Full text data of PSME1
PSME1
(IFI5111)
[Confidence: high (present in two of the MS resources)]
Proteasome activator complex subunit 1 (11S regulator complex subunit alpha; REG-alpha; Activator of multicatalytic protease subunit 1; Interferon gamma up-regulated I-5111 protein; IGUP I-5111; Proteasome activator 28 subunit alpha; PA28a; PA28alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Proteasome activator complex subunit 1 (11S regulator complex subunit alpha; REG-alpha; Activator of multicatalytic protease subunit 1; Interferon gamma up-regulated I-5111 protein; IGUP I-5111; Proteasome activator 28 subunit alpha; PA28a; PA28alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00030154
IPI00030154 Proteasome activator complex subunit 1 The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins 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
IPI00030154 Proteasome activator complex subunit 1 The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins 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
Q06323
ID PSME1_HUMAN Reviewed; 249 AA.
AC Q06323; A6NJG9; Q6IBM2; Q9UEF4;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1995, sequence version 1.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Proteasome activator complex subunit 1;
DE AltName: Full=11S regulator complex subunit alpha;
DE Short=REG-alpha;
DE AltName: Full=Activator of multicatalytic protease subunit 1;
DE AltName: Full=Interferon gamma up-regulated I-5111 protein;
DE Short=IGUP I-5111;
DE AltName: Full=Proteasome activator 28 subunit alpha;
DE Short=PA28a;
DE Short=PA28alpha;
GN Name=PSME1; Synonyms=IFI5111;
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 1).
RC TISSUE=Lung fibroblast;
RX PubMed=8269930; DOI=10.1111/j.1432-1033.1993.tb18392.x;
RA Honore B., Leffers H., Madsen P., Celis J.E.;
RT "Interferon-gamma up-regulates a unique set of proteins in human
RT keratinocytes. Molecular cloning and expression of the cDNA encoding
RT the RGD-sequence-containing protein IGUP I-5111.";
RL Eur. J. Biochem. 218:421-430(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC TISSUE=Blood;
RX PubMed=8051173;
RA Realini C., Dubiel W., Pratt G., Ferrell K., Rechsteiner M.;
RT "Molecular cloning and expression of a gamma-interferon-inducible
RT activator of the multicatalytic protease.";
RL J. Biol. Chem. 269:20727-20732(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=10199920; DOI=10.1007/s002510050517;
RA McCusker D., Wilson M., Trowsdale J.;
RT "Organization of the genes encoding the human proteasome activators
RT PA28alpha and beta.";
RL Immunogenetics 49:438-445(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Spleen;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 43-118.
RX PubMed=9590240;
RA Kohda K., Ishibashi T., Shimbara N., Tanaka K., Matsuda Y.,
RA Kasahara M.;
RT "Characterization of the mouse PA28 activator complex gene family:
RT complete organizations of the three member genes and a physical map of
RT the approximately 150-kb region containing the alpha- and beta-subunit
RT genes.";
RL J. Immunol. 160:4923-4935(1998).
RN [11]
RP PROTEIN SEQUENCE OF 25-35; 191-197 AND 199-209.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [12]
RP SUBUNIT.
RX PubMed=9385652;
RA Johnston S.C., Whitby F.G., Realini C., Rechsteiner M., Hill C.P.;
RT "The proteasome 11S regulator subunit REG alpha (PA28 alpha) is a
RT heptamer.";
RL Protein Sci. 6:2469-2473(1997).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [14]
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).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=9403698; DOI=10.1038/37670;
RA Knowlton J.R., Johnston S.C., Whitby F.G., Realini C., Zhang Z.,
RA Rechsteiner M., Hill C.P.;
RT "Structure of the proteasome activator REGalpha (PA28alpha).";
RL Nature 390:639-643(1997).
CC -!- FUNCTION: Implicated in immunoproteasome assembly and required for
CC efficient antigen processing. The PA28 activator complex enhances
CC the generation of class I binding peptides by altering the
CC cleavage pattern of the proteasome.
