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leucyl-cystinyl aminopeptidase (LNPEP, cystinyl aminopeptidase, oxytocinase, OTase, insulin-regulated membrane aminopeptidase, insulin-responsive aminopeptidase, IRAP, placental leucine aminopeptidase, P-LAP)
Function:
- cleaves N-terminal amino acid, before Cys, Leu & other amino acid residues
- degrades peptide hormones
- oxytocin
- vasopressin
- angiotensin 3
- neuronal peptides in brain?
- met-enkephalin
- dynorphin
- binds angiotensin IV; may be angiotensin IV receptor brain
- binds tankyrases 1 & 2
Cofactor: binds 1 Zn+2 ion per subunit
Structure:
- N-glycosylated
- homodimer
Compartment:
- cell membrane
- resides in intracellular vesicles together with GLUT4
- may translocate to the cell surface in response to insulin &/or oxytocin
- pregnancy serum form: secreted
- pregnancy serum form is derived from the membrane-bound form by proteolytic processing
- in brain only the membrane-bound form is found
Alternative splicing: named isoforms=3
Expression:
- expressed in placenta, heart, kidney & small intestine > neuronal cells in the brain, in skeletal muscle, spleen, liver, testes & colon
General
aminopeptidase
cell surface receptor
glycoprotein
metalloprotein
oligomerizing protein
Properties
CONFIGURATION: dimer
SIZE: MW = 117 kD
entity length = 1025 aa
COMPARTMENT: plasma membrane
MOTIF: Dileucine internalization motif {53-54}
Dileucine internalization motif {76-77}
Tankyrase binding {96-101}
transmembrane domain {111-131}
N-glycosylation site {N145}
proteolytic site {154-155}
N-glycosylation site {N184}
N-glycosylation site {N215}
N-glycosylation site {N256}
N-glycosylation site {N266}
N-glycosylation site {N368}
N-glycosylation site {N374}
N-glycosylation site {N448}
Zn+2-binding site
SITE: 464-464
glutamate residue {E465}
Zn+2-binding site
SITE: 468-468
Zn+2-binding site
SITE: 487-487
N-glycosylation site {N525}
N-glycosylation site {N578}
N-glycosylation site {N598}
N-glycosylation site {N664}
N-glycosylation site {N682}
N-glycosylation site {N760}
N-glycosylation site {N834}
N-glycosylation site {N850}
N-glycosylation site {N989}
Database Correlations
OMIM 151300
UniProt Q9UIQ6
Pfam PF01433
ENZYME 3.4.11.3
References
- UniProt :accession Q9UIQ6
- Taylor A.
Aminopeptidases: structure and function.
FASEB J. 1993 Feb 1;7(2):290-8. Review.
PMID: 8440407