KiSS-1 receptor

Details

Name
KiSS-1 receptor
Synonyms
  • AXOR12
  • G-protein coupled receptor 54
  • G-protein coupled receptor OT7T175
  • GPR54
  • hOT7T175
  • Hypogonadotropin-1
  • KiSS-1R
  • Kisspeptins receptor
  • Metastin receptor
Gene Name
KISS1R
Organism
Humans
Amino acid sequence
>lcl|BSEQ0017111|KiSS-1 receptor
MHTVATSGPNASWGAPANASGCPGCGANASDGPVPSPRAVDAWLVPLFFAALMLLGLVGN
SLVIYVICRHKPMRTVTNFYIANLAATDVTFLLCCVPFTALLYPLPGWVLGDFMCKFVNY
IQQVSVQATCATLTAMSVDRWYVTVFPLRALHRRTPRLALAVSLSIWVGSAAVSAPVLAL
HRLSPGPRAYCSEAFPSRALERAFALYNLLALYLLPLLATCACYAAMLRHLGRVAVRPAP
ADSALQGQVLAERAGAVRAKVSRLVAAVVLLFAACWGPIQLFLVLQALGPAGSWHPRSYA
AYALKTWAHCMSYSNSALNPLLYAFLGSHFRQAFRRVCPCAPRRPRRPRRPGPSDPAAPH
AELLRLGSHPAPARAQKPGSSGLAARGLCVLGEDNAPL
Number of residues
398
Molecular Weight
42585.445
Theoretical pI
10.09
GO Classification
Functions
neuropeptide receptor activity
Processes
G-protein coupled receptor signaling pathway / neuropeptide signaling pathway / phospholipase C-activating G-protein coupled receptor signaling pathway
Components
cell surface / integral component of membrane / integral component of plasma membrane / intracellular membrane-bounded organelle / plasma membrane
General Function
Neuropeptide receptor activity
Specific Function
Receptor for metastin (kisspeptin-54 or kp-54), a C-terminally amidated peptide of KiSS1. KiSS1 is a metastasis suppressor protein that suppresses metastases in malignant melanomas and in some breast carcinomas without affecting tumorigenicity. The metastasis suppressor properties may be mediated in part by cell cycle arrest and induction of apoptosis in malignant cells. The receptor is essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/KISS1R system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood. The receptor is also probably involved in the regulation and fine-tuning of trophoblast invasion generated by the trophoblast itself. Analysis of the transduction pathways activated by the receptor identifies coupling to phospholipase C and intracellular calcium release through pertussis toxin-insensitive G(q) proteins.
Pfam Domain Function
Transmembrane Regions
47-67 79-101 121-138 158-178 203-223 264-284 306-328
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0017112|KiSS-1 receptor (KISS1R)
ATGCACACCGTGGCTACGTCCGGACCCAACGCGTCCTGGGGGGCACCGGCCAACGCCTCC
GGCTGCCCGGGCTGTGGCGCCAACGCCTCGGACGGCCCAGTCCCTTCGCCGCGGGCCGTG
GACGCCTGGCTCGTGCCGCTCTTCTTCGCGGCGCTGATGCTGCTGGGCCTGGTGGGGAAC
TCGCTGGTCATCTACGTCATCTGCCGCCACAAGCCGATGCGGACCGTGACCAACTTCTAC
ATCGCCAACCTGGCGGCCACGGACGTGACCTTCCTCCTGTGCTGCGTCCCCTTCACGGCC
CTGCTGTACCCGCTGCCCGGCTGGGTGCTGGGCGACTTCATGTGCAAGTTCGTCAACTAC
ATCCAGCAGGTCTCGGTGCAGGCCACGTGTGCCACTCTGACCGCCATGAGTGTGGACCGC
TGGTACGTGACGGTGTTCCCGTTGCGCGCCCTGCACCGCCGCACGCCCCGCCTGGCGCTG
GCTGTCAGCCTCAGCATCTGGGTAGGCTCTGCGGCGGTGTCTGCGCCGGTGCTCGCCCTG
CACCGCCTGTCACCCGGGCCGCGCGCCTACTGCAGTGAGGCCTTCCCCAGCCGCGCCCTG
GAGCGCGCCTTCGCACTGTACAACCTGCTGGCGCTGTACCTGCTGCCGCTGCTCGCCACC
TGCGCCTGCTATGCGGCCATGCTGCGCCACCTGGGCCGGGTCGCCGTGCGCCCCGCGCCC
GCCGATAGCGCCCTGCAGGGGCAGGTGCTGGCAGAGCGCGCAGGCGCCGTGCGGGCCAAG
GTCTCGCGGCTGGTGGCGGCCGTGGTCCTGCTCTTCGCCGCCTGCTGGGGCCCCATCCAG
CTGTTCCTGGTGCTGCAGGCGCTGGGCCCCGCGGGCTCCTGGCACCCACGCAGCTACGCC
GCCTACGCGCTTAAGACCTGGGCTCACTGCATGTCCTACAGCAACTCCGCGCTGAACCCG
CTGCTCTACGCCTTCCTGGGCTCGCACTTCCGACAGGCCTTCCGCCGCGTCTGCCCCTGC
GCGCCGCGCCGCCCCCGCCGCCCCCGCCGGCCCGGACCCTCGGACCCCGCAGCCCCACAC
GCGGAGCTGCTCCGCCTGGGGTCCCACCCGGCCCCCGCCAGGGCGCAGAAGCCAGGGAGC
AGTGGGCTGGCCGCGCGCGGGCTGTGCGTCCTGGGGGAGGACAACGCCCCTCTCTGA
Chromosome Location
19
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ969F8
UniProtKB Entry NameKISSR_HUMAN
GenBank Gene IDAY253982
GenAtlas IDKISS1R
HGNC IDHGNC:4510
General References
  1. Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, Terao Y, Kumano S, Takatsu Y, Masuda Y, Ishibashi Y, Watanabe T, Asada M, Yamada T, Suenaga M, Kitada C, Usuki S, Kurokawa T, Onda H, Nishimura O, Fujino M: Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001 May 31;411(6837):613-7. [Article]
  2. Clements MK, McDonald TP, Wang R, Xie G, O'Dowd BF, George SR, Austin CP, Liu Q: FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54. Biochem Biophys Res Commun. 2001 Jun 29;284(5):1189-93. [Article]
  3. Muir AI, Chamberlain L, Elshourbagy NA, Michalovich D, Moore DJ, Calamari A, Szekeres PG, Sarau HM, Chambers JK, Murdock P, Steplewski K, Shabon U, Miller JE, Middleton SE, Darker JG, Larminie CG, Wilson S, Bergsma DJ, Emson P, Faull R, Philpott KL, Harrison DC: AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem. 2001 Aug 3;276(31):28969-75. Epub 2001 May 31. [Article]