CC -!- SUBUNIT: Heterodimer of PSME1 and PSME2, which forms a hexameric
CC ring. PSME1 can form homoheptamers.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q06323-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q06323-2; Sequence=VSP_046880;
CC Note=Gene prediction based on EST data;
CC -!- INDUCTION: By IFNG/IFN-gamma.
CC -!- SIMILARITY: Belongs to the PA28 family.
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DR EMBL; L07633; AAA16521.1; -; mRNA.
DR EMBL; U10360; AAA53230.1; -; Genomic_DNA.
DR EMBL; AF078829; AAF02217.1; -; Genomic_DNA.
DR EMBL; BT019337; AAV38144.1; -; mRNA.
DR EMBL; AK312211; BAG35144.1; -; mRNA.
DR EMBL; CR456780; CAG33061.1; -; mRNA.
DR EMBL; AL136295; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW66105.1; -; Genomic_DNA.
DR EMBL; BC000352; AAH00352.1; -; mRNA.
DR EMBL; BC007503; AAH07503.1; -; mRNA.
DR EMBL; AB007137; BAA28836.1; -; Genomic_DNA.
DR PIR; A54859; A54859.
DR RefSeq; NP_006254.1; NM_006263.3.
DR UniGene; Hs.75348; -.
DR PDB; 1AVO; X-ray; 2.80 A; A/C/E/G/I/K/M=4-63, B/D/F/H/J/L/N=104-242.
DR PDBsum; 1AVO; -.
DR ProteinModelPortal; Q06323; -.
DR SMR; Q06323; 4-63, 104-242.
DR IntAct; Q06323; 19.
DR MINT; MINT-5002728; -.
DR STRING; 9606.ENSP00000372155; -.
DR PhosphoSite; Q06323; -.
DR DMDM; 1170519; -.
DR DOSAC-COBS-2DPAGE; Q06323; -.
DR OGP; Q06323; -.
DR SWISS-2DPAGE; Q06323; -.
DR PaxDb; Q06323; -.
DR PRIDE; Q06323; -.
DR DNASU; 5720; -.
DR Ensembl; ENST00000206451; ENSP00000206451; ENSG00000092010.
DR Ensembl; ENST00000382708; ENSP00000372155; ENSG00000092010.
DR GeneID; 5720; -.
DR KEGG; hsa:5720; -.
DR UCSC; uc001wmh.3; human.
DR CTD; 5720; -.
DR GeneCards; GC14P024605; -.
DR HGNC; HGNC:9568; PSME1.
DR HPA; HPA006632; -.
DR MIM; 600654; gene.
DR neXtProt; NX_Q06323; -.
DR PharmGKB; PA33914; -.
DR eggNOG; NOG265006; -.
DR HOGENOM; HOG000282822; -.
DR HOVERGEN; HBG053745; -.
DR KO; K06696; -.
DR OMA; TQISKYY; -.
DR OrthoDB; EOG7GTT4C; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_13505; Proteasome mediated degradation of PAK-2p34.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_383; DNA Replication.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6850; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_71; Gene Expression.
DR EvolutionaryTrace; Q06323; -.
DR GeneWiki; PSME1; -.
DR GenomeRNAi; 5720; -.
DR NextBio; 22232; -.
DR PRO; PR:Q06323; -.
DR ArrayExpress; Q06323; -.
DR Bgee; Q06323; -.
DR CleanEx; HS_PSME1; -.
DR Genevestigator; Q06323; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0008537; C:proteasome activator complex; IEA:InterPro.
DR GO; GO:0000502; C:proteasome complex; TAS:ProtInc.
DR GO; GO:0061133; F:endopeptidase activator activity; IEA:Ensembl.
DR GO; GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; 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:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic 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:0006521; P:regulation of cellular amino acid metabolic process; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR Gene3D; 1.20.120.180; -; 1.
DR Gene3D; 1.20.5.120; -; 1.
DR InterPro; IPR009077; Proteasome_activ_pa28.
