Full text data of PSMB5
PSMB5
(LMPX, MB1, X)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Proteasome subunit beta type-5; 3.4.25.1 (Macropain epsilon chain; Multicatalytic endopeptidase complex epsilon chain; Proteasome chain 6; Proteasome epsilon chain; Proteasome subunit MB1; Proteasome subunit X; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Proteasome subunit beta type-5; 3.4.25.1 (Macropain epsilon chain; Multicatalytic endopeptidase complex epsilon chain; Proteasome chain 6; Proteasome epsilon chain; Proteasome subunit MB1; Proteasome subunit X; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P28074
ID PSB5_HUMAN Reviewed; 263 AA.
AC P28074; B2R4N9; B4DUM9; D3DS43; E9PAV2; Q16242; Q6PEW2; Q7Z3B5;
read moreAC Q86T01; Q9TNN9;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 3.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Proteasome subunit beta type-5;
DE EC=3.4.25.1;
DE AltName: Full=Macropain epsilon chain;
DE AltName: Full=Multicatalytic endopeptidase complex epsilon chain;
DE AltName: Full=Proteasome chain 6;
DE AltName: Full=Proteasome epsilon chain;
DE AltName: Full=Proteasome subunit MB1;
DE AltName: Full=Proteasome subunit X;
DE Flags: Precursor;
GN Name=PSMB5; Synonyms=LMPX, MB1, X;
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 [GENOMIC DNA].
RX PubMed=8753855; DOI=10.1007/s002510050121;
RA Abdulla S., Beck S., Belich M., Jackson A., Nakamura T., Trowsdale J.;
RT "Divergent intron arrangement in the MB1/LMP7 proteasome gene pair.";
RL Immunogenetics 44:254-258(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skeletal muscle;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Endometrial adenocarcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
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 [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] (ISOFORMS 1 AND 3).
RC TISSUE=Embryonic stem cell, Hypothalamus, and Skin;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-203 (ISOFORM 2).
RC TISSUE=Cervix carcinoma;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-263 (ISOFORM 1), AND INDUCTION.
RX PubMed=8066462; DOI=10.1126/science.8066462;
RA Akiyama K.-Y., Yokota K.-Y., Kagawa S., Shimbara N., Tamura T.,
RA Akioka H., Nothwang H.G., Noda C., Tanaka K., Ichihara A.;
RT "cDNA cloning and interferon gamma down-regulation of proteasomal
RT subunits X and Y.";
RL Science 265:1231-1234(1994).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 49-263 (ISOFORM 1).
RX PubMed=7820546; DOI=10.1016/S0960-9822(00)00174-3;
RA Belich M.P., Glynne R.J., Senger G., Sheer D., Trowsdale J.;
RT "Proteasome components with reciprocal expression to that of the MHC-
RT encoded LMP proteins.";
RL Curr. Biol. 4:769-776(1994).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 56-263 (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 [11]
RP PROTEIN SEQUENCE OF 60-85.
RX PubMed=2306472; DOI=10.1016/0167-4838(90)90165-C;
RA Lee L.W., Moomaw C.R., Orth K., McGuire M.J., DeMartino G.N.,
RA Slaughter C.A.;
RT "Relationships among the subunits of the high molecular weight
RT proteinase, macropain (proteasome).";
RL Biochim. Biophys. Acta 1037:178-185(1990).
RN [12]
RP PROTEIN SEQUENCE OF 201-216 AND 226-239.
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 [13]
RP PROTEIN SEQUENCE OF 201-216, AND SUBUNIT.
RC TISSUE=Kidney;
RX PubMed=8163024; DOI=10.1016/0014-5793(94)80612-8;
RA Akiyama K., Kagawa S., Tamura T., Shimbara N., Takashina M.,
RA Kristensen P., Hendil K.B., Tanaka K., Ichihara A.;
RT "Replacement of proteasome subunits X and Y by LMP7 and LMP2 induced
RT by interferon-gamma for acquirement of the functional diversity
RT responsible for antigen processing.";
RL FEBS Lett. 343:85-88(1994).
RN [14]
RP ERRATUM.
RX PubMed=7864893; DOI=10.1006/bbrc.1995.1294;
RA Kristensen P., Johnsen A.H., Uerkvitz W., Tanaka K., Hendil K.B.;
RL Biochem. Biophys. Res. Commun. 207:1059-1059(1995).
RN [15]
RP INDUCTION.
RX PubMed=8663318; DOI=10.1074/jbc.271.29.17275;
RA Gaczynska M., Goldberg A.L., Tanaka K., Hendil K.B., Rock K.L.;
RT "Proteasome subunits X and Y alter peptidase activities in opposite
RT ways to the interferon-gamma-induced subunits LMP2 and LMP7.";
RL J. Biol. Chem. 271:17275-17280(1996).
RN [16]
RP INTERACTION WITH HIV-1 TAT.
RX PubMed=14550573; DOI=10.1016/S0014-5793(03)01025-1;
RA Apcher G.S., Heink S., Zantopf D., Kloetzel P.-M., Schmid H.-P.,
RA Mayer R.J., Krueger E.;
RT "Human immunodeficiency virus-1 Tat protein interacts with distinct
RT proteasomal alpha and beta subunits.";
RL FEBS Lett. 553:200-204(2003).
