ID PSA_MOUSE Reviewed; 920 AA.
AC Q11011; Q3UZE0; Q5PR74; Q91VJ8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 2.
DT 27-MAR-2024, entry version 189.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=7592939; DOI=10.1074/jbc.270.45.26931;
RA Constam D.B., Tobler A.R., Rensing-Ehl A., Kemler I., Hersh L.B.,
RA Fontana A.;
RT "Puromycin-sensitive aminopeptidase. Sequence analysis, expression, and
RT functional characterization.";
RL J. Biol. Chem. 270:26931-26939(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Mammary tumor;
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 [LARGE SCALE MRNA] OF 26-920.
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=10407043; DOI=10.1523/jneurosci.19-14-06068.1999;
RA Osada T., Ikegami S., Takiguchi-Hayashi K., Yamazaki Y., Katoh-Fukui Y.,
RA Higashinakagawa T., Sakaki Y., Takeuchi T.;
RT "Increased anxiety and impaired pain response in puromycin-sensitive
RT aminopeptidase gene-deficient mice obtained by a mouse gene-trap method.";
RL J. Neurosci. 19:6068-6078(1999).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=11376108; DOI=10.1210/mend.15.6.0644;
RA Osada T., Watanabe G., Sakaki Y., Takeuchi T.;
RT "Puromycin-sensitive aminopeptidase is essential for the maternal
RT recognition of pregnancy in mice.";
RL Mol. Endocrinol. 15:882-893(2001).
RN [8]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=11376114; DOI=10.1210/mend.15.6.0643;
RA Osada T., Watanabe G., Kondo S., Toyoda M., Sakaki Y., Takeuchi T.;
RT "Male reproductive defects caused by puromycin-sensitive aminopeptidase
RT deficiency in mice.";
RL Mol. Endocrinol. 15:960-971(2001).
RN [9]
RP NITRATION [LARGE SCALE ANALYSIS] AT TYR-465, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16800626; DOI=10.1021/bi060474w;
RA Sacksteder C.A., Qian W.-J., Knyushko T.V., Wang H., Chin M.H., Lacan G.,
RA Melega W.P., Camp D.G. II, Smith R.D., Smith D.J., Squier T.C.,
RA Bigelow D.J.;
RT "Endogenously nitrated proteins in mouse brain: links to neurodegenerative
RT disease.";
RL Biochemistry 45:8009-8022(2006).
RN [10]
RP DISRUPTION PHENOTYPE.
RX PubMed=18209067; DOI=10.4049/jimmunol.180.3.1704;
RA Towne C.F., York I.A., Neijssen J., Karow M.L., Murphy A.J.,
RA Valenzuela D.M., Yancopoulos G.D., Neefjes J.J., Rock K.L.;
RT "Puromycin-sensitive aminopeptidase limits MHC class I presentation in
RT dendritic cells but does not affect CD8 T cell responses during viral
RT infections.";
RL J. Immunol. 180:1704-1712(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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.
CC {ECO:0000269|PubMed:7592939}.
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+) (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:7592939}.
CC Nucleus {ECO:0000269|PubMed:7592939}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest expression in brain,
CC particularly the striatum and hippocampus. Expressed in Sertoli cells.
CC {ECO:0000269|PubMed:10407043, ECO:0000269|PubMed:11376114,
CC ECO:0000269|PubMed:7592939}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit dwarfism, increased anxiety,
CC impaired pain responses and do not reproduce as well as wild-type mice.
CC More MHC class I molecules are displayed on dendritic cell surfaces.
CC {ECO:0000269|PubMed:10407043, ECO:0000269|PubMed:11376108,
CC ECO:0000269|PubMed:11376114, ECO:0000269|PubMed:18209067}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-46 is the initiator.
CC {ECO:0000305}.
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DR EMBL; U35646; AAC52409.1; -; mRNA.
DR EMBL; AL627445; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466556; EDL16075.1; -; Genomic_DNA.
DR EMBL; BC009653; AAH09653.1; -; mRNA.
DR EMBL; BC086798; AAH86798.1; -; mRNA.
DR EMBL; BC098212; AAH98212.1; -; mRNA.
DR EMBL; AK133898; BAE21917.1; -; mRNA.
DR CCDS; CCDS25317.1; -.
DR PIR; T10052; T10052.
DR RefSeq; NP_032968.2; NM_008942.2.
DR AlphaFoldDB; Q11011; -.
DR SMR; Q11011; -.
DR BioGRID; 202409; 22.
DR IntAct; Q11011; 6.
DR MINT; Q11011; -.
DR STRING; 10090.ENSMUSP00000001480; -.
DR MEROPS; M01.010; -.
DR GlyGen; Q11011; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q11011; -.
