ID KISS1_HUMAN Reviewed; 138 AA. AC Q15726; A8K6N0; Q9HBP1; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 23-MAR-2010, sequence version 4. DT 02-SEP-2026, entry version 187. DE RecName: Full=Metastasis-suppressor KiSS-1; DE AltName: Full=Kisspeptin-1; DE Contains: DE RecName: Full=Metastin {ECO:0000303|PubMed:11385580}; DE AltName: Full=Kisspeptin-54 {ECO:0000303|PubMed:11457843}; DE Contains: DE RecName: Full=Kisspeptin-14 {ECO:0000303|PubMed:11457843}; DE Contains: DE RecName: Full=Kisspeptin-13 {ECO:0000303|PubMed:11457843}; DE Contains: DE RecName: Full=Kisspeptin-10; DE Flags: Precursor; GN Name=KISS1; ORFNames=PP5098; 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], TISSUE SPECIFICITY, AND VARIANTS ARG-81 AND RP TRP-GLY-ALA-GLY-ALA-GLY-GLN-138 EXT. RX PubMed=8944003; DOI=10.1093/jnci/88.23.1731; RA Lee J.-H., Miele M.E., Hicks D.J., Phillips K.K., Trent J.M., RA Weissman B.E., Welch D.R.; RT "KiSS-1, a novel human malignant melanoma metastasis-suppressor gene."; RL J. Natl. Cancer Inst. 88:1731-1737(1996). RN [2] RP ERRATUM OF PUBMED:8944003. RA Lee J.-H., Miele M.E., Hicks D.J., Phillips K.K., Trent J.M., RA Weissman B.E., Welch D.R.; RL J. Natl. Cancer Inst. 89:1549-1549(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ARG-81 AND RP TRP-GLY-ALA-GLY-ALA-GLY-GLN-138 EXT. RX PubMed=9806840; DOI=10.1006/geno.1998.5566; RA West A., Vojta P.J., Welch D.R., Weissman B.E.; RT "Chromosome localization and genomic structure of the KiSS-1 metastasis RT suppressor gene (KISS1)."; RL Genomics 54:145-148(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ARG-81 AND RP TRP-GLY-ALA-GLY-ALA-GLY-GLN-138 EXT. RC TISSUE=Term placenta; RA Qiao C., Lin Q.D., Xu W.X., He Y., Wang C.H.; RT "Cloned KiSS-1 gene from human term placenta."; RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin; 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 [9] RP PROTEIN SEQUENCE OF 68-88, AMIDATION AT PHE-121, FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Placenta; 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 [10] RP FUNCTION, TISSUE SPECIFICITY, AND MASS SPECTROMETRY. 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 [11] RP FUNCTION. 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. 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 TISSUE SPECIFICITY. RX PubMed=12574233; DOI=10.1210/jc.2002-021235; RA Horikoshi Y., Matsumoto H., Takatsu Y., Ohtaki T., Kitada C., Usuki S., RA Fujino M.; RT "Dramatic elevation of plasma metastin concentrations in human pregnancy: RT metastin as a novel placenta-derived hormone in humans."; RL J. Clin. Endocrinol. Metab. 88:914-919(2003). RN [14] RP PROTEOLYTIC PROCESSING BY MMP2 AND MMP9, AND FUNCTION. RX PubMed=12879005; DOI=10.1038/sj.onc.1206542; RA Takino T., Koshikawa N., Miyamori H., Tanaka M., Sasaki T., Okada Y., RA Seiki M., Sato H.; RT "Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by RT matrix metalloproteinases."; RL Oncogene 22:4617-4626(2003). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-112, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=15144186; DOI=10.1021/ac035352d; RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., RA Peters E.C.; RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [16] RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND FUNCTION. 