RN [17]
RP INTERACTION WITH ABCB1 AND TAP1.
RX PubMed=15488952; DOI=10.1016/j.molimm.2004.07.005;
RA Begley G.S., Horvath A.R., Taylor J.C., Higgins C.F.;
RT "Cytoplasmic domains of the transporter associated with antigen
RT processing and P-glycoprotein interact with subunits of the
RT proteasome.";
RL Mol. Immunol. 42:137-141(2005).
RN [18]
RP INTERACTION WITH POMP.
RX PubMed=15944226; DOI=10.1073/pnas.0501711102;
RA Heink S., Ludwig D., Kloetzel P.-M., Krueger E.;
RT "IFN-gamma-induced immune adaptation of the proteasome system is an
RT accelerated and transient response.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:9241-9246(2005).
RN [19]
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 [20]
RP INDUCTION.
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 [21]
RP FUNCTION, AND MUTAGENESIS OF ALA-108.
RX PubMed=18565852; DOI=10.1182/blood-2007-08-104950;
RA Oerlemans R., Franke N.E., Assaraf Y.G., Cloos J., van Zantwijk I.,
RA Berkers C.R., Scheffer G.L., Debipersad K., Vojtekova K., Lemos C.,
RA van der Heijden J.W., Ylstra B., Peters G.J., Kaspers G.L.,
RA Dijkmans B.A., Scheper R.J., Jansen G.;
RT "Molecular basis of bortezomib resistance: proteasome subunit beta5
RT (PSMB5) gene mutation and overexpression of PSMB5 protein.";
RL Blood 112:2489-2499(2008).
RN [22]
RP FUNCTION, AND MUTAGENESIS OF ALA-108.
RX PubMed=18502982; DOI=10.1124/jpet.108.138131;
RA Lue S., Yang J., Song X., Gong S., Zhou H., Guo L., Song N., Bao X.,
RA Chen P., Wang J.;
RT "Point mutation of the proteasome beta5 subunit gene is an important
RT mechanism of bortezomib resistance in bortezomib-selected variants of
RT Jurkat T cell lymphoblastic lymphoma/leukemia line.";
RL J. Pharmacol. Exp. Ther. 326:423-431(2008).
RN [23]
RP MUTAGENESIS OF ALA-108 AND ALA-109.
RX PubMed=19426847; DOI=10.1016/j.exphem.2009.04.001;
RA Lue S., Yang J., Chen Z., Gong S., Zhou H., Xu X., Wang J.;
RT "Different mutants of PSMB5 confer varying bortezomib resistance in T
RT lymphoblastic lymphoma/leukemia cells derived from the Jurkat cell
RT line.";
RL Exp. Hematol. 37:831-837(2009).
RN [24]
RP INDUCTION BY SULFORAPHANE.
RX PubMed=18602823; DOI=10.1016/j.jnutbio.2008.02.002;
RA Ramirez M.C., Singletary K.;
RT "Regulation of estrogen receptor alpha expression in human breast
RT cancer cells by sulforaphane.";
RL J. Nutr. Biochem. 20:195-201(2009).
RN [25]
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. This unit is responsible of the chymotrypsin-like
CC activity of the proteasome and is one of the principal target of
CC the proteasome inhibitor bortezomib. May catalyze basal processing
CC of intracellular antigens. Plays a role in the protection against
CC oxidative damage through the Nrf2-ARE pathway (By 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. This subunit can be displaced by
CC the equivalent immune-specific subunit PSMB8. Directly interacts
CC with POMP. Interacts with HIV-1 TAT protein. Interacts with ABCB1
CC and TAP1.
CC -!- INTERACTION:
CC Q9Y244:POMP; NbExp=3; IntAct=EBI-357828, EBI-696895;
CC P20618:PSMB1; NbExp=3; IntAct=EBI-357828, EBI-372273;
CC Q99436:PSMB7; NbExp=7; IntAct=EBI-357828, EBI-603319;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P28074-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P28074-2; Sequence=VSP_041263;
CC Name=3;
CC IsoId=P28074-3; Sequence=VSP_045686;
CC Note=No experimental confirmation available;
CC -!- INDUCTION: Down-regulated by IFNG/IFN-gamma (at protein level).
CC Induced in breast cancer tissue. Up-regulated by sulforaphane in
CC breast cancer cells.
CC -!- SIMILARITY: Belongs to the peptidase T1B family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP35423.1; Type=Erroneous initiation;
CC Sequence=BAA06097.1; Type=Erroneous initiation;
CC Sequence=CAD97956.1; Type=Erroneous initiation;
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DR EMBL; X95586; CAA64838.1; -; Genomic_DNA.
DR EMBL; AK300714; BAG62391.1; -; mRNA.
DR EMBL; AK311895; BAG34836.1; -; mRNA.
DR EMBL; BX538001; CAD97956.1; ALT_INIT; mRNA.
DR EMBL; AL132780; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW66193.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66195.1; -; Genomic_DNA.
