PSA4_HUMAN
ID PSA4_HUMAN Reviewed; 261 AA.
AC P25789; D3DW86; Q53XP2; Q567Q5; Q8TBD1;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 227.
DE RecName: Full=Proteasome subunit alpha type-4;
DE AltName: Full=Macropain subunit C9;
DE AltName: Full=Multicatalytic endopeptidase complex subunit C9;
DE AltName: Full=Proteasome component C9;
DE AltName: Full=Proteasome subunit L;
GN Name=PSMA4; Synonyms=HC9, PSC9;
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 [MRNA] (ISOFORM 1).
RX PubMed=2025653; DOI=10.1016/0167-4781(91)90090-9;
RA Tamura T., Lee D.H., Osaka F., Fujiwara T., Shin S., Chung C.H., Tanaka K.,
RA Ichihara A.;
RT "Molecular cloning and sequence analysis of cDNAs for five major subunits
RT of human proteasomes (multi-catalytic proteinase complexes).";
RL Biochim. Biophys. Acta 1089:95-102(1991).
RN [2]
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 vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Blood, Brain, Lung, Pancreas, and Urinary bladder;
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 [6]
RP PROTEIN SEQUENCE OF 18-39.
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 partial
RT sequencing.";
RL Biochem. Biophys. Res. Commun. 205:1785-1789(1994).
RN [7]
RP FUNCTION IN ANTIGEN PRESENTATION.
RX PubMed=8610016; DOI=10.1038/381166a0;
RA Groettrup M., Soza A., Eggers M., Kuehn L., Dick T.P., Schild H.,
RA Rammensee H.G., Koszinowski U.H., Kloetzel P.M.;
RT "A role for the proteasome regulator PA28alpha in antigen presentation.";
RL Nature 381:166-168(1996).
RN [8]
RP INTERACTION WITH HTLV-1 TAX (MICROBIAL INFECTION).
RX PubMed=8692272; DOI=10.1038/381328a0;
RA Rousset R., Desbois C., Bantignies F., Jalinot P.;
RT "Effects on NF-kappa B1/p105 processing of the interaction between the
RT HTLV-1 transactivator Tax and the proteasome.";
RL Nature 381:328-331(1996).
RN [9]
RP INDUCTION BY BO-653 AND PROBUCOL.
RX PubMed=11521686; DOI=10.5551/jat1994.7.223;
RA Takabe W., Mataki C., Wada Y., Ishii M., Izumi A., Aburatani H.,
RA Hamakubo T., Niki E., Kodama T., Noguchi N.;
RT "Gene expression induced by BO-653, probucol and BHQ in human endothelial
RT cells.";
RL J. Atheroscler. Thromb. 7:223-230(2000).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=12181345; DOI=10.1091/mbc.e02-03-0122;
RA Lafarga M., Berciano M.T., Pena E., Mayo I., Castano J.G., Bohmann D.,
RA Rodrigues J.P., Tavanez J.P., Carmo-Fonseca M.;
RT "Clastosome: a subtype of nuclear body enriched in 19S and 20S proteasomes,
RT ubiquitin, and protein substrates of proteasome.";
RL Mol. Biol. Cell 13:2771-2782(2002).
RN [11]
RP FUNCTION.
RX PubMed=15244466; DOI=10.1021/bm049957a;
RA Yano M., Koumoto Y., Kanesaki Y., Wu X., Kido H.;
RT "20S proteasome prevents aggregation of heat-denatured proteins without
RT PA700 regulatory subcomplex like a molecular chaperone.";
RL Biomacromolecules 5:1465-1469(2004).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-75, AND IDENTIFICATION BY
RP 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 26S
RT proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION BY
RP 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 [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-127 AND LYS-176, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-173, AND IDENTIFICATION BY
RP 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 [19]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27176742; DOI=10.1515/hsz-2016-0176;
RA Rut W., Drag M.;
RT "Human 20S proteasome activity towards fluorogenic peptides of various
RT chain lengths.";
RL Biol. Chem. 397:921-926(2016).
RN [20]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS), AND SUBUNIT.
RX PubMed=26133119; DOI=10.1038/ncomms8573;
RA da Fonseca P.C., Morris E.P.;
RT "Cryo-EM reveals the conformation of a substrate analogue in the human 20S
RT proteasome core.";
RL Nat. Commun. 6:7573-7573(2015).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 2-251, AND SUBUNIT.
RX PubMed=25599644; DOI=10.1016/j.str.2014.11.017;
RA Harshbarger W., Miller C., Diedrich C., Sacchettini J.;
RT "Crystal structure of the human 20S proteasome in complex with
RT carfilzomib.";
RL Structure 23:418-424(2015).
RN [22]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS), AND SUBUNIT.
RX PubMed=27428775; DOI=10.1038/nsmb.3273;
RA Huang X., Luan B., Wu J., Shi Y.;
RT "An atomic structure of the human 26S proteasome.";
RL Nat. Struct. Mol. Biol. 23:778-785(2016).
RN [23]
RP STRUCTURE BY ELECTRON MICROSCOPY (4.02 ANGSTROMS), AND SUBUNIT.
RX PubMed=27342858; DOI=10.1073/pnas.1608050113;
RA Schweitzer A., Aufderheide A., Rudack T., Beck F., Pfeifer G.,
RA Plitzko J.M., Sakata E., Schulten K., Foerster F., Baumeister W.;
RT "Structure of the human 26S proteasome at a resolution of 3.9 Aa.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:7816-7821(2016).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS), AND SUBUNIT.
