636(2001). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT HH8 SER-148, AND VARIANT HIS-364. RX PubMed=14573733; DOI=10.1056/nejmoa035322; RA Seminara S.B., Messager S., Chatzidaki E.E., Thresher R.R., RA Acierno J.S. Jr., Shagoury J.K., Bo-Abbas Y., Kuohung W., Schwinof K.M., RA Hendrick A.G., Zahn D., Dixon J., Kaiser U.B., Slaugenhaupt S.A., RA Gusella J.F., O'Rahilly S., Carlton M.B.L., Crowley W.F. Jr., RA Aparicio S.A.J.R., Colledge W.H.; RT "The GPR54 gene as a regulator of puberty."; RL N. Engl. J. Med. 349:1614-1627(2003). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Kidney; RA Kaighin V.A., Martin A.L., Aronstam R.S.; RT "Isolation of cDNA coding for human KISS1 receptor (KISS1R)."; RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT HIS-364. 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT HIS-364. 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 [10] RP REVIEW. RX PubMed=15519892; DOI=10.1016/j.tem.2004.09.008; RA Colledge W.H.; RT "GPR54 and puberty."; RL Trends Endocrinol. Metab. 15:448-453(2004). RN [11] RP INVOLVEMENT IN CELL MOBILITY AND GROWTH INHIBITION. RX PubMed=11527393; DOI=10.1006/bbrc.2001.5470; RA Hori A., Honda S., Asada M., Ohtaki T., Oda K., Watanabe T., Shintani Y., RA Yamada T., Suenaga M., Kitada C., Onda H., Kurokawa T., Nishimura O., RA Fujino M.; RT "Metastin suppresses the motility and growth of CHO cells transfected with RT its receptor."; RL Biochem. Biophys. Res. Commun. 286:958-963(2001). RN [12] RP TISSUE SPECIFICITY, AND POSSIBLE INVOLVEMENT IN INVASION/MIGRATION OF RP TROPHOBLAST CELLS. RX PubMed=12414911; DOI=10.1210/jc.2002-021093; RA Janneau J.-L., Maldonado-Estrada J., Tachdjian G., Miran I., Motte N., RA Saulnier P., Sabourin J.-C., Cote J.-F., Simon B., Frydman R., Chaouat G., RA Bellet D.; RT "Transcriptional expression of genes involved in cell invasion and RT migration by normal and tumoral trophoblast cells."; RL J. Clin. Endocrinol. Metab. 87:5336-5339(2002). RN [13] RP INVOLVEMENT IN THYROID CANCER. RX PubMed=11994395; DOI=10.1210/jcem.87.5.8626; RA Ringel M.D., Hardy E., Bernet V.J., Burch H.B., Schuppert F., Burman K.D., RA Saji M.; RT "Metastin receptor is overexpressed in papillary thyroid cancer and RT activates MAP kinase in thyroid cancer cells."; RL J. Clin. Endocrinol. Metab. 87:2399-2399(2002). RN [14] RP INVOLVEMENT IN HH8. RX PubMed=12944565; DOI=10.1073/pnas.1834399100; RA de Roux N., Genin E., Carel J.-C., Matsuda F., Chaussain J.-L., Milgrom E.; RT "Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived RT peptide receptor GPR54."; RL Proc. Natl. Acad. Sci. U.S.A. 100:10972-10976(2003). RN [15] RP POSSIBLE INVOLVEMENT IN HEPATOCELLULAR CARCINOMA. RX PubMed=12898236; DOI=10.1007/s00432-003-0469-z; RA Ikeguchi M., Hirooka Y., Kaibara N.; RT "Quantitative reverse transcriptase polymerase chain reaction analysis for RT KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in RT hepatocellular carcinoma."; RL J. Cancer Res. Clin. Oncol. 129:531-535(2003). RN [16] RP POSSIBLE INVOLVEMENT IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA. RX PubMed=14977840; DOI=10.1158/1078-0432.ccr-1519-02; RA Ikeguchi M., Yamaguchi K., Kaibara N.; RT "Clinical significance of the loss of KiSS-1 and orphan G-protein-coupled RT receptor (hOT7T175) gene expression in esophageal squamous cell RT carcinoma."; RL Clin. Cancer Res. 10:1379-1383(2004). RN [17] RP TISSUE SPECIFICITY, AND ROLE IN THROPHOBLAST MIGRATION AND INVASION. RX PubMed=15020672; DOI=10.1242/jcs.00971; RA Bilban M., Ghaffari-Tabrizi N., Hintermann E., Bauer S., Molzer S., RA Zoratti C., Malli R., Sharabi A., Hiden U., Graier W., Knoefler M., RA Andreae F., Wagner O., Quaranta V., Desoye G.; RT "Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological RT invasion inhibitor of primary human trophoblasts."; RL J. Cell Sci. 117:1319-1328(2004). RN [18] RP CHARACTERIZATION OF METASTASIS SUPPRESSOR PROPERTIES. RX PubMed=15596153; DOI=10.1016/j.bbrc.2004.11.094; RA Becker J.A.J., Mirjolet J.