ID   PSA1_HUMAN              Reviewed;         263 AA.
AC   P25786; A8K400; Q9BRV9;
DT   01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1992, sequence version 1.
DT   25-JAN-2012, entry version 141.
DE   RecName: Full=Proteasome subunit alpha type-1;
DE            EC=3.4.25.1;
DE   AltName: Full=30 kDa prosomal protein;
DE            Short=PROS-30;
DE   AltName: Full=Macropain subunit C2;
DE   AltName: Full=Multicatalytic endopeptidase complex subunit C2;
DE   AltName: Full=Proteasome component C2;
DE   AltName: Full=Proteasome nu chain;
GN   Name=PSMA1; Synonyms=HC2, NU, PROS30, PSC2;
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] (ISOFORM SHORT).
RX   MEDLINE=91363412; PubMed=1888762; DOI=10.1016/0167-4838(91)90020-Z;
RA   DeMartino G.N., Orth K., McCullough M.L., Lee L.W., Munn T.Z.,
RA   Moomaw C.R., Dawson P.A., Slaughter C.A.;
RT   "The primary structures of four subunits of the human, high-molecular-
RT   weight proteinase, macropain (proteasome), are distinct but
RT   homologous.";
RL   Biochim. Biophys. Acta 1079:29-38(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RX   MEDLINE=91223105; PubMed=2025653; DOI=10.1016/0167-4781(91)90090-9;
RA   Tamura T., Lee D.H., Osaka F., Fujiwara T., Shin S., Chung C.H.,
RA   Tanaka K., Ichihara A.;
RT   "Molecular cloning and sequence analysis of cDNAs for five major
RT   subunits of human proteasomes (multi-catalytic proteinase
RT   complexes).";
RL   Biochim. Biophys. Acta 1089:95-102(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX   MEDLINE=93013039; PubMed=1398136; DOI=10.1016/0378-1119(92)90098-A;
RA   Silva-Pereira I., Bey F., Coux O., Scherrer K.;
RT   "Two mRNAs exist for the Hs PROS-30 gene encoding a component of human
RT   prosomes.";
RL   Gene 120:235-242(1992).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC   TISSUE=Bone marrow, Brain, Ovary, Placenta, and Prostate;
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   [7]
RP   PROTEIN SEQUENCE OF 4-18; 63-82; 97-107 AND 244-256, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA   Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL   Submitted (DEC-2008) to UniProtKB.
RN   [8]
RP   PROTEIN SEQUENCE OF 63-82.
RX   PubMed=7811265; DOI=10.1006/bbrc.1994.2876;
RA   Kristensen P., Johnsen A.H., Uerkvitz W., Tanaka K., Hendil K.B.;
RT   "Human proteasome subunits from 2-dimensional gels identified by
RT   partial sequencing.";
RL   Biochem. Biophys. Res. Commun. 205:1785-1789(1994).
RN   [9]
RP   INDUCTION, AND MASS SPECTROMETRY.
RX   PubMed=17127214; DOI=10.1016/S1672-0229(06)60029-6;
RA   Deng S., Xing T., Zhou H., Xiong R., Lu Y., Wen B., Liu S., Yang J.;
RT   "Comparative proteome analysis of breast cancer and adjacent normal
RT   breast tissues in human.";
RL   Genomics Proteomics Bioinformatics 4:165-172(2006).
RN   [10]
RP   INDUCTION.
RX   PubMed=16317774; DOI=10.1002/pmic.200500218;
RA   Cui F., Wang Y., Wang J., Wei K., Hu J., Liu F., Wang H., Zhao X.,
RA   Zhang X., Yang X.;
RT   "The up-regulation of proteasome subunits and lysosomal proteases in
RT   hepatocellular carcinomas of the HBx gene knockin transgenic mice.";
RL   Proteomics 6:498-504(2006).
RN   [11]
RP   INTERACTION WITH NOTCH3.
RX   PubMed=17292860; DOI=10.1016/j.bbrc.2007.01.151;
RA   Zhang Y., Jia L., Lee S.J., Wang M.M.;
RT   "Conserved signal peptide of Notch3 inhibits interaction with
RT   proteasome.";
RL   Biochem. Biophys. Res. Commun. 355:245-251(2007).
RN   [12]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RC   TISSUE=Embryonic kidney;
RX   PubMed=17323924; DOI=10.1021/bi061994u;
RA   Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.;
RT   "Mass spectrometric characterization of the affinity-purified human
RT   26S proteasome complex.";
RL   Biochemistry 46:3553-3565(2007).
RN   [13]
RP   INDUCTION, AND MASS SPECTROMETRY.
