PSB8_HUMAN
ID PSB8_HUMAN Reviewed; 276 AA.
AC P28062; B0UZC0; Q29824; Q5JNW6; Q5QNR8; Q96J48;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 3.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=Proteasome subunit beta type-8;
DE EC=3.4.25.1;
DE AltName: Full=Low molecular mass protein 7;
DE AltName: Full=Macropain subunit C13;
DE AltName: Full=Multicatalytic endopeptidase complex subunit C13;
DE AltName: Full=Proteasome component C13;
DE AltName: Full=Proteasome subunit beta-5i;
DE AltName: Full=Really interesting new gene 10 protein;
DE Flags: Precursor;
GN Name=PSMB8; Synonyms=LMP7, PSMB5i, RING10, Y2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8458375; DOI=10.1002/eji.1830230414;
RA Glynne R., Kerr L.A., Mockridge I., Beck S., Kelly A., Trowsdale J.;
RT "The major histocompatibility complex-encoded proteasome component LMP7:
RT alternative first exons and post-translational processing.";
RL Eur. J. Immunol. 23:860-866(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1453454; DOI=10.1016/0022-2836(92)90832-5;
RA Beck S., Kelly A., Radley E., Khurshid F., Alderton R.P., Trowsdale J.;
RT "DNA sequence analysis of 66 kb of the human MHC class II region encoding a
RT cluster of genes for antigen processing.";
RL J. Mol. Biol. 228:433-441(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1922342; DOI=10.1038/353357a0;
RA Glynne R., Powis S.H., Beck S., Kelly A., Kerr L.A., Trowsdale J.;
RT "A proteasome-related gene between the two ABC transporter loci in the
RT class II region of the human MHC.";
RL Nature 353:357-360(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1429565; DOI=10.1016/s0021-9258(18)41645-6;
RA Fruh K., Yang Y., Arnold D., Chambers J., Wu L., Waters J.B., Spies T.,
RA Peterson P.A.;
RT "Alternative exon usage and processing of the major histocompatibility
RT complex-encoded proteasome subunits.";
RL J. Biol. Chem. 267:22131-22140(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8344725; DOI=10.1007/bf00210482;
RA Meinhardt T., Graf U., Hammerling G.J.;
RT "Different genomic structure of mouse and human Lmp7 genes:
RT characterization of MHC-encoded proteasome genes.";
RL Immunogenetics 38:373-379(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8568858; DOI=10.1006/jmbi.1996.0001;
RA Beck S., Abdulla S., Alderton R.P., Glynne R.J., Gut I.G., Hosking L.K.,
RA Jackson A., Kelly A., Newell W.R., Sanseau P., Radley E., Thorpe K.L.,
RA Trowsdale J.;
RT "Evolutionary dynamics of non-coding sequences within the class II region
RT of the human MHC.";
RL J. Mol. Biol. 255:1-13(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE LMP7C), AND VARIANT LYS-49.
RA Maksymowych W.P.;
RT "Sequence analysis of the HLA-linked LMP7 gene.";
RL Submitted (NOV-1994) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 191-269.
RC TISSUE=Blood;
RX PubMed=9157092; DOI=10.1016/0198-8859(95)00172-7;
RA Kim T.G., Lee Y.H., Choi H.B., Han H.;
RT "Two newly discovered alleles of major histocompatibility complex-encoded
RT LMP7 in Korean populations.";
RL Hum. Immunol. 46:61-64(1996).
RN [12]
RP FUNCTION.
RX PubMed=8163024; DOI=10.1016/0014-5793(94)80612-8;
RA Akiyama K., Kagawa S., Tamura T., Shimbara N., Takashina M., Kristensen P.,
RA Hendil K.B., Tanaka K., Ichihara A.;
RT "Replacement of proteasome subunits X and Y by LMP7 and LMP2 induced by
RT interferon-gamma for acquirement of the functional diversity responsible
RT for antigen processing.";
RL FEBS Lett. 343:85-88(1994).
RN [13]
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 ways to
RT the interferon-gamma-induced subunits LMP2 and LMP7.";
RL J. Biol. Chem. 271:17275-17280(1996).
RN [14]
RP INDUCTION BY TNF AND IFNG.
RX PubMed=11493458; DOI=10.1182/blood.v98.4.1108;
RA Hallermalm K., Seki K., Wei C., Castelli C., Rivoltini L., Kiessling R.,
RA Levitskaya J.;
RT "Tumor necrosis factor-alpha induces coordinated changes in major
RT histocompatibility class I presentation pathway, resulting in increased
RT stability of class I complexes at the cell surface.";
RL Blood 98:1108-1115(2001).
RN [15]
RP DEVELOPMENTAL STAGE.
RX PubMed=11717192; DOI=10.1093/intimm/13.12.1515;
RA Li J., Schuler-Thurner B., Schuler G., Huber C., Seliger B.;
RT "Bipartite regulation of different components of the MHC class I antigen-
RT processing machinery during dendritic cell maturation.";
RL Int. Immunol. 13:1515-1523(2001).
