KiSS1-derived peptide receptor

KISS1 receptor
Identifiers
Symbols	KISS1R ; AXOR12; CPPB1; GPR54; HH8; HOT7T175; KISS-1R
External IDs	OMIM: 604161 MGI: 2148793 HomoloGene: 11411 IUPHAR: 266 ChEMBL: 5413 GeneCards: KISS1R Gene
Gene ontology Molecular function • protein binding • neuropeptide receptor activity Cellular component • plasma membrane • integral component of plasma membrane • cell surface • integral component of membrane Biological process • G-protein coupled receptor signaling pathway • phospholipase C-activating G-protein coupled receptor signaling pathway • neuropeptide signaling pathway Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	84634	114229
Ensembl	ENSG00000116014	ENSMUSG00000035773
UniProt	Q969F8	Q91V45
RefSeq (mRNA)	NM_032551	NM_053244
RefSeq (protein)	NP_115940	NP_444474
Location (UCSC)	Chr 19: 0.92 – 0.92 Mb	Chr 10: 79.92 – 79.92 Mb
PubMed search

The KiSS1-derived peptide receptor (also known as GPR54 or the Kisspeptin receptor) is a G protein-coupled receptor^[1] which binds the peptide hormone kisspeptin (metastin).^[2][3][4] Kisspeptin is encoded by the metastasis suppressor gene KISS1, which is expressed in a variety of endocrine and gonadal tissues.^[5] Activation of the kisspeptin receptor is linked to the phospholipase C and inositol trisphosphate second messenger cascades inside the cell.^[6]

Function

Kisspeptin is involved in the regulation of endocrine function and the onset of puberty, with activation of the kisspeptin receptor triggering release of gonadotropin-releasing hormone (GnRH),^[7][8] and release of kisspeptin itself being inhibited by oestradiol but enhanced by GnRH.^[9] Reductions in kisspeptin levels with age may conversely be one of the reasons behind age-related declines in levels of other endocrine hormones such as luteinizing hormone.^[10]

Ligands

No non-peptide ligands for this receptor have yet been discovered, but as of 2009 both selective agonist and antagonist peptides are known.

Agonists

• Kisspeptin
• Kisspeptin-10 (112-121 C-terminal fragment)^[11]

Antagonists

• Kisspeptin-10 analogues modified with amino substitutions^[12]

References

1. Lee DK, Nguyen T, O'Neill GP, Cheng R, Liu Y, Howard AD, Coulombe N, Tan CP, Tang-Nguyen AT, George SR, O'Dowd BF (Mar 1999). "Discovery of a receptor related to the galanin receptors". FEBS Letters 446 (1): 103–7. doi:10.1016/S0014-5793(99)00009-5. PMID 10100623.
2. 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 (May 2001). "Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor". Nature 411 (6837): 613–7. doi:10.1038/35079135. PMID 11385580.
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 (Aug 2001). "AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1". The Journal of Biological Chemistry 276 (31): 28969–75. doi:10.1074/jbc.M102743200. PMID 11387329.
4. Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, Brézillon S, Tyldesley R, Suarez-Huerta N, Vandeput F, Blanpain C, Schiffmann SN, Vassart G, Parmentier M (Sep 2001). "The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54". The Journal of Biological Chemistry 276 (37): 34631–6. doi:10.1074/jbc.M104847200. PMID 11457843.
5. Richard N, Corvaisier S, Camacho E, Kottler ML (Jan 2009). "KiSS-1 and GPR54 at the pituitary level: overview and recent insights". Peptides 30 (1): 123–9. doi:10.1016/j.peptides.2008.09.015. PMID 18948153.
6. Liu X, Lee K, Herbison AE (Sep 2008). "Kisspeptin excites gonadotropin-releasing hormone neurons through a phospholipase C/calcium-dependent pathway regulating multiple ion channels". Endocrinology 149 (9): 4605–14. doi:10.1210/en.2008-0321. PMID 18483150.
7. Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM (Feb 2005). "Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates". Proceedings of the National Academy of Sciences of the United States of America 102 (6): 2129–34. doi:10.1073/pnas.0409822102. PMC 548549. PMID 15684075.
8. Plant TM, Ramaswamy S, Dipietro MJ (Feb 2006). "Repetitive activation of hypothalamic G protein-coupled receptor 54 with intravenous pulses of kisspeptin in the juvenile monkey (Macaca mulatta) elicits a sustained train of gonadotropin-releasing hormone discharges". Endocrinology 147 (2): 1007–13. doi:10.1210/en.2005-1261. PMID 16282350.
9. Richard N, Galmiche G, Corvaisier S, Caraty A, Kottler ML (Mar 2008). "KiSS-1 and GPR54 genes are co-expressed in rat gonadotrophs and differentially regulated in vivo by oestradiol and gonadotrophin-releasing hormone". Journal of Neuroendocrinology 20 (3): 381–93. doi:10.1111/j.1365-2826.2008.01653.x. PMID 18208554.
10. Neal-Perry G, Lebesgue D, Lederman M, Shu J, Zeevalk GD, Etgen AM (Aug 2009). "The excitatory peptide kisspeptin restores the luteinizing hormone surge and modulates amino acid neurotransmission in the medial preoptic area of middle-aged rats". Endocrinology 150 (8): 3699–708. doi:10.1210/en.2008-1667. PMC 2717872. PMID 19423763.
11. Mikkelsen JD, Bentsen AH, Ansel L, Simonneaux V, Juul A (Jan 2009). "Comparison of the effects of peripherally administered kisspeptins". Regulatory Peptides 152 (1-3): 95–100. doi:10.1016/j.regpep.2008.10.001. PMID 18940206.
12. Roseweir AK, Kauffman AS, Smith JT, Guerriero KA, Morgan K, Pielecka-Fortuna J, Pineda R, Gottsch ML, Tena-Sempere M, Moenter SM, Terasawa E, Clarke IJ, Steiner RA, Millar RP (Mar 2009). "Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation". The Journal of Neuroscience 29 (12): 3920–9. doi:10.1523/JNEUROSCI.5740-08.2009. PMC 3035813. PMID 19321788.

