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P55786 (PSA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Puromycin-sensitive aminopeptidase

Short name=PSA
EC=3.4.11.14
Alternative name(s):
Cytosol alanyl aminopeptidase
Short name=AAP-S
Gene names
Name:NPEPPS
Synonyms:PSA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length919 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Aminopeptidase with broad substrate specificity for several peptides. Involved in proteolytic events essential for cell growth and viability. May act as regulator of neuropeptide activity. Plays a role in the antigen-processing pathway for MHC class I molecules. Involved in the N-terminal trimming of cytotoxic T-cell epitope precursors. Digests the poly-Q peptides found in many cellular proteins. Digests tau from normal brain more efficiently than tau from Alzheimer disease brain. Ref.6 Ref.7 Ref.9 Ref.10 Ref.11

Catalytic activity

Release of an N-terminal amino acid, preferentially alanine, from a wide range of peptides, amides and arylamides.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Enzyme regulation

Strongly inhibited by bestatin, leuhistin, actinonin, amastatin, 1,10-phenanthroline, DFP, PCMBS, Zn2+, Cd2+, Co2+, Cu2+, Hg2+, EDTA and puromycin. Not inhibited by PMSF, and only slightly inhibited by leupeptin and aprotinin. Activity is increased by Mg2+ and Ca2+. Ref.6 Ref.9 Ref.10

Subunit structure

Monomer. Ref.6

Subcellular location

Cytoplasmcytosol. Nucleus Potential Ref.6.

Tissue specificity

Detected in liver, epithelium of renal tubules, epithelium of small and large intestine, gastric epithelial cells, and alveoli of the lung (at protein level). Ref.6

Sequence similarities

Belongs to the peptidase M1 family.

Caution

It is uncertain whether Met-1 or Met-45 is the initiator. N-terminal sequencing in Ref.6 suggests that Met-45 is used, followed by methionine initiator removal.

Biophysicochemical properties

Kinetic parameters:

KM=2.20 mM for Lys-p-NA Ref.6 Ref.9

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 µM for Ala-MCA

KM=189 µM for Met-MCA

KM=220 µM for Lys-MCA

KM=91 µM for Leu-MCA

KM=167 µM 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.

Sequence caution

The sequence AAH65294.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAA68964.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 919919Puromycin-sensitive aminopeptidase
PRO_0000095116

Regions

Region316 – 3205Substrate binding By similarity
Motif726 – 7305Nuclear localization signal Potential

Sites

Active site3531Proton acceptor By similarity
Metal binding3521Zinc; catalytic By similarity
Metal binding3561Zinc; catalytic By similarity
Metal binding3751Zinc; catalytic By similarity
Binding site1801Substrate By similarity
Site4381Transition state stabilizer By similarity

Amino acid modifications

Modified residue4641Nitrated tyrosine By similarity

Experimental info

Mutagenesis3531E → A: Reduces catalytic activity by 25,000-fold to 100,000-fold. Ref.8
Mutagenesis3531E → Q: Reduces catalytic activity by 5,000-fold to 15,000-fold. Ref.8
Mutagenesis3531E → V: Reduces catalytic activity by 300,000-fold to 500,000-fold. Ref.8
Mutagenesis4381Y → F: Reduces catalytic activity by 1,000-fold to 2,500-fold. Ref.8
Sequence conflict1841A → P in CAA68964. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P55786 [UniParc].

Last modified August 31, 2004. Version 2.
Checksum: 873C9BF75494A057

FASTA919103,276
        10         20         30         40         50         60 
MWLAAAAPSL ARRLLFLGPP PPPLLLLVFS RSSRRRLHSL GLAAMPEKRP FERLPADVSP 

        70         80         90        100        110        120 
INYSLCLKPD LLDFTFEGKL EAAAQVRQAT NQIVMNCADI DIITASYAPE GDEEIHATGF 

       130        140        150        160        170        180 
NYQNEDEKVT LSFPSTLQTG TGTLKIDFVG ELNDKMKGFY RSKYTTPSGE VRYAAVTQFE 

       190        200        210        220        230        240 
ATDARRAFPC WDEPAIKATF DISLVVPKDR VALSNMNVID RKPYPDDENL VEVKFARTPV 

       250        260        270        280        290        300 
MSTYLVAFVV GEYDFVETRS KDGVCVRVYT PVGKAEQGKF ALEVAAKTLP FYKDYFNVPY 

       310        320        330        340        350        360 
PLPKIDLIAI ADFAAGAMEN WGLVTYRETA LLIDPKNSCS SSRQWVALVV GHELAHQWFG 

       370        380        390        400        410        420 
NLVTMEWWTH LWLNEGFASW IEYLCVDHCF PEYDIWTQFV SADYTRAQEL DALDNSHPIE 

       430        440        450        460        470        480 
VSVGHPSEVD EIFDAISYSK GASVIRMLHD YIGDKDFKKG MNMYLTKFQQ KNAATEDLWE 

       490        500        510        520        530        540 
SLENASGKPI AAVMNTWTKQ MGFPLIYVEA EQVEDDRLLR LSQKKFCAGG SYVGEDCPQW 

       550        560        570        580        590        600 
MVPITISTSE DPNQAKLKIL MDKPEMNVVL KNVKPDQWVK LNLGTVGFYR TQYSSAMLES 

       610        620        630        640        650        660 
LLPGIRDLSL PPVDRLGLQN DLFSLARAGI ISTVEVLKVM EAFVNEPNYT VWSDLSCNLG 

       670        680        690        700        710        720 
ILSTLLSHTD FYEEIQEFVK DVFSPIGERL GWDPKPGEGH LDALLRGLVL GKLGKAGHKA 