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 [17] RP FUNCTION. RX PubMed=15219839; DOI=10.1016/j.bbrc.2004.05.185; RA Matsui H., Takatsu Y., Kumano S., Matsumoto H., Ohtaki T.; RT "Peripheral administration of metastin induces marked gonadotropin release RT and ovulation in the rat."; RL Biochem. Biophys. Res. Commun. 320:383-388(2004). RN [18] RP FUNCTION. 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 FUNCTION. RX PubMed=25147978; DOI=10.1210/en.2014-1304; RA Ahow M., Min L., Pampillo M., Nash C., Wen J., Soltis K., Carroll R.S., RA Glidewell-Kenney C.A., Mellon P.L., Bhattacharya M., Tobet S.A., RA Kaiser U.B., Babwah A.V.; RT "KISS1R signals independently of Galphaq/11 and triggers LH secretion via RT the beta-arrestin pathway in the male mouse."; RL Endocrinology 155:4433-4446(2014). RN [20] RP FUNCTION (KISSPEPTIN-10). RX PubMed=38512807; DOI=10.1165/rcmb.2023-0469oc; RA Balraj P., Ambhore N.S., Ramakrishnan Y.S., Borkar N.A., Banerjee P., RA Reza M.I., Varadharajan S., Kumar A., Pabelick C.M., Prakash Y.S., RA Sathish V.; RT "Kisspeptin/KISS1R Signaling Modulates Human Airway Smooth Muscle Cell RT Migration."; RL Am. J. Respir. Cell Mol. Biol. 70:507-518(2024). RN [21] {ECO:0007744|PDB:8ZJD} RP STRUCTURE BY ELECTRON MICROSCOPY (3.06 ANGSTROMS) OF 112-121 IN COMPLEX RP WITH KISS1R AND G PROTEINS. RX PubMed=38935498; DOI=10.1016/j.celrep.2024.114389; RA Shen S., Wang D., Liu H., He X., Cao Y., Chen J., Li S., Cheng X., Xu H.E., RA Duan J.; RT "Structural basis for hormone recognition and distinctive Gq protein RT coupling by the kisspeptin receptor."; RL Cell Rep. 43:114389-114389(2024). RN [22] {ECO:0007744|PDB:8XGS} RP STRUCTURE BY ELECTRON MICROSCOPY (2.95 ANGSTROMS) OF 68-121 IN COMPLEX WITH RP KISS1R; GNAQ; GNB1 AND GNG2, AND FUNCTION (METASTIN). RX PubMed=39151001; DOI=10.1126/sciadv.adn7771; RA Wu Z., Chen G., Qiu C., Yan X., Xu L., Jiang S., Xu J., Han R., Shi T., RA Liu Y., Gao W., Wang Q., Li J., Ye F., Pan X., Zhang Z., Ning P., Zhang B., RA Chen J., Du Y.; RT "Structural basis for the ligand recognition and G protein subtype RT selectivity of kisspeptin receptor."; RL Sci. Adv. 10:eadn7771-eadn7771(2024). RN [23] RP VARIANTS LYS-20; ARG-36 AND ARG-81, AND FUNCTION. 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 [24] RP VARIANT HH13 LYS-115, CHARACTERIZATION OF VARIANT HH13 LYS-115, INVOLVEMENT RP IN HH13, AND FUNCTION. RX PubMed=22335740; DOI=10.1056/nejmoa1111184; RA Topaloglu A.K., Tello J.A., Kotan L.D., Ozbek M.N., Yilmaz M.B., RA Erdogan S., Gurbuz F., Temiz F., Millar R.P., Yuksel B.; RT "Inactivating KISS1 mutation and hypogonadotropic hypogonadism."; RL N. Engl. J. Med. 366:629-635(2012). CC -!- FUNCTION: Kisspeptins are ligands for the G protein-coupled receptor CC KISS1R/GPR54 (PubMed:11385580, PubMed:11457843, PubMed:11527393, CC PubMed:12879005, PubMed:15020672, PubMed:15596153). The hypothalamic CC KISS1/KISS1R signaling system plays a central role in the regulation of CC the hypothalamic-pituitary-gonadal reproductive axis by modulating the CC secretion of gonadotropin-releasing hormone (GnRH) from GnRH neurons CC (PubMed:15219839, PubMed:15598687, PubMed:22335740). In these neurons, CC kisspeptin binding to its receptor activates G(q)-dependent signaling, CC leading to phospholipase C (PLC) activation, and hydrolysis of CC phosphatidylinositol 4,5-bisphosphate (PIP2) (PubMed:15598687, CC PubMed:22335740). The subsequent rise in intracellular calcium levels CC results in the inhibition of inward rectifier potassium