DR EMBL; BC004146; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC057840; AAH57840.1; -; mRNA.
DR EMBL; BC107720; AAI07721.1; -; mRNA.
DR EMBL; CD048996; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BX248299; CAD62626.1; -; mRNA.
DR EMBL; D29011; BAA06097.1; ALT_INIT; mRNA.
DR EMBL; S74378; AAB33092.1; -; mRNA.
DR EMBL; BT006777; AAP35423.1; ALT_INIT; mRNA.
DR PIR; A54589; A54589.
DR PIR; I52906; I52906.
DR PIR; PC2328; PC2328.
DR PIR; S08189; S08189.
DR RefSeq; NP_001124197.1; NM_001130725.1.
DR RefSeq; NP_001138404.1; NM_001144932.1.
DR RefSeq; NP_002788.1; NM_002797.3.
DR UniGene; Hs.422990; -.
DR ProteinModelPortal; P28074; -.
DR SMR; P28074; 34-260.
DR DIP; DIP-27540N; -.
DR IntAct; P28074; 23.
DR MINT; MINT-1161576; -.
DR STRING; 9606.ENSP00000355325; -.
DR BindingDB; P28074; -.
DR ChEMBL; CHEMBL4662; -.
DR DrugBank; DB00188; Bortezomib.
DR GuidetoPHARMACOLOGY; 2406; -.
DR MEROPS; T01.P01; -.
DR PhosphoSite; P28074; -.
DR DMDM; 187608890; -.
DR REPRODUCTION-2DPAGE; IPI00479306; -.
DR PaxDb; P28074; -.
DR PRIDE; P28074; -.
DR DNASU; 5693; -.
DR Ensembl; ENST00000361611; ENSP00000355325; ENSG00000100804.
DR Ensembl; ENST00000425762; ENSP00000395206; ENSG00000100804.
DR Ensembl; ENST00000493471; ENSP00000452424; ENSG00000100804.
DR GeneID; 5693; -.
DR KEGG; hsa:5693; -.
DR UCSC; uc001wii.3; human.
DR CTD; 5693; -.
DR GeneCards; GC14M023485; -.
DR HGNC; HGNC:9542; PSMB5.
DR HPA; HPA049518; -.
DR MIM; 600306; gene.
DR neXtProt; NX_P28074; -.
DR PharmGKB; PA33887; -.
DR eggNOG; COG0638; -.
DR HOVERGEN; HBG108297; -.
DR InParanoid; P28074; -.
DR KO; K02737; -.
DR OMA; LRAIMHA; -.
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 GeneWiki; PSMB5; -.
DR GenomeRNAi; 5693; -.
DR NextBio; 22114; -.
DR PRO; PR:P28074; -.
DR ArrayExpress; P28074; -.
DR Bgee; P28074; -.
DR CleanEx; HS_PSMB5; -.
DR Genevestigator; P28074; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005839; C:proteasome core complex; ISS:UniProtKB.
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: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:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
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:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR InterPro; IPR000243; Pept_T1A_subB.
DR InterPro; IPR016050; Proteasome_bsu_CS.
DR InterPro; IPR001353; Proteasome_sua/b.
DR InterPro; IPR023333; Proteasome_suB-type.
DR Pfam; PF00227; Proteasome; 1.
DR PRINTS; PR00141; PROTEASOME.
DR PROSITE; PS00854; PROTEASOME_BETA_1; 1.
DR PROSITE; PS51476; PROTEASOME_BETA_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Host-virus interaction; Hydrolase; Nucleus;
KW Polymorphism; Protease; Proteasome; Reference proteome;
KW Threonine protease; Zymogen.
FT PROPEP 1 59 Removed in mature form.
FT /FTId=PRO_0000026589.
FT CHAIN 60 263 Proteasome subunit beta type-5.
FT /FTId=PRO_0000026590.
FT ACT_SITE 60 60 Nucleophile.
FT BINDING 108 108 Bortezomib; via amide nitrogen (By
FT similarity).
FT VAR_SEQ 1 103 Missing (in isoform 3).
FT /FTId=VSP_045686.
FT VAR_SEQ 169 263 GLYYVDSEGNRISGATFSVGSGSVYAYGVMDRGYSYDLEVE
FT QAYDLARRAIYQATYRDAYSGGAVNLYHVREDGWIRVSSDN
FT VADLHEKYSGSTP -> VSEVLCLKPKSFGMYLFCGCAERI
FT GNMARPLLRGQ (in isoform 2).
FT /FTId=VSP_041263.
FT VARIANT 24 24 R -> C (in dbSNP:rs11543947).
FT /FTId=VAR_051549.
FT MUTAGEN 108 108 A->T: Displays resistance to the
FT bortezomib, a proteasome inhibitor of the
FT chymotrypsin-like activity. Displays high
FT resistance to the bortezomib, a
FT proteasome inhibitor of the chymotrypsin-
FT like activity; when associated with V-
FT 109.
FT MUTAGEN 108 108 A->V: Displays high resistance to the
FT bortezomib, a proteasome inhibitor of the
FT chymotrypsin-like activity.
FT MUTAGEN 109 109 A->V: Displays high resistance to the
FT bortezomib, a proteasome inhibitor of the
FT chymotrypsin-like activity; when
FT associated with T-108.
FT CONFLICT 3 6 LASV -> IRGR (in Ref. 8; BAA06097).
FT CONFLICT 3 5 LAS -> HEG (in Ref. 6; BC004146).
FT CONFLICT 85 85 I -> F (in Ref. 11; AA sequence).
FT CONFLICT 109 109 A -> G (in Ref. 9; AAB33092).
FT CONFLICT 158 158 T -> S (in Ref. 9; AAB33092).
SQ SEQUENCE 263 AA; 28480 MW; AED4A73DF41AA6EF CRC64;
MALASVLERP LPVNQRGFFG LGGRADLLDL GPGSLSDGLS LAAPGWGVPE EPGIEMLHGT
TTLAFKFRHG VIVAADSRAT AGAYIASQTV KKVIEINPYL LGTMAGGAAD CSFWERLLAR
QCRIYELRNK ERISVAAASK LLANMVYQYK GMGLSMGTMI CGWDKRGPGL YYVDSEGNRI
SGATFSVGSG SVYAYGVMDR GYSYDLEVEQ AYDLARRAIY QATYRDAYSG GAVNLYHVRE
DGWIRVSSDN VADLHEKYSG STP
//
ID PSB5_HUMAN Reviewed; 263 AA.
AC P28074; B2R4N9; B4DUM9; D3DS43; E9PAV2; Q16242; Q6PEW2; Q7Z3B5;
read moreAC Q86T01; Q9TNN9;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 3.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Proteasome subunit beta type-5;
DE EC=3.4.25.1;
DE AltName: Full=Macropain epsilon chain;
DE AltName: Full=Multicatalytic endopeptidase complex epsilon chain;
DE AltName: Full=Proteasome chain 6;
DE AltName: Full=Proteasome epsilon chain;
DE AltName: Full=Proteasome subunit MB1;
DE AltName: Full=Proteasome subunit X;
DE Flags: Precursor;
GN Name=PSMB5; Synonyms=LMPX, MB1, X;
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 [GENOMIC DNA].
RX PubMed=8753855; DOI=10.1007/s002510050121;
RA Abdulla S., Beck S., Belich M., Jackson A., Nakamura T., Trowsdale J.;
RT "Divergent intron arrangement in the MB1/LMP7 proteasome gene pair.";
RL Immunogenetics 44:254-258(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skeletal muscle;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Endometrial adenocarcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
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 [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] (ISOFORMS 1 AND 3).
RC TISSUE=Embryonic stem cell, Hypothalamus, and Skin;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-203 (ISOFORM 2).
RC TISSUE=Cervix carcinoma;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-263 (ISOFORM 1), AND INDUCTION.
RX PubMed=8066462; DOI=10.1126/science.8066462;
RA Akiyama K.-Y., Yokota K.-Y., Kagawa S., Shimbara N., Tamura T.,
RA Akioka H., Nothwang H.G., Noda C., Tanaka K., Ichihara A.;
RT "cDNA cloning and interferon gamma down-regulation of proteasomal
RT subunits X and Y.";
RL Science 265:1231-1234(1994).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 49-263 (ISOFORM 1).
RX PubMed=7820546; DOI=10.1016/S0960-9822(00)00174-3;
RA Belich M.P., Glynne R.J., Senger G., Sheer D., Trowsdale J.;
RT "Proteasome components with reciprocal expression to that of the MHC-
RT encoded LMP proteins.";
RL Curr. Biol. 4:769-776(1994).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 56-263 (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 [11]
RP PROTEIN SEQUENCE OF 60-85.
RX PubMed=2306472; DOI=10.1016/0167-4838(90)90165-C;
RA Lee L.W., Moomaw C.R., Orth K., McGuire M.J., DeMartino G.N.,
RA Slaughter C.A.;
RT "Relationships among the subunits of the high molecular weight
RT proteinase, macropain (proteasome).";
RL Biochim. Biophys. Acta 1037:178-185(1990).
RN [12]
RP PROTEIN SEQUENCE OF 201-216 AND 226-239.
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 [13]
RP PROTEIN SEQUENCE OF 201-216, AND SUBUNIT.
RC TISSUE=Kidney;
RX PubMed=8163024; DOI=10.1016/0014-5793(94)80612-8;
RA Akiyama K., Kagawa S., Tamura T., Shimbara N., Takashina M.,
RA Kristensen P., Hendil K.B., Tanaka K., Ichihara A.;
RT "Replacement of proteasome subunits X and Y by LMP7 and LMP2 induced
RT by interferon-gamma for acquirement of the functional diversity
RT responsible for antigen processing.";
RL FEBS Lett. 343:85-88(1994).
RN [14]
RP ERRATUM.
RX PubMed=7864893; DOI=10.1006/bbrc.1995.1294;
RA Kristensen P., Johnsen A.H., Uerkvitz W., Tanaka K., Hendil K.B.;
RL Biochem. Biophys. Res. Commun. 207:1059-1059(1995).
RN [15]
RP INDUCTION.