       730        740        750        760        770        780 
TLEEARRRFK DHVEGKQILS ADLRSPVYLT VLKHGDGTTL DIMLKLHKQA DMQEEKNRIE 

       790        800        810        820        830        840 
RVLGATLLPD LIQKVLTFAL SEEVRPQDTV SVIGGVAGGS KHGRKAAWKF IKDNWEELYN 

       850        860        870        880        890        900 
RYQGGFLISR LIKLSVEGFA VDKMAGEVKA FFESHPAPSA ERTIQQCCEN ILLNAAWLKR 

       910 
DAESIHQYLL QRKASPPTV 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of the human puromycin-sensitive aminopeptidase and evidence for expression in neurons."
Tobler A.R., Constam D.B., Schmitt-Graeff A., Malipiero U., Schlapbach R., Fontana A.
J. Neurochem. 68:889-897(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal brain.
[2]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 31-919.
Tissue: Lung.
[4]"Human puromycin-sensitive aminopeptidase: cloning of 3' UTR, evidence for a polymorphism at a.a. 140 and refined chromosomal localization to 17q21."
Bauer W.O., Nanda I., Beck G., Schmid M., Jakob F.
Cytogenet. Cell Genet. 92:221-224(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 45-919.
Tissue: Skeletal muscle.
[5]"Cloning and analysis of the gene for the human puromycin-sensitive aminopeptidase."
Thompson M.W., Tobler A., Fontana A., Hersh L.B.
Biochem. Biophys. Res. Commun. 258:234-240(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 45-85.
[6]"Puromycin-sensitive alanyl aminopeptidase from human liver cytosol: purification and characterization."
Yamamoto Y., Li Y.H., Ushiyama I., Nishimura A., Ohkubo I., Nishi K.
Forensic Sci. Int. 113:143-146(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 46-105, FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Liver.
[7]"Two new proteases in the MHC class I processing pathway."
Stoltze L., Schirle M., Schwarz G., Schroter C., Thompson M.W., Hersh L.B., Kalbacher H., Stevanovic S., Rammensee H.G., Schild H.
Nat. Immunol. 1:413-418(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Mutation of active site residues of the puromycin-sensitive aminopeptidase: conversion of the enzyme into a catalytically inactive binding protein."
Thompson M.W., Govindaswami M., Hersh L.B.
Arch. Biochem. Biophys. 413:236-242(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLU-353 AND TYR-438, ACTIVE SITE.
[9]"Degradation of tau protein by puromycin-sensitive aminopeptidase in vitro."
Sengupta S., Horowitz P.M., Karsten S.L., Jackson G.R., Geschwind D.H., Fu Y., Berry R.W., Binder L.I.
Biochemistry 45:15111-15119(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[10]"Puromycin-sensitive aminopeptidase is the major peptidase responsible for digesting polyglutamine sequences released by proteasomes during protein degradation."
Bhutani N., Venkatraman P., Goldberg A.L.
EMBO J. 26:1385-1396(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION.
[11]"Cytosolic aminopeptidases influence MHC class I-mediated antigen presentation in an allele-dependent manner."
Kim E., Kwak H., Ahn K.
J. Immunol. 183:7379-7387(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y07701 mRNA. Translation: CAA68964.1. Different initiation.
AC025682 Genomic DNA. No translation available.
BC065294 mRNA. Translation: AAH65294.2. Different initiation.
AJ132583 mRNA. Translation: CAA10709.1.
AF252387 Genomic DNA. Translation: AAF70086.1.
CCDSCCDS45721.1.
RefSeqNP_006301.3. NM_006310.3.
UniGeneHs.443837.

3D structure databases

ProteinModelPortalP55786.
SMRP55786. Positions 42-910.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114897. 40 interactions.
IntActP55786. 6 interactions.
MINTMINT-4999844.
STRING9606.ENSP00000320324.

Chemistry

BindingDBP55786.
ChEMBLCHEMBL2264.

Protein family/group databases

MEROPSM01.010.

PTM databases

PhosphoSiteP55786.

Polymorphism databases

DMDM51704228.

Proteomic databases

MaxQBP55786.
PaxDbP55786.
PeptideAtlasP55786.
PRIDEP55786.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000322157; ENSP00000320324; ENSG00000141279.
GeneID9520.
KEGGhsa:9520.
UCSCuc002ilr.4. human.

Organism-specific databases

CTD9520.
GeneCardsGC17P045608.
H-InvDBHIX0013922.
HGNCHGNC:7900. NPEPPS.
HPAHPA021453.
HPA045649.
MIM606793. gene.
neXtProtNX_P55786.
PharmGKBPA31703.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0308.
HOGENOMHOG000106482.
HOVERGENHBG106325.
InParanoidP55786.
KOK08776.
OMARTVQQCC.
PhylomeDBP55786.
TreeFamTF300395.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP55786.
BgeeP55786.
CleanExHS_NPEPPS.
GenevestigatorP55786.

Family and domain databases

InterProIPR024571. ERAP1-like_C_dom.
IPR001930. Peptidase_M1.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERPTHR11533. PTHR11533. 1 hit.
PfamPF11838. ERAP1_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSPR00756. ALADIPTASE.
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNPEPPS. human.
GeneWikiNPEPPS.
GenomeRNAi9520.
NextBio35678.
PMAP-CutDBP55786.
PROP55786.
SOURCESearch...

Entry information

Entry namePSA_HUMAN
AccessionPrimary (citable) accession number: P55786
Secondary accession number(s): Q6P145, Q9NP16, Q9UEM2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: August 31, 2004
Last modified: July 9, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM