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P55786

- PSA_HUMAN

UniProt

P55786 - PSA_HUMAN

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Protein

Puromycin-sensitive aminopeptidase

Gene
NPEPPS, PSA
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.5 Publications

Catalytic activityi

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

Cofactori

Binds 1 zinc ion per subunit By similarity.

Enzyme regulationi

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+.3 Publications

Kineticsi

  1. KM=2.20 mM for Lys-p-NA2 Publications
  2. KM=0.25 mM for Leu-p-NA
  3. KM=0.27 mM for Ala-p-NA
  4. KM=0.80 mM for Met-p-NA
  5. KM=0.47 mM for Pro-p-NA
  6. KM=0.21 mM for Val-p-NA
  7. KM=182 µM for Ala-MCA
  8. KM=189 µM for Met-MCA
  9. KM=220 µM for Lys-MCA
  10. KM=91 µM for Leu-MCA
  11. KM=167 µM for Phe-MCA

pH dependencei

Optimum pH is 7.5. Stable from pH 5.0 to 8.0.

Temperature dependencei

Stable up to 40 degrees Celsius.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei180 – 1801Substrate By similarity
Metal bindingi352 – 3521Zinc; catalytic By similarity
Active sitei353 – 3531Proton acceptor By similarity
Metal bindingi356 – 3561Zinc; catalytic By similarity
Metal bindingi375 – 3751Zinc; catalytic By similarity
Sitei438 – 4381Transition state stabilizer By similarity

GO - Molecular functioni

  1. aminopeptidase activity Source: ProtInc
  2. metallopeptidase activity Source: UniProtKB-KW
  3. zinc ion binding Source: InterPro

GO - Biological processi

  1. antigen processing and presentation of peptide antigen via MHC class I Source: Reactome
  2. cellular response to hypoxia Source: UniProtKB
  3. protein polyubiquitination Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Aminopeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.

Protein family/group databases

MEROPSiM01.010.

Names & Taxonomyi

Protein namesi
Recommended name:
Puromycin-sensitive aminopeptidase (EC:3.4.11.14)
Short name:
PSA
Alternative name(s):
Cytosol alanyl aminopeptidase
Short name:
AAP-S
Gene namesi
Name:NPEPPS
Synonyms:PSA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:7900. NPEPPS.

Subcellular locationi

Cytoplasmcytosol. Nucleus Reviewed prediction 1 Publication

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. extracellular vesicular exosome Source: UniProt
  3. nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi353 – 3531E → A: Reduces catalytic activity by 25,000-fold to 100,000-fold. 1 Publication
Mutagenesisi353 – 3531E → Q: Reduces catalytic activity by 5,000-fold to 15,000-fold. 1 Publication
Mutagenesisi353 – 3531E → V: Reduces catalytic activity by 300,000-fold to 500,000-fold. 1 Publication
Mutagenesisi438 – 4381Y → F: Reduces catalytic activity by 1,000-fold to 2,500-fold. 1 Publication

Organism-specific databases

PharmGKBiPA31703.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 919919Puromycin-sensitive aminopeptidasePRO_0000095116Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei464 – 4641Nitrated tyrosine By similarity

Keywords - PTMi

Nitration

Proteomic databases

MaxQBiP55786.
PaxDbiP55786.
PeptideAtlasiP55786.
PRIDEiP55786.

PTM databases

PhosphoSiteiP55786.

Miscellaneous databases

PMAP-CutDBP55786.

Expressioni

Tissue specificityi

Detected in liver, epithelium of renal tubules, epithelium of small and large intestine, gastric epithelial cells, and alveoli of the lung (at protein level).1 Publication

Gene expression databases

ArrayExpressiP55786.
BgeeiP55786.
CleanExiHS_NPEPPS.
GenevestigatoriP55786.

Organism-specific databases

HPAiHPA021453.
HPA045649.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi114897. 40 interactions.
IntActiP55786. 6 interactions.
MINTiMINT-4999844.
STRINGi9606.ENSP00000320324.

Structurei

3D structure databases

ProteinModelPortaliP55786.
SMRiP55786. Positions 42-910.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni316 – 3205Substrate binding By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi726 – 7305Nuclear localization signal Reviewed prediction

Sequence similaritiesi

Belongs to the peptidase M1 family.

Phylogenomic databases

eggNOGiCOG0308.
HOGENOMiHOG000106482.
HOVERGENiHBG106325.
InParanoidiP55786.
KOiK08776.
OMAiRTVQQCC.
PhylomeDBiP55786.
TreeFamiTF300395.

