Full text data of NPEPPS
NPEPPS
(PSA)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Puromycin-sensitive aminopeptidase; PSA; 3.4.11.14 (Cytosol alanyl aminopeptidase; AAP-S)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Puromycin-sensitive aminopeptidase; PSA; 3.4.11.14 (Cytosol alanyl aminopeptidase; AAP-S)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00026216
IPI00026216 Puromycin-sensitive aminopeptidase Aminopeptidase with broad substrate specificity to several peptides. Involved in proteolytic events essential for cell growth and viability. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00026216 Puromycin-sensitive aminopeptidase Aminopeptidase with broad substrate specificity to several peptides. Involved in proteolytic events essential for cell growth and viability. soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P55786
ID PSA_HUMAN Reviewed; 919 AA.
AC P55786; Q6P145; Q9NP16; Q9UEM2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 31-AUG-2004, sequence version 2.
DT 22-JAN-2014, entry version 130.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal brain;
RX PubMed=9048733;
RA Tobler A.R., Constam D.B., Schmitt-Graeff A., Malipiero U.,
RA Schlapbach R., Fontana A.;
RT "Cloning of the human puromycin-sensitive aminopeptidase and evidence
RT for expression in neurons.";
RL J. Neurochem. 68:889-897(1997).
RN [2]
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.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA 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
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 31-919.
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 45-919.
RC TISSUE=Skeletal muscle;
RX PubMed=11435692;
RA Bauer W.O., Nanda I., Beck G., Schmid M., Jakob F.;
RT "Human puromycin-sensitive aminopeptidase: cloning of 3' UTR, evidence
RT for a polymorphism at a.a. 140 and refined chromosomal localization to
RT 17q21.";
RL Cytogenet. Cell Genet. 92:221-224(2001).
RN [5]
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 [6]
RP PROTEIN SEQUENCE OF 46-105, FUNCTION, ENZYME REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND
RP TISSUE 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 [7]
RP FUNCTION.
RX PubMed=11062501; DOI=10.1038/80852;
RA Stoltze L., Schirle M., Schwarz G., Schroter C., Thompson M.W.,
RA Hersh L.B., 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 [8]
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 [9]
RP FUNCTION, ENZYME REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17154549; DOI=10.1021/bi061830d;
RA Sengupta S., Horowitz P.M., Karsten S.L., Jackson G.R.,
RA Geschwind D.H., 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 [10]
RP FUNCTION, AND ENZYME 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
RT for digesting polyglutamine sequences released by proteasomes during
RT protein degradation.";
RL EMBO J. 26:1385-1396(2007).
RN [11]
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 [12]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Aminopeptidase with broad substrate specificity for
CC several peptides. Involved in proteolytic events essential for
CC cell growth and viability. May act as regulator of neuropeptide
CC activity. Plays a role in the antigen-processing pathway for MHC
CC class I molecules. Involved in the N-terminal trimming of
CC cytotoxic T-cell epitope precursors. Digests the poly-Q peptides
CC found in many cellular proteins. Digests tau from normal brain
CC more efficiently than tau from Alzheimer disease brain.
CC -!- CATALYTIC ACTIVITY: Release of an N-terminal amino acid,
CC preferentially alanine, from a wide range of peptides, amides and
CC arylamides.
CC -!- COFACTOR: Binds 1 zinc ion per subunit (By similarity).
CC -!- ENZYME REGULATION: Strongly inhibited by bestatin, leuhistin,
CC actinonin, amastatin, 1,10-phenanthroline, DFP, PCMBS, Zn(2+),
CC Cd(2+), Co(2+), Cu(2+), Hg(2+), EDTA and puromycin. Not inhibited
CC by PMSF, and only slightly inhibited by leupeptin and aprotinin.