-F., Bernard J., Burgeon E., Simons M.-J., RA Vassart G., Parmentier M., Libert F.; RT "Activation of GPR54 promotes cell cycle arrest and apoptosis of human RT tumor cells through a specific transcriptional program not shared by other RT G(q)-coupled receptors."; RL Biochem. Biophys. Res. Commun. 326:677-686(2005). RN [19] RP VARIANTS HH8 ARG-223 AND LEU-297, VARIANT HIS-364, AND CHARACTERIZATION OF RP VARIANTS HH8 ARG-223 AND LEU-297. RX PubMed=15598687; DOI=10.1210/jc.2004-1418; RA Semple R.K., Achermann J.C., Ellery J., Farooqi I.S., Karet F.E., RA Stanhope R.G., O'rahilly S., Aparicio S.A.; RT "Two novel missense mutations in G protein-coupled receptor 54 in a patient RT with hypogonadotropic hypogonadism."; RL J. Clin. Endocrinol. Metab. 90:1849-1855(2005). RN [20] RP VARIANT HH8 PRO-102. RX PubMed=17164310; DOI=10.1210/jc.2006-2147; RA Tenenbaum-Rakover Y., Commenges-Ducos M., Iovane A., Aumas C., Admoni O., RA de Roux N.; RT "Neuroendocrine phenotype analysis in five patients with isolated RT hypogonadotropic hypogonadism due to a L102P inactivating mutation of RT GPR54."; RL J. Clin. Endocrinol. Metab. 92:1137-1144(2007). RN [21] RP VARIANT CPPB1 PRO-386, AND CHARACTERIZATION OF VARIANT CPPB1 PRO-386. RX PubMed=18272894; DOI=10.1056/nejmoa073443; RA Teles M.G., Bianco S.D.C., Brito V.N., Trarbach E.B., Kuohung W., Xu S., RA Seminara S.B., Mendonca B.B., Kaiser U.B., Latronico A.C.; RT "A GPR54-activating mutation in a patient with central precocious RT puberty."; RL N. Engl. J. Med. 358:709-715(2008). RN [22] RP VARIANTS HH8 THR-189 AND ASP-194. RX PubMed=23643382; DOI=10.1016/j.ajhg.2013.04.008; RA Miraoui H., Dwyer A.A., Sykiotis G.P., Plummer L., Chung W., Feng B., RA Beenken A., Clarke J., Pers T.H., Dworzynski P., Keefe K., Niedziela M., RA Raivio T., Crowley W.F. Jr., Seminara S.B., Quinton R., Hughes V.A., RA Kumanov P., Young J., Yialamas M.A., Hall J.E., Van Vliet G., RA Chanoine J.P., Rubenstein J., Mohammadi M., Tsai P.S., Sidis Y., Lage K., RA Pitteloud N.; RT "Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in RT individuals with congenital hypogonadotropic hypogonadism."; RL Am. J. Hum. Genet. 92:725-743(2013). RN [23] RP VARIANT HH8 LEU-262. RX PubMed=25077900; DOI=10.1210/jc.2014-2110; RA Marcos S., Sarfati J., Leroy C., Fouveaut C., Parent P., Metz C., RA Wolczynski S., Gerard M., Bieth E., Kurtz F., Verier-Mine O., Perrin L., RA Archambeaud F., Cabrol S., Rodien P., Hove H., Prescott T., Lacombe D., RA Christin-Maitre S., Touraine P., Hieronimus S., Dewailly D., Young J., RA Pugeat M., Hardelin J.P., Dode C.; RT "The prevalence of CHD7 missense versus truncating mutations is higher in RT patients with Kallmann syndrome than in typical CHARGE patients."; RL J. Clin. Endocrinol. Metab. 99:E2138-2143(2014). CC -!- FUNCTION: Receptor for metastin (kisspeptin-54 or kp-54), a C- CC terminally amidated peptide of KiSS1. KiSS1 is a metastasis suppressor CC protein that suppresses metastases in malignant melanomas and in some CC breast carcinomas without affecting tumorigenicity. The metastasis CC suppressor properties may be mediated in part by cell cycle arrest and CC induction of apoptosis in malignant cells. The receptor is essential CC for normal gonadotropin-released hormone physiology and for puberty. CC The hypothalamic KiSS1/KISS1R system is a pivotal factor in central CC regulation of the gonadotropic axis at puberty and in adulthood. The CC receptor is also probably involved in the regulation and fine-tuning of CC trophoblast invasion generated by the trophoblast itself. Analysis of CC the transduction pathways activated by the receptor identifies coupling CC to phospholipase C and intracellular calcium release through pertussis CC toxin-insensitive G(q) proteins. {ECO:0000269|PubMed:15020672}. CC -!