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Identification
HMDB Protein ID HMDBP07764
Secondary Accession Numbers
  • 13473
Name KiSS-1 receptor
Synonyms
  1. G-protein coupled receptor 54
  2. G-protein coupled receptor OT7T175
  3. Hypogonadotropin-1
  4. KiSS-1R
  5. Kisspeptins receptor
  6. Metastin receptor
  7. hOT7T175
Gene Name KISS1R
Protein Type Unknown
Biological Properties
General Function Involved in G-protein coupled receptor protein signaling pathway
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
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
membrane part
intrinsic to membrane
integral to membrane
Process
signaling
signaling pathway
cell surface receptor linked signaling pathway
g-protein coupled receptor protein signaling pathway
Cellular Location
  1. Cell membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 19p13.3
SNPs KISS1R
Gene Sequence
>1197 bp
ATGCACACCGTGGCTACGTCCGGACCCAACGCGTCCTGGGGGGCACCGGCCAACGCCTCC
GGCTGCCCGGGCTGTGGCGCCAACGCCTCGGACGGCCCAGTCCCTTCGCCGCGGGCCGTG
GACGCCTGGCTCGTGCCGCTCTTCTTCGCGGCGCTGATGCTGCTGGGCCTGGTGGGGAAC
TCGCTGGTCATCTACGTCATCTGCCGCCACAAGCCGATGCGGACCGTGACCAACTTCTAC
ATCGCCAACCTGGCGGCCACGGACGTGACCTTCCTCCTGTGCTGCGTCCCCTTCACGGCC
CTGCTGTACCCGCTGCCCGGCTGGGTGCTGGGCGACTTCATGTGCAAGTTCGTCAACTAC
ATCCAGCAGGTCTCGGTGCAGGCCACGTGTGCCACTCTGACCGCCATGAGTGTGGACCGC
TGGTACGTGACGGTGTTCCCGTTGCGCGCCCTGCACCGCCGCACGCCCCGCCTGGCGCTG
GCTGTCAGCCTCAGCATCTGGGTAGGCTCTGCGGCGGTGTCTGCGCCGGTGCTCGCCCTG
CACCGCCTGTCACCCGGGCCGCGCGCCTACTGCAGTGAGGCCTTCCCCAGCCGCGCCCTG
GAGCGCGCCTTCGCACTGTACAACCTGCTGGCGCTGTACCTGCTGCCGCTGCTCGCCACC
TGCGCCTGCTATGCGGCCATGCTGCGCCACCTGGGCCGGGTCGCCGTGCGCCCCGCGCCC
GCCGATAGCGCCCTGCAGGGGCAGGTGCTGGCAGAGCGCGCAGGCGCCGTGCGGGCCAAG
GTCTCGCGGCTGGTGGCGGCCGTGGTCCTGCTCTTCGCCGCCTGCTGGGGCCCCATCCAG
CTGTTCCTGGTGCTGCAGGCGCTGGGCCCCGCGGGCTCCTGGCACCCACGCAGCTACGCC
GCCTACGCGCTTAAGACCTGGGCTCACTGCATGTCCTACAGCAACTCCGCGCTGAACCCG
CTGCTCTACGCCTTCCTGGGCTCGCACTTCCGACAGGCCTTCCGCCGCGTCTGCCCCTGC
GCGCCGCGCCGCCCCCGCCGCCCCCGCCGGCCCGGACCCTCGGACCCCGCAGCCCCACAC
GCGGAGCTGCACCGCCTGGGGTCCCACCCGGCCCCCGCCAGGGCGCAGAAGCCAGGGAGC
AGTGGGCTGGCCGCGCGCGGGCTGTGCGTCCTGGGGGAGGACAACGCCCCTCTCTGA
Protein Properties
Number of Residues 398
Molecular Weight 42585.4
Theoretical pI 10.09
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 47-67
  • 79-101
  • 121-138
  • 158-178
  • 203-223
  • 264-284
  • 306-328
Protein Sequence
>KiSS-1 receptor
MHTVATSGPNASWGAPANASGCPGCGANASDGPVPSPRAVDAWLVPLFFAALMLLGLVGN
SLVIYVICRHKPMRTVTNFYIANLAATDVTFLLCCVPFTALLYPLPGWVLGDFMCKFVNY
IQQVSVQATCATLTAMSVDRWYVTVFPLRALHRRTPRLALAVSLSIWVGSAAVSAPVLAL
HRLSPGPRAYCSEAFPSRALERAFALYNLLALYLLPLLATCACYAAMLRHLGRVAVRPAP
ADSALQGQVLAERAGAVRAKVSRLVAAVVLLFAACWGPIQLFLVLQALGPAGSWHPRSYA
AYALKTWAHCMSYSNSALNPLLYAFLGSHFRQAFRRVCPCAPRRPRRPRRPGPSDPAAPH
AELLRLGSHPAPARAQKPGSSGLAARGLCVLGEDNAPL
GenBank ID Protein 14041798
UniProtKB/Swiss-Prot ID Q969F8
UniProtKB/Swiss-Prot Entry Name KISSR_HUMAN
PDB IDs Not Available
GenBank Gene ID AB051065
GeneCard ID KISS1R
GenAtlas ID KISS1R
HGNC ID HGNC:4510
References
General References
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  2. 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. [PubMed:15057824 ]
  3. 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. [PubMed:11385580 ]
  4. 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. [PubMed:11414709 ]
  5. 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. [PubMed:11387329 ]
  6. 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. [PubMed:11457843 ]
  7. 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. [PubMed:14573733 ]
  8. Colledge WH: GPR54 and puberty. Trends Endocrinol Metab. 2004 Nov;15(9):448-53. [PubMed:15519892 ]
  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. [PubMed:11527393 ]
  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. [PubMed:12414911 ]
  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. [PubMed:11994395 ]
  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. [PubMed:12944565 ]
  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. [PubMed:12898236 ]
  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. [PubMed:14977840 ]
  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. [PubMed:15020672 ]
  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. [PubMed:15596153 ]
  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. [PubMed:15598687 ]
  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. [PubMed:17164310 ]
  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. [PubMed:18272894 ]