RN [16]
RP INTERACTION WITH HIV-1 TAT (MICROBIAL INFECTION).
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 INDUCTION BY TETRODOTOXIN.
RX PubMed=15501285; DOI=10.1016/j.toxicon.2004.07.018;
RA Raghavendra Prasad H.S., Qi Z., Srinivasan K.N., Gopalakrishnakone P.;
RT "Potential effects of tetrodotoxin exposure to human glial cells postulated
RT using microarray approach.";
RL Toxicon 44:597-608(2004).
RN [18]
RP INDUCTION BY IFNG AND IRF1.
RX PubMed=15907481; DOI=10.1016/j.febslet.2005.04.012;
RA Namiki S., Nakamura T., Oshima S., Yamazaki M., Sekine Y., Tsuchiya K.,
RA Okamoto R., Kanai T., Watanabe M.;
RT "IRF-1 mediates upregulation of LMP7 by IFN-gamma and concerted expression
RT of immunosubunits of the proteasome.";
RL FEBS Lett. 579:2781-2787(2005).
RN [19]
RP INTERACTION WITH 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 processing
RT and P-glycoprotein interact with subunits of the proteasome.";
RL Mol. Immunol. 42:137-141(2005).
RN [20]
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 [21]
RP FUNCTION.
RX PubMed=16423992; DOI=10.1158/0008-5472.can-05-2872;
RA Heink S., Fricke B., Ludwig D., Kloetzel P.M., Krueger E.;
RT "Tumor cell lines expressing the proteasome subunit isoform LMP7E1 exhibit
RT immunoproteasome deficiency.";
RL Cancer Res. 66:649-652(2006).
RN [22]
RP INDUCTION BY HEAT SHOCK.
RX PubMed=17142736; DOI=10.4049/jimmunol.177.12.8393;
RA Callahan M.K., Wohlfert E.A., Menoret A., Srivastava P.K.;
RT "Heat shock up-regulates lmp2 and lmp7 and enhances presentation of
RT immunoproteasome-dependent epitopes.";
RL J. Immunol. 177:8393-8399(2006).
RN [23]
RP INDUCTION.
RX PubMed=17262812; DOI=10.1002/ibd.20110;
RA Wu F., Dassopoulos T., Cope L., Maitra A., Brant S.R., Harris M.L.,
RA Bayless T.M., Parmigiani G., Chakravarti S.;
RT "Genome-wide gene expression differences in Crohn's disease and ulcerative
RT colitis from endoscopic pinch biopsies: insights into distinctive
RT pathogenesis.";
RL Inflamm. Bowel Dis. 13:807-821(2007).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5 (ISOFORM 2), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP INDUCTION BY IFNG, AND FUNCTION.
RX PubMed=19443843; DOI=10.1161/atvbaha.109.189407;
RA Yang Z., Gagarin D., St Laurent G. III, Hammell N., Toma I., Hu C.A.,
RA Iwasa A., McCaffrey T.A.;
RT "Cardiovascular inflammation and lesion cell apoptosis: a novel connection
RT via the interferon-inducible immunoproteasome.";
RL Arterioscler. Thromb. Vasc. Biol. 29:1213-1219(2009).
RN [26]
RP INDUCTION.
RX PubMed=19619915; DOI=10.1016/j.imbio.2009.06.020;
RA Eisemann J., Prechtel A.T., Muehl-Zuerbes P., Steinkasserer A., Kummer M.;
RT "Herpes simplex virus type I infection of mature dendritic cells leads to
RT reduced LMP7-mRNA-expression levels.";
RL Immunobiology 214:861-867(2009).
RN [27]
RP INDUCTION BY PR-957.
RX PubMed=19525961; DOI=10.1038/nm.1978;
RA Muchamuel T., Basler M., Aujay M.A., Suzuki E., Kalim K.W., Lauer C.,
RA Sylvain C., Ring E.R., Shields J., Jiang J., Shwonek P., Parlati F.,
RA Demo S.D., Bennett M.K., Kirk C.J., Groettrup M.;
RT "A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine
RT production and attenuates progression of experimental arthritis.";
RL Nat. Med. 15:781-787(2009).
RN [28]
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., Buerckstuemmer T.,
RA 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 [29]
RP FUNCTION IN ADIPOCYTE DIFFERENTIATION, VARIANT PRAAS1 VAL-201, AND
RP CHARACTERIZATION OF VARIANT PRAAS1 VAL-201.
RX PubMed=21881205; DOI=10.1172/jci58414;
RA Kitamura A., Maekawa Y., Uehara H., Izumi K., Kawachi I., Nishizawa M.,
RA Toyoshima Y., Takahashi H., Standley D.M., Tanaka K., Hamazaki J.,
RA Murata S., Obara K., Toyoshima I., Yasutomo K.;
RT "A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation
RT and lipodystrophy in humans.";
RL J. Clin. Invest. 121:4150-4160(2011).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [32]
RP FUNCTION.
