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   24-JAN-2024, entry version 177.
DE   RecName: Full=Metastasis-suppressor KiSS-1;
DE   AltName: Full=Kisspeptin-1;
DE   Contains:
DE     RecName: Full=Metastin;
DE     AltName: Full=Kisspeptin-54;
DE   Contains:
DE     RecName: Full=Kisspeptin-14;
DE   Contains:
DE     RecName: Full=Kisspeptin-13;
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].
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 VARIANT ARG-81.
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 VARIANT ARG-81.
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   ACTION ON BREAST CARCINOMA.
RX   PubMed=9192814;
RA   Lee J.-H., Welch D.R.;
RT   "Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after
RT   transfection with the metastasis suppressor gene, KiSS-1.";
RL   Cancer Res. 57:2384-2387(1997).
RN   [11]
RP   FUNCTION.
RX   PubMed=9185708;
RX   DOI=10.1002/(sici)1097-0215(19970611)71:6<1035::aid-ijc20>3.0.co;2-b;
RA   Lee J.-H., Welch D.R.;
RT   "Identification of highly expressed genes in metastasis-suppressed
RT   chromosome 6/human malignant melanoma hybrid cells using subtractive
RT   hybridization and differential display.";
RL   Int. J. Cancer 71:1035-1044(1997).
RN   [12]
RP   POSSIBLE FUNCTION.
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   [13]
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   [14]
RP   FUNCTION IN REPRESSION OF MPP9 EXPRESSION.
RX   PubMed=11060311; DOI=10.1074/jbc.m008681200;
RA   Yan C., Wang H., Boyd D.D.;
RT   "KiSS-1 represses 92-kDa type IV collagenase expression by down-regulating
RT   NF-kappa B binding to the promoter as a consequence of IkappaBalpha-induced
RT   block of p65/p50 nuclear translocation.";
RL   J. Biol. Chem. 276:1164-1172(2001).
RN   [15]
RP   INDUCTION, AND DOWN-REGULATION DURING THE PROGRESSION OF MELANOMA.
RX   PubMed=11606374;
RA   Shirasaki F., Takata M., Hatta N., Takehara K.;
RT   "Loss of expression of the metastasis suppressor gene KiSS1 during melanoma
RT   progression and its association with LOH of chromosome 6q16.3-q23.";
RL   Cancer Res. 61:7422-7425(2001).
RN   [16]
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   [17]
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   [18]
RP   POTENTIAL TUMOR SUPPRESSION ROLE IN BLADDER CANCER.
RX   PubMed=12547718; DOI=10.1016/s0002-9440(10)63854-0;
RA   Sanchez-Carbayo M., Capodieci P., Cordon-Cardo C.;
RT   "Tumor suppressor role of KiSS-1 in bladder cancer: loss of KiSS-1
RT   expression is associated with bladder cancer progression and clinical
RT   outcome.";
RL   Am. J. Pathol. 162:609-617(2003).
RN   [19]
RP   POSSIBLE FUNCTION AS A PLACENTA-DERIVED HORMONE.
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   [20]
RP   PROTEOLYTIC PROCESSING BY MMP2 AND MMP9, AND POSSIBLE USE AS AN
RP   ANTIMETASTATIC AGENT.
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   [21]
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   [22]
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   [23]
RP   POSSIBLE INVOLVEMENT IN ESOPHAGAL 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   [24]
RP   TISSUE SPECIFICITY, AND INVOLVEMENT 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   [25]
RP   POSSIBLE ROLE IN GASTRIC CANCER INVASION.
RX   PubMed=15300798; DOI=10.1002/ijc.20357;
RA   Dhar D.K., Naora H., Kubota H., Maruyama R., Yoshimura H., Tonomoto Y.,
RA   Tachibana M., Ono T., Otani H., Nagasue N.;
RT   "Downregulation of KiSS-1 expression is responsible for tumor invasion and
RT   worse prognosis in gastric carcinoma.";
RL   Int. J. Cancer 111:868-872(2004).
RN   [26]
RP   POSSIBLE ROLE IN GONADOPTROPIN RELEASE.
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   [27]
RP   FUNCTION IN STIMULATION OF THE HYPOTHALAMIC-PITUITARY-GONADAL AXIS.
RX   PubMed=15500545; DOI=10.1111/j.1365-2826.2004.01240.x;
RA   Thompson E.L., Patterson M., Murphy K.G., Smith K.L., Dhillo W.S.,
RA   Todd J.F., Ghatei M.A., Bloom S.R.;
RT   "Central and peripheral administration of kisspeptin-10 stimulates the
RT   hypothalamic-pituitary-gonadal axis.";
RL   J. Neuroendocrinol. 16:850-858(2004).
RN   [28]
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   [29]
RP   VARIANTS LYS-20; ARG-36 AND ARG-81.
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   [30]
RP   VARIANT HH13 LYS-115, AND CHARACTERIZATION OF VARIANT HH13 LYS-115.