CC Activity is increased by Mg(2+) and Ca(2+).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.20 mM for Lys-p-NA;
CC KM=0.25 mM for Leu-p-NA;
CC KM=0.27 mM for Ala-p-NA;
CC KM=0.80 mM for Met-p-NA;
CC KM=0.47 mM for Pro-p-NA;
CC KM=0.21 mM for Val-p-NA;
CC KM=182 uM for Ala-MCA;
CC KM=189 uM for Met-MCA;
CC KM=220 uM for Lys-MCA;
CC KM=91 uM for Leu-MCA;
CC KM=167 uM for Phe-MCA;
CC pH dependence:
CC Optimum pH is 7.5. Stable from pH 5.0 to 8.0;
CC Temperature dependence:
CC Stable up to 40 degrees Celsius;
CC -!- SUBUNIT: Monomer.
CC -!- INTERACTION:
CC P56537:EIF6; NbExp=1; IntAct=EBI-1046129, EBI-372243;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Nucleus (Potential).
CC -!- TISSUE SPECIFICITY: Detected in liver, epithelium of renal
CC tubules, epithelium of small and large intestine, gastric
CC epithelial cells, and alveoli of the lung (at protein level).
CC -!- SIMILARITY: Belongs to the peptidase M1 family.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-45 is the initiator.
CC N-terminal sequencing in PubMed:10978616 suggests that Met-45 is
CC used, followed by methionine initiator removal.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH65294.2; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAA68964.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; Y07701; CAA68964.1; ALT_INIT; 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 RefSeq; NP_006301.3; NM_006310.3.
DR UniGene; Hs.443837; -.
DR ProteinModelPortal; P55786; -.
DR SMR; P55786; 42-910.
DR IntAct; P55786; 6.
DR MINT; MINT-4999844; -.
DR STRING; 9606.ENSP00000320324; -.
DR BindingDB; P55786; -.
DR ChEMBL; CHEMBL2264; -.
DR MEROPS; M01.010; -.
DR PhosphoSite; P55786; -.
DR DMDM; 51704228; -.
DR PaxDb; P55786; -.
DR PeptideAtlas; P55786; -.
DR PRIDE; P55786; -.
DR Ensembl; ENST00000322157; ENSP00000320324; ENSG00000141279.
DR GeneID; 9520; -.
DR KEGG; hsa:9520; -.
DR UCSC; uc002ilr.4; human.
DR CTD; 9520; -.
DR GeneCards; GC17P045608; -.
DR H-InvDB; HIX0013922; -.
DR HGNC; HGNC:7900; NPEPPS.
DR HPA; HPA021453; -.
DR HPA; HPA045649; -.
DR MIM; 606793; gene.
DR neXtProt; NX_P55786; -.
DR PharmGKB; PA31703; -.
DR eggNOG; COG0308; -.
DR HOGENOM; HOG000106482; -.
DR HOVERGEN; HBG106325; -.
DR InParanoid; P55786; -.
DR KO; K08776; -.
DR OMA; KFQHKNA; -.
DR PhylomeDB; P55786; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; NPEPPS; human.
DR GeneWiki; NPEPPS; -.
DR GenomeRNAi; 9520; -.
DR NextBio; 35678; -.
DR PMAP-CutDB; P55786; -.
DR PRO; PR:P55786; -.
DR ArrayExpress; P55786; -.
DR Bgee; P55786; -.
DR CleanEx; HS_NPEPPS; -.
DR Genevestigator; P55786; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004177; F:aminopeptidase activity; TAS:ProtInc.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR015568; NPEPPS.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_N.
DR PANTHER; PTHR11533; PTHR11533; 1.
DR PANTHER; PTHR11533:SF64; PTHR11533:SF64; 1.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Aminopeptidase; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Metal-binding; Metalloprotease;
KW Nitration; Nucleus; Protease; Reference proteome; Zinc.
FT CHAIN 1 919 Puromycin-sensitive aminopeptidase.
FT /FTId=PRO_0000095116.
FT REGION 316 320 Substrate binding (By similarity).
FT MOTIF 726 730 Nuclear localization signal (Potential).
FT ACT_SITE 353 353 Proton acceptor (By similarity).
FT METAL 352 352 Zinc; catalytic (By similarity).
FT METAL 356 356 Zinc; catalytic (By similarity).
FT METAL 375 375 Zinc; catalytic (By similarity).
FT BINDING 180 180 Substrate (By similarity).