DR InterPro; IPR003186; Proteasome_activ_pa28_C.
DR InterPro; IPR003185; Proteasome_activ_pa28_N.
DR PANTHER; PTHR10660; PTHR10660; 1.
DR Pfam; PF02251; PA28_alpha; 1.
DR Pfam; PF02252; PA28_beta; 1.
DR SUPFAM; SSF47216; SSF47216; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Polymorphism; Proteasome;
KW Reference proteome.
FT CHAIN 1 249 Proteasome activator complex subunit 1.
FT /FTId=PRO_0000161779.
FT VAR_SEQ 224 249 AVLYDIILKNFEKLKKPRGETKGMIY -> VRRQGQGRGGQ
FT RQLSQATHSLTLQARG (in isoform 2).
FT /FTId=VSP_046880.
FT VARIANT 55 55 S -> N (in dbSNP:rs1803830).
FT /FTId=VAR_011993.
FT VARIANT 244 244 T -> K (in dbSNP:rs14930).
FT /FTId=VAR_011994.
FT HELIX 8 30
FT HELIX 32 45
FT HELIX 47 49
FT HELIX 108 137
FT HELIX 148 190
FT HELIX 196 232
FT HELIX 234 238
SQ SEQUENCE 249 AA; 28723 MW; 5E27727E5A0B0AAB CRC64;
MAMLRVQPEA QAKVDVFRED LCTKTENLLG SYFPKKISEL DAFLKEPALN EANLSNLKAP
LDIPVPDPVK EKEKEERKKQ QEKEDKDEKK KGEDEDKGPP CGPVNCNEKI VVLLQRLKPE
IKDVIEQLNL VTTWLQLQIP RIEDGNNFGV AVQEKVFELM TSLHTKLEGF HTQISKYFSE
RGDAVTKAAK QPHVGDYRQL VHELDEAEYR DIRLMVMEIR NAYAVLYDII LKNFEKLKKP
RGETKGMIY
//
ID PSME1_HUMAN Reviewed; 249 AA.
AC Q06323; A6NJG9; Q6IBM2; Q9UEF4;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1995, sequence version 1.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Proteasome activator complex subunit 1;
DE AltName: Full=11S regulator complex subunit alpha;
DE Short=REG-alpha;
DE AltName: Full=Activator of multicatalytic protease subunit 1;
DE AltName: Full=Interferon gamma up-regulated I-5111 protein;
DE Short=IGUP I-5111;
DE AltName: Full=Proteasome activator 28 subunit alpha;
DE Short=PA28a;
DE Short=PA28alpha;
GN Name=PSME1; Synonyms=IFI5111;
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 1).
RC TISSUE=Lung fibroblast;
RX PubMed=8269930; DOI=10.1111/j.1432-1033.1993.tb18392.x;
RA Honore B., Leffers H., Madsen P., Celis J.E.;
RT "Interferon-gamma up-regulates a unique set of proteins in human
RT keratinocytes. Molecular cloning and expression of the cDNA encoding
RT the RGD-sequence-containing protein IGUP I-5111.";
RL Eur. J. Biochem. 218:421-430(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC TISSUE=Blood;
RX PubMed=8051173;
RA Realini C., Dubiel W., Pratt G., Ferrell K., Rechsteiner M.;
RT "Molecular cloning and expression of a gamma-interferon-inducible
RT activator of the multicatalytic protease.";
RL J. Biol. Chem. 269:20727-20732(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=10199920; DOI=10.1007/s002510050517;
RA McCusker D., Wilson M., Trowsdale J.;
RT "Organization of the genes encoding the human proteasome activators
RT PA28alpha and beta.";
RL Immunogenetics 49:438-445(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Spleen;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 43-118.
RX PubMed=9590240;
RA Kohda K., Ishibashi T., Shimbara N., Tanaka K., Matsuda Y.,
RA Kasahara M.;
RT "Characterization of the mouse PA28 activator complex gene family:
RT complete organizations of the three member genes and a physical map of
RT the approximately 150-kb region containing the alpha- and beta-subunit
RT genes.";
RL J. Immunol. 160:4923-4935(1998).
