ID   PSA_HUMAN               Reviewed;         919 AA.
AC   P55786; B7Z463; Q6P145; Q9NP16; Q9UEM2;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   31-AUG-2004, sequence version 2.
DT   03-MAY-2023, entry version 203.
DE   RecName: Full=Puromycin-sensitive aminopeptidase;
DE            Short=PSA;
DE            EC=3.4.11.14;
DE   AltName: Full=Cytosol alanyl aminopeptidase;
DE            Short=AAP-S;
GN   Name=NPEPPS; Synonyms=PSA;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Fetal brain;
RX   PubMed=9048733; DOI=10.1046/j.1471-4159.1997.68030889.x;
RA   Tobler A.R., Constam D.B., Schmitt-Graeff A., Malipiero U., Schlapbach R.,
RA   Fontana A.;
RT   "Cloning of the human puromycin-sensitive aminopeptidase and evidence for
RT   expression in neurons.";
RL   J. Neurochem. 68:889-897(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 31-919 (ISOFORM 1).
RC   TISSUE=Lung;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 45-919 (ISOFORM 1).
RC   TISSUE=Skeletal muscle;
RX   PubMed=11435692; DOI=10.1159/000056907;
RA   Bauer W.O., Nanda I., Beck G., Schmid M., Jakob F.;
RT   "Human puromycin-sensitive aminopeptidase: cloning of 3' UTR, evidence for
RT   a polymorphism at a.a. 140 and refined chromosomal localization to 17q21.";
RL   Cytogenet. Cell Genet. 92:221-224(2001).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 45-85.
RX   PubMed=10329370; DOI=10.1006/bbrc.1999.0604;
RA   Thompson M.W., Tobler A., Fontana A., Hersh L.B.;
RT   "Cloning and analysis of the gene for the human puromycin-sensitive
RT   aminopeptidase.";
RL   Biochem. Biophys. Res. Commun. 258:234-240(1999).
RN   [7]
RP   PROTEIN SEQUENCE OF 46-105, FUNCTION, ACTIVITY REGULATION,
RP   BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Liver;
RX   PubMed=10978616; DOI=10.1016/s0379-0738(00)00280-2;
RA   Yamamoto Y., Li Y.H., Ushiyama I., Nishimura A., Ohkubo I., Nishi K.;
RT   "Puromycin-sensitive alanyl aminopeptidase from human liver cytosol:
RT   purification and characterization.";
RL   Forensic Sci. Int. 113:143-146(2000).
RN   [8]
RP   FUNCTION.
RX   PubMed=11062501; DOI=10.1038/80852;
RA   Stoltze L., Schirle M., Schwarz G., Schroter C., Thompson M.W., Hersh L.B.,
RA   Kalbacher H., Stevanovic S., Rammensee H.G., Schild H.;
RT   "Two new proteases in the MHC class I processing pathway.";
RL   Nat. Immunol. 1:413-418(2000).
RN   [9]
RP   MUTAGENESIS OF GLU-353 AND TYR-438, AND ACTIVE SITE.
RX   PubMed=12729622; DOI=10.1016/s0003-9861(03)00123-1;
RA   Thompson M.W., Govindaswami M., Hersh L.B.;
RT   "Mutation of active site residues of the puromycin-sensitive
RT   aminopeptidase: conversion of the enzyme into a catalytically inactive
RT   binding protein.";
RL   Arch. Biochem. Biophys. 413:236-242(2003).
RN   [10]
RP   FUNCTION, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=17154549; DOI=10.1021/bi061830d;
RA   Sengupta S., Horowitz P.M., Karsten S.L., Jackson G.R., Geschwind D.H.,
RA   Fu Y., Berry R.W., Binder L.I.;
RT   "Degradation of tau protein by puromycin-sensitive aminopeptidase in
RT   vitro.";
RL   Biochemistry 45:15111-15119(2006).
RN   [11]
RP   FUNCTION, AND ACTIVITY REGULATION.
RX   PubMed=17318184; DOI=10.1038/sj.emboj.7601592;
RA   Bhutani N., Venkatraman P., Goldberg A.L.;
RT   "Puromycin-sensitive aminopeptidase is the major peptidase responsible for
RT   digesting polyglutamine sequences released by proteasomes during protein
RT   degradation.";
RL   EMBO J. 26:1385-1396(2007).
RN   [12]
RP   FUNCTION.
RX   PubMed=19917696; DOI=10.4049/jimmunol.0901489;
RA   Kim E., Kwak H., Ahn K.;
RT   "Cytosolic aminopeptidases influence MHC class I-mediated antigen
RT   presentation in an allele-dependent manner.";
RL   J. Immunol. 183:7379-7387(2009).
RN   [13]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: Aminopeptidase with broad substrate specificity for several
CC       peptides. Involved in proteolytic events essential for cell growth and
CC       viability. May act as regulator of neuropeptide activity. Plays a role
CC       in the antigen-processing pathway for MHC class I molecules. Involved
CC       in the N-terminal trimming of cytotoxic T-cell epitope precursors.
CC       Digests the poly-Q peptides found in many cellular proteins. Digests
CC       tau from normal brain more efficiently than tau from Alzheimer disease
CC       brain. {ECO:0000269|PubMed:10978616, ECO:0000269|PubMed:11062501,
CC       ECO:0000269|PubMed:17154549, ECO:0000269|PubMed:17318184,
CC       ECO:0000269|PubMed:19917696}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Release of an N-terminal amino acid, preferentially alanine,
CC         from a wide range of peptides, amides and arylamides.; EC=3.4.11.14;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: Strongly inhibited by bestatin, leuhistin,
CC       actinonin, amastatin, 1,10-phenanthroline, DFP, PCMBS, Zn(2+), Cd(2+),
CC       Co(2+), Cu(2+), Hg(2+), EDTA and puromycin. Not inhibited by PMSF, and
CC       only slightly inhibited by leupeptin and aprotinin. Activity is
CC       increased by Mg(2+) and Ca(2+). {ECO:0000269|PubMed:10978616,
CC       ECO:0000269|PubMed:17154549, ECO:0000269|PubMed:17318184}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=2.20 mM for Lys-p-NA {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC         KM=0.25 mM for Leu-p-NA {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC         KM=0.27 mM for Ala-p-NA {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC         KM=0.80 mM for Met-p-NA {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC         KM=0.47 mM for Pro-p-NA {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC         KM=0.21 mM for Val-p-NA {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC         KM=182 uM for Ala-MCA {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC         KM=189 uM for Met-MCA {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC         KM=220 uM for Lys-MCA {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC         KM=91 uM for Leu-MCA {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC         KM=167 uM for Phe-MCA {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC       pH dependence:
CC         Optimum pH is 7.5. Stable from pH 5.0 to 8.0.
CC         {ECO:0000269|PubMed:10978616, ECO:0000269|PubMed:17154549};
CC       Temperature dependence:
CC         Stable up to 40 degrees Celsius. {ECO:0000269|PubMed:10978616,
CC         ECO:0000269|PubMed:17154549};
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:10978616}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10978616}.
CC       Nucleus {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P55786-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P55786-2; Sequence=VSP_056446, VSP_056447;
CC   -!- TISSUE SPECIFICITY: Detected in liver, epithelium of renal tubules,
CC       epithelium of small and large intestine, gastric epithelial cells, and
CC       alveoli of the lung (at protein level). {ECO:0000269|PubMed:10978616}.
CC   -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC   -!- CAUTION: It is uncertain whether Met-1 or Met-45 is the initiator. N-
CC       terminal sequencing in PubMed:10978616 suggests that Met-45 is used,
CC       followed by methionine initiator removal. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH65294.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=CAA68964.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; Y07701; CAA68964.1; ALT_INIT; mRNA.
DR   EMBL; AK296887; BAH12449.1; -; mRNA.
DR   EMBL; AC025682; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC065294; AAH65294.2; ALT_INIT; mRNA.
DR   EMBL; AJ132583; CAA10709.1; -; mRNA.
DR   EMBL; AF252387; AAF70086.1; -; Genomic_DNA.
DR   CCDS; CCDS45721.1; -. [P55786-1]
DR   RefSeq; NP_001317186.1; NM_001330257.1.
DR   RefSeq; NP_006301.3; NM_006310.3. [P55786-1]
DR   AlphaFoldDB; P55786; -.
DR   SMR; P55786; -.
DR   BioGRID; 114897; 159.
DR   IntAct; P55786; 31.
DR   MINT; P55786; -.
DR   STRING; 9606.ENSP00000320324; -.
DR   BindingDB; P55786; -.
DR   ChEMBL; CHEMBL2264; -.
DR   DrugBank; DB11638; Artenimol.
DR   DrugBank; DB11781; Tosedostat.
DR   GuidetoPHARMACOLOGY; 1575; -.
DR   MEROPS; M01.010; -.
DR   GlyCosmos; P55786; 1 site, 1 glycan.
DR   GlyGen; P55786; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P55786; -.
DR   MetOSite; P55786; -.
DR   PhosphoSitePlus; P55786; -.
DR   SwissPalm; P55786; -.
DR   BioMuta; NPEPPS; -.
DR   DMDM; 51704228; -.
DR   CPTAC; CPTAC-415; -.
DR   CPTAC; CPTAC-416; -.
DR   EPD; P55786; -.
DR   jPOST; P55786; -.
DR   MassIVE; P55786; -.
DR   MaxQB; P55786; -.
DR   PaxDb; P55786; -.
DR   PeptideAtlas; P55786; -.
DR   PRIDE; P55786; -.
DR   ProteomicsDB; 56864; -. [P55786-1]
DR   ProteomicsDB; 6572; -.
DR   Antibodypedia; 8552; 284 antibodies from 29 providers.
DR   DNASU; 9520; -.
DR   Ensembl; ENST00000322157.9; ENSP00000320324.4; ENSG00000141279.18. [P55786-1]
DR   Ensembl; ENST00000677120.1; ENSP00000503682.1; ENSG00000141279.18. [P55786-1]
DR   GeneID; 9520; -.
DR   KEGG; hsa:9520; -.
DR   MANE-Select; ENST00000322157.9; ENSP00000320324.4; NM_006310.4; NP_006301.3.
DR   UCSC; uc002ilr.5; human. [P55786-1]
DR   AGR; HGNC:7900; -.
DR   CTD; 9520; -.
DR   DisGeNET; 9520; -.
DR   GeneCards; NPEPPS; -.
DR   HGNC; HGNC:7900; NPEPPS.
DR   HPA; ENSG00000141279; Low tissue specificity.
DR   MIM; 606793; gene.
DR   neXtProt; NX_P55786; -.
DR   OpenTargets; ENSG00000141279; -.
DR   PharmGKB; PA31703; -.
DR   VEuPathDB; HostDB:ENSG00000141279; -.
DR   eggNOG; KOG1046; Eukaryota.
DR   GeneTree; ENSGT00940000155246; -.
DR   HOGENOM; CLU_003705_0_1_1; -.
DR   InParanoid; P55786; -.
DR   OMA; MMEYVAI; -.
DR   OrthoDB; 3085317at2759; -.
DR   PhylomeDB; P55786; -.
DR   TreeFam; TF300395; -.
DR   PathwayCommons; P55786; -.
DR   Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   SABIO-RK; P55786; -.
DR   SignaLink; P55786; -.
DR   BioGRID-ORCS; 9520; 280 hits in 1160 CRISPR screens.
DR   ChiTaRS; NPEPPS; human.
DR   GeneWiki; NPEPPS; -.
DR   GenomeRNAi; 9520; -.
DR   Pharos; P55786; Tchem.
DR   PRO; PR:P55786; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; P55786; protein.
DR   Bgee; ENSG00000141279; Expressed in esophagus squamous epithelium and 201 other tissues.
DR   ExpressionAtlas; P55786; baseline and differential.
DR   Genevisible; P55786; HS.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0004177; F:aminopeptidase activity; EXP:Reactome.
DR   GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR   GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR   GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR   GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
DR   GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL.
DR   GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   CDD; cd09601; M1_APN-Q_like; 1.
DR   Gene3D; 1.25.50.20; -; 1.
DR   Gene3D; 2.60.40.1910; -; 1.
DR   Gene3D; 1.10.390.10; Neutral Protease Domain 2; 1.
DR   Gene3D; 2.60.40.1730; tricorn interacting facor f3 domain; 1.
DR   InterPro; IPR045357; Aminopeptidase_N-like_N.
DR   InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR   InterPro; IPR024571; ERAP1-like_C_dom.
DR   InterPro; IPR034016; M1_APN-typ.
DR   InterPro; IPR001930; Peptidase_M1.
DR   InterPro; IPR014782; Peptidase_M1_dom.
DR   InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR   PANTHER; PTHR11533; PROTEASE M1 ZINC METALLOPROTEASE; 1.
DR   PANTHER; PTHR11533:SF285; PUROMYCIN-SENSITIVE AMINOPEPTIDASE-RELATED; 1.
DR   Pfam; PF11838; ERAP1_C; 1.
DR   Pfam; PF01433; Peptidase_M1; 1.
DR   Pfam; PF17900; Peptidase_M1_N; 1.
DR   PRINTS; PR00756; ALADIPTASE.
DR   SUPFAM; SSF63737; Leukotriene A4 hydrolase N-terminal domain; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Aminopeptidase; Cytoplasm; Direct protein sequencing;
KW   Hydrolase; Metal-binding; Metalloprotease; Nitration; Nucleus; Protease;
KW   Reference proteome; Zinc.
FT   CHAIN           1..919
FT                   /note="Puromycin-sensitive aminopeptidase"
FT                   /id="PRO_0000095116"
FT   MOTIF           726..730
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        353
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         180
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         316..320
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         352
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         356
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         375
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   SITE            438
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         464
FT                   /note="3'-nitrotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q11011"
FT   VAR_SEQ         1..44
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_056446"
FT   VAR_SEQ         181..216
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_056447"
FT   MUTAGEN         353
FT                   /note="E->A: Reduces catalytic activity by 25,000-fold to
FT                   100,000-fold."
FT                   /evidence="ECO:0000269|PubMed:12729622"
FT   MUTAGEN         353
FT                   /note="E->Q: Reduces catalytic activity by 5,000-fold to
FT                   15,000-fold."
FT                   /evidence="ECO:0000269|PubMed:12729622"
FT   MUTAGEN         353
FT                   /note="E->V: Reduces catalytic activity by 300,000-fold to
FT                   500,000-fold."
FT                   /evidence="ECO:0000269|PubMed:12729622"
FT   MUTAGEN         438
FT                   /note="Y->F: Reduces catalytic activity by 1,000-fold to
FT                   2,500-fold."
FT                   /evidence="ECO:0000269|PubMed:12729622"
FT   CONFLICT        184
FT                   /note="A -> P (in Ref. 1; CAA68964)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   919 AA;  103276 MW;  873C9BF75494A057 CRC64;
     MWLAAAAPSL ARRLLFLGPP PPPLLLLVFS RSSRRRLHSL GLAAMPEKRP FERLPADVSP
     INYSLCLKPD LLDFTFEGKL EAAAQVRQAT NQIVMNCADI DIITASYAPE GDEEIHATGF
     NYQNEDEKVT LSFPSTLQTG TGTLKIDFVG ELNDKMKGFY RSKYTTPSGE VRYAAVTQFE
     ATDARRAFPC WDEPAIKATF DISLVVPKDR VALSNMNVID RKPYPDDENL VEVKFARTPV
     MSTYLVAFVV GEYDFVETRS KDGVCVRVYT PVGKAEQGKF ALEVAAKTLP FYKDYFNVPY
     PLPKIDLIAI ADFAAGAMEN WGLVTYRETA LLIDPKNSCS SSRQWVALVV GHELAHQWFG
     NLVTMEWWTH LWLNEGFASW IEYLCVDHCF PEYDIWTQFV SADYTRAQEL DALDNSHPIE
     VSVGHPSEVD EIFDAISYSK GASVIRMLHD YIGDKDFKKG MNMYLTKFQQ KNAATEDLWE
     SLENASGKPI AAVMNTWTKQ MGFPLIYVEA EQVEDDRLLR LSQKKFCAGG SYVGEDCPQW
     MVPITISTSE DPNQAKLKIL MDKPEMNVVL KNVKPDQWVK LNLGTVGFYR TQYSSAMLES
     LLPGIRDLSL PPVDRLGLQN DLFSLARAGI ISTVEVLKVM EAFVNEPNYT VWSDLSCNLG
     ILSTLLSHTD FYEEIQEFVK DVFSPIGERL GWDPKPGEGH LDALLRGLVL GKLGKAGHKA
     TLEEARRRFK DHVEGKQILS ADLRSPVYLT VLKHGDGTTL DIMLKLHKQA DMQEEKNRIE
     RVLGATLLPD LIQKVLTFAL SEEVRPQDTV SVIGGVAGGS KHGRKAAWKF IKDNWEELYN
     RYQGGFLISR LIKLSVEGFA VDKMAGEVKA FFESHPAPSA ERTIQQCCEN ILLNAAWLKR
     DAESIHQYLL QRKASPPTV
//