DR MetOSite; Q11011; -.
DR PhosphoSitePlus; Q11011; -.
DR SwissPalm; Q11011; -.
DR EPD; Q11011; -.
DR jPOST; Q11011; -.
DR MaxQB; Q11011; -.
DR PaxDb; 10090-ENSMUSP00000001480; -.
DR PeptideAtlas; Q11011; -.
DR ProteomicsDB; 291537; -.
DR Pumba; Q11011; -.
DR Antibodypedia; 8552; 306 antibodies from 29 providers.
DR DNASU; 19155; -.
DR Ensembl; ENSMUST00000001480.14; ENSMUSP00000001480.8; ENSMUSG00000001441.14.
DR GeneID; 19155; -.
DR KEGG; mmu:19155; -.
DR UCSC; uc007ldv.2; mouse.
DR AGR; MGI:1101358; -.
DR CTD; 9520; -.
DR MGI; MGI:1101358; Npepps.
DR VEuPathDB; HostDB:ENSMUSG00000001441; -.
DR eggNOG; KOG1046; Eukaryota.
DR GeneTree; ENSGT00940000155246; -.
DR InParanoid; Q11011; -.
DR OMA; MMEYVAI; -.
DR OrthoDB; 3085317at2759; -.
DR PhylomeDB; Q11011; -.
DR TreeFam; TF300395; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR BioGRID-ORCS; 19155; 4 hits in 78 CRISPR screens.
DR ChiTaRS; Npepps; mouse.
DR PRO; PR:Q11011; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q11011; Protein.
DR Bgee; ENSMUSG00000001441; Expressed in rostral migratory stream and 275 other cell types or tissues.
DR ExpressionAtlas; Q11011; baseline and differential.
DR Genevisible; Q11011; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004177; F:aminopeptidase activity; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
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:SF174; 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 Aminopeptidase; Cytoplasm; Hydrolase; Metal-binding; Metalloprotease;
KW Nitration; Nucleus; Protease; Reference proteome; Zinc.
FT CHAIN 1..920
FT /note="Puromycin-sensitive aminopeptidase"
FT /id="PRO_0000095117"
FT MOTIF 727..731
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 354
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 181
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 317..321
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 353
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 357
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 376
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT SITE 439
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT MOD_RES 465
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0007744|PubMed:16800626"
FT CONFLICT 185
FT /note="A -> P (in Ref. 1; AAC52409)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 920 AA; 103325 MW; BECF4139F074A356 CRC64;
MWLAAAVPSL ARRLLLLGPP PPPLLLLLSR SSRRRRRLHS LGLAAMPEKR PFERLPAEVS
PINYSLCLKP DLLDFTFEGK LEAAAQVRQA TNQIVMNCAD IDIITASYAP EGDEEIHATG
FNYQNEDEKV TLSFPSTLQT GTGTLKIDFV GELNDKMKGF YRSRYTTPAG EVRYAAVTQF
EATDARRAFP CWDEPAIKAT FDISLVVPKD RVALSNMNVI DRKPYPDDEN LVEVKFARTP
VMSTYLVAFV VGEYDFVETR SKDGVCVRVY TPVGKAEQGK FALEVAAKTL PFYKDYFNVP
YPLPKIDLIA IADFAAGAME NWGLVTYRET ALLIDPKNSC SSSRQWVALV VGHELAHQWF
GNLVTMEWWT HLWLNEGFAS WIEYLCVDHC FPEYDIWTQF VSADYTRAQE LDALDNSHPI
EVSVGHPSEV DEIFDAISYS KGASVIRMLH DYIGDKDFKK GMNMYLTKFQ QKNAATEDLW
ESLESASGKP IAAVMNTWTK QMGFPLIYVE AEQVEDDRVL KLSQKKFCAS GPYGGEDCPQ
WMVPITISTS EDPNQAKLKI LMDKPEMSVV LKNVKPDQWV KLNLGTVGFY RTQYSSAMLE
SLLPGIRDLS LPPVDRLGLQ NDLFSLARAG IISTVEVLKV MEAFVNEPNY TVWSDLSCNL
GILSTLLSHT DFYEEIQEFV KDVFSPIGER LGWDPKPGEG HLDALLRGLV LGKLGKAGHK
ATLEEARRRF KEHVEGKQIL SADLRSPVYL TVLKHGDGAT LDIMLKLHKQ ADMQEEKNRI
ERVLGATLSP ELIQKVLTFA LSEEVRPQDT VSVIGGVAGG SKHGRKAAWK FIKDNWEELH
NRYQGGFLIS RLIKLSVEGF AVDKMAGEVK AFFESHPAPS AERTIQQCCE NILLNAAWLK
RDADSIHQYL LQRKTSPPSV
//