RX PubMed=8663318; DOI=10.1074/jbc.271.29.17275;
RA Gaczynska M., Goldberg A.L., Tanaka K., Hendil K.B., Rock K.L.;
RT "Proteasome subunits X and Y alter peptidase activities in opposite
RT ways to the interferon-gamma-induced subunits LMP2 and LMP7.";
RL J. Biol. Chem. 271:17275-17280(1996).
RN [16]
RP INTERACTION WITH HIV-1 TAT.
RX PubMed=14550573; DOI=10.1016/S0014-5793(03)01025-1;
RA Apcher G.S., Heink S., Zantopf D., Kloetzel P.-M., Schmid H.-P.,
RA Mayer R.J., Krueger E.;
RT "Human immunodeficiency virus-1 Tat protein interacts with distinct
RT proteasomal alpha and beta subunits.";
RL FEBS Lett. 553:200-204(2003).
RN [17]
RP INTERACTION WITH ABCB1 AND TAP1.
RX PubMed=15488952; DOI=10.1016/j.molimm.2004.07.005;
RA Begley G.S., Horvath A.R., Taylor J.C., Higgins C.F.;
RT "Cytoplasmic domains of the transporter associated with antigen
RT processing and P-glycoprotein interact with subunits of the
RT proteasome.";
RL Mol. Immunol. 42:137-141(2005).
RN [18]
RP INTERACTION WITH POMP.
RX PubMed=15944226; DOI=10.1073/pnas.0501711102;
RA Heink S., Ludwig D., Kloetzel P.-M., Krueger E.;
RT "IFN-gamma-induced immune adaptation of the proteasome system is an
RT accelerated and transient response.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:9241-9246(2005).
RN [19]
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 [20]
RP INDUCTION.
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 [21]
RP FUNCTION, AND MUTAGENESIS OF ALA-108.
RX PubMed=18565852; DOI=10.1182/blood-2007-08-104950;
RA Oerlemans R., Franke N.E., Assaraf Y.G., Cloos J., van Zantwijk I.,
RA Berkers C.R., Scheffer G.L., Debipersad K., Vojtekova K., Lemos C.,
RA van der Heijden J.W., Ylstra B., Peters G.J., Kaspers G.L.,
RA Dijkmans B.A., Scheper R.J., Jansen G.;
RT "Molecular basis of bortezomib resistance: proteasome subunit beta5
RT (PSMB5) gene mutation and overexpression of PSMB5 protein.";
RL Blood 112:2489-2499(2008).
RN [22]
RP FUNCTION, AND MUTAGENESIS OF ALA-108.
RX PubMed=18502982; DOI=10.1124/jpet.108.138131;
RA Lue S., Yang J., Song X., Gong S., Zhou H., Guo L., Song N., Bao X.,
RA Chen P., Wang J.;
RT "Point mutation of the proteasome beta5 subunit gene is an important
RT mechanism of bortezomib resistance in bortezomib-selected variants of
RT Jurkat T cell lymphoblastic lymphoma/leukemia line.";
RL J. Pharmacol. Exp. Ther. 326:423-431(2008).
RN [23]
RP MUTAGENESIS OF ALA-108 AND ALA-109.
RX PubMed=19426847; DOI=10.1016/j.exphem.2009.04.001;
RA Lue S., Yang J., Chen Z., Gong S., Zhou H., Xu X., Wang J.;
RT "Different mutants of PSMB5 confer varying bortezomib resistance in T
RT lymphoblastic lymphoma/leukemia cells derived from the Jurkat cell
RT line.";
RL Exp. Hematol. 37:831-837(2009).
RN [24]
RP INDUCTION BY SULFORAPHANE.
RX PubMed=18602823; DOI=10.1016/j.jnutbio.2008.02.002;
RA Ramirez M.C., Singletary K.;
RT "Regulation of estrogen receptor alpha expression in human breast
RT cancer cells by sulforaphane.";
RL J. Nutr. Biochem. 20:195-201(2009).
RN [25]
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. This unit is responsible of the chymotrypsin-like
CC activity of the proteasome and is one of the principal target of
CC the proteasome inhibitor bortezomib. May catalyze basal processing
CC of intracellular antigens. Plays a role in the protection against
CC oxidative damage through the Nrf2-ARE pathway (By 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. This subunit can be displaced by
CC the equivalent immune-specific subunit PSMB8. Directly interacts
CC with POMP. Interacts with HIV-1 TAT protein. Interacts with ABCB1
CC and TAP1.
CC -!- INTERACTION:
CC Q9Y244:POMP; NbExp=3; IntAct=EBI-357828, EBI-696895;
CC P20618:PSMB1; NbExp=3; IntAct=EBI-357828, EBI-372273;
CC Q99436:PSMB7; NbExp=7; IntAct=EBI-357828, EBI-603319;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P28074-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P28074-2; Sequence=VSP_041263;
CC Name=3;
CC IsoId=P28074-3; Sequence=VSP_045686;
CC Note=No experimental confirmation available;
CC -!- INDUCTION: Down-regulated by IFNG/IFN-gamma (at protein level).