Family and domain databases

InterProiIPR024571. ERAP1-like_C_dom.
IPR001930. Peptidase_M1.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERiPTHR11533. PTHR11533. 1 hit.
PfamiPF11838. ERAP1_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSiPR00756. ALADIPTASE.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P55786-1 [UniParc]FASTAAdd to Basket

« Hide

MWLAAAAPSL ARRLLFLGPP PPPLLLLVFS RSSRRRLHSL GLAAMPEKRP    50
FERLPADVSP INYSLCLKPD LLDFTFEGKL EAAAQVRQAT NQIVMNCADI 100
DIITASYAPE GDEEIHATGF NYQNEDEKVT LSFPSTLQTG TGTLKIDFVG 150
ELNDKMKGFY RSKYTTPSGE VRYAAVTQFE ATDARRAFPC WDEPAIKATF 200
DISLVVPKDR VALSNMNVID RKPYPDDENL VEVKFARTPV MSTYLVAFVV 250
GEYDFVETRS KDGVCVRVYT PVGKAEQGKF ALEVAAKTLP FYKDYFNVPY 300
PLPKIDLIAI ADFAAGAMEN WGLVTYRETA LLIDPKNSCS SSRQWVALVV 350
GHELAHQWFG NLVTMEWWTH LWLNEGFASW IEYLCVDHCF PEYDIWTQFV 400
SADYTRAQEL DALDNSHPIE VSVGHPSEVD EIFDAISYSK GASVIRMLHD 450
YIGDKDFKKG MNMYLTKFQQ KNAATEDLWE SLENASGKPI AAVMNTWTKQ 500
MGFPLIYVEA EQVEDDRLLR LSQKKFCAGG SYVGEDCPQW MVPITISTSE 550
DPNQAKLKIL MDKPEMNVVL KNVKPDQWVK LNLGTVGFYR TQYSSAMLES 600
LLPGIRDLSL PPVDRLGLQN DLFSLARAGI ISTVEVLKVM EAFVNEPNYT 650
VWSDLSCNLG ILSTLLSHTD FYEEIQEFVK DVFSPIGERL GWDPKPGEGH 700
LDALLRGLVL GKLGKAGHKA TLEEARRRFK DHVEGKQILS ADLRSPVYLT 750
VLKHGDGTTL DIMLKLHKQA DMQEEKNRIE RVLGATLLPD LIQKVLTFAL 800
SEEVRPQDTV SVIGGVAGGS KHGRKAAWKF IKDNWEELYN RYQGGFLISR 850
LIKLSVEGFA VDKMAGEVKA FFESHPAPSA ERTIQQCCEN ILLNAAWLKR 900
DAESIHQYLL QRKASPPTV 919
Length:919
Mass (Da):103,276
Last modified:August 31, 2004 - v2
Checksum:i873C9BF75494A057
GO

Sequence cautioni

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 conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti184 – 1841A → P in CAA68964. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS45721.1.
RefSeqiNP_006301.3. NM_006310.3.
UniGeneiHs.443837.

Genome annotation databases

EnsembliENST00000322157; ENSP00000320324; ENSG00000141279.
GeneIDi9520.
KEGGihsa:9520.
UCSCiuc002ilr.4. human.

Polymorphism databases

DMDMi51704228.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS45721.1.
RefSeqi NP_006301.3. NM_006310.3.
UniGenei Hs.443837.

3D structure databases

ProteinModelPortali P55786.
SMRi P55786. Positions 42-910.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114897. 40 interactions.
IntActi P55786. 6 interactions.
MINTi MINT-4999844.
STRINGi 9606.ENSP00000320324.

Chemistry

BindingDBi P55786.
ChEMBLi CHEMBL2264.

Protein family/group databases

MEROPSi M01.010.

PTM databases

PhosphoSitei P55786.

Polymorphism databases

DMDMi 51704228.

Proteomic databases

MaxQBi P55786.
PaxDbi P55786.
PeptideAtlasi P55786.
PRIDEi P55786.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000322157 ; ENSP00000320324 ; ENSG00000141279 .
GeneIDi 9520.
KEGGi hsa:9520.
UCSCi uc002ilr.4. human.

Organism-specific databases

CTDi 9520.
GeneCardsi GC17P045608.
H-InvDB HIX0013922.
HGNCi HGNC:7900. NPEPPS.
HPAi HPA021453.
HPA045649.
MIMi 606793. gene.
neXtProti NX_P55786.
PharmGKBi PA31703.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0308.
HOGENOMi HOG000106482.
HOVERGENi HBG106325.
InParanoidi P55786.
KOi K08776.
OMAi RTVQQCC.
PhylomeDBi P55786.
TreeFami TF300395.

Enzyme and pathway databases

Reactomei REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSi NPEPPS. human.
GeneWikii NPEPPS.
GenomeRNAii 9520.
NextBioi 35678.
PMAP-CutDB P55786.
PROi P55786.
SOURCEi Search...

Gene expression databases

ArrayExpressi P55786.
Bgeei P55786.
CleanExi HS_NPEPPS.
Genevestigatori P55786.

Family and domain databases

InterProi IPR024571. ERAP1-like_C_dom.
IPR001930. Peptidase_M1.
IPR014782. Peptidase_M1_N.
[Graphical view ]
PANTHERi PTHR11533. PTHR11533. 1 hit.
Pfami PF11838. ERAP1_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view ]
PRINTSi PR00756. ALADIPTASE.
PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiPSA_HUMAN
AccessioniPrimary (citable) accession number: P55786
Secondary accession number(s): Q6P145, Q9NP16, Q9UEM2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: August 31, 2004
Last modified: September 3, 2014
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Caution

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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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