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: Metastasis suppressor protein in malignant melanomas and in
CC       some breast cancers. May regulate events downstream of cell-matrix
CC       adhesion, perhaps involving cytoskeletal reorganization. Generates a C-
CC       terminally amidated peptide, metastin which functions as the endogenous
CC       ligand of the G-protein coupled receptor GPR54. Activation of the
CC       receptor inhibits cell proliferation and cell migration, key
CC       characteristics of tumor metastasis. Kp-10 is a decapeptide derived
CC       from the primary translation product, isolated in conditioned medium of
CC       first trimester trophoblast. Kp-10, but not other kisspeptins,
CC       increased intracellular Ca(2+) levels in isolated first trimester
CC       trophoblasts. Kp-10 is a paracrine/endocrine regulator in fine-tuning
CC       trophoblast invasion generated by the trophoblast itself. The receptor
CC       is also essential for normal gonadotropin-released hormone physiology
CC       and for puberty. The hypothalamic KiSS1/GPR54 system is a pivotal
CC       factor in central regulation of the gonadotropic axis at puberty and in
CC       adulthood. {ECO:0000269|PubMed:11060311, ECO:0000269|PubMed:11385580,
CC       ECO:0000269|PubMed:15500545, ECO:0000269|PubMed:9185708}.
CC   -!- INTERACTION:
CC       Q15726; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-23759979, EBI-947187;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Very high expression in placenta, with the next
CC       highest level in testis and moderate levels in pancreas, liver, small
CC       intestine and brain at much lower levels. Expression levels increased
CC       in both early placentas and molar pregnancies and are reduced in
CC       choriocarcinoma cells. Expressed at higher levels in first trimester
CC       trophoblasts than at term of gestation, but only expressed in the
CC       villous trophoblast. {ECO:0000269|PubMed:11385580,
CC       ECO:0000269|PubMed:12414911, ECO:0000269|PubMed:15020672}.
CC   -!- INDUCTION: Down-regulated during the progression of melanoma in vivo.
CC       Diminishes MMP9 expression by effecting reduced NF-kappa-B binding to
CC       the promoter. {ECO:0000269|PubMed:11606374}.
CC   -!- PTM: Processed by MMP2 and MMP9.
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   -!- SIMILARITY: Belongs to the KISS1 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC79512.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=AAM78592.1; Type=Frameshift; Evidence={ECO:0000305};
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; U43527; AAC79512.1; ALT_FRAME; mRNA.
DR   EMBL; AY117143; AAM78592.1; ALT_FRAME; 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_002256.3.
DR   AlphaFoldDB; Q15726; -.
DR   BioGRID; 110014; 13.
DR   IntAct; Q15726; 1.
DR   STRING; 9606.ENSP00000356162; -.
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; 378 antibodies from 32 providers.
DR   DNASU; 3814; -.
DR   Ensembl; ENST00000367194.5; ENSP00000356162.4; ENSG00000170498.10.
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   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   neXtProt; NX_Q15726; -.
DR   OpenTargets; ENSG00000170498; -.
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; PA30127; -.
DR   VEuPathDB; HostDB:ENSG00000170498; -.
DR   eggNOG; ENOG502SFM2; Eukaryota.
DR   GeneTree; ENSGT00390000008827; -.
DR   HOGENOM; CLU_119112_0_0_1; -.
DR   InParanoid; Q15726; -.
DR   OMA; PMENPRS; -.
DR   OrthoDB; 4605953at2759; -.
DR   PhylomeDB; Q15726; -.
DR   TreeFam; TF338233; -.
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   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   ExpressionAtlas; Q15726; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
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:0060112; P:generation of ovulation cycle rhythm; IEA:Ensembl.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR   GO; GO:0060124; P:positive regulation of growth hormone secretion; IEA:Ensembl.
DR   GO; GO:0033686; P:positive regulation of luteinizing hormone secretion; IEA:Ensembl.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR   GO; GO:0050806; P:positive regulation of synaptic transmission; IEA:Ensembl.
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   Genevisible; Q15726; HS.
PE   1: Evidence at protein level;
KW   Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW   Disease variant; Hypogonadotropic hypogonadism; Phosphoprotein;
KW   Reference proteome; Secreted; 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        65..89
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            118..119
FT                   /note="Cleavage; by MMP2 and MMP9"
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:9806840, ECO:0000269|Ref.4"
FT                   /id="VAR_021398"
FT   VARIANT         115
FT                   /note="N -> K (in HH13; significantly reduced efficacy as
FT                   well as potency)"
FT                   /evidence="ECO:0000269|PubMed:22335740"
FT                   /id="VAR_069179"
SQ   SEQUENCE   138 AA;  14705 MW;  0F0A1E1D66EDC22A CRC64;
     MNSLVSWQLL LFLCATHFGE PLEKVASVGN SRPTGQQLES LGLLAPGEQS LPCTERKPAA
     TARLSRRGTS LSPPPESSGS PQQPGLSAPH SRQIPAPQGA VLVQREKDLP NYNWNSFGLR
     FGKREAAPGN HGRSAGRG
//