RX PubMed=27049119; DOI=10.1038/srep24032;
RA Ebstein F., Textoris-Taube K., Keller C., Golnik R., Vigneron N.,
RA Van den Eynde B.J., Schuler-Thurner B., Schadendorf D., Lorenz F.K.,
RA Uckert W., Urban S., Lehmann A., Albrecht-Koepke N., Janek K., Henklein P.,
RA Niewienda A., Kloetzel P.M., Mishto M.;
RT "Proteasomes generate spliced epitopes by two different mechanisms and as
RT efficiently as non-spliced epitopes.";
RL Sci. Rep. 6:24032-24032(2016).
RN [33]
RP VARIANT PRAAS1 MET-75, AND CHARACTERIZATION OF VARIANT PRAAS1 MET-75.
RX PubMed=21129723; DOI=10.1016/j.ajhg.2010.10.031;
RA Agarwal A.K., Xing C., DeMartino G.N., Mizrachi D., Hernandez M.D.,
RA Sousa A.B., Martinez de Villarreal L., dos Santos H.G., Garg A.;
RT "PSMB8 encoding the beta5i proteasome subunit is mutated in joint
RT contractures, muscle atrophy, microcytic anemia, and panniculitis-induced
RT lipodystrophy syndrome.";
RL Am. J. Hum. Genet. 87:866-872(2010).
RN [34]
RP VARIANT PRAAS1 MET-75.
RX PubMed=21953331; DOI=10.1002/art.33368;
RA Liu Y., Ramot Y., Torrelo A., Paller A.S., Si N., Babay S., Kim P.W.,
RA Sheikh A., Lee C.C., Chen Y., Vera A., Zhang X., Goldbach-Mansky R.,
RA Zlotogorski A.;
RT "Mutations in proteasome subunit beta type 8 cause chronic atypical
RT neutrophilic dermatosis with lipodystrophy and elevated temperature with
RT evidence of genetic and phenotypic heterogeneity.";
RL Arthritis Rheum. 64:895-907(2012).
RN [35]
RP VARIANT PRAAS1 VAL-201, AND CHARACTERIZATION OF VARIANT PRAAS1 VAL-201.
RX PubMed=21852578; DOI=10.1073/pnas.1106015108;
RA Arima K., Kinoshita A., Mishima H., Kanazawa N., Kaneko T., Mizushima T.,
RA Ichinose K., Nakamura H., Tsujino A., Kawakami A., Matsunaka M., Kasagi S.,
RA Kawano S., Kumagai S., Ohmura K., Mimori T., Hirano M., Ueno S., Tanaka K.,
RA Tanaka M., Toyoshima I., Sugino H., Yamakawa A., Tanaka K., Niikawa N.,
RA Furukawa F., Murata S., Eguchi K., Ida H., Yoshiura K.;
RT "Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8)
RT mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:14914-14919(2011).
RN [36]
RP VARIANTS PRAAS1 MET-75 AND GLN-105, AND CHARACTERIZATION OF VARIANTS PRAAS1
RP MET-75.
RX PubMed=26524591; DOI=10.1172/jci81260;
RA Brehm A., Liu Y., Sheikh A., Marrero B., Omoyinmi E., Zhou Q.,
RA Montealegre G., Biancotto A., Reinhardt A., Almeida de Jesus A.,
RA Pelletier M., Tsai W.L., Remmers E.F., Kardava L., Hill S., Kim H.,
RA Lachmann H.J., Megarbane A., Chae J.J., Brady J., Castillo R.D., Brown D.,
RA Casano A.V., Gao L., Chapelle D., Huang Y., Stone D., Chen Y., Sotzny F.,
RA Lee C.C., Kastner D.L., Torrelo A., Zlotogorski A., Moir S., Gadina M.,
RA McCoy P., Wesley R., Rother K., Hildebrand P.W., Brogan P., Krueger E.,
RA Aksentijevich I., Goldbach-Mansky R.;
RT "Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS
RT patients promote type I IFN production.";
RL J. Clin. Invest. 125:4196-4211(2015).
RN [37]
RP VARIANT PRAAS1 PRO-94.
RX PubMed=26567544; DOI=10.1007/s00431-015-2668-4;
RA Cavalcante M.P., Brunelli J.B., Miranda C.C., Novak G.V., Malle L.,
RA Aikawa N.E., Jesus A.A., Silva C.A.;
RT "CANDLE syndrome: chronic atypical neutrophilic dermatosis with
RT lipodystrophy and elevated temperature-a rare case with a novel mutation.";
RL Eur. J. Pediatr. 175:735-740(2016).