channels and CC activation of TRPC-like cation channels, leading to GnRH neurons CC depolarization and stimulation (By similarity). In addition to this CC pathway, kisspeptin also triggers G(q)-independent signaling via beta- CC arrestin, leading to MAPK cascade activation and ERK1/ERK2 CC phosphorylation (PubMed:25147978). Kisspeptins are also involved in the CC regulation of other processes including cell growth, cell proliferation CC and cell migration (PubMed:11385580, PubMed:11457843, PubMed:11527393, CC PubMed:12879005, PubMed:15020672, PubMed:15596153). CC {ECO:0000250|UniProtKB:Q6Y4S4, ECO:0000269|PubMed:11385580, CC ECO:0000269|PubMed:11457843, ECO:0000269|PubMed:11527393, CC ECO:0000269|PubMed:12879005, ECO:0000269|PubMed:15020672, CC ECO:0000269|PubMed:15219839, ECO:0000269|PubMed:15596153, CC ECO:0000269|PubMed:15598687, ECO:0000269|PubMed:22335740, CC ECO:0000269|PubMed:25147978}. CC -!- FUNCTION: [Kisspeptin-10]: Binds the G protein-coupled receptor CC KISS1R/GPR54 and triggers G protein-coupled receptor signaling via CC activation of G(q) and phosphatidylinositol 4,5-bisphosphate (PIP2) CC hydrolysis by phospholipase C (PubMed:11457843, PubMed:22335740). CC Binding to the receptor also activates beta-arrestin-dependent CC signaling resulting in ERK1/2 phosphorylation (PubMed:11457843, CC PubMed:25147978). Activation of the receptor inhibits cell CC proliferation and cell migration, and is involved in the regulation of CC trophoblast invasion during early stages of pregnancy. Is also involved CC in the modulation of airway smooth muscle cells migration CC (PubMed:11457843, PubMed:15020672, PubMed:38512807). In bone tissue, CC activation of KISS1R by kisspeptin-10 recruits phosphatase DUSP18 and CC SRC to the KISS1R C-terminus through a G(q)-dependent signaling CC pathway. This leads to DUSP18-mediated dephosphorylation of SRC, down- CC regulation of osteoclast differentiation and activity, and consequently CC suppression of bone resorption (By similarity). CC {ECO:0000250|UniProtKB:Q6Y4S4, ECO:0000269|PubMed:11457843, CC ECO:0000269|PubMed:15020672, ECO:0000269|PubMed:22335740, CC ECO:0000269|PubMed:25147978, ECO:0000269|PubMed:38512807}. CC -!- FUNCTION: [Metastin]: Receptor binding triggers G protein-coupled CC receptor signaling via activation of G(q) and phosphatidylinositol 4,5- CC bisphosphate (PIP2) hydrolysis by phospholipase C. CC {ECO:0000269|PubMed:39151001}. CC -!- INTERACTION: CC Q15726; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-23759979, EBI-947187; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15020672}. CC -!- TISSUE SPECIFICITY: High expression in placenta (PubMed:8944003, CC PubMed:11385580, PubMed:11457843, PubMed:12574233). Expression levels CC increased in both early placentas and molar pregnancies and are reduced CC in choriocarcinoma cells. In first trimester trophoblasts is expressed CC at higher levels than at term of gestation, but only expressed in the CC villous trophoblast (PubMed:15020672). Also expressed in testis, CC pancreas, liver, small intestine. {ECO:0000269|PubMed:11385580, CC ECO:0000269|PubMed:11457843, ECO:0000269|PubMed:12414911, CC ECO:0000269|PubMed:12574233, ECO:0000269|PubMed:15020672, CC ECO:0000269|PubMed:8944003}. CC -!- PTM: Processed by MMP2 and MMP9. {ECO:0000269|PubMed:12879005}. CC -!