RN [11]
RP PROTEIN SEQUENCE OF 25-35; 191-197 AND 199-209.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel
RT protein database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [12]
RP SUBUNIT.
RX PubMed=9385652;
RA Johnston S.C., Whitby F.G., Realini C., Rechsteiner M., Hill C.P.;
RT "The proteasome 11S regulator subunit REG alpha (PA28 alpha) is a
RT heptamer.";
RL Protein Sci. 6:2469-2473(1997).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [14]
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).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=9403698; DOI=10.1038/37670;
RA Knowlton J.R., Johnston S.C., Whitby F.G., Realini C., Zhang Z.,
RA Rechsteiner M., Hill C.P.;
RT "Structure of the proteasome activator REGalpha (PA28alpha).";
RL Nature 390:639-643(1997).
CC -!- FUNCTION: Implicated in immunoproteasome assembly and required for
CC efficient antigen processing. The PA28 activator complex enhances
CC the generation of class I binding peptides by altering the
CC cleavage pattern of the proteasome.
CC -!- SUBUNIT: Heterodimer of PSME1 and PSME2, which forms a hexameric
CC ring. PSME1 can form homoheptamers.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q06323-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q06323-2; Sequence=VSP_046880;
CC Note=Gene prediction based on EST data;
CC -!- INDUCTION: By IFNG/IFN-gamma.
CC -!- SIMILARITY: Belongs to the PA28 family.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; L07633; AAA16521.1; -; mRNA.
DR EMBL; U10360; AAA53230.1; -; Genomic_DNA.
DR EMBL; AF078829; AAF02217.1; -; Genomic_DNA.
DR EMBL; BT019337; AAV38144.1; -; mRNA.
DR EMBL; AK312211; BAG35144.1; -; mRNA.
DR EMBL; CR456780; CAG33061.1; -; mRNA.
DR EMBL; AL136295; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW66105.1; -; Genomic_DNA.
DR EMBL; BC000352; AAH00352.1; -; mRNA.
DR EMBL; BC007503; AAH07503.1; -; mRNA.
DR EMBL; AB007137; BAA28836.1; -; Genomic_DNA.
DR PIR; A54859; A54859.
DR RefSeq; NP_006254.1; NM_006263.3.
DR UniGene; Hs.75348; -.
DR PDB; 1AVO; X-ray; 2.80 A; A/C/E/G/I/K/M=4-63, B/D/F/H/J/L/N=104-242.
DR PDBsum; 1AVO; -.
DR ProteinModelPortal; Q06323; -.
DR SMR; Q06323; 4-63, 104-242.
DR IntAct; Q06323; 19.
DR MINT; MINT-5002728; -.
DR STRING; 9606.ENSP00000372155; -.
DR PhosphoSite; Q06323; -.
DR DMDM; 1170519; -.
DR DOSAC-COBS-2DPAGE; Q06323; -.
DR OGP; Q06323; -.
DR SWISS-2DPAGE; Q06323; -.
DR PaxDb; Q06323; -.
DR PRIDE; Q06323; -.
DR DNASU; 5720; -.
DR Ensembl; ENST00000206451; ENSP00000206451; ENSG00000092010.
DR Ensembl; ENST00000382708; ENSP00000372155; ENSG00000092010.
DR GeneID; 5720; -.
DR KEGG; hsa:5720; -.
DR UCSC; uc001wmh.3; human.
DR CTD; 5720; -.
DR GeneCards; GC14P024605; -.
DR HGNC; HGNC:9568; PSME1.
DR HPA; HPA006632; -.
DR MIM; 600654; gene.
DR neXtProt; NX_Q06323; -.
DR PharmGKB; PA33914; -.
DR eggNOG; NOG265006; -.
DR HOGENOM; HOG000282822; -.
DR HOVERGEN; HBG053745; -.
DR KO; K06696; -.
