KISSR_HUMAN
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 03-AUG-2022, entry version 167.
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";
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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 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 GlyGen; Q969F8; 3 sites.
DR iPTMnet; Q969F8; -.
DR PhosphoSitePlus; Q969F8; -.
DR BioMuta; KISS1R; -.
DR DMDM; 125987836; -.
DR PaxDb; Q969F8; -.
DR PeptideAtlas; Q969F8; -.
DR PRIDE; Q969F8; -.
DR ProteomicsDB; 75750; -.
DR Antibodypedia; 10260; 355 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 CTD; 84634; -.
DR DisGeNET; 84634; -.
DR GeneCards; KISS1R; -.
DR GeneReviews; KISS1R; -.
DR HGNC; HGNC:4510; KISS1R.
DR HPA; ENSG00000116014; Tissue enriched (brain).
DR MalaCards; KISS1R; -.
DR MIM; 176400; phenotype.
DR MIM; 604161; gene.
DR MIM; 614837; phenotype.
DR neXtProt; NX_Q969F8; -.
DR OpenTargets; ENSG00000116014; -.
DR Orphanet; 169615; Idiopathic central precocious puberty.
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; QTYCSES; -.
DR OrthoDB; 1294084at2759; -.
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; 14 hits in 1070 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 92 other tissues.
DR ExpressionAtlas; Q969F8; baseline and differential.
DR Genevisible; Q969F8; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005929; C:cilium; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
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: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 InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR008103; KiSS_1_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01728; KISS1RECEPTR.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disease variant; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Hypogonadotropic hypogonadism; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; 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; phenotype consistent with normosmic
FT idiopathic hypogonadotropic hypogonadism; benign variant;
FT the patient also carries a mutation in FGFR1;
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