- INTERACTION: CC Q969F8; P50148: GNAQ; NbExp=2; IntAct=EBI-8481408, EBI-3909604; CC Q969F8; P67775: PPP2CA; NbExp=3; IntAct=EBI-8481408, EBI-712311; CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC -!- TISSUE SPECIFICITY: Most highly expressed in the pancreas, placenta and CC spinal cord, with lower-level of expression in peripheral blood CC leukocytes, kidney, lung, fetal liver, stomach, small intestine, CC testes, spleen, thymus, adrenal glands and lymph nodes. In the adult CC brain, expressed in the superior frontal gyrus, putamen, caudate CC nucleus, cingulate gyrus, nucleus accumbens, hippocampus, pons and CC amygdala, as well as the hypothalamus and pituitary. Expression levels CC are higher in early (7-9 weeks) than term placentas. Expression levels CC were increased in both early placentas and molar pregnancies and were CC reduced in choriocarcinoma cells. Expressed at higher levels in first CC trimester trophoblasts than at term of gestation. Also found in the CC extravillous trophoblast suggesting endocrine/paracrine activation CC mechanism. {ECO:0000269|PubMed:11385580, ECO:0000269|PubMed:11387329, CC ECO:0000269|PubMed:11414709, ECO:0000269|PubMed:11457843, CC ECO:0000269|PubMed:12414911, ECO:0000269|PubMed:15020672}. CC -!- INDUCTION: Expressed at higher levels in first trimester trophoblasts CC than at term of gestation. CC -!- DISEASE: Hypogonadotropic hypogonadism 8 with or without anosmia (HH8) CC [MIM:614837]: A disorder characterized by absent or incomplete sexual CC maturation by the age of 18 years, in conjunction with low levels of CC circulating gonadotropins and testosterone and no other abnormalities CC of the hypothalamic-pituitary axis. In some cases, it is associated CC with non-reproductive phenotypes, such as anosmia, cleft palate, and CC sensorineural hearing loss. Anosmia or hyposmia is related to the CC absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism CC is due to deficiency in gonadotropin-releasing hormone and probably CC results from a failure of embryonic migration of gonadotropin-releasing CC hormone-synthesizing neurons. In the presence of anosmia, idiopathic CC hypogonadotropic hypogonadism is referred to as Kallmann syndrome, CC whereas in the presence of a normal sense of smell, it has been termed CC normosmic idiopathic hypogonadotropic hypogonadism (nIHH). CC {ECO:0000269|PubMed:12944565, ECO:0000269|PubMed:14573733, CC ECO:0000269|PubMed:15598687, ECO:0000269|PubMed:17164310, CC ECO:0000269|PubMed:23643382, ECO:0000269|PubMed:25077900}. Note=The CC disease is caused by variants affecting distinct genetic loci, CC including the gene represented in this entry. The genetics of CC hypogonadotropic hypogonadism involves various modes of transmission. CC Oligogenic inheritance has been reported in some patients carrying CC mutations in KISS1R as well as in other HH-associated genes including CC FGFR1 and IL17RD (PubMed:23643382). {ECO:0000269|PubMed:23643382}. CC -!- DISEASE: Precocious puberty, central 1 (CPPB1) [MIM:176400]: A CC condition defined as the development of secondary sexual CC characteristics in boys and girls at a chronological age that is 2.5 CC standard deviations below the mean age at onset of puberty in the CC population. Central precocious puberty results from premature CC activation of the hypothalamic-pituitary-gonadal axis. CC {ECO:0000269|PubMed:18272894}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Tintin's blight - Issue 58 CC of May 2005; CC URL="https://web.expasy.org/spotlight/back_issues/058"; 