CC Induced in breast cancer tissue. Up-regulated by sulforaphane in
CC breast cancer cells.
CC -!- SIMILARITY: Belongs to the peptidase T1B family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP35423.1; Type=Erroneous initiation;
CC Sequence=BAA06097.1; Type=Erroneous initiation;
CC Sequence=CAD97956.1; Type=Erroneous initiation;
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DR EMBL; X95586; CAA64838.1; -; Genomic_DNA.
DR EMBL; AK300714; BAG62391.1; -; mRNA.
DR EMBL; AK311895; BAG34836.1; -; mRNA.
DR EMBL; BX538001; CAD97956.1; ALT_INIT; mRNA.
DR EMBL; AL132780; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW66193.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66195.1; -; Genomic_DNA.
DR EMBL; BC004146; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC057840; AAH57840.1; -; mRNA.
DR EMBL; BC107720; AAI07721.1; -; mRNA.
DR EMBL; CD048996; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BX248299; CAD62626.1; -; mRNA.
DR EMBL; D29011; BAA06097.1; ALT_INIT; mRNA.
DR EMBL; S74378; AAB33092.1; -; mRNA.
DR EMBL; BT006777; AAP35423.1; ALT_INIT; mRNA.
DR PIR; A54589; A54589.
DR PIR; I52906; I52906.
DR PIR; PC2328; PC2328.
DR PIR; S08189; S08189.
DR RefSeq; NP_001124197.1; NM_001130725.1.
DR RefSeq; NP_001138404.1; NM_001144932.1.
DR RefSeq; NP_002788.1; NM_002797.3.
DR UniGene; Hs.422990; -.
DR ProteinModelPortal; P28074; -.
DR SMR; P28074; 34-260.
DR DIP; DIP-27540N; -.
DR IntAct; P28074; 23.
DR MINT; MINT-1161576; -.
DR STRING; 9606.ENSP00000355325; -.
DR BindingDB; P28074; -.
DR ChEMBL; CHEMBL4662; -.
DR DrugBank; DB00188; Bortezomib.
DR GuidetoPHARMACOLOGY; 2406; -.
DR MEROPS; T01.P01; -.
DR PhosphoSite; P28074; -.
DR DMDM; 187608890; -.
DR REPRODUCTION-2DPAGE; IPI00479306; -.
DR PaxDb; P28074; -.
DR PRIDE; P28074; -.
DR DNASU; 5693; -.
DR Ensembl; ENST00000361611; ENSP00000355325; ENSG00000100804.
DR Ensembl; ENST00000425762; ENSP00000395206; ENSG00000100804.
DR Ensembl; ENST00000493471; ENSP00000452424; ENSG00000100804.
DR GeneID; 5693; -.
DR KEGG; hsa:5693; -.
DR UCSC; uc001wii.3; human.
DR CTD; 5693; -.
DR GeneCards; GC14M023485; -.
DR HGNC; HGNC:9542; PSMB5.
DR HPA; HPA049518; -.
DR MIM; 600306; gene.
DR neXtProt; NX_P28074; -.
DR PharmGKB; PA33887; -.
DR eggNOG; COG0638; -.
DR HOVERGEN; HBG108297; -.
DR InParanoid; P28074; -.
DR KO; K02737; -.
DR OMA; LRAIMHA; -.
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 GeneWiki; PSMB5; -.
DR GenomeRNAi; 5693; -.
DR NextBio; 22114; -.
DR PRO; PR:P28074; -.
DR ArrayExpress; P28074; -.
DR Bgee; P28074; -.
DR CleanEx; HS_PSMB5; -.
DR Genevestigator; P28074; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005839; C:proteasome core complex; ISS:UniProtKB.
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: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:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
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:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0016032; P:viral process; TAS:Reactome.
DR InterPro; IPR000243; Pept_T1A_subB.
DR InterPro; IPR016050; Proteasome_bsu_CS.
DR InterPro; IPR001353; Proteasome_sua/b.
DR InterPro; IPR023333; Proteasome_suB-type.
DR Pfam; PF00227; Proteasome; 1.
DR PRINTS; PR00141; PROTEASOME.
DR PROSITE; PS00854; PROTEASOME_BETA_1; 1.
DR PROSITE; PS51476; PROTEASOME_BETA_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Host-virus interaction; Hydrolase; Nucleus;
KW Polymorphism; Protease; Proteasome; Reference proteome;
KW Threonine protease; Zymogen.
FT PROPEP 1 59 Removed in mature form.
FT /FTId=PRO_0000026589.
FT CHAIN 60 263 Proteasome subunit beta type-5.
FT /FTId=PRO_0000026590.
FT ACT_SITE 60 60 Nucleophile.
FT BINDING 108 108 Bortezomib; via amide nitrogen (By
FT similarity).
FT VAR_SEQ 1 103 Missing (in isoform 3).
FT /FTId=VSP_045686.
FT VAR_SEQ 169 263 GLYYVDSEGNRISGATFSVGSGSVYAYGVMDRGYSYDLEVE
FT QAYDLARRAIYQATYRDAYSGGAVNLYHVREDGWIRVSSDN
FT VADLHEKYSGSTP -> VSEVLCLKPKSFGMYLFCGCAERI
FT GNMARPLLRGQ (in isoform 2).