FT SITE 438 438 Transition state stabilizer (By
FT similarity).
FT MOD_RES 464 464 Nitrated tyrosine (By similarity).
FT MUTAGEN 353 353 E->A: Reduces catalytic activity by
FT 25,000-fold to 100,000-fold.
FT MUTAGEN 353 353 E->Q: Reduces catalytic activity by
FT 5,000-fold to 15,000-fold.
FT MUTAGEN 353 353 E->V: Reduces catalytic activity by
FT 300,000-fold to 500,000-fold.
FT MUTAGEN 438 438 Y->F: Reduces catalytic activity by
FT 1,000-fold to 2,500-fold.
FT CONFLICT 184 184 A -> P (in Ref. 1; CAA68964).
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
//
ID PSA_HUMAN Reviewed; 919 AA.
AC P55786; Q6P145; Q9NP16; Q9UEM2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 31-AUG-2004, sequence version 2.
DT 22-JAN-2014, entry version 130.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal brain;
RX PubMed=9048733;
RA Tobler A.R., Constam D.B., Schmitt-Graeff A., Malipiero U.,
RA Schlapbach R., Fontana A.;
RT "Cloning of the human puromycin-sensitive aminopeptidase and evidence
RT for expression in neurons.";
RL J. Neurochem. 68:889-897(1997).
RN [2]
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.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA 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
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 31-919.
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 45-919.
RC TISSUE=Skeletal muscle;
RX PubMed=11435692;
RA Bauer W.O., Nanda I., Beck G., Schmid M., Jakob F.;
RT "Human puromycin-sensitive aminopeptidase: cloning of 3' UTR, evidence
RT for a polymorphism at a.a. 140 and refined chromosomal localization to
RT 17q21.";
RL Cytogenet. Cell Genet. 92:221-224(2001).
RN [5]
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 [6]
RP PROTEIN SEQUENCE OF 46-105, FUNCTION, ENZYME REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND
RP TISSUE 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 [7]
RP FUNCTION.
RX PubMed=11062501; DOI=10.1038/80852;
RA Stoltze L., Schirle M., Schwarz G., Schroter C., Thompson M.W.,
RA Hersh L.B., 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 [8]
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 [9]
RP FUNCTION, ENZYME REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17154549; DOI=10.1021/bi061830d;
RA Sengupta S., Horowitz P.M., Karsten S.L., Jackson G.R.,
RA Geschwind D.H., 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 [10]
RP FUNCTION, AND ENZYME 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
RT for digesting polyglutamine sequences released by proteasomes during
RT protein degradation.";
RL EMBO J. 26:1385-1396(2007).
RN [11]
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 [12]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Aminopeptidase with broad substrate specificity for
CC several peptides. Involved in proteolytic events essential for
CC cell growth and viability. May act as regulator of neuropeptide
CC activity. Plays a role in the antigen-processing pathway for MHC
CC class I molecules. Involved in the N-terminal trimming of
CC cytotoxic T-cell epitope precursors. Digests the poly-Q peptides
CC found in many cellular proteins. Digests tau from normal brain
CC more efficiently than tau from Alzheimer disease brain.
CC -!- CATALYTIC ACTIVITY: Release of an N-terminal amino acid,
CC preferentially alanine, from a wide range of peptides, amides and
CC arylamides.
CC -!- COFACTOR: Binds 1 zinc ion per subunit (By similarity).
CC -!- ENZYME REGULATION: Strongly inhibited by bestatin, leuhistin,
CC actinonin, amastatin, 1,10-phenanthroline, DFP, PCMBS, Zn(2+),
CC Cd(2+), Co(2+), Cu(2+), Hg(2+), EDTA and puromycin. Not inhibited
CC by PMSF, and only slightly inhibited by leupeptin and aprotinin.
