{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q969F8","secondaryAccessions":["A5D8U2","B2RTV1","Q96QG0"],"uniProtkbId":"KISSR_HUMAN","entryAudit":{"firstPublicDate":"2005-03-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-02-06","entryVersion":185,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"KiSS-1 receptor"},"shortNames":[{"value":"KiSS-1R"}]},"alternativeNames":[{"fullName":{"value":"G protein-coupled receptor 54"}},{"fullName":{"value":"G protein-coupled receptor OT7T175"},"shortNames":[{"value":"hOT7T175"}]},{"fullName":{"value":"Hypogonadotropin-1"}},{"fullName":{"value":"Kisspeptins receptor"}},{"fullName":{"value":"Metastin receptor"}}]},"genes":[{"geneName":{"value":"KISS1R"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"11387329"}],"value":"AXOR12"},{"value":"GPR54"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q91V45"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11457843"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11527393"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12944565"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14573733"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15020672"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15596153"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15598687"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17164310"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18272894"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25147978"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38346942"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38512807"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39151001"}],"value":"Receptor for kisspeptins (kisspeptin-10, kisspeptin-13, kisspeptin-14 and metastin/kisspeptin-54) (PubMed:11457843, PubMed:11527393, PubMed:15020672, PubMed:15596153). The hypothalamic KISS1/KISS1R signaling system plays a central role in the regulation of the hypothalamic-pituitary-gonadal reproductive axis by modulating the secretion of gonadotropin-releasing hormone (GnRH) from GnRH neurons (PubMed:12944565, PubMed:14573733, PubMed:15598687, PubMed:17164310, PubMed:18272894). In these neurons, kisspeptin binding to its receptor activates G(q)-dependent signaling, leading to phospholipase C (PLC) activation, and hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) (PubMed:14573733, PubMed:15598687, PubMed:39151001). The subsequent rise in intracellular calcium levels results in the inhibition of inward rectifier potassium channels and activation of TRPC-like cation channels, leading to GnRH neurons depolarization and stimulation (By similarity). In addition to this pathway, kisspeptin also triggers G(q)-independent signaling via beta-arrestin, leading to MAPK cascade activation and ERK1/ERK2 phosphorylation (PubMed:25147978). Furthermore, activation of KISS1R by kisspeptin-10 recruits phosphatase DUSP18 and SRC to the KISS1R C-terminus through a G(q)-dependent signaling pathway, leading to DUSP18-mediated dephosphorylation of SRC (PubMed:38346942). In bone tissue, this results in down-regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption (By similarity). KISS1R is also involved in the regulation of other processes, including cell proliferation and cell migration (PubMed:11457843, PubMed:11527393, PubMed:15020672, PubMed:15596153, PubMed:38512807)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q91V45"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38346942"}],"value":"Interacts with SRC and DUSP18; the interaction depends on receptor activation by kisspeptin-10 and is required for DUSP18-mediated dephosphorylation of SRC (PubMed:38346942). Interaction with SRC and DUSP18 is relevant for down-regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q969F8","intActId":"EBI-8481408"},"interactantTwo":{"uniProtKBAccession":"P50148","geneName":"GNAQ","intActId":"EBI-3909604"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969F8","intActId":"EBI-8481408"},"interactantTwo":{"uniProtKBAccession":"P67775","geneName":"PPP2CA","intActId":"EBI-712311"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969F8","intActId":"EBI-8481408"},"interactantTwo":{"uniProtKBAccession":"O60894","geneName":"RAMP1","intActId":"EBI-962893"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969F8","intActId":"EBI-8481408"},"interactantTwo":{"uniProtKBAccession":"O60895","geneName":"RAMP2","intActId":"EBI-9009040"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q969F8","intActId":"EBI-8481408"},"interactantTwo":{"uniProtKBAccession":"O60896","geneName":"RAMP3","intActId":"EBI-720447"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18772143"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000255"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11385580"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11387329"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11414709"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11457843"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12414911"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15020672"}],"value":"Expressed in the pancreas, placenta and spinal cord, with lower-level of expression in peripheral blood leukocytes, kidney, lung, fetal liver, stomach, small intestine, testes, spleen, thymus, adrenal glands and lymph nodes. In the adult brain, expressed in the superior frontal gyrus, putamen, caudate nucleus, cingulate gyrus, nucleus accumbens, hippocampus, pons and amygdala, as well as the hypothalamus and pituitary. Expression levels are higher in early (7-9 weeks) than term placentas. Expression levels were increased in both early placentas and molar pregnancies and were reduced in choriocarcinoma cells. Expressed at higher levels in first trimester trophoblasts than at term of gestation. Also found in the extravillous trophoblast suggesting endocrine/paracrine activation mechanism"}],"commentType":"TISSUE SPECIFICITY"},{"commentType":"DISEASE","disease":{"diseaseId":"Hypogonadotropic hypogonadism 8 with or without anosmia","diseaseAccession":"DI-03568","acronym":"HH8","description":"A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). HH8 inheritance pattern is autosomal recessive.","diseaseCrossReference":{"database":"MIM","id":"614837"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12944565"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14573733"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15598687"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17164310"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18772143"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23643382"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25077900"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25147978"}]},"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23643382"}],"value":"The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in KISS1R as well as in other HH-associated genes including FGFR1 and IL17RD (PubMed:23643382)"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Precocious puberty, central 1","diseaseAccession":"DI-01332","acronym":"CPPB1","description":"A condition defined as the development of secondary sexual characteristics in boys and girls at a chronological age that is 2.5 standard deviations below the mean age at onset of puberty in the population. Central precocious puberty results from premature activation of the hypothalamic-pituitary-gonadal axis.","diseaseCrossReference":{"database":"MIM","id":"176400"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18272894"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00521"}],"value":"Belongs to the G protein-coupled receptor 1 family"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"Protein Spotlight","resourceUrl":"https://www.proteinspotlight.org/back_issues/058","ftp":false,"note":"Tintin's blight - Issue 58 of May 2005"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":398,"modifier":"EXACT"}},"description":"KiSS-1 receptor","featureId":"PRO_0000069695"},{"type":"Topological 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