Further reading

• Colledge WH (Nov 2004). "GPR54 and puberty". Trends in Endocrinology and Metabolism 15 (9): 448–53. doi:10.1016/j.tem.2004.09.008. PMID 15519892.
• Kaiser UB, Kuohung W (Apr 2005). "KiSS-1 and GPR54 as new players in gonadotropin regulation and puberty". Endocrine 26 (3): 277–84. doi:10.1385/ENDO:26:3:277. PMID 16034182.
• Seminara SB (2006). "Metastin and its G protein-coupled receptor, GPR54: critical pathway modulating GnRH secretion". Frontiers in Neuroendocrinology 26 (3-4): 131–8. doi:10.1016/j.yfrne.2005.10.001. PMID 16309735.
• Tena-Sempere M (2006). "GPR54 and kisspeptin in reproduction". Human Reproduction Update 12 (5): 631–9. doi:10.1093/humupd/dml023. PMID 16731583.
• Cerrato F, Seminara SB (Mar 2007). "Human genetics of GPR54". Reviews in Endocrine & Metabolic Disorders 8 (1): 47–55. doi:10.1007/s11154-007-9027-3. PMID 17334928.
• Lee DK, Nguyen T, O'Neill GP, Cheng R, Liu Y, Howard AD, Coulombe N, Tan CP, Tang-Nguyen AT, George SR, O'Dowd BF (Mar 1999). "Discovery of a receptor related to the galanin receptors". FEBS Letters 446 (1): 103–7. doi:10.1016/S0014-5793(99)00009-5. PMID 10100623.
• 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 (May 2001). "Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor". Nature 411 (6837): 613–7. doi:10.1038/35079135. PMID 11385580.
• 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 (Aug 2001). "AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1". The Journal of Biological Chemistry 276 (31): 28969–75. doi:10.1074/jbc.M102743200. PMID 11387329.
• Clements MK, McDonald TP, Wang R, Xie G, O'Dowd BF, George SR, Austin CP, Liu Q (Jun 2001). "FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54". Biochemical and Biophysical Research Communications 284 (5): 1189–93. doi:10.1006/bbrc.2001.5098. PMID 11414709.
• Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, Brézillon S, Tyldesley R, Suarez-Huerta N, Vandeput F, Blanpain C, Schiffmann SN, Vassart G, Parmentier M (Sep 2001). "The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54". The Journal of Biological Chemistry 276 (37): 34631–6. doi:10.1074/jbc.M104847200. PMID 11457843.
• 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 (Sep 2001). "Metastin suppresses the motility and growth of CHO cells transfected with its receptor". Biochemical and Biophysical Research Communications 286 (5): 958–63. doi:10.1006/bbrc.2001.5470. PMID 11527393.
• Ringel MD, Hardy E, Bernet VJ, Burch HB, Schuppert F, Burman KD, Saji M (May 2002). "Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells". The Journal of Clinical Endocrinology and Metabolism 87 (5): 2399. doi:10.1210/jc.87.5.2399. PMID 11994395.
• Janneau JL, Maldonado-Estrada J, Tachdjian G, Miran I, Motté N, Saulnier P, Sabourin JC, Coté JF, Simon B, Frydman R, Chaouat G, Bellet D (Nov 2002). "Transcriptional expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells". The Journal of Clinical Endocrinology and Metabolism 87 (11): 5336–9. doi:10.1210/jc.2002-021093. PMID 12414911.
• Bo-Abbas Y, Acierno JS, Shagoury JK, Crowley WF, Seminara SB (Jun 2003). "Autosomal recessive idiopathic hypogonadotropic hypogonadism: genetic analysis excludes mutations in the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes". The Journal of Clinical Endocrinology and Metabolism 88 (6): 2730–7. doi:10.1210/jc.2002-021948. PMID 12788881.
• Ikeguchi M, Hirooka Y, Kaibara N (Sep 2003). "Quantitative reverse transcriptase polymerase chain reaction analysis for KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in hepatocellular carcinoma". Journal of Cancer Research and Clinical Oncology 129 (9): 531–5. doi:10.1007/s00432-003-0469-z. PMID 12898236.
• de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E (Sep 2003). "Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54". Proceedings of the National Academy of Sciences of the United States of America 100 (19): 10972–6. doi:10.1073/pnas.1834399100. PMC 196911. PMID 12944565.
• Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS, 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, Aparicio SA, Colledge WH (Oct 2003). "The GPR54 gene as a regulator of puberty". The New England Journal of Medicine 349 (17): 1614–27. doi:10.1056/NEJMoa035322. PMID 14573733.
• Ikeguchi M, Yamaguchi K, Kaibara N (Feb 2004). "Clinical significance of the loss of KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in esophageal squamous cell carcinoma". Clinical Cancer Research 10 (4): 1379–83. doi:10.1158/1078-0432.CCR-1519-02. PMID 14977840.
• Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C, Malli R, Sharabi A, Hiden U, Graier W, Knöfler M, Andreae F, Wagner O, Quaranta V, Desoye G (Mar 2004). "Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts". Journal of Cell Science 117 (Pt 8): 1319–28. doi:10.1242/jcs.00971. PMID 15020672.

External links

• "KiSS1-Derived Peptide Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
• KISS1R protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.