CC Activity is increased by Mg(2+) and Ca(2+).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.20 mM for Lys-p-NA;
CC KM=0.25 mM for Leu-p-NA;
CC KM=0.27 mM for Ala-p-NA;
CC KM=0.80 mM for Met-p-NA;
CC KM=0.47 mM for Pro-p-NA;
CC KM=0.21 mM for Val-p-NA;
CC KM=182 uM for Ala-MCA;
CC KM=189 uM for Met-MCA;
CC KM=220 uM for Lys-MCA;
CC KM=91 uM for Leu-MCA;
CC KM=167 uM for Phe-MCA;
CC pH dependence:
CC Optimum pH is 7.5. Stable from pH 5.0 to 8.0;
CC Temperature dependence:
CC Stable up to 40 degrees Celsius;
CC -!- SUBUNIT: Monomer.
CC -!- INTERACTION:
CC P56537:EIF6; NbExp=1; IntAct=EBI-1046129, EBI-372243;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Nucleus (Potential).
CC -!- TISSUE SPECIFICITY: Detected in liver, epithelium of renal
CC tubules, epithelium of small and large intestine, gastric
CC epithelial cells, and alveoli of the lung (at protein level).
CC -!- SIMILARITY: Belongs to the peptidase M1 family.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-45 is the initiator.
CC N-terminal sequencing in PubMed:10978616 suggests that Met-45 is
CC used, followed by methionine initiator removal.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH65294.2; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAA68964.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; Y07701; CAA68964.1; ALT_INIT; 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 RefSeq; NP_006301.3; NM_006310.3.
DR UniGene; Hs.443837; -.
DR ProteinModelPortal; P55786; -.
DR SMR; P55786; 42-910.
DR IntAct; P55786; 6.
DR MINT; MINT-4999844; -.
DR STRING; 9606.ENSP00000320324; -.
DR BindingDB; P55786; -.
DR ChEMBL; CHEMBL2264; -.
DR MEROPS; M01.010; -.
DR PhosphoSite; P55786; -.
DR DMDM; 51704228; -.
DR PaxDb; P55786; -.
DR PeptideAtlas; P55786; -.
DR PRIDE; P55786; -.
DR Ensembl; ENST00000322157; ENSP00000320324; ENSG00000141279.
DR GeneID; 9520; -.
DR KEGG; hsa:9520; -.
DR UCSC; uc002ilr.4; human.
DR CTD; 9520; -.
DR GeneCards; GC17P045608; -.
DR H-InvDB; HIX0013922; -.
DR HGNC; HGNC:7900; NPEPPS.
DR HPA; HPA021453; -.
DR HPA; HPA045649; -.
DR MIM; 606793; gene.
DR neXtProt; NX_P55786; -.
DR PharmGKB; PA31703; -.
DR eggNOG; COG0308; -.
DR HOGENOM; HOG000106482; -.
DR HOVERGEN; HBG106325; -.
DR InParanoid; P55786; -.
DR KO; K08776; -.
DR OMA; KFQHKNA; -.
DR PhylomeDB; P55786; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; NPEPPS; human.
DR GeneWiki; NPEPPS; -.
DR GenomeRNAi; 9520; -.
DR NextBio; 35678; -.
DR PMAP-CutDB; P55786; -.
DR PRO; PR:P55786; -.
DR ArrayExpress; P55786; -.
DR Bgee; P55786; -.
DR CleanEx; HS_NPEPPS; -.
DR Genevestigator; P55786; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004177; F:aminopeptidase activity; TAS:ProtInc.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR015568; NPEPPS.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_N.
DR PANTHER; PTHR11533; PTHR11533; 1.
DR PANTHER; PTHR11533:SF64; PTHR11533:SF64; 1.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Aminopeptidase; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Metal-binding; Metalloprotease;
KW Nitration; Nucleus; Protease; Reference proteome; Zinc.
FT CHAIN 1 919 Puromycin-sensitive aminopeptidase.
FT /FTId=PRO_0000095116.
FT REGION 316 320 Substrate binding (By similarity).
FT MOTIF 726 730 Nuclear localization signal (Potential).
FT ACT_SITE 353 353 Proton acceptor (By similarity).
FT METAL 352 352 Zinc; catalytic (By similarity).
FT METAL 356 356 Zinc; catalytic (By similarity).
FT METAL 375 375 Zinc; catalytic (By similarity).
FT BINDING 180 180 Substrate (By similarity).