FT /FTId=VSP_041263.
FT VARIANT 24 24 R -> C (in dbSNP:rs11543947).
FT /FTId=VAR_051549.
FT MUTAGEN 108 108 A->T: Displays resistance to the
FT bortezomib, a proteasome inhibitor of the
FT chymotrypsin-like activity. Displays high
FT resistance to the bortezomib, a
FT proteasome inhibitor of the chymotrypsin-
FT like activity; when associated with V-
FT 109.
FT MUTAGEN 108 108 A->V: Displays high resistance to the
FT bortezomib, a proteasome inhibitor of the
FT chymotrypsin-like activity.
FT MUTAGEN 109 109 A->V: Displays high resistance to the
FT bortezomib, a proteasome inhibitor of the
FT chymotrypsin-like activity; when
FT associated with T-108.
FT CONFLICT 3 6 LASV -> IRGR (in Ref. 8; BAA06097).
FT CONFLICT 3 5 LAS -> HEG (in Ref. 6; BC004146).
FT CONFLICT 85 85 I -> F (in Ref. 11; AA sequence).
FT CONFLICT 109 109 A -> G (in Ref. 9; AAB33092).
FT CONFLICT 158 158 T -> S (in Ref. 9; AAB33092).
SQ SEQUENCE 263 AA; 28480 MW; AED4A73DF41AA6EF CRC64;
MALASVLERP LPVNQRGFFG LGGRADLLDL GPGSLSDGLS LAAPGWGVPE EPGIEMLHGT
TTLAFKFRHG VIVAADSRAT AGAYIASQTV KKVIEINPYL LGTMAGGAAD CSFWERLLAR
QCRIYELRNK ERISVAAASK LLANMVYQYK GMGLSMGTMI CGWDKRGPGL YYVDSEGNRI
SGATFSVGSG SVYAYGVMDR GYSYDLEVEQ AYDLARRAIY QATYRDAYSG GAVNLYHVRE
DGWIRVSSDN VADLHEKYSG STP
//
MIM
600306
*RECORD*
*FIELD* NO
600306
*FIELD* TI
*600306 PROTEASOME SUBUNIT, BETA-TYPE, 5; PSMB5
;;PROTEASOME SUBUNIT X;;
PSX LARGE MULTIFUNCTIONAL PROTEASE X; LMPX;;
read morePROTEASOME SUBUNIT BETA-5
*FIELD* TX
DESCRIPTION
Proteasomes are the proteolytic complex responsible for major
histocompatibility complex (MHC) class I-restricted antigen presentation
(Akiyama et al., 1994).
See PSMB2 (602175) for further discussion of beta-type proteasome
subunits.
CLONING
Akiyama et al. (1994) cloned the full-length cDNA and showed that PSMB5
has high amino acid similarity to PSMB8 (177046).
GENE FUNCTION
Akiyama et al. (1994) showed that treatment with interferon-gamma (IFNG;
147570) increased expression of MHC-encoded LMP2 (PSMB9; 177045) and
LMP7 (PSMB8; 177046) subunits of the proteasome and decreased expression
of 2 proteasomal subunits PSMB5 and PSMB6, which altered the proteolytic
specificity of proteasomes. IFNG may induce subunit replacements of
PSMB5 and PSMB6, producing proteasomes that may be more appropriate for
the immunologic processing of endogenous antigens.
Bortezomib, a reversible proteasome inhibitor used in the treatment of
refractory multiple myeloma (see 254500), targets primarily the
chymotrypsin-like activity of PSMB5. To study the molecular basis of
bortezomib resistance, Oerlemans et al. (2008) generated high levels of
acquired resistance in human myelomonocytic THP1 cells by exposure to
stepwise increasing concentrations of bortezomib. Analysis of resistant
cells revealed that those with higher levels of resistance were
homozygous for a missense mutation in the highly conserved
substrate/inhibitory binding domain of PSMB5. In addition, there was
dramatic overexpression of PSM5B protein, but not of other proteasome
subunits. RNAi-mediated silencing of PSMB5 expression resulted in
restoration of bortezomib sensitivity in resistant cells. Oerlemans et
al. (2008) concluded that bortezomib resistance is associated with
selective overexpression of a mutant PSMB5 protein.
MAPPING
The PSMB5 gene was mapped to chromosome 14q11.2 by Belich et al. (1994).
McCusker et al. (1997) demonstrated that the PSMB5 gene is located on
14q11.2 within 1 Mb of the genes encoding the alpha (600654) and beta
(602161) subunits of the PA28 complex.
*FIELD* RF
1. Akiyama, K.; Yokota, K.; Kagawa, S.; Shimbara, N.; Tamura, T.;
Akioka, H.; Nothwang, H. G.; Noda, C.; Tanaka, K.; Ichihara, A.:
cDNA cloning and interferon gamma down-regulation of proteasomal subunits
X and Y. Science 265: 1231-1234, 1994.
2. 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.