CC -!- FUNCTION: The proteasome is a multicatalytic proteinase complex which
CC is characterized by its ability to cleave peptides with Arg, Phe, Tyr,
CC Leu, and Glu adjacent to the leaving group at neutral or slightly basic
CC pH. The proteasome has an ATP-dependent proteolytic activity. This
CC subunit is involved in antigen processing to generate class I binding
CC peptides. Replacement of PSMB5 by PSMB8 increases the capacity of the
CC immunoproteasome to cleave model peptides after hydrophobic and basic
CC residues. Involved in the generation of spliced peptides resulting from
CC the ligation of two separate proteasomal cleavage products that are not
CC contiguous in the parental protein (PubMed:27049119). Acts as a major
CC component of interferon gamma-induced sensitivity. Plays a key role in
CC apoptosis via the degradation of the apoptotic inhibitor MCL1. May be
CC involved in the inflammatory response pathway. In cancer cells,
CC substitution of isoform 1 (E2) by isoform 2 (E1) results in
CC immunoproteasome deficiency. Required for the differentiation of
CC preadipocytes into adipocytes. {ECO:0000269|PubMed:16423992,
CC ECO:0000269|PubMed:19443843, ECO:0000269|PubMed:21881205,
CC ECO:0000269|PubMed:27049119, ECO:0000269|PubMed:8163024}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of peptide bonds with very broad specificity.;
CC EC=3.4.25.1;
CC -!- SUBUNIT: The 26S proteasome consists of a 20S proteasome core and two
CC 19S regulatory subunits. The 20S proteasome core is composed of 28
CC subunits that are arranged in four stacked rings, resulting in a
CC barrel-shaped structure. The two end rings are each formed by seven
CC alpha subunits, and the two central rings are each formed by seven beta
CC subunits. The catalytic chamber with the active sites is on the inside
CC of the barrel. Component of the immunoproteasome, where it displaces
CC the equivalent housekeeping subunit PSMB5. Component of the
CC spermatoproteasome, a form of the proteasome specifically found in
CC testis. Directly interacts with POMP. Interacts with TAP1.
CC {ECO:0000269|PubMed:15488952, ECO:0000269|PubMed:15944226}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 TAT protein.
CC {ECO:0000269|PubMed:14550573}.
CC -!- INTERACTION:
CC P28062; PRO_0000037573 [P27958]; Xeno; NbExp=4; IntAct=EBI-372294, EBI-3649474;
CC P28062-2; P05067: APP; NbExp=3; IntAct=EBI-372312, EBI-77613;
CC P28062-2; P54253: ATXN1; NbExp=6; IntAct=EBI-372312, EBI-930964;
CC P28062-2; Q9BVJ7: DUSP23; NbExp=5; IntAct=EBI-372312, EBI-724940;
CC P28062-2; Q96EK6: GNPNAT1; NbExp=3; IntAct=EBI-372312, EBI-3913338;
CC P28062-2; P28799: GRN; NbExp=3; IntAct=EBI-372312, EBI-747754;
CC P28062-2; P04792: HSPB1; NbExp=3; IntAct=EBI-372312, EBI-352682;
CC P28062-2; P42858: HTT; NbExp=3; IntAct=EBI-372312, EBI-466029;
CC P28062-2; Q0VD86: INCA1; NbExp=3; IntAct=EBI-372312, EBI-6509505;
CC P28062-2; O60333-2: KIF1B; NbExp=3; IntAct=EBI-372312, EBI-10975473;
CC P28062-2; O15116: LSM1; NbExp=3; IntAct=EBI-372312, EBI-347619;
CC P28062-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-372312, EBI-16439278;
CC P28062-2; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-372312, EBI-10271199;
CC P28062-2; Q99471: PFDN5; NbExp=3; IntAct=EBI-372312, EBI-357275;
CC P28062-2; P62487: POLR2G; NbExp=3; IntAct=EBI-372312, EBI-347928;
CC P28062-2; Q04864-2: REL; NbExp=3; IntAct=EBI-372312, EBI-10829018;
CC P28062-2; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-372312, EBI-396669;
CC P28062-2; Q9Y5X3-2: SNX5; NbExp=3; IntAct=EBI-372312, EBI-12229025;
CC P28062-2; P00441: SOD1; NbExp=3; IntAct=EBI-372312, EBI-990792;
CC P28062-2; Q13148: TARDBP; NbExp=6; IntAct=EBI-372312, EBI-372899;
CC P28062-2; Q96A09: TENT5B; NbExp=3; IntAct=EBI-372312, EBI-752030;
CC P28062-2; Q13114: TRAF3; NbExp=3; IntAct=EBI-372312, EBI-357631;
CC P28062-2; Q15645: TRIP13; NbExp=3; IntAct=EBI-372312, EBI-358993;
CC P28062-2; Q5T6F2: UBAP2; NbExp=3; IntAct=EBI-372312, EBI-2514383;
CC P28062-2; O76024: WFS1; NbExp=3; IntAct=EBI-372312, EBI-720609;
CC P28062-2; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-372312, EBI-12040603;
CC P28062-2; A6XGL0: YJEFN3; NbExp=3; IntAct=EBI-372312, EBI-13070200;
CC P28062-2; Q9H0C1: ZMYND12; NbExp=3; IntAct=EBI-372312, EBI-12030590;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU00809}.
CC Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=LMP7B, LMP7-E2;
CC IsoId=P28062-1; Sequence=Displayed;
CC Name=2; Synonyms=LMP7A, LMP7-E1;
CC IsoId=P28062-2; Sequence=VSP_005287;
CC -!- DEVELOPMENTAL STAGE: Highly expressed in immature dendritic cells (at
CC protein level). {ECO:0000269|PubMed:11717192}.