RX   PubMed=17004105; DOI=10.1007/s10549-006-9393-7;
RA   Deng S., Zhou H., Xiong R., Lu Y., Yan D., Xing T., Dong L., Tang E.,
RA   Yang H.;
RT   "Over-expression of genes and proteins of ubiquitin specific
RT   peptidases (USPs) and proteasome subunits (PSs) in breast cancer
RT   tissue observed by the methods of RFDD-PCR and proteomics.";
RL   Breast Cancer Res. Treat. 104:21-30(2007).
RN   [14]
RP   UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-115 AND LYS-208, AND MASS
RP   SPECTROMETRY.
RX   PubMed=18781797; DOI=10.1021/pr800468j;
RA   Meierhofer D., Wang X., Huang L., Kaiser P.;
RT   "Quantitative analysis of global ubiquitination in HeLa cells by mass
RT   spectrometry.";
RL   J. Proteome Res. 7:4566-4576(2008).
RN   [15]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [16]
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: The proteasome is a multicatalytic proteinase complex
CC       which is characterized by its ability to cleave peptides with Arg,
CC       Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or
CC       slightly basic pH. The proteasome has an ATP-dependent proteolytic
CC       activity. Mediates the lipopolysaccharide-induced signal
CC       transduction in the macrophage proteasome (By similarity). Might
CC       be involved in the anti-inflammatory response of macrophages
CC       during the interaction with C.albicans heat-inactivated cells (By
CC       similarity).
CC   -!- CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad
CC       specificity.
CC   -!- SUBUNIT: The 26S proteasome consists of a 20S proteasome core and
CC       two 19S regulatory subunits. The 20S proteasome core is composed
CC       of 28 subunits that are arranged in four stacked rings, resulting
CC       in a barrel-shaped structure. The two end rings are each formed by
CC       seven alpha subunits, and the two central rings are each formed by
CC       seven beta subunits. The catalytic chamber with the active sites
CC       is on the inside of the barrel. Interacts with bacterial
CC       lipopolysaccharide (LPS) (By similarity). Interacts with NOTCH3.
CC   -!- INTERACTION:
CC       P25787:PSMA2; NbExp=5; IntAct=EBI-359352, EBI-603262;
CC       P25788:PSMA3; NbExp=3; IntAct=EBI-359352, EBI-348380;
CC       P25789:PSMA4; NbExp=3; IntAct=EBI-359352, EBI-359310;
CC       O14818:PSMA7; NbExp=7; IntAct=EBI-359352, EBI-603272;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Short;
CC         IsoId=P25786-1; Sequence=Displayed;
CC       Name=Long;
CC         IsoId=P25786-2; Sequence=VSP_005279;
CC   -!- INDUCTION: Induced in breast cancer tissue (at protein level). Up-
CC       regulated in liver tumor tissues.
CC   -!- SIMILARITY: Belongs to the peptidase T1A family.
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DR   EMBL; X61969; CAA43961.1; -; mRNA.
DR   EMBL; D00759; BAA00656.1; -; mRNA.
DR   EMBL; M64992; AAA92734.1; -; mRNA.
DR   EMBL; AK290765; BAF83454.1; -; mRNA.
DR   EMBL; CH471064; EAW68479.1; -; Genomic_DNA.
DR   EMBL; BC002577; AAH02577.1; -; mRNA.
DR   EMBL; BC005932; AAH05932.1; -; mRNA.
DR   EMBL; BC008472; AAH08472.1; -; mRNA.
DR   EMBL; BC009576; AAH09576.1; -; mRNA.
DR   EMBL; BC015105; AAH15105.1; -; mRNA.
DR   EMBL; BC015356; AAH15356.1; -; mRNA.
DR   EMBL; BC022372; AAH22372.1; -; mRNA.
DR   IPI; IPI00016832; -.
DR   IPI; IPI00472442; -.
DR   PIR; JC1445; JC1445.
DR   RefSeq; NP_002777.1; NM_002786.3.
DR   RefSeq; NP_683877.1; NM_148976.2.
DR   UniGene; Hs.102798; -.
DR   ProteinModelPortal; P25786; -.
DR   SMR; P25786; 4-241.
DR   DIP; DIP-29369N; -.
DR   IntAct; P25786; 49.
DR   MINT; MINT-1155600; -.
DR   STRING; P25786; -.
DR   MEROPS; T01.976; -.
DR   PhosphoSite; P25786; -.
DR   DMDM; 130848; -.
DR   Aarhus/Ghent-2DPAGE; 2223; IEF.
DR   OGP; P25786; -.
DR   REPRODUCTION-2DPAGE; IPI00016832; -.
DR   PRIDE; P25786; -.
DR   Ensembl; ENST00000249924; ENSP00000249924; ENSG00000129084.
DR   Ensembl; ENST00000396393; ENSP00000379675; ENSG00000129084.
DR   GeneID; 5682; -.
DR   KEGG; hsa:5682; -.
DR   UCSC; uc001mlk.1; human.
DR   UCSC; uc001mll.1; human.
DR   CTD; 5682; -.
DR   GeneCards; GC11M014526; -.