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. Oerlemans, R.; Franke, N. E.; Assaraf, Y. G.; Cloos, J.; van Zantwijk,
I.; Berkers, C. R.; Scheffer, G. L.; Debipersad, K.; Vojtekova, K.;
Lemos, C.; van der Heijden, J. W.; Ylstra, B.; Peters, G. J.; Kaspers,
G. L.; Dijkmans, B. A. C.; Scheper, R. J.; Jansen, G.: Molecular
basis of bortezomib resistance: proteasome subunit beta-5 (PSMB5)
gene mutation and overexpression of PSMB5 protein. Blood 112: 2489-2499,
2008.
*FIELD* CN
Marla J. F. O'Neill - updated: 6/8/2009
Victor A. McKusick - updated: 12/8/1997
*FIELD* CD
Victor A. McKusick: 1/11/1995
*FIELD* ED
carol: 04/06/2011
wwang: 6/24/2009
terry: 6/8/2009
mgross: 6/25/2007
dkim: 7/23/1998
mark: 12/12/1997
terry: 12/8/1997
jamie: 1/29/1997
mark: 6/13/1995
carol: 1/11/1995
*RECORD*
*FIELD* NO
600306
*FIELD* TI
*600306 PROTEASOME SUBUNIT, BETA-TYPE, 5; PSMB5
;;PROTEASOME SUBUNIT X;;
PSX LARGE MULTIFUNCTIONAL PROTEASE X; LMPX;;
read morePROTEASOME SUBUNIT BETA-5
*FIELD* TX
DESCRIPTION
Proteasomes are the proteolytic complex responsible for major
histocompatibility complex (MHC) class I-restricted antigen presentation
(Akiyama et al., 1994).
See PSMB2 (602175) for further discussion of beta-type proteasome
subunits.
CLONING
Akiyama et al. (1994) cloned the full-length cDNA and showed that PSMB5
has high amino acid similarity to PSMB8 (177046).
GENE FUNCTION
Akiyama et al. (1994) showed that treatment with interferon-gamma (IFNG;
147570) increased expression of MHC-encoded LMP2 (PSMB9; 177045) and
LMP7 (PSMB8; 177046) subunits of the proteasome and decreased expression
of 2 proteasomal subunits PSMB5 and PSMB6, which altered the proteolytic
specificity of proteasomes. IFNG may induce subunit replacements of
PSMB5 and PSMB6, producing proteasomes that may be more appropriate for
the immunologic processing of endogenous antigens.
Bortezomib, a reversible proteasome inhibitor used in the treatment of
refractory multiple myeloma (see 254500), targets primarily the
chymotrypsin-like activity of PSMB5. To study the molecular basis of
bortezomib resistance, Oerlemans et al. (2008) generated high levels of
acquired resistance in human myelomonocytic THP1 cells by exposure to
stepwise increasing concentrations of bortezomib. Analysis of resistant
cells revealed that those with higher levels of resistance were
homozygous for a missense mutation in the highly conserved
substrate/inhibitory binding domain of PSMB5. In addition, there was
dramatic overexpression of PSM5B protein, but not of other proteasome
subunits. RNAi-mediated silencing of PSMB5 expression resulted in
restoration of bortezomib sensitivity in resistant cells. Oerlemans et
al. (2008) concluded that bortezomib resistance is associated with
selective overexpression of a mutant PSMB5 protein.
MAPPING
The PSMB5 gene was mapped to chromosome 14q11.2 by Belich et al. (1994).
McCusker et al. (1997) demonstrated that the PSMB5 gene is located on
14q11.2 within 1 Mb of the genes encoding the alpha (600654) and beta
(602161) subunits of the PA28 complex.
*FIELD* RF
1. Akiyama, K.; Yokota, K.; Kagawa, S.; Shimbara, N.; Tamura, T.;
Akioka, H.; Nothwang, H. G.; Noda, C.; Tanaka, K.; Ichihara, A.:
cDNA cloning and interferon gamma down-regulation of proteasomal subunits
X and Y. Science 265: 1231-1234, 1994.
2. 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.
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. Oerlemans, R.; Franke, N. E.; Assaraf, Y. G.; Cloos, J.; van Zantwijk,
I.; Berkers, C. R.; Scheffer, G. L.; Debipersad, K.; Vojtekova, K.;
Lemos, C.; van der Heijden, J. W.; Ylstra, B.; Peters, G. J.; Kaspers,
G. L.; Dijkmans, B. A. C.; Scheper, R. J.; Jansen, G.: Molecular
basis of bortezomib resistance: proteasome subunit beta-5 (PSMB5)
gene mutation and overexpression of PSMB5 protein. Blood 112: 2489-2499,
2008.
*FIELD* CN
Marla J. F. O'Neill - updated: 6/8/2009
Victor A. McKusick - updated: 12/8/1997
*FIELD* CD
Victor A. McKusick: 1/11/1995
*FIELD* ED
carol: 04/06/2011
wwang: 6/24/2009
terry: 6/8/2009
mgross: 6/25/2007
dkim: 7/23/1998
mark: 12/12/1997
terry: 12/8/1997
jamie: 1/29/1997
mark: 6/13/1995
carol: 1/11/1995