CC -!- INDUCTION: Up-regulated by IFNG/IFN-gamma and IRF1 (at protein level).
CC Up-regulated by TNF (at protein level). Up-regulated by tetrodotoxin
CC (TTX) in glial cells. Up-regulated in Crohn's bowel disease (CD). Down-
CC regulated by the selective inhibitor PR-957. Down-regulated in mature
CC dendritic cells by HSV-1 infection. Up-regulated by heat shock
CC treatment. {ECO:0000269|PubMed:11493458, ECO:0000269|PubMed:15501285,
CC ECO:0000269|PubMed:15907481, ECO:0000269|PubMed:17142736,
CC ECO:0000269|PubMed:17262812, ECO:0000269|PubMed:19443843,
CC ECO:0000269|PubMed:19525961, ECO:0000269|PubMed:19619915,
CC ECO:0000269|PubMed:8663318}.
CC -!- PTM: Autocleaved. The resulting N-terminal Thr residue of the mature
CC subunit is responsible for the nucleophile proteolytic activity.
CC {ECO:0000250|UniProtKB:O35955}.
CC -!- DISEASE: Proteasome-associated autoinflammatory syndrome 1 (PRAAS1)
CC [MIM:256040]: An autosomal recessive autoinflammatory disorder
CC characterized by early childhood onset of recurrent fever, joint
CC stiffness and severe contractures of the hands and feet, and
CC erythematous skin lesions with subsequent development of lipodystrophy
CC and laboratory evidence of immune dysregulation. Accompanying features
CC may include muscle weakness and atrophy, hepatosplenomegaly, and
CC microcytic anemia. {ECO:0000269|PubMed:21129723,
CC ECO:0000269|PubMed:21852578, ECO:0000269|PubMed:21881205,
CC ECO:0000269|PubMed:21953331, ECO:0000269|PubMed:26524591,
CC ECO:0000269|PubMed:26567544}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase T1B family. {ECO:0000255|PROSITE-
CC ProRule:PRU00809}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X66401; CAA47026.1; -; Genomic_DNA.
DR EMBL; X62598; CAA44482.1; -; mRNA.
DR EMBL; Z14982; CAA78705.1; -; Genomic_DNA.
DR EMBL; Z14982; CAA78706.1; -; Genomic_DNA.
DR EMBL; L11045; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X87344; CAA60786.1; -; Genomic_DNA.
DR EMBL; X87344; CAA60787.1; -; Genomic_DNA.
DR EMBL; U17496; AAA56777.1; -; mRNA.
DR EMBL; U17497; AAA56778.1; -; mRNA.
DR EMBL; AL671681; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL669918; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL935043; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX682530; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX088556; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT009502; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX927138; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR762476; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR753889; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03644.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03645.1; -; Genomic_DNA.
DR EMBL; BC001114; AAH01114.1; -; mRNA.
DR EMBL; U32863; AAA80235.1; -; Genomic_DNA.
DR EMBL; U32862; AAA80234.1; -; Genomic_DNA.
DR CCDS; CCDS4756.1; -. [P28062-2]
DR CCDS; CCDS4757.1; -. [P28062-1]
DR PIR; A44324; A44324.
DR PIR; C44324; C44324.
DR PIR; G01564; G01564.
DR PIR; G02018; G02018.
DR RefSeq; NP_004150.1; NM_004159.4. [P28062-2]
DR RefSeq; NP_683720.2; NM_148919.3. [P28062-1]
DR PDB; 5L5A; X-ray; 2.40 A; K/Y=73-210.
DR PDB; 5L5B; X-ray; 2.80 A; K/Y=73-210.
DR PDB; 5L5D; X-ray; 2.80 A; K/Y=73-210.
DR PDB; 5L5E; X-ray; 2.90 A; K/Y=73-210.
DR PDB; 5L5F; X-ray; 2.50 A; K/Y=73-210.
DR PDB; 5L5H; X-ray; 2.60 A; K/Y=73-210.
DR PDB; 5L5I; X-ray; 2.90 A; K/Y=73-210.
DR PDB; 5L5J; X-ray; 2.90 A; K/Y=73-210.
DR PDB; 5L5O; X-ray; 2.60 A; K/Y=73-210.
DR PDB; 5L5P; X-ray; 2.80 A; K/Y=73-210.
DR PDB; 5L5Q; X-ray; 2.80 A; K/Y=73-210.
DR PDB; 5L5R; X-ray; 2.90 A; K/Y=73-210.
DR PDB; 5L5S; X-ray; 2.60 A; K/Y=73-210.
DR PDB; 5L5T; X-ray; 2.90 A; K/Y=73-210.
DR PDB; 5L5U; X-ray; 2.60 A; K/Y=73-210.
DR PDB; 5L5V; X-ray; 2.70 A; K/Y=73-210.
DR PDB; 5LTT; X-ray; 2.70 A; K/Y=73-210.
DR PDB; 5M2B; X-ray; 2.70 A; K/Y=73-210.
DR PDB; 6AVO; EM; 3.80 A; C/D=73-276.
DR PDB; 6E5B; X-ray; 2.77 A; K/Y=1-276.
DR PDB; 7AWE; X-ray; 2.29 A; L/Z=73-275.
DR PDB; 7B12; X-ray; 2.43 A; L/Z=73-275.
DR PDBsum; 5L5A; -.
DR PDBsum; 5L5B; -.
DR PDBsum; 5L5D; -.
DR PDBsum; 5L5E; -.
DR PDBsum; 5L5F; -.
DR PDBsum; 5L5H; -.
DR PDBsum; 5L5I; -.
DR PDBsum; 5L5J; -.
DR PDBsum; 5L5O; -.
DR PDBsum; 5L5P; -.
DR PDBsum; 5L5Q; -.
DR PDBsum; 5L5R; -.
DR PDBsum; 5L5S; -.
DR PDBsum; 5L5T; -.
DR PDBsum; 5L5U; -.
DR PDBsum; 5L5V; -.
DR PDBsum; 5LTT; -.
DR PDBsum; 5M2B; -.
DR PDBsum; 6AVO; -.
DR PDBsum; 6E5B; -.
DR PDBsum; 7AWE; -.
DR PDBsum; 7B12; -.
DR AlphaFoldDB; P28062; -.
DR SMR; P28062; -.
DR BioGRID; 111669; 103.
DR IntAct; P28062; 36.
DR MINT; P28062; -.
DR STRING; 9606.ENSP00000364016; -.
DR BindingDB; P28062; -.
DR ChEMBL; CHEMBL5620; -.
DR DrugBank; DB08889; Carfilzomib.
DR DrugCentral; P28062; -.
DR GuidetoPHARMACOLOGY; 2408; -.
DR MEROPS; T01.015; -.
DR iPTMnet; P28062; -.
DR PhosphoSitePlus; P28062; -.
DR SwissPalm; P28062; -.
DR BioMuta; PSMB8; -.
DR DMDM; 334302881; -.
DR EPD; P28062; -.
DR jPOST; P28062; -.
DR MassIVE; P28062; -.
DR MaxQB; P28062; -.
DR PaxDb; P28062; -.
DR PeptideAtlas; P28062; -.
DR PRIDE; P28062; -.
DR ProteomicsDB; 54437; -. [P28062-1]
DR ProteomicsDB; 54438; -. [P28062-2]
DR Antibodypedia; 28713; 414 antibodies from 41 providers.
DR DNASU; 5696; -.
DR Ensembl; ENST00000374881.3; ENSP00000364015.2; ENSG00000204264.12. [P28062-2]
DR Ensembl; ENST00000374882.8; ENSP00000364016.4; ENSG00000204264.12. [P28062-1]
DR Ensembl; ENST00000383236.8; ENSP00000372723.4; ENSG00000206298.8. [P28062-1]
DR Ensembl; ENST00000383238.4; ENSP00000372725.4; ENSG00000206298.8. [P28062-2]
DR Ensembl; ENST00000416134.2; ENSP00000397057.2; ENSG00000235715.6. [P28062-2]
DR Ensembl; ENST00000416564.2; ENSP00000408825.2; ENSG00000226201.6. [P28062-2]
DR Ensembl; ENST00000421445.6; ENSP00000402406.2; ENSG00000236443.6. [P28062-1]
DR Ensembl; ENST00000429645.6; ENSP00000394155.2; ENSG00000226201.6. [P28062-1]
DR Ensembl; ENST00000435978.6; ENSP00000414731.2; ENSG00000231631.6. [P28062-2]
DR Ensembl; ENST00000436627.2; ENSP00000392693.2; ENSG00000230669.6. [P28062-2]
DR Ensembl; ENST00000438442.6; ENSP00000404585.2; ENSG00000231631.6. [P28062-1]
DR Ensembl; ENST00000441960.6; ENSP00000407539.2; ENSG00000230034.8. [P28062-2]
DR Ensembl; ENST00000452573.2; ENSP00000412618.2; ENSG00000236443.6. [P28062-2]
DR Ensembl; ENST00000455660.6; ENSP00000406797.2; ENSG00000230669.6. [P28062-1]
DR Ensembl; ENST00000457261.6; ENSP00000414770.2; ENSG00000235715.6. [P28062-1]
DR GeneID; 5696; -.
DR KEGG; hsa:5696; -.
DR MANE-Select; ENST00000374882.8; ENSP00000364016.4; NM_148919.4; NP_683720.2.
DR UCSC; uc003ocf.4; human. [P28062-1]
DR CTD; 5696; -.
DR DisGeNET; 5696; -.
DR GeneCards; PSMB8; -.
DR HGNC; HGNC:9545; PSMB8.
DR HPA; ENSG00000204264; Low tissue specificity.
DR MalaCards; PSMB8; -.
DR MIM; 177046; gene.
DR MIM; 256040; phenotype.
