Leucyl-cystinyl aminopeptidase

Function

Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain.

Classification

Family (Pfam)

PF11838 ERAP1_C, PF01433 Peptidase_M1, PF17900 Peptidase_M1_N

InterPro

Aminopeptidase_N-like_N, Aminopeptidase_N-like_N_sf, ERAP1-like_C_dom, M1_APN-typ, Peptidase_M1, Peptidase_M1_aminopeptidases, Peptidase_M1_dom, Peptidase_M4/M1_CTD_sf

Functional cluster

Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 11

• 4P8Q X-ray 3.02A
• 4PJ6 X-ray 2.96A
• 4Z7I X-ray 3.31A
• 5C97 X-ray 3.37A
• 5JHQ X-ray 3.20A
• 5MJ6 X-ray 2.53A
• 6YDX X-ray 3.20A
• 7ZYF X-ray 2.81A
• 8CGP X-ray 2.62A
• 8CGW X-ray 3.03A
• 8P0I X-ray 3.50A

A predicted model is available from AlphaFold.

Gene Ontology · 20

• GO:0030659 cytoplasmic vesicle membrane
• GO:0005829 cytosol
• GO:0031905 early endosome lumen
• GO:0005576 extracellular region
• GO:0005765 lysosomal membrane
• GO:0016020 membrane
• GO:0048471 perinuclear region of cytoplasm
• GO:0005886 plasma membrane
• GO:0004177 aminopeptidase activity
• GO:0070006 metalloaminopeptidase activity
• GO:0008237 metallopeptidase activity
• GO:0008270 zinc ion binding
• GO:0002480 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent
• GO:0007267 cell-cell signaling
• GO:0007565 female pregnancy
• GO:0120163 negative regulation of cold-induced thermogenesis
• GO:0010813 neuropeptide catabolic process
• GO:0000209 protein polyubiquitination
• GO:0006508 proteolysis
• GO:0008217 regulation of blood pressure

Drugs targeting this protein · 1

• TOSEDOSTAT inhibitor

Related proteins · sequence + function similarity

• Leucyl-cystinyl aminopeptidase 0.98
• Leucyl-cystinyl aminopeptidase 0.98
• Endoplasmic reticulum aminopeptidase 2 0.94
• Endoplasmic reticulum aminopeptidase 2 0.94
• Endoplasmic reticulum aminopeptidase 1 0.94
• Endoplasmic reticulum aminopeptidase 1 0.93
• Endoplasmic reticulum aminopeptidase 2 0.92
• Endoplasmic reticulum aminopeptidase 1 0.91
• Glutamyl aminopeptidase 0.88
• Aminopeptidase Q 0.87
• Glutamyl aminopeptidase 0.87
• Glutamyl aminopeptidase 0.86

Literature · 14 cited papers

• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat. Biotechnol. · 2009
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. J. Biol. Chem. · 2001
• Expression of placental leucine aminopeptidase/oxytocinase in neuronal cells and its action on neuronal peptides. Eur. J. Biochem. · 2001
• Structure of the human oxytocinase/insulin-regulated aminopeptidase gene and localization to chromosome 5q21. Eur. J. Biochem. · 2000
• The complete amino acid sequence of human placental oxytocinase. Biochim. Biophys. Acta · 1997
• Human placental leucine aminopeptidase/oxytocinase. A new member of type II membrane-spanning zinc metallopeptidase family. J. Biol. Chem. · 1996
• … and 2 more in the literature graph