DR OMA; TQISKYY; -.
DR OrthoDB; EOG7GTT4C; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_13505; Proteasome mediated degradation of PAK-2p34.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR Reactome; REACT_383; DNA Replication.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6850; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_71; Gene Expression.
DR EvolutionaryTrace; Q06323; -.
DR GeneWiki; PSME1; -.
DR GenomeRNAi; 5720; -.
DR NextBio; 22232; -.
DR PRO; PR:Q06323; -.
DR ArrayExpress; Q06323; -.
DR Bgee; Q06323; -.
DR CleanEx; HS_PSME1; -.
DR Genevestigator; Q06323; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0008537; C:proteasome activator complex; IEA:InterPro.
DR GO; GO:0000502; C:proteasome complex; TAS:ProtInc.
DR GO; GO:0061133; F:endopeptidase activator activity; IEA:Ensembl.
DR GO; GO:0031145; P:anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; TAS:Reactome.
DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; 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:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0016071; P:mRNA metabolic process; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic 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:0006521; P:regulation of cellular amino acid metabolic process; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR Gene3D; 1.20.120.180; -; 1.
DR Gene3D; 1.20.5.120; -; 1.
DR InterPro; IPR009077; Proteasome_activ_pa28.
DR InterPro; IPR003186; Proteasome_activ_pa28_C.
DR InterPro; IPR003185; Proteasome_activ_pa28_N.
DR PANTHER; PTHR10660; PTHR10660; 1.
DR Pfam; PF02251; PA28_alpha; 1.
DR Pfam; PF02252; PA28_beta; 1.
DR SUPFAM; SSF47216; SSF47216; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Polymorphism; Proteasome;
KW Reference proteome.
FT CHAIN 1 249 Proteasome activator complex subunit 1.
FT /FTId=PRO_0000161779.
FT VAR_SEQ 224 249 AVLYDIILKNFEKLKKPRGETKGMIY -> VRRQGQGRGGQ
FT RQLSQATHSLTLQARG (in isoform 2).
FT /FTId=VSP_046880.
FT VARIANT 55 55 S -> N (in dbSNP:rs1803830).
FT /FTId=VAR_011993.
FT VARIANT 244 244 T -> K (in dbSNP:rs14930).
FT /FTId=VAR_011994.
FT HELIX 8 30
FT HELIX 32 45
FT HELIX 47 49
FT HELIX 108 137
FT HELIX 148 190
FT HELIX 196 232
FT HELIX 234 238
SQ SEQUENCE 249 AA; 28723 MW; 5E27727E5A0B0AAB CRC64;
MAMLRVQPEA QAKVDVFRED LCTKTENLLG SYFPKKISEL DAFLKEPALN EANLSNLKAP
LDIPVPDPVK EKEKEERKKQ QEKEDKDEKK KGEDEDKGPP CGPVNCNEKI VVLLQRLKPE
IKDVIEQLNL VTTWLQLQIP RIEDGNNFGV AVQEKVFELM TSLHTKLEGF HTQISKYFSE
RGDAVTKAAK QPHVGDYRQL VHELDEAEYR DIRLMVMEIR NAYAVLYDII LKNFEKLKKP
RGETKGMIY
//
MIM
600654
*RECORD*
*FIELD* NO
600654
*FIELD* TI
*600654 PROTEASOME ACTIVATOR SUBUNIT 1; PSME1
;;PROTEASOME ACTIVATOR 28-ALPHA;;
PA28-ALPHA; PA28A;;
read moreINTERFERON-GAMMA-INDUCIBLE PROTEIN 5111; IFI5111;;
MCP ACTIVATOR, 29-KD SUBUNIT
*FIELD* TX
Interferon-gamma (147570) upregulates transcription of perhaps 15 to 20
different proteins. Honore et al. (1993) identified one such protein and
isolated its cDNA from a library derived from MRC-5 V2 fibroblasts. The
cDNA, designated IGUP-5111, encodes a polypeptide with a predicted
weight of 28.7 kD. Subsequently, Realini et al. (1994) cloned the
identical protein which they identified as a gamma-interferon-inducible
activator of multicatalytic protease (MCP). MCP is an ATP-dependent
protease that degrades proteins conjugated to ubiquitin (191339). In the
presence of ATP, MCP associates with a particle containing at least 15
different polypeptides to form a 26S enzyme. An activator composed of 2
distinct subunits has been isolated from red cells that can stimulate
MCP by binding reversibly to it in the absence of nucleotides. The 2
subunits, of 29 and 31 kD, are complexed as a hexamer. The IFI5111 cDNA
represents the smaller subunit. The predicted protein is 249 amino acids
in length and contains KEKE motifs which are also found in 2 MCP
subunits and in various chaperonins, including hsp90 (see 140571), hsp70
(see 140550), and calnexin (114217). The recombinantly expressed protein
was shown to react with antibodies to the red blood cell activator and
had the expected electrophoretic properties. It was also able to bind
and activate MCP. As expected from the study by Honore et al. (1993),
gamma-interferon treatment of HeLa cells resulted in synthesis of the
29-kD MCP activator.