- DISEASE: Hypogonadotropic hypogonadism 13 with or without anosmia CC (HH13) [MIM:614842]: A disorder characterized by absent or incomplete CC sexual maturation by the age of 18 years, in conjunction with low CC levels of circulating gonadotropins and testosterone and no other CC abnormalities of the hypothalamic-pituitary axis. In some cases, it is CC associated with non-reproductive phenotypes, such as anosmia, cleft CC palate, and sensorineural hearing loss. Anosmia or hyposmia is related CC to the absence or hypoplasia of the olfactory bulbs and tracts. CC Hypogonadism is due to deficiency in gonadotropin-releasing hormone and CC probably results from a failure of embryonic migration of gonadotropin- CC releasing hormone-synthesizing neurons. In the presence of anosmia, CC idiopathic hypogonadotropic hypogonadism is referred to as Kallmann CC syndrome, whereas in the presence of a normal sense of smell, it has CC been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). CC {ECO:0000269|PubMed:22335740}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Was originally identified as a metastasis suppressor CC gene. {ECO:0000269|PubMed:8944003}. CC -!- SIMILARITY: Belongs to the KISS1 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Tintin's blight - Issue 58 CC of May 2005; CC URL="https://www.proteinspotlight.org/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; U43527; AAC79512.1; -; mRNA. DR EMBL; AY117143; AAM78592.1; -; mRNA. DR EMBL; AF218017; AAG17259.1; -; mRNA. DR EMBL; AL592114; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK291695; BAF84384.1; -; mRNA. DR EMBL; BC022819; AAH22819.1; -; mRNA. DR CCDS; CCDS41454.1; -. DR RefSeq; NP_002247.3; NM_002256.4. DR PDB; 8XGS; EM; 2.95 A; F=68-121. DR PDB; 8ZJD; EM; 3.06 A; L=112-121. DR AlphaFoldDB; Q15726; -. DR EMDB; EMD-38331; -. DR EMDB; EMD-60141; -. DR SMR; Q15726; -. DR BioGRID; 110014; 13. DR FunCoup; Q15726; 384. DR IntAct; Q15726; 9. DR NDEx; IQUERY-CP-KISS1; 2 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000356162; -. DR BindingDB; Q15726; -. DR DrugBank; DB11975; TAK-448. DR iPTMnet; Q15726; -. DR PhosphoSitePlus; Q15726; -. DR BioMuta; KISS1; -. DR MassIVE; Q15726; -. DR PaxDb; 9606-ENSP00000356162; -. DR PeptideAtlas; Q15726; -. DR ProteomicsDB; 60723; -. DR Antibodypedia; 34554; 324 antibodies from 33 providers. DR DNASU; 3814; -. DR Ensembl; ENST00000367194.5; ENSP00000356162.4; ENSG00000170498.11. DR Ensembl; ENST00000882445.1; ENSP00000552504.1; ENSG00000170498.11. DR GeneID; 3814; -. DR KEGG; hsa:3814; -. DR MANE-Select; ENST00000367194.5; ENSP00000356162.4; NM_002256.4; NP_002247.3. DR UCSC; uc001har.4; human. DR AGR; HGNC:6341; -. DR ClinPGx; PA30127; -. DR CTD; 3814; -. DR DisGeNET; 3814; -. DR GeneCards; KISS1; -. DR GeneReviews; KISS1; -. DR HGNC; HGNC:6341; KISS1. DR HPA; ENSG00000170498; Tissue enriched (placenta). DR MalaCards; KISS1; -. DR MIM; 603286; gene. DR MIM; 614842; phenotype. DR OpenTargets; ENSG00000170498; -. DR Orphanet; 650097; Genetic central precocious puberty in male. DR Orphanet; 432; Normosmic congenital hypogonadotropic hypogonadism. DR VEuPathDB; HostDB:ENSG00000170498; -. DR eggNOG; ENOG502SFM2; Eukaryota. DR GeneTree; ENSGT00390000008827; -. DR HOGENOM; CLU_119112_0_0_1; -. DR InParanoid; Q15726; -. DR OMA; LAHLIPW; -. DR OrthoDB; 9899812at2759; -. DR PAN-GO; Q15726; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q15726; -. DR PathwayCommons; Q15726; -. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SignaLink; Q15726; -. DR SIGNOR; Q15726; -. DR Agora; ENSG00000170498; -. DR BioGRID-ORCS; 3814; 37 hits in 1142 CRISPR screens. DR ChiTaRS; KISS1; human. DR GeneWiki; Kisspeptin; -. DR GenomeRNAi; 3814; -. DR Pharos; Q15726; Tbio. DR PRO; PR:Q15726; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q15726; protein. DR Bgee; ENSG00000170498; Expressed in placenta and 77 other cell types or tissues. DR GO; GO:0005576; C:extracellular region; EXP:UniProtKB. DR GO; GO:0031773; F:kisspeptin receptor binding; IBA:GO_Central. DR GO; GO:0007010; P:cytoskeleton organization; TAS:ProtInc. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0045779; P:negative regulation of bone resorption; ISS:UniProtKB. DR GO; GO:0033686; P:positive regulation of luteinizing hormone secretion; IBA:GO_Central. DR DisProt; DP01173; -. DR InterPro; IPR020207; Metastasis-suppressor_KiSS-1. DR PANTHER; PTHR16955; METASTASIS-SUPPRESSOR KISS-1; 1. DR PANTHER; PTHR16955:SF6; METASTASIS-SUPPRESSOR KISS-1; 1. DR Pfam; PF15152; Kisspeptin; 1. DR PDBsum; 8XGS; -. DR PDBsum; 8ZJD; -. PE 1: Evidence at protein level; KW 3D-structure; Amidation; Cleavage on pair of basic residues; KW Direct protein sequencing; Disease variant; Hypogonadotropic hypogonadism; KW Phosphoprotein; Proteomics identification; Reference proteome; Secreted; KW Signal. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT CHAIN 20..138 FT /note="Metastasis-suppressor KiSS-1" FT /id="PRO_0000021544" FT PEPTIDE 68..121 FT /note="Metastin" FT /id="PRO_0000021545" FT PEPTIDE 108..121 FT /note="Kisspeptin-14" FT /id="PRO_0000021546" FT PEPTIDE 109..121 FT /note="Kisspeptin-13" FT /id="PRO_0000021547" FT PEPTIDE 112..121 FT /note="Kisspeptin-10" FT /id="PRO_0000021548" FT REGION 28..101 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 112..121 FT /note="Essential for receptor binding and receptor FT activation" FT REGION 115..138 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 28..39 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 77..89 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 118..119 FT /note="Cleavage; by MMP2 and MMP9" FT /evidence="ECO:0000269|PubMed:12879005" FT MOD_RES 112 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15144186" FT MOD_RES 121 FT /note="Phenylalanine amide" FT /evidence="ECO:0000269|PubMed:11385580" FT VARIANT 20 FT /note="E -> K (in dbSNP:rs12998)" FT /evidence="ECO:0000269|PubMed:15598687" FT /id="VAR_021396" FT VARIANT 36 FT /note="Q -> R (in dbSNP:rs35431622)" FT /evidence="ECO:0000269|PubMed:15598687" FT /id="VAR_021397" FT VARIANT 81 FT /note="P -> R (in dbSNP:rs4889)" FT /evidence="ECO:0000269|PubMed:15598687, FT ECO:0000269|PubMed:8944003, ECO:0000269|PubMed:9806840, FT ECO:0000269|Ref.4" FT /id="VAR_021398" FT VARIANT 115 FT /note="N -> K (in HH13; likely pathogenic; severely FT decreased receptor ligand activity; reduced phospholipase FT C-activating G protein-coupled receptor signaling)" FT /evidence="ECO:0000269|PubMed:22335740" FT /id="VAR_069179" FT VARIANT 138 FT /note="G -> GWGAGAGQ (in dbSNP:rs1429366684)" FT /evidence="ECO:0000269|PubMed:8944003, FT ECO:0000269|PubMed:9806840, ECO:0000269|Ref.4" FT /id="VAR_091089" FT HELIX 114..116 FT /evidence="ECO:0007829|PDB:8ZJD" SQ SEQUENCE 138 AA; 14705 MW; 0F0A1E1D66EDC22A CRC64; MNSLVSWQLL LFLCATHFGE PLEKVASVGN SRPTGQQLES LGLLAPGEQS LPCTERKPAA TARLSRRGTS LSPPPESSGS PQQPGLSAPH SRQIPAPQGA VLVQREKDLP NYNWNSFGLR FGKREAAPGN HGRSAGRG //