DR neXtProt; NX_P28062; -.
DR NIAGADS; ENSG00000204264; -.
DR OpenTargets; ENSG00000204264; -.
DR Orphanet; 324977; Proteasome-associated autoinflammatory syndrome.
DR PharmGKB; PA33890; -.
DR VEuPathDB; HostDB:ENSG00000204264; -.
DR eggNOG; KOG0175; Eukaryota.
DR GeneTree; ENSGT00940000157293; -.
DR HOGENOM; CLU_035750_7_1_1; -.
DR InParanoid; P28062; -.
DR OMA; IQIEMAH; -.
DR PhylomeDB; P28062; -.
DR TreeFam; TF106223; -.
DR PathwayCommons; P28062; -.
DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR Reactome; R-HSA-1236978; Cross-presentation of soluble exogenous antigens (endosomes).
DR Reactome; R-HSA-174084; Autodegradation of Cdh1 by Cdh1:APC/C.
DR Reactome; R-HSA-174113; SCF-beta-TrCP mediated degradation of Emi1.
DR Reactome; R-HSA-174154; APC/C:Cdc20 mediated degradation of Securin.
DR Reactome; R-HSA-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
DR Reactome; R-HSA-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR Reactome; R-HSA-180534; Vpu mediated degradation of CD4.
DR Reactome; R-HSA-180585; Vif-mediated degradation of APOBEC3G.
DR Reactome; R-HSA-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-HSA-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-HSA-202424; Downstream TCR signaling.
DR Reactome; R-HSA-211733; Regulation of activated PAK-2p34 by proteasome mediated degradation.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-HSA-349425; Autodegradation of the E3 ubiquitin ligase COP1.
DR Reactome; R-HSA-350562; Regulation of ornithine decarboxylase (ODC).
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR Reactome; R-HSA-450408; AUF1 (hnRNP D0) binds and destabilizes mRNA.
DR Reactome; R-HSA-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-HSA-4641257; Degradation of AXIN.
DR Reactome; R-HSA-4641258; Degradation of DVL.
DR Reactome; R-HSA-5358346; Hedgehog ligand biogenesis.
DR Reactome; R-HSA-5362768; Hh mutants are degraded by ERAD.
DR Reactome; R-HSA-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-HSA-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-HSA-5610783; Degradation of GLI2 by the proteasome.
DR Reactome; R-HSA-5610785; GLI3 is processed to GLI3R by the proteasome.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs.
DR Reactome; R-HSA-5668541; TNFR2 non-canonical NF-kB pathway.
DR Reactome; R-HSA-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-HSA-5678895; Defective CFTR causes cystic fibrosis.
DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-HSA-5689603; UCH proteinases.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-68867; Assembly of the pre-replicative complex.
DR Reactome; R-HSA-68949; Orc1 removal from chromatin.
DR Reactome; R-HSA-69017; CDK-mediated phosphorylation and removal of Cdc6.
DR Reactome; R-HSA-69481; G2/M Checkpoints.
DR Reactome; R-HSA-69601; Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
DR Reactome; R-HSA-75815; Ubiquitin-dependent degradation of Cyclin D.
DR Reactome; R-HSA-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint.
DR Reactome; R-HSA-8854050; FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity.
DR Reactome; R-HSA-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs.
DR Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR Reactome; R-HSA-9604323; Negative regulation of NOTCH4 signaling.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-HSA-9762114; GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; P28062; -.
DR SIGNOR; P28062; -.
DR BioGRID-ORCS; 5696; 11 hits in 1090 CRISPR screens.
DR ChiTaRS; PSMB8; human.
DR GeneWiki; PSMB8; -.
DR GenomeRNAi; 5696; -.
DR Pharos; P28062; Tclin.
DR PRO; PR:P28062; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P28062; protein.
DR Bgee; ENSG00000204264; Expressed in granulocyte and 96 other tissues.
DR ExpressionAtlas; P28062; baseline and differential.
DR Genevisible; P28062; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000502; C:proteasome complex; IDA:UniProtKB.
DR GO; GO:0005839; C:proteasome core complex; ISS:UniProtKB.
DR GO; GO:0019774; C:proteasome core complex, beta-subunit complex; ISS:UniProtKB.
DR GO; GO:1990111; C:spermatoproteasome complex; ISS:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IBA:GO_Central.
DR GO; GO:0004298; F:threonine-type endopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0019882; P:antigen processing and presentation; IEA:Ensembl.
DR GO; GO:0045444; P:fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IBA:GO_Central.
DR GO; GO:0052548; P:regulation of endopeptidase activity; IMP:UniProtKB.
DR Gene3D; 3.60.20.10; -; 1.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR InterPro; IPR000243; Pept_T1A_subB.
DR InterPro; IPR035705; Proteasome_beta8.
DR InterPro; IPR016050; Proteasome_bsu_CS.
DR InterPro; IPR001353; Proteasome_sua/b.
DR InterPro; IPR023333; Proteasome_suB-type.
DR PANTHER; PTHR11599:SF53; PTHR11599:SF53; 1.