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; AB051065; BAB55446.1; -; mRNA. DR EMBL; AF343725; AAK83235.1; -; mRNA. DR EMBL; AJ309020; CAC40817.1; -; mRNA. DR EMBL; AY029541; AAK33126.1; -; mRNA. DR EMBL; AY253981; AAP82929.1; -; mRNA. DR EMBL; AY253982; AAP82930.1; -; mRNA. DR EMBL; EU883577; ACG60651.1; -; mRNA. DR EMBL; AC005379; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471139; EAW69583.1; -; Genomic_DNA. DR EMBL; BC140825; AAI40826.1; -; mRNA. DR EMBL; BC141812; AAI41813.1; -; mRNA. DR CCDS; CCDS12049.1; -. DR RefSeq; NP_115940.2; NM_032551.4. DR PDB; 7YQE; X-ray; 3.50 A; A/B=333-357. DR PDBsum; 7YQE; -. DR AlphaFoldDB; Q969F8; -. DR SMR; Q969F8; -. DR BioGRID; 124162; 4. DR IntAct; Q969F8; 20. DR MINT; Q969F8; -. DR STRING; 9606.ENSP00000234371; -. DR BindingDB; Q969F8; -. DR ChEMBL; CHEMBL5413; -. DR DrugBank; DB05967; ANZ-100. DR DrugCentral; Q969F8; -. DR GuidetoPHARMACOLOGY; 266; -. DR TCDB; 9.A.14.13.14; the g-protein-coupled receptor (gpcr) family. DR GlyCosmos; Q969F8; 3 sites, No reported glycans. DR GlyGen; Q969F8; 3 sites. DR iPTMnet; Q969F8; -. DR PhosphoSitePlus; Q969F8; -. DR BioMuta; KISS1R; -. DR DMDM; 125987836; -. DR MassIVE; Q969F8; -. DR PaxDb; 9606-ENSP00000234371; -. DR PeptideAtlas; Q969F8; -. DR ProteomicsDB; 75750; -. DR Antibodypedia; 10260; 387 antibodies from 34 providers. DR DNASU; 84634; -. DR Ensembl; ENST00000234371.10; ENSP00000234371.3; ENSG00000116014.10. DR GeneID; 84634; -. DR KEGG; hsa:84634; -. DR MANE-Select; ENST00000234371.10; ENSP00000234371.3; NM_032551.5; NP_115940.2. DR UCSC; uc002lqk.4; human. DR AGR; HGNC:4510; -. DR CTD; 84634; -. DR DisGeNET; 84634; -. DR GeneCards; KISS1R; -. DR GeneReviews; KISS1R; -. DR HGNC; HGNC:4510; KISS1R. DR HPA; ENSG00000116014; Group enriched (brain, pancreas, pituitary gland). DR MalaCards; KISS1R; -. DR MIM; 176400; phenotype. DR MIM; 604161; gene. DR MIM; 614837; phenotype. DR neXtProt; NX_Q969F8; -. DR OpenTargets; ENSG00000116014; -. DR Orphanet; 650077; Genetic central precocious puberty in female. DR Orphanet; 650097; Genetic central precocious puberty in male. DR Orphanet; 432; Normosmic congenital hypogonadotropic hypogonadism. DR PharmGKB; PA28899; -. DR VEuPathDB; HostDB:ENSG00000116014; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT00940000157017; -. DR HOGENOM; CLU_009579_6_4_1; -. DR InParanoid; Q969F8; -. DR OMA; YPLPTWV; -. DR OrthoDB; 2915794at2759; -. DR PhylomeDB; Q969F8; -. DR TreeFam; TF315737; -. DR PathwayCommons; Q969F8; -. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SignaLink; Q969F8; -. DR SIGNOR; Q969F8; -. DR BioGRID-ORCS; 84634; 17 hits in 1148 CRISPR screens. DR GeneWiki; KiSS1-derived_peptide_receptor; -. DR GenomeRNAi; 84634; -. DR Pharos; Q969F8; Tchem. DR PRO; PR:Q969F8; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q969F8; Protein. DR Bgee; ENSG00000116014; Expressed in pons and 93 other cell types or tissues. DR ExpressionAtlas; Q969F8; baseline and differential. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0005929; C:cilium; IDA:MGI. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central. DR GO; GO:0008188; F:neuropeptide receptor activity; IDA:UniProtKB. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; NAS:UniProtKB. DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central. DR CDD; cd15095; 7tmA_KiSS1R; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR008103; KiSS_1_rcpt. DR PANTHER; PTHR24230; G-PROTEIN COUPLED RECEPTOR; 1. DR PANTHER; PTHR24230:SF78; KISS-1 RECEPTOR; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR01728; KISS1RECEPTR. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; Q969F8; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disease variant; Disulfide bond; KW G-protein coupled receptor; Glycoprotein; Hypogonadotropic hypogonadism; KW Membrane; Receptor; Reference proteome; Transducer; Transmembrane; KW Transmembrane helix. FT CHAIN 1..398 FT /note="KiSS-1 receptor" FT /id="PRO_0000069695" FT TOPO_DOM 1..46 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 47..67 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 68..78 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 79..101 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 102..120 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 121..138 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 139..157 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 158..178 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 179..202 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 203..223 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 224..263 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 264..284 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 285..305 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 306..328 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 329..398 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 341..363 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 10 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 18 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 28 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 115..191 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT VARIANT 102 FT /note="L -> P (in HH8; absence of inositol phosphate FT accumulation under kisspeptin challenge; normal affinity FT for kisspeptin; dbSNP:rs104894703)" FT /evidence="ECO:0000269|PubMed:17164310" FT /id="VAR_043906" FT VARIANT 148 FT /note="L -> S (in HH8; 65% reduction of inositol phosphate FT production; dbSNP:rs28939719)" FT /evidence="ECO:0000269|PubMed:14573733" FT /id="VAR_021392" FT VARIANT 189 FT /note="A -> T (in HH8; benign; the patient also carries a FT mutation in FGFR1; phenotype consistent with normosmic FT idiopathic hypogonadotropic hypogonadism; FT dbSNP:rs73507527)" FT /evidence="ECO:0000269|PubMed:23643382" FT /id="VAR_069961" FT VARIANT 194 FT /note="A -> D (in HH8; phenotype consistent with Kallmann FT syndrome; the patient also carries a mutation in IL17RD; FT dbSNP:rs397514699)" FT /evidence="ECO:0000269|PubMed:23643382" FT /id="VAR_069962" FT VARIANT 223 FT /note="C -> R (in HH8; exhibit profoundly impaired FT signaling)" FT /evidence="ECO:0000269|PubMed:15598687" FT /id="VAR_021393" FT VARIANT 262 FT /note="S -> L (in HH8; dbSNP:rs745580229)" FT /evidence="ECO:0000269|PubMed:25077900" FT /id="VAR_072975" FT VARIANT 297 FT /note="R -> L (in HH8; mild reduction in ligand-stimulated FT activity across the ligand dose range; dbSNP:rs144670595)" FT /evidence="ECO:0000269|PubMed:15598687" FT /id="VAR_021394" FT VARIANT 364 FT /note="L -> H (in dbSNP:rs350132)" FT /evidence="ECO:0000269|PubMed:11385580, FT ECO:0000269|PubMed:11414709, ECO:0000269|PubMed:11457843, FT ECO:0000269|PubMed:14573733, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15598687, ECO:0000269|Ref.8" FT /id="VAR_021395" FT VARIANT 386 FT /note="R -> P (in CPPB1; reduced rate of decline in FT inositol phosphate accumulation after kisspeptin FT stimulation; prolonged phosphorylation of ERK; FT dbSNP:rs121908499)" FT /evidence="ECO:0000269|PubMed:18272894" FT /id="VAR_043907" SQ SEQUENCE 398 AA; 42586 MW; ECAE2208848F5B06 CRC64; MHTVATSGPN ASWGAPANAS GCPGCGANAS DGPVPSPRAV DAWLVPLFFA ALMLLGLVGN SLVIYVICRH KPMRTVTNFY IANLAATDVT FLLCCVPFTA LLYPLPGWVL GDFMCKFVNY IQQVSVQATC ATLTAMSVDR WYVTVFPLRA LHRRTPRLAL AVSLSIWVGS AAVSAPVLAL HRLSPGPRAY CSEAFPSRAL ERAFALYNLL ALYLLPLLAT CACYAAMLRH LGRVAVRPAP ADSALQGQVL AERAGAVRAK VSRLVAAVVL LFAACWGPIQ LFLVLQALGP AGSWHPRSYA AYALKTWAHC MSYSNSALNP LLYAFLGSHF RQAFRRVCPC APRRPRRPRR PGPSDPAAPH AELLRLGSHP APARAQKPGS SGLAARGLCV LGEDNAPL //