  4. Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, Brezillon S, Tyldesley R, Suarez-Huerta N, Vandeput F, Blanpain C, Schiffmann SN, Vassart G, Parmentier M: The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001 Sep 14;276(37):34631-6. Epub 2001 Jul 16. [Article]
  5. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, Zahn D, Dixon J, Kaiser UB, Slaugenhaupt SA, Gusella JF, O'Rahilly S, Carlton MB, Crowley WF Jr, Aparicio SA, Colledge WH: The GPR54 gene as a regulator of puberty. N Engl J Med. 2003 Oct 23;349(17):1614-27. [Article]
  6. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. [Article]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Colledge WH: GPR54 and puberty. Trends Endocrinol Metab. 2004 Nov;15(9):448-53. [Article]
  9. Hori A, Honda S, Asada M, Ohtaki T, Oda K, Watanabe T, Shintani Y, Yamada T, Suenaga M, Kitada C, Onda H, Kurokawa T, Nishimura O, Fujino M: Metastin suppresses the motility and growth of CHO cells transfected with its receptor. Biochem Biophys Res Commun. 2001 Sep 7;286(5):958-63. [Article]
  10. Janneau JL, Maldonado-Estrada J, Tachdjian G, Miran I, Motte N, Saulnier P, Sabourin JC, Cote JF, Simon B, Frydman R, Chaouat G, Bellet D: Transcriptional expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells. J Clin Endocrinol Metab. 2002 Nov;87(11):5336-9. [Article]
  11. Ringel MD, Hardy E, Bernet VJ, Burch HB, Schuppert F, Burman KD, Saji M: Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells. J Clin Endocrinol Metab. 2002 May;87(5):2399. [Article]
  12. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E: Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10972-6. Epub 2003 Aug 27. [Article]
  13. Ikeguchi M, Hirooka Y, Kaibara N: Quantitative reverse transcriptase polymerase chain reaction analysis for KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in hepatocellular carcinoma. J Cancer Res Clin Oncol. 2003 Sep;129(9):531-5. Epub 2003 Jul 25. [Article]
  14. Ikeguchi M, Yamaguchi K, Kaibara N: Clinical significance of the loss of KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in esophageal squamous cell carcinoma. Clin Cancer Res. 2004 Feb 15;10(4):1379-83. [Article]
  15. Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C, Malli R, Sharabi A, Hiden U, Graier W, Knofler M, Andreae F, Wagner O, Quaranta V, Desoye G: Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci. 2004 Mar 15;117(Pt 8):1319-28. [Article]
  16. Becker JA, Mirjolet JF, Bernard J, Burgeon E, Simons MJ, Vassart G, Parmentier M, Libert F: Activation of GPR54 promotes cell cycle arrest and apoptosis of human tumor cells through a specific transcriptional program not shared by other Gq-coupled receptors. Biochem Biophys Res Commun. 2005 Jan 21;326(3):677-86. [Article]
  17. Semple RK, Achermann JC, Ellery J, Farooqi IS, Karet FE, Stanhope RG, O'rahilly S, Aparicio SA: Two novel missense mutations in g protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2005 Mar;90(3):1849-55. Epub 2004 Dec 14. [Article]
  18. Tenenbaum-Rakover Y, Commenges-Ducos M, Iovane A, Aumas C, Admoni O, de Roux N: Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54. J Clin Endocrinol Metab. 2007 Mar;92(3):1137-44. Epub 2006 Dec 12. [Article]
  19. Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, Xu S, Seminara SB, Mendonca BB, Kaiser UB, Latronico AC: A GPR54-activating mutation in a patient with central precocious puberty. N Engl J Med. 2008 Feb 14;358(7):709-15. doi: 10.1056/NEJMoa073443. [Article]
  20. Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, Chanoine JP, Rubenstein J, Mohammadi M, Tsai PS, Sidis Y, Lage K, Pitteloud N: Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008. [Article]
  21. Marcos S, Sarfati J, Leroy C, Fouveaut C, Parent P, Metz C, Wolczynski S, Gerard M, Bieth E, Kurtz F, Verier-Mine O, Perrin L, Archambeaud F, Cabrol S, Rodien P, Hove H, Prescott T, Lacombe D, Christin-Maitre S, Touraine P, Hieronimus S, Dewailly D, Young J, Pugeat M, Hardelin JP, Dode C: The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients. J Clin Endocrinol Metab. 2014 Oct;99(10):E2138-43. doi: 10.1210/jc.2014-2110. Epub 2014 Jul 31. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05967ANZ-100investigationalunknownDetails