The PA28 complex is an alternative proteasome activator that does not
employ the use of ubiquitin. The complex is composed of 2 homologous
subunits called PA28-alpha (PSME1) and -beta (PSME2; 602161), which form
a hexameric ring. The PA28 complex is expressed constitutively in
antigen-presenting cells, its expression is upregulated by
interferon-gamma (147570), and it appears to be involved in the
presentation of endogenous antigens by MHC class I molecules.
McCusker et al. (1999) sequenced the PSME1 and PSME2 genes. They found
that each gene comprises 11 exons, consistent with gene duplication
during vertebrate evolution. The intron/exon organization of the genes
was highly conserved, the major difference being the absence of the exon
encoding the lysine and glutamic acid-rich KEKE motif in the gene
product of the PSME2 gene.
McCusker et al. (1997) demonstrated that the genes encoding the alpha
and beta subunits of the PA28 complex are closely linked on 14q11.2,
within 1 Mb of the beta proteasome locus PSMB5 (600306). The PSMB5 gene
had been mapped to 14q11.2 by Belich et al. (1994). McCusker et al.
(1997) used 2-color fluorescence in situ hybridization to determine the
relative proximity of PSMB5 and PSME1. The PSME1 and PSME2 genes were
found to lie within 30 to 40 kb of each other on band 14q11.2.
In vitro, PA28 binds and activates proteasomes. Preckel et al. (1999)
demonstrated that mice with a disrupted Pa28b gene lack Pa28a and Pa28b
polypeptides, demonstrating that Pa28 functions as a heterooligomer in
vivo. Processing of antigenic epitopes derived from exogenous or
endogenous antigens is altered in Pa28 -/- mice. Cytotoxic T-lymphocyte
responses are impaired and assembly of immunoproteasomes is greatly
inhibited in mice lacking Pa28. These results showed that PA28 is
necessary for immunoproteasome assembly and is required for efficient
antigen processing, thus demonstrating the importance of PA28-mediated
proteasome function in immune responses.
*FIELD* RF
1. Belich, M. P.; Glynne, R. J.; Senger, G.; Sheer, D.; Trowsdale,
J.: Proteasome components with reciprocal expression to that of the
MHC-encoded LMP proteins. Curr. Biol. 4: 769-776, 1994.
2. Honore, B.; Leffers, H.; Madsen, P.; Celis, J. E.: Interferon-gamma
up-regulates a unique set of proteins in human keratinocytes: molecular
cloning and expression of the cDNA encoding the RGD-sequence-containing
protein IGUP I5111. Europ. J. Biochem. 218: 421-430, 1993.
3. McCusker, D.; Jones, T.; Sheer, D.; Trowsdale, J.: Genetic relationships
of the genes encoding the human proteasome beta subunits and the proteasome
PA28 complex. Genomics 45: 362-367, 1997.