FT SITE 438 438 Transition state stabilizer (By
FT similarity).
FT MOD_RES 464 464 Nitrated tyrosine (By similarity).
FT MUTAGEN 353 353 E->A: Reduces catalytic activity by
FT 25,000-fold to 100,000-fold.
FT MUTAGEN 353 353 E->Q: Reduces catalytic activity by
FT 5,000-fold to 15,000-fold.
FT MUTAGEN 353 353 E->V: Reduces catalytic activity by
FT 300,000-fold to 500,000-fold.
FT MUTAGEN 438 438 Y->F: Reduces catalytic activity by
FT 1,000-fold to 2,500-fold.
FT CONFLICT 184 184 A -> P (in Ref. 1; CAA68964).
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
//
MIM
606793
*RECORD*
*FIELD* NO
606793
*FIELD* TI
*606793 AMINOPEPTIDASE, PUROMYCIN-SENSITIVE; NPEPPS
;;PSA;;
METALLOPROTEASE MP100; MP100
read more*FIELD* TX
DESCRIPTION
Aminopeptidases are a group of exopeptidases that hydrolyze amino acids
from the N terminus of a peptide substrate. Puromycin-sensitive
aminopeptidase (EC 3.4.11.14) contains the zinc-binding domain
characteristic of the gluzincin group of zinc metalloproteases (see
605896).
CLONING
Tobler et al. (1997) cloned PSA from a human fetal brain cDNA library
using the mouse PSA cDNA as probe. They established that translation is
initiated at the second of 2 possible start codons, resulting in a
deduced 875-amino acid protein with a molecular mass of 99 kD by
SDS-PAGE. PSA contains a zinc-binding motif conserved among gluzincin
aminopeptidases and shares 98% sequence identity with the mouse protein.
Northern blot analysis detected ubiquitous expression of a 4.8-kb
transcript, with highest expression in brain. By in situ hybridization
of adult human brain sections, expression was localized to the
perikaryon of neurons of the cortex and cerebellum. Using
immunofluorescence localization of transfected HeLa cells, Tobler et al.
(1997) found that PSA localizes to the perinuclear cytoplasm and shows a
filamentous staining pattern. Bauer et al. (2001) cloned PSA cDNA from a
human skeletal muscle library. Northern blot analysis detected major and
minor transcripts of 4.8 and 4.2 kb, respectively. Huber et al. (1999)
determined that PSA is identical to the metalloprotease MP100 that was
originally isolated as a beta-secretase candidate from human brain by
Schonlein et al. (1994).
GENE FUNCTION
Huber et al. (1999) were able to colocalize and coimmunoprecipitate PSA
with beta-amyloid precursor protein (104760); however, PSA did not
increase production of the amyloid-beta peptide in cotransfected cells.
By RT-PCR, but not by Northern blot analysis, Bauer et al. (2001) found
that PSA was upregulated in human leukemic cells following vitamin D
stimulation.
GENE STRUCTURE
Thompson et al. (1999) determined that the PSA gene contains 23 exons
spanning approximately 40 kb. They found that the active site motif iis
split between exons 9 and 10. Analysis of the 5-prime flanking region
indicated that the gene lacks a TATA box, is GC rich, and contains 5
putative SP1 (189906)-binding sites.
MAPPING
By FISH, Bauer et al. (2001) mapped the PSA gene to chromosome 17q21.
Osada et al. (1999) mapped the mouse Psa gene to a region of syntenic
homology on chromosome 11.
POPULATION GENETICS
By analyzing short-read mapping depth for 159 human genomes, Sudmant et
al. (2010) demonstrated accurate estimation of absolute copy number for
duplications as small as 1.9 kb pairs, ranging from 0 to 48 copies.
Sudmant et al. (2010) identified 4.1 million 'singly unique nucleotide'
positions informative in distinguishing specific copies and used them to
genotype the copy and content of specific paralogs within highly
duplicated gene families. These data identified human-specific
expansions in genes associated with brain development, such as GPRIN2
(611240) and SRGAP2 (606524), which have been implicated in neurite
outgrowth and branching. Also included were the brain-specific HYDIN2
gene (610813), associated with micro- and macrocephaly; DRD5 (126453), a
dopamine D5 receptor; and the GTF2I (601679) transcription factors,
whose deletion has been associated with visual-spatial and sociability
deficits among Williams-Beuren syndrome (194050) patients, among others.
