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puromycin-sensitive aminopeptidase; PSA; cytosol alanyl aminopeptidase; arylamidase AAP-S (NPEPPS, PSA)
Function:
- aminopeptidase with broad substrate specificity for several peptides
- role in proteolytic events essential for cell growth & viability
- may act as regulator of neuropeptide activity
- role in the antigen-processing pathway for MHC class I molecules
- role in N-terminal trimming of cytotoxic T-cell epitope precursors
- digests the polyglutamine tract peptides found in many cellular proteins
- digests tau from normal brain more efficiently than tau from Alzheimer disease brain
- release of an N-terminal amino acid, preferentially alanine, from a wide range of peptides, amides & arylamides
- activity is increased by Mg+2 & Ca+2
Kinetic parameters:
- KM=2.20 mM for Lys-p-NA
- KM=0.25 mM for Leu-p-NA
- KM=0.27 mM for Ala-p-NA
- KM=0.80 mM for Met-p-NA
- KM=0.47 mM for Pro-p-NA
- KM=0.21 mM for Val-p-NA
- KM=182 uM for Ala-MCA
- KM=189 uM for Met-MCA
- KM=220 uM for Lys-MCA
- KM=91 uM for Leu-MCA
- KM=167 uM for Phe-MCA
- pH dependence:
- optimum pH is 7.5
- stable from pH 5.0 to 8.0
- temperature dependence: stable up to 40 degrees celsius
Cofactor: binds 1 Zn+2 per subunit (putative)
Inhibition:
- strongly inhibited by bestatin, leuhistin, actinonin, amastatin, 1,10-phenanthroline, DFP, PCMBS, Zn+2, Cd+2, Co+2, Cu+2, Hg+2, EDTA & puromycin
- not inhibited by PMSF
- only slightly inhibited by leupeptin & aprotinin
Structure:
- monomer
- belongs to the peptidase M1 family
Compartment: cytoplasm, cytosol, nucleus (putative)
Expression:
- expressed in liver
- expressed in epithelium (at protein level) of:
a) renal tubules
b) stomach, small intestine, colon
c) alveoli of the lung
Laboratory:
- arylamidase in serum
- arylamidase in urine
Note:
- uncertain whether Met-1 or Met-45 is the initiator
- N-terminal sequencing suggests that Met-45 is used, followed by removal of the initiator methionine
General
aminopeptidase
metalloprotein
nuclear protein
Properties
SIZE: entity length = 919 aa
MW = 103 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: binding site
SITE: 180-180
FOR-BINDING-OF: Substrate
Substrate binding {316-320}
Zn+2-binding site
SITE: 352-352
glutamate residue {E353}
Zn+2-binding site
SITE: 356-356
Zn+2-binding site
SITE: 375-375
tyrosine residue {438}
active site
nuclear translocation signal {726-730}
Database Correlations
OMIM 606793
UniProt P55786
Pfam PF01433
Entrez Gene 9520
Kegg hsa:9520
ENZYME 3.4.11.14
References
- UniProt :accession P55786
- Wiktionary: arylamidase
https://en.wiktionary.org/wiki/arylamidase