4. McCusker, D.; Wilson, M.; Trowsdale, J.: Organization of the genes
encoding the human proteasome activators PA28-alpha and beta. Immunogenetics 49:
438-445, 1999.
5. Preckel, T.; Fung-Leung, W.-P.; Cai, Z.; Vitiello, A.; Salter-Cid,
L.; Winqvist, O.; Wolfe, T. G.; Von Herrath, M.; Angulo, A.; Ghazal,
P.; Lee, J.-D.; Fourie, A. M.; Wu, Y.; Pang, J.; Ngo, K.; Peterson,
P. A.; Fruh, K.; Yang, Y.: Impaired immunoproteasome assembly and
immune responses in PA28 -/- mice. Science 286: 2162-2165, 1999.
6. Realini, C.; Dubiel, W.; Pratt, G.; Ferrell, K.; Rechsteiner, M.
: Molecular cloning and expression of a gamma-interferon-inducible
activator of the multicatalytic protease. J. Biol. Chem. 269: 20727-20732,
1994.
*FIELD* CN
Victor A. McKusick - updated: 6/8/1999
Victor A. McKusick - updated: 12/10/1997
*FIELD* CD
Alan F. Scott: 7/18/1995
*FIELD* ED
carol: 05/12/2004
terry: 3/21/2001
alopez: 12/9/1999
carol: 9/29/1999
mgross: 7/22/1999
jlewis: 6/17/1999
terry: 6/8/1999
carol: 5/24/1999
dkim: 9/21/1998
carol: 8/20/1998
dkim: 7/30/1998
mark: 12/10/1997
joanna: 12/8/1995
mark: 8/18/1995
*RECORD*
*FIELD* NO
600654
*FIELD* TI
*600654 PROTEASOME ACTIVATOR SUBUNIT 1; PSME1
;;PROTEASOME ACTIVATOR 28-ALPHA;;
PA28-ALPHA; PA28A;;
read moreINTERFERON-GAMMA-INDUCIBLE PROTEIN 5111; IFI5111;;
MCP ACTIVATOR, 29-KD SUBUNIT
*FIELD* TX
Interferon-gamma (147570) upregulates transcription of perhaps 15 to 20
different proteins. Honore et al. (1993) identified one such protein and
isolated its cDNA from a library derived from MRC-5 V2 fibroblasts. The
cDNA, designated IGUP-5111, encodes a polypeptide with a predicted
weight of 28.7 kD. Subsequently, Realini et al. (1994) cloned the
identical protein which they identified as a gamma-interferon-inducible
activator of multicatalytic protease (MCP). MCP is an ATP-dependent
protease that degrades proteins conjugated to ubiquitin (191339). In the
presence of ATP, MCP associates with a particle containing at least 15
different polypeptides to form a 26S enzyme. An activator composed of 2
distinct subunits has been isolated from red cells that can stimulate
MCP by binding reversibly to it in the absence of nucleotides. The 2
subunits, of 29 and 31 kD, are complexed as a hexamer. The IFI5111 cDNA
represents the smaller subunit. The predicted protein is 249 amino acids
in length and contains KEKE motifs which are also found in 2 MCP
subunits and in various chaperonins, including hsp90 (see 140571), hsp70
(see 140550), and calnexin (114217). The recombinantly expressed protein
was shown to react with antibodies to the red blood cell activator and
had the expected electrophoretic properties. It was also able to bind
and activate MCP. As expected from the study by Honore et al. (1993),
gamma-interferon treatment of HeLa cells resulted in synthesis of the
29-kD MCP activator.
The PA28 complex is an alternative proteasome activator that does not
employ the use of ubiquitin. The complex is composed of 2 homologous
subunits called PA28-alpha (PSME1) and -beta (PSME2; 602161), which form
a hexameric ring. The PA28 complex is expressed constitutively in
antigen-presenting cells, its expression is upregulated by
interferon-gamma (147570), and it appears to be involved in the
presentation of endogenous antigens by MHC class I molecules.
