Leucyl/cystinyl aminopeptidase, also known as cystinyl aminopeptidase (CAP), insulin-regulated aminopeptidase (IRAP), human placental leucine aminopeptidase (PLAP), oxytocinase, and vasopressinase, is an enzyme of the aminopeptidase group that in humans is encoded by the LNPEPgene.[1][2]
This gene encodes a zinc-dependent aminopeptidase (metalloexopeptidase) that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step in the conversion of angiotensinogen to angiotensin IV (AT4) and is also a receptor for AT4. Alternative splicing results in multiple transcript variants encoding different isoforms.[2]
Mutations in this gene have been associated to psoriasis risk.(doi:10.1038/jid.2013.317)
↑Rogi T, Tsujimoto M, Nakazato H, Mizutani S, Tomoda Y (February 1996). "Human placental leucine aminopeptidase/oxytocinase. A new member of type II membrane-spanning zinc metallopeptidase family". J Biol Chem. 271 (1): 56–61. doi:10.1074/jbc.271.1.56. PMID8550619.
↑Sbodio, Juan I; Chi Nai-Wen (August 2002). "Identification of a tankyrase-binding motif shared by IRAP, TAB182, and human TRF1 but not mouse TRF1. NuMA contains this RXXPDG motif and is a novel tankyrase partner". J. Biol. Chem. United States. 277 (35): 31887–92. doi:10.1074/jbc.M203916200. ISSN0021-9258. PMID12080061.
↑Chi, N W; Lodish H F (December 2000). "Tankyrase is a golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles". J. Biol. Chem. UNITED STATES. 275 (49): 38437–44. doi:10.1074/jbc.M007635200. ISSN0021-9258. PMID10988299.
Albiston AL, Mustafa T, McDowall SG, et al. (2003). "AT4 receptor is insulin-regulated membrane aminopeptidase: potential mechanisms of memory enhancement". Trends Endocrinol. Metab. 14 (2): 72–7. doi:10.1016/S1043-2760(02)00037-1. PMID12591177.
Keller SR (2004). "The insulin-regulated aminopeptidase: a companion and regulator of GLUT4". Front. Biosci. 8: s410–20. doi:10.2741/1078. PMID12700100.
Nomura S, Ito T, Yamamoto E, et al. (2005). "Gene regulation and physiological function of placental leucine aminopeptidase/oxytocinase during pregnancy". Biochim. Biophys. Acta. 1751 (1): 19–25. doi:10.1016/j.bbapap.2005.04.006. PMID15894523.
Mizutani S, Shibata K, Kikkawa F, et al. (2007). "Essential role of placental leucine aminopeptidase in gynecologic malignancy". Expert Opin. Ther. Targets. 11 (4): 453–61. doi:10.1517/14728222.11.4.453. PMID17373876.
Tsujimoto M, Mizutani S, Adachi H, et al. (1992). "Identification of human placental leucine aminopeptidase as oxytocinase". Arch. Biochem. Biophys. 292 (2): 388–92. doi:10.1016/0003-9861(92)90007-J. PMID1731608.
Mizutani S, Akiyama H, Kurauchi O, et al. (1985). "In vitro degradation of angiotensin II (A-II) by human placental subcellular fractions, pregnancy sera and purified placental aminopeptidases". Acta Endocrinol. 110 (1): 135–9. doi:10.1530/acta.0.1100135. PMID3898693.
Beckman L, Björling G, Christodoulou C (1966). "Pregnancy enzymes and placental polymorphism. II. Leucine aminopeptidase". Acta genetica et statistica medica. 16 (2): 122–31. doi:10.1159/000151957. PMID5953194.
Itoh C, Watanabe M, Nagamatsu A, et al. (1997). "Two molecular species of oxytocinase (L-cystine aminopeptidase) in human placenta: purification and characterization". Biol. Pharm. Bull. 20 (1): 20–4. doi:10.1248/bpb.20.20. PMID9013800.
Laustsen PG, Rasmussen TE, Petersen K, et al. (1997). "The complete amino acid sequence of human placental oxytocinase". Biochim. Biophys. Acta. 1352 (1): 1–7. doi:10.1016/S0167-4781(97)00036-5. PMID9177475.
Nagasaka T, Nomura S, Okamura M, et al. (1998). "Immunohistochemical localization of placental leucine aminopeptidase/oxytocinase in normal human placental, fetal and adult tissues". Reprod. Fertil. Dev. 9 (8): 747–53. doi:10.1071/R97055. PMID9733056.
Horio J, Nomura S, Okada M, et al. (1999). "Structural organization of the 5'-end and chromosomal assignment of human placental leucine aminopeptidase/insulin-regulated membrane aminopeptidase gene". Biochem. Biophys. Res. Commun. 262 (1): 269–74. doi:10.1006/bbrc.1999.1184. PMID10448104.
Rasmussen TE, Pedraza-Díaz S, Hardré R, et al. (2000). "Structure of the human oxytocinase/insulin-regulated aminopeptidase gene and localization to chromosome 5q21". Eur. J. Biochem. 267 (8): 2297–306. doi:10.1046/j.1432-1327.2000.01234.x. PMID10759854.
Nakanishi Y, Nomura S, Okada M, et al. (2001). "Immunoaffinity purification and characterization of native placental leucine aminopeptidase/oxytocinase from human placenta". Placenta. 21 (7): 628–34. doi:10.1053/plac.2000.0564. PMID10985965.
Chi NW, Lodish HF (2001). "Tankyrase is a golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles". J. Biol. Chem. 275 (49): 38437–44. doi:10.1074/jbc.M007635200. PMID10988299.
Matsumoto H, Nagasaka T, Hattori A, et al. (2001). "Expression of placental leucine aminopeptidase/oxytocinase in neuronal cells and its action on neuronal peptides". Eur. J. Biochem. 268 (11): 3259–66. doi:10.1046/j.1432-1327.2001.02221.x. PMID11389728.
Iwase A, Nomura S, Mizutani S (2001). "Characterization of a secretase activity for placental leucine aminopeptidase". Arch. Biochem. Biophys. 393 (1): 163–9. doi:10.1006/abbi.2001.2489. PMID11516173.
Ito T, Nomura S, Okada M, et al. (2001). "Transcriptional regulation of human placental leucine aminopeptidase/oxytocinase gene". Mol. Hum. Reprod. 7 (9): 887–94. doi:10.1093/molehr/7.9.887. PMID11517297.
External links
The MEROPS online database for peptidases and their inhibitors: M01.011