The data of Sudmant et al. (2010) also revealed extensive population
genetic diversity, especially among the genes NPEPPS, UGT2B17 (601903),
and NBPF1 (610501), as well as LILRA3 (604818), which is the most highly
stratified gene by copy number in the human genome. In addition, Sudmant
et al. (2010) detected signatures consistent with gene conversion in the
human species.
ANIMAL MODEL
Karsten et al. (2006) identified the Npepps gene as a tau (MAPT; 157140)
modifier by using a cross-species functional genomic approach to analyze
gene expression in mice. Npepps expression was increased in multiple
brain regions in a mouse model of frontotemporal dementia (FTD; 600274)
compared to control mice. In Drosophila, Npepps protected against
tau-induced neurodegeneration, whereas loss of Npepps exacerbated
neurodegeneration. Immunoblot, SDS-PAGE, and Western blot analyses
showed that human NPEPPS directly proteolyzed and significantly
diminished human tau. Western blot analysis of 6 brains derived from
human FTD patients showed increased NPEPPS expression, particularly in
the cerebellum.
*FIELD* RF
1. Bauer, W. O.; Nanda, I.; Beck, G.; Schmid, M.; Jakob, F.: Human
puromycin-sensitive aminopeptidase: cloning of 3-prime UTR, evidence
for a polymorphism at aa 140 and refined chromosomal localization
to 17q21. Cytogenet. Cell Genet. 92: 221-224, 2001.
2. Huber, G.; Thompson, A.; Gruninger, F.; Mechler, H.; Hochstrasser,
R.; Hauri, H.-P.; Malherbe, P.: cDNA cloning and molecular characterization
of human brain metalloprotease MP100: a beta-secretase candidate? J.
Neurochem. 72: 1215-1223, 1999.
3. Karsten, S. L.; Sang, T.-K.; Gehman, L. T.; Chatterjee, S.; Liu,
J.; Lawless, G. M.; Sengupta, S.; Berry, R. W.; Pomakian, J.; Oh,
H. S.; Schulz, C.; Hui, K.-S.; Wiedau-Pazos, M.; Vinters, H. V.; Binder,
L. I.; Geschwind, D. H.; Jackson, G. R.: A genomic screen for modifiers
of tauopathy identified puromycin-sensitive aminopeptidase as an inhibitor
of tau-induced neurodegeneration. Neuron 51: 549-560, 2006.
4. Osada, T.; Sakaki, Y.; Takeuchi, T.: Puromycin-sensitive aminopeptidase
gene (Psa) maps to mouse chromosome 11. Genomics 56: 361-362, 1999.
5. Schonlein, C.; Loffler, J.; Huber, G.: Purification and characterization
of a novel metalloprotease from human brain with the ability to cleave
substrates derived from the N-terminus of beta-amyloid protein. Biochem.
Biophys. Res. Commun. 201: 45-53, 1994.
6. Sudmant, P. H.; Kitzman, J. O.; Antonacci, F.; Alkan, C.; Malig,
M.; Tsalenko, A.; Sampas, N.; Bruhn, L.; Shendure, J.; 1000 Genomes
Project; Eichler, E. E.: Diversity of human copy number variation
and multicopy genes. Science 330: 641-646, 2010.
7. Thompson, M. W.; Tobler, A.; Fontana, A.; Hersh, L. B.: Cloning
and analysis of the gene for the human puromycin-sensitive aminopeptidase. Biochem.
Biophys. Res. Commun. 258: 234-240, 1999.
8. Tobler, A. R.; Constam, D. B.; Schmitt-Graff, A.; Malipiero, U.;
Schlapbach, R.; Fontana, A.: Cloning of the human puromycin-sensitive
aminopeptidase and evidence for expression in neurons. J. Neurochem. 68:
889-897, 1997.