DR   H-InvDB; HIX0009467; -.
DR   HGNC; HGNC:9530; PSMA1.
DR   HPA; HPA037646; -.
DR   MIM; 602854; gene.
DR   neXtProt; NX_P25786; -.
DR   eggNOG; prNOG15820; -.
DR   HOVERGEN; HBG105373; -.
DR   OMA; KGPHIYQ; -.
DR   OrthoDB; EOG4S1T7S; -.
DR   PhylomeDB; P25786; -.
DR   Reactome; REACT_111102; Signal Transduction.
DR   Reactome; REACT_111217; Metabolism.
DR   Reactome; REACT_13505; Proteasome mediated degradation of PAK-2p34.
DR   Reactome; REACT_152; Cell Cycle, Mitotic.
DR   Reactome; REACT_1538; Cell Cycle Checkpoints.
DR   Reactome; REACT_383; DNA Replication.
DR   Reactome; REACT_578; Apoptosis.
DR   Reactome; REACT_6185; HIV Infection.
DR   Reactome; REACT_6850; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR   Reactome; REACT_6900; Immune System.
DR   NextBio; 22062; -.
DR   ArrayExpress; P25786; -.
DR   Bgee; P25786; -.
DR   CleanEx; HS_PSMA1; -.
DR   Genevestigator; P25786; -.
DR   GermOnline; ENSG00000129084; Homo sapiens.
DR   GO; GO:0005813; C:centrosome; IDA:HPA.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005844; C:polysome; TAS:ProtInc.
DR   GO; GO:0019773; C:proteasome core complex, alpha-subunit complex; IEA:InterPro.
DR   GO; GO:0005515; F:protein binding; IPI:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; TAS:ProtInc.
DR   GO; GO:0004298; F:threonine-type endopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
DR   GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR   GO; GO:0006915; P:apoptotic process; TAS:Reactome.
DR   GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; TAS:Reactome.
DR   GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome.
DR   GO; GO:0000216; P:M/G1 transition of mitotic cell cycle; TAS:Reactome.
DR   GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR   GO; GO:0051436; P:negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; TAS:Reactome.
DR   GO; GO:0051437; P:positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; TAS:Reactome.
DR   GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR   GO; GO:0042981; P:regulation of apoptotic process; TAS:Reactome.
DR   GO; GO:0006521; P:regulation of cellular amino acid metabolic process; TAS:Reactome.
DR   GO; GO:0000084; P:S phase of mitotic cell cycle; TAS:Reactome.
DR   GO; GO:0016032; P:viral reproduction; TAS:Reactome.
DR   InterPro; IPR000426; Proteasome_asu_N.
DR   InterPro; IPR023332; Proteasome_suA-type.
DR   InterPro; IPR001353; Proteasome_sua/b.
DR   KO; K02725; -.
DR   Pfam; PF00227; Proteasome; 1.
DR   Pfam; PF10584; Proteasome_A_N; 1.
DR   SMART; SM00948; Proteasome_A_N; 1.
DR   PROSITE; PS00388; PROTEASOME_A_1; 1.
DR   PROSITE; PS51475; PROTEASOME_A_2; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Complete proteome; Cytoplasm;
KW   Direct protein sequencing; Hydrolase; Immunity; Isopeptide bond;
KW   Nucleus; Phosphoprotein; Protease; Proteasome; Reference proteome;
KW   Threonine protease; Ubl conjugation.
FT   CHAIN         1    263       Proteasome subunit alpha type-1.
FT                                /FTId=PRO_0000124060.
FT   MOD_RES       1      1       N-acetylmethionine.
FT   MOD_RES      14     14       Phosphoserine.
FT   CROSSLNK    115    115       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ubiquitin).
FT   CROSSLNK    208    208       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ubiquitin).
FT   VAR_SEQ       1      1       M -> MQLSKVK (in isoform Long).
FT                                /FTId=VSP_005279.
FT   CONFLICT     14     15       SP -> TA (in Ref. 3; AAA92734).
FT   CONFLICT     37     37       G -> V (in Ref. 6; AAH05932).
SQ   SEQUENCE   263 AA;  29556 MW;  3F159C5BCEFE8DED CRC64;
     MFRNQYDNDV TVWSPQGRIH QIEYAMEAVK QGSATVGLKS KTHAVLVALK RAQSELAAHQ
     KKILHVDNHI GISIAGLTAD ARLLCNFMRQ ECLDSRFVFD RPLPVSRLVS LIGSKTQIPT
     QRYGRRPYGV GLLIAGYDDM GPHIFQTCPS ANYFDCRAMS IGARSQSART YLERHMSEFM
     ECNLNELVKH GLRALRETLP AEQDLTTKNV SIGIVGKDLE FTIYDDDDVS PFLEGLEERP
     QRKAQPAQPA DEPAEKADEP MEH
//