McCusker et al. (1999) sequenced the PSME1 and PSME2 genes. They found
that each gene comprises 11 exons, consistent with gene duplication
during vertebrate evolution. The intron/exon organization of the genes
was highly conserved, the major difference being the absence of the exon
encoding the lysine and glutamic acid-rich KEKE motif in the gene
product of the PSME2 gene.
McCusker et al. (1997) demonstrated that the genes encoding the alpha
and beta subunits of the PA28 complex are closely linked on 14q11.2,
within 1 Mb of the beta proteasome locus PSMB5 (600306). The PSMB5 gene
had been mapped to 14q11.2 by Belich et al. (1994). McCusker et al.
(1997) used 2-color fluorescence in situ hybridization to determine the
relative proximity of PSMB5 and PSME1. The PSME1 and PSME2 genes were
found to lie within 30 to 40 kb of each other on band 14q11.2.
In vitro, PA28 binds and activates proteasomes. Preckel et al. (1999)
demonstrated that mice with a disrupted Pa28b gene lack Pa28a and Pa28b
polypeptides, demonstrating that Pa28 functions as a heterooligomer in
vivo. Processing of antigenic epitopes derived from exogenous or
endogenous antigens is altered in Pa28 -/- mice. Cytotoxic T-lymphocyte
responses are impaired and assembly of immunoproteasomes is greatly
inhibited in mice lacking Pa28. These results showed that PA28 is
necessary for immunoproteasome assembly and is required for efficient
antigen processing, thus demonstrating the importance of PA28-mediated
proteasome function in immune responses.
*FIELD* RF
1. Belich, M. P.; Glynne, R. J.; Senger, G.; Sheer, D.; Trowsdale,
J.: Proteasome components with reciprocal expression to that of the
MHC-encoded LMP proteins. Curr. Biol. 4: 769-776, 1994.
2. Honore, B.; Leffers, H.; Madsen, P.; Celis, J. E.: Interferon-gamma
up-regulates a unique set of proteins in human keratinocytes: molecular
cloning and expression of the cDNA encoding the RGD-sequence-containing
protein IGUP I5111. Europ. J. Biochem. 218: 421-430, 1993.
3. McCusker, D.; Jones, T.; Sheer, D.; Trowsdale, J.: Genetic relationships
of the genes encoding the human proteasome beta subunits and the proteasome
PA28 complex. Genomics 45: 362-367, 1997.
4. McCusker, D.; Wilson, M.; Trowsdale, J.: Organization of the genes
encoding the human proteasome activators PA28-alpha and beta. Immunogenetics 49:
438-445, 1999.
5. Preckel, T.; Fung-Leung, W.-P.; Cai, Z.; Vitiello, A.; Salter-Cid,
L.; Winqvist, O.; Wolfe, T. G.; Von Herrath, M.; Angulo, A.; Ghazal,
P.; Lee, J.-D.; Fourie, A. M.; Wu, Y.; Pang, J.; Ngo, K.; Peterson,
P. A.; Fruh, K.; Yang, Y.: Impaired immunoproteasome assembly and
immune responses in PA28 -/- mice. Science 286: 2162-2165, 1999.
6. Realini, C.; Dubiel, W.; Pratt, G.; Ferrell, K.; Rechsteiner, M.
: Molecular cloning and expression of a gamma-interferon-inducible
activator of the multicatalytic protease. J. Biol. Chem. 269: 20727-20732,
1994.
*FIELD* CN
Victor A. McKusick - updated: 6/8/1999
Victor A. McKusick - updated: 12/10/1997
*FIELD* CD
Alan F. Scott: 7/18/1995
*FIELD* ED
carol: 05/12/2004
terry: 3/21/2001
alopez: 12/9/1999
carol: 9/29/1999
mgross: 7/22/1999
jlewis: 6/17/1999
terry: 6/8/1999
carol: 5/24/1999
dkim: 9/21/1998
carol: 8/20/1998
dkim: 7/30/1998
mark: 12/10/1997
joanna: 12/8/1995
mark: 8/18/1995