*FIELD* CN
Ada Hamosh - updated: 11/23/2010
Cassandra L. Kniffin - updated: 10/11/2007
*FIELD* CD
Patricia A. Hartz: 3/26/2002
*FIELD* ED
alopez: 11/24/2010
terry: 11/23/2010
wwang: 10/19/2007
ckniffin: 10/11/2007
carol: 3/26/2002
*RECORD*
*FIELD* NO
606793
*FIELD* TI
*606793 AMINOPEPTIDASE, PUROMYCIN-SENSITIVE; NPEPPS
;;PSA;;
METALLOPROTEASE MP100; MP100
read more*FIELD* TX
DESCRIPTION
Aminopeptidases are a group of exopeptidases that hydrolyze amino acids
from the N terminus of a peptide substrate. Puromycin-sensitive
aminopeptidase (EC 3.4.11.14) contains the zinc-binding domain
characteristic of the gluzincin group of zinc metalloproteases (see
605896).
CLONING
Tobler et al. (1997) cloned PSA from a human fetal brain cDNA library
using the mouse PSA cDNA as probe. They established that translation is
initiated at the second of 2 possible start codons, resulting in a
deduced 875-amino acid protein with a molecular mass of 99 kD by
SDS-PAGE. PSA contains a zinc-binding motif conserved among gluzincin
aminopeptidases and shares 98% sequence identity with the mouse protein.
Northern blot analysis detected ubiquitous expression of a 4.8-kb
transcript, with highest expression in brain. By in situ hybridization
of adult human brain sections, expression was localized to the
perikaryon of neurons of the cortex and cerebellum. Using
immunofluorescence localization of transfected HeLa cells, Tobler et al.
(1997) found that PSA localizes to the perinuclear cytoplasm and shows a
filamentous staining pattern. Bauer et al. (2001) cloned PSA cDNA from a
human skeletal muscle library. Northern blot analysis detected major and
minor transcripts of 4.8 and 4.2 kb, respectively. Huber et al. (1999)
determined that PSA is identical to the metalloprotease MP100 that was
originally isolated as a beta-secretase candidate from human brain by
Schonlein et al. (1994).
GENE FUNCTION
Huber et al. (1999) were able to colocalize and coimmunoprecipitate PSA
with beta-amyloid precursor protein (104760); however, PSA did not
increase production of the amyloid-beta peptide in cotransfected cells.
By RT-PCR, but not by Northern blot analysis, Bauer et al. (2001) found
that PSA was upregulated in human leukemic cells following vitamin D
stimulation.
GENE STRUCTURE
Thompson et al. (1999) determined that the PSA gene contains 23 exons
spanning approximately 40 kb. They found that the active site motif iis
split between exons 9 and 10. Analysis of the 5-prime flanking region
indicated that the gene lacks a TATA box, is GC rich, and contains 5
putative SP1 (189906)-binding sites.
MAPPING
By FISH, Bauer et al. (2001) mapped the PSA gene to chromosome 17q21.
Osada et al. (1999) mapped the mouse Psa gene to a region of syntenic
homology on chromosome 11.
POPULATION GENETICS
By analyzing short-read mapping depth for 159 human genomes, Sudmant et
al. (2010) demonstrated accurate estimation of absolute copy number for
duplications as small as 1.9 kb pairs, ranging from 0 to 48 copies.
Sudmant et al. (2010) identified 4.1 million 'singly unique nucleotide'
positions informative in distinguishing specific copies and used them to
genotype the copy and content of specific paralogs within highly
duplicated gene families. These data identified human-specific
expansions in genes associated with brain development, such as GPRIN2
(611240) and SRGAP2 (606524), which have been implicated in neurite
outgrowth and branching. Also included were the brain-specific HYDIN2
gene (610813), associated with micro- and macrocephaly; DRD5 (126453), a
dopamine D5 receptor; and the GTF2I (601679) transcription factors,
whose deletion has been associated with visual-spatial and sociability
deficits among Williams-Beuren syndrome (194050) patients, among others.