DR Pfam; PF00227; Proteasome; 1.
DR PRINTS; PR00141; PROTEASOME.
DR SUPFAM; SSF56235; SSF56235; 1.
DR PROSITE; PS00854; PROTEASOME_BETA_1; 1.
DR PROSITE; PS51476; PROTEASOME_BETA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Differentiation;
KW Disease variant; Host-virus interaction; Hydrolase; Immunity; Nucleus;
KW Phosphoprotein; Protease; Proteasome; Reference proteome;
KW Threonine protease; Zymogen.
FT PROPEP 1..72
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000026597"
FT CHAIN 73..276
FT /note="Proteasome subunit beta type-8"
FT /id="PRO_0000026598"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 73
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT SITE 72..73
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:O35955"
FT VAR_SEQ 1..49
FT /note="MALLDVCGAPRGQRPESALPVAGSGRRSDPGHYSFSMRSPELALPRGMQ ->
FT MLIGTPTPRDTTPSSWLTSSLLVEAAPLDDTTLPTPVSSGCPGLE (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1922342"
FT /id="VSP_005287"
FT VARIANT 8
FT /note="G -> R (in allele LMP7C; dbSNP:rs114772012)"
FT /id="VAR_006488"
FT VARIANT 30..32
FT /note="PGH -> RPD (in allele LPM7C)"
FT /id="VAR_006489"
FT VARIANT 49
FT /note="Q -> K (in dbSNP:rs2071543)"
FT /evidence="ECO:0000269|Ref.7"
FT /id="VAR_065204"
FT VARIANT 74
FT /note="T -> S (in dbSNP:rs17220206)"
FT /id="VAR_057046"
FT VARIANT 75
FT /note="T -> M (in PRAAS1; markedly decreased chymotrypsin-
FT like activity consistent with a decrease in proteasomal
FT activity and loss of function; some patients are
FT heterozygotes for this mutation and also carry a mutation
FT in PSMA3; patients' cells show reduction of proteasome
FT content and endopeptidase activity of the proteasome;
FT dbSNP:rs748082671)"
FT /evidence="ECO:0000269|PubMed:21129723,
FT ECO:0000269|PubMed:26524591"
FT /id="VAR_065291"
FT VARIANT 94
FT /note="A -> P (in PRAAS1; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26567544"
FT /id="VAR_075256"
FT VARIANT 105
FT /note="K -> Q (in PRAAS1; some patients are heterozygotes
FT for this mutation and also carry a mutation in PSMB4;
FT dbSNP:rs1554239543)"
FT /evidence="ECO:0000269|PubMed:26524591"
FT /id="VAR_075257"
FT VARIANT 201
FT /note="G -> V (in PRAAS1; affects immunoproteasome
FT assembly; reduced proteasome levels; reduced chymotrypsin-
FT like activity consistent with a decrease in proteasomal
FT activity; dbSNP:rs387906680)"
FT /evidence="ECO:0000269|PubMed:21852578,
FT ECO:0000269|PubMed:21881205"
FT /id="VAR_066449"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:7AWE"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:7AWE"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:7AWE"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:7AWE"
FT STRAND 106..110
FT /evidence="ECO:0007829|PDB:7AWE"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:7AWE"
FT HELIX 121..142
FT /evidence="ECO:0007829|PDB:7AWE"
FT HELIX 148..161
FT /evidence="ECO:0007829|PDB:7AWE"
FT TURN 162..164
FT /evidence="ECO:0007829|PDB:7AWE"
FT STRAND 169..177
FT /evidence="ECO:0007829|PDB:7AWE"
FT STRAND 180..186
FT /evidence="ECO:0007829|PDB:7AWE"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:7AWE"
FT STRAND 196..201
FT /evidence="ECO:0007829|PDB:7AWE"
FT HELIX 204..214
FT /evidence="ECO:0007829|PDB:7AWE"
FT HELIX 221..238
FT /evidence="ECO:0007829|PDB:7AWE"
FT STRAND 244..252
FT /evidence="ECO:0007829|PDB:7AWE"
FT STRAND 255..263
FT /evidence="ECO:0007829|PDB:7AWE"
FT HELIX 264..273
FT /evidence="ECO:0007829|PDB:7AWE"
FT MOD_RES P28062-2:5
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305"
SQ SEQUENCE 276 AA; 30354 MW; 4F689501677DBD44 CRC64;
MALLDVCGAP RGQRPESALP VAGSGRRSDP GHYSFSMRSP ELALPRGMQP TEFFQSLGGD
GERNVQIEMA HGTTTLAFKF QHGVIAAVDS RASAGSYISA LRVNKVIEIN PYLLGTMSGC
AADCQYWERL LAKECRLYYL RNGERISVSA ASKLLSNMMC QYRGMGLSMG SMICGWDKKG
PGLYYVDEHG TRLSGNMFST GSGNTYAYGV MDSGYRPNLS PEEAYDLGRR AIAYATHRDS
YSGGVVNMYH MKEDGWVKVE STDVSDLLHQ YREANQ
