Leucyl/cystinyl aminopeptidase

LNPEP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4PJ6, 4P8Q, 4Z7I, 5C97
Identifiers
Aliases	LNPEP, CAP, IRAP, P-LAP, PLAP, leucyl/cystinyl aminopeptidase, leucyl and cystinyl aminopeptidase
External IDs	OMIM: 151300 MGI: 2387123 HomoloGene: 21148 GeneCards: LNPEP
Gene location (Human) Chr. Chromosome 5 (human) Band 5q15 Start 96,935,394 bp End 97,037,513 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17|17 A3.2 Start 17,741,672 bp End 17,845,312 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in visceral pleura Brodmann area 23 tibia parietal pleura superficial temporal artery saphenous vein germinal epithelium middle temporal gyrus spongy bone seminal vesicula Top expressed in ascending aorta aortic valve superior cervical ganglion hand ciliary body otolith organ utricle body of femur subcutaneous adipose tissue myocardium of ventricle More reference expression data BioGPS n/a
Gene ontology Molecular function peptide binding metal ion binding peptidase activity protein binding aminopeptidase activity metallopeptidase activity metalloaminopeptidase activity hydrolase activity zinc ion binding Cellular component integral component of membrane cytosol membrane plasma membrane integral component of plasma membrane intracellular anatomical structure extracellular region lysosomal membrane perinuclear region of cytoplasm early endosome lumen cytoplasmic vesicle membrane Biological process SMAD protein signal transduction female pregnancy cell-cell signaling protein polyubiquitination antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent proteolysis regulation of blood pressure protein catabolic process membrane organization signal transduction peptide catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4012 240028 Ensembl ENSG00000113441 ENSMUSG00000023845 UniProt Q9UIQ6 Q8C129 RefSeq (mRNA) NM_175920 NM_005575 NM_172827 RefSeq (protein) NP_005566 NP_787116 NP_766415 Location (UCSC) Chr 5: 96.94 – 97.04 Mb Chr 17: 17.74 – 17.85 Mb PubMed search
Wikidata
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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 LNPEP gene.

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.

Mutations in this gene have been associated to psoriasis risk.(doi:10.1038/jid.2013.317)

Interactions

Cystinyl aminopeptidase has been shown to interact with TNKS2.

Further reading

• 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. PMID 12591177. S2CID 6481079.
• Keller SR (2004). "The insulin-regulated aminopeptidase: a companion and regulator of GLUT4". Front. Biosci. 8 (6): s410–20. doi:10.2741/1078. PMID 12700100.
• Keller SR (2005). "Role of the insulin-regulated aminopeptidase IRAP in insulin action and diabetes". Biol. Pharm. Bull. 27 (6): 761–4. doi:10.1248/bpb.27.761. PMID 15187412.
• 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. PMID 15894523.
• Tsujimoto M, Hattori A (2005). "The oxytocinase subfamily of M1 aminopeptidases". Biochim. Biophys. Acta. 1751 (1): 9–18. doi:10.1016/j.bbapap.2004.09.011. PMID 16054015.
• 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. PMID 17373876. S2CID 42839602.
• 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. PMID 1731608.
• 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. PMID 3898693.
• 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. PMID 5953194.
• 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. PMID 9013800.
• 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. PMID 9177475.
• 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. PMID 9733056.
• 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. PMID 10448104.
• 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. PMID 10759854.
• 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. PMID 10985965.
• 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. PMID 10988299.
• 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. PMID 11389728.
• 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. PMID 11516173.
• 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. PMID 11517297.

External links

• The MEROPS online database for peptidases and their inhibitors: M01.011
• Cystinyl+aminopeptidase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)