The data of Sudmant et al. (2010) also revealed extensive population
genetic diversity, especially among the genes NPEPPS, UGT2B17 (601903),
and NBPF1 (610501), as well as LILRA3 (604818), which is the most highly
stratified gene by copy number in the human genome. In addition, Sudmant
et al. (2010) detected signatures consistent with gene conversion in the
human species.
ANIMAL MODEL
Karsten et al. (2006) identified the Npepps gene as a tau (MAPT; 157140)
modifier by using a cross-species functional genomic approach to analyze
gene expression in mice. Npepps expression was increased in multiple
brain regions in a mouse model of frontotemporal dementia (FTD; 600274)
compared to control mice. In Drosophila, Npepps protected against
tau-induced neurodegeneration, whereas loss of Npepps exacerbated
neurodegeneration. Immunoblot, SDS-PAGE, and Western blot analyses
showed that human NPEPPS directly proteolyzed and significantly
diminished human tau. Western blot analysis of 6 brains derived from
human FTD patients showed increased NPEPPS expression, particularly in
the cerebellum.
*FIELD* RF
1. Bauer, W. O.; Nanda, I.; Beck, G.; Schmid, M.; Jakob, F.: Human
puromycin-sensitive aminopeptidase: cloning of 3-prime UTR, evidence
for a polymorphism at aa 140 and refined chromosomal localization
to 17q21. Cytogenet. Cell Genet. 92: 221-224, 2001.
2. Huber, G.; Thompson, A.; Gruninger, F.; Mechler, H.; Hochstrasser,
R.; Hauri, H.-P.; Malherbe, P.: cDNA cloning and molecular characterization
of human brain metalloprotease MP100: a beta-secretase candidate? J.
Neurochem. 72: 1215-1223, 1999.
3. Karsten, S. L.; Sang, T.-K.; Gehman, L. T.; Chatterjee, S.; Liu,
J.; Lawless, G. M.; Sengupta, S.; Berry, R. W.; Pomakian, J.; Oh,
H. S.; Schulz, C.; Hui, K.-S.; Wiedau-Pazos, M.; Vinters, H. V.; Binder,
L. I.; Geschwind, D. H.; Jackson, G. R.: A genomic screen for modifiers
of tauopathy identified puromycin-sensitive aminopeptidase as an inhibitor
of tau-induced neurodegeneration. Neuron 51: 549-560, 2006.
4. Osada, T.; Sakaki, Y.; Takeuchi, T.: Puromycin-sensitive aminopeptidase
gene (Psa) maps to mouse chromosome 11. Genomics 56: 361-362, 1999.
5. Schonlein, C.; Loffler, J.; Huber, G.: Purification and characterization
of a novel metalloprotease from human brain with the ability to cleave
substrates derived from the N-terminus of beta-amyloid protein. Biochem.
Biophys. Res. Commun. 201: 45-53, 1994.
6. Sudmant, P. H.; Kitzman, J. O.; Antonacci, F.; Alkan, C.; Malig,
M.; Tsalenko, A.; Sampas, N.; Bruhn, L.; Shendure, J.; 1000 Genomes
Project; Eichler, E. E.: Diversity of human copy number variation
and multicopy genes. Science 330: 641-646, 2010.
7. Thompson, M. W.; Tobler, A.; Fontana, A.; Hersh, L. B.: Cloning
and analysis of the gene for the human puromycin-sensitive aminopeptidase. Biochem.
Biophys. Res. Commun. 258: 234-240, 1999.
8. Tobler, A. R.; Constam, D. B.; Schmitt-Graff, A.; Malipiero, U.;
Schlapbach, R.; Fontana, A.: Cloning of the human puromycin-sensitive
aminopeptidase and evidence for expression in neurons. J. Neurochem. 68:
889-897, 1997.
*FIELD* CN
Ada Hamosh - updated: 11/23/2010
Cassandra L. Kniffin - updated: 10/11/2007
*FIELD* CD
Patricia A. Hartz: 3/26/2002
*FIELD* ED
alopez: 11/24/2010
terry: 11/23/2010
wwang: 10/19/2007
ckniffin: 10/11/2007
carol: 3/26/2002