RX PubMed=27493187; DOI=10.1126/science.aaf8993;
RA Schrader J., Henneberg F., Mata R.A., Tittmann K., Schneider T.R.,
RA Stark H., Bourenkov G., Chari A.;
RT "The inhibition mechanism of human 20S proteasomes enables next-generation
RT inhibitor design.";
RL Science 353:594-598(2016).
RN [25]
RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) IN COMPLEX WITH AKIRIN2,
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=34711951; DOI=10.1038/s41586-021-04035-8;
RA de Almeida M., Hinterndorfer M., Brunner H., Grishkovskaya I., Singh K.,
RA Schleiffer A., Jude J., Deswal S., Kalis R., Vunjak M., Lendl T., Imre R.,
RA Roitinger E., Neumann T., Kandolf S., Schutzbier M., Mechtler K.,
RA Versteeg G.A., Haselbach D., Zuber J.;
RT "AKIRIN2 controls the nuclear import of proteasomes in vertebrates.";
RL Nature 599:491-496(2021).
CC -!- FUNCTION: Component of the 20S core proteasome complex involved in the
CC proteolytic degradation of most intracellular proteins. This complex
CC plays numerous essential roles within the cell by associating with
CC different regulatory particles. Associated with two 19S regulatory
CC particles, forms the 26S proteasome and thus participates in the ATP-
CC dependent degradation of ubiquitinated proteins. The 26S proteasome
CC plays a key role in the maintenance of protein homeostasis by removing
CC misfolded or damaged proteins that could impair cellular functions, and
CC by removing proteins whose functions are no longer required. Associated
CC with the PA200 or PA28, the 20S proteasome mediates ubiquitin-
CC independent protein degradation. This type of proteolysis is required
CC in several pathways including spermatogenesis (20S-PA200 complex) or
CC generation of a subset of MHC class I-presented antigenic peptides
CC (20S-PA28 complex). {ECO:0000269|PubMed:15244466,
CC ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}.
CC -!- SUBUNIT: The 26S proteasome consists of a 20S proteasome core and two
CC 19S regulatory subunits. The 20S proteasome core is a barrel-shaped
CC complex made of 28 subunits that are arranged in four stacked rings.
CC The two outer rings are each formed by seven alpha subunits, and the
CC two inner rings are formed by seven beta subunits. The proteolytic
CC activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.
CC {ECO:0000269|PubMed:25599644, ECO:0000269|PubMed:26133119,
CC ECO:0000269|PubMed:27342858, ECO:0000269|PubMed:27428775,
CC ECO:0000269|PubMed:27493187, ECO:0000269|PubMed:34711951}.
CC -!- SUBUNIT: (Microbial infection) Interaction with HTLV-1 TAX protein
CC favors NFKB1 activation. {ECO:0000269|PubMed:8692272}.
CC -!- INTERACTION:
CC P25789; P54253: ATXN1; NbExp=7; IntAct=EBI-359310, EBI-930964;
CC P25789; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-359310, EBI-11530605;
CC P25789; Q08379: GOLGA2; NbExp=3; IntAct=EBI-359310, EBI-618309;
CC P25789; Q16665: HIF1A; NbExp=4; IntAct=EBI-359310, EBI-447269;
CC P25789; P42858: HTT; NbExp=4; IntAct=EBI-359310, EBI-466029;
CC P25789; Q13422: IKZF1; NbExp=3; IntAct=EBI-359310, EBI-745305;
CC P25789; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-359310, EBI-11522367;
CC P25789; P25786: PSMA1; NbExp=7; IntAct=EBI-359310, EBI-359352;
CC P25789; P25787: PSMA2; NbExp=8; IntAct=EBI-359310, EBI-603262;
CC P25789; P25788: PSMA3; NbExp=4; IntAct=EBI-359310, EBI-348380;
CC P25789; P60900: PSMA6; NbExp=5; IntAct=EBI-359310, EBI-357793;
CC P25789; O14818: PSMA7; NbExp=11; IntAct=EBI-359310, EBI-603272;
CC P25789; Q04864-2: REL; NbExp=3; IntAct=EBI-359310, EBI-10829018;
CC P25789; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-359310, EBI-1105213;
CC P25789; O00635: TRIM38; NbExp=3; IntAct=EBI-359310, EBI-2130415;
CC P25789; Q99PV5: Bhlhe41; Xeno; NbExp=2; IntAct=EBI-359310, EBI-6143801;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12181345,
CC ECO:0000269|PubMed:34711951}. Nucleus {ECO:0000269|PubMed:12181345,
CC ECO:0000269|PubMed:34711951}. Note=Translocated from the cytoplasm into
CC the nucleus following interaction with AKIRIN2, which bridges the
CC proteasome with the nuclear import receptor IPO9 (PubMed:34711951).
CC Colocalizes with TRIM5 in the cytoplasmic bodies (By similarity).
CC {ECO:0000250|UniProtKB:Q9R1P0, ECO:0000269|PubMed:34711951}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P25789-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P25789-2; Sequence=VSP_043102;
CC -!- INDUCTION: Down-regulated by antioxidants BO-653 and probucol.
CC {ECO:0000269|PubMed:11521686}.
CC -!- SIMILARITY: Belongs to the peptidase T1A family. {ECO:0000255|PROSITE-
CC ProRule:PRU00808}.
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DR EMBL; D00763; BAA00660.1; -; mRNA.
DR EMBL; BT009784; AAP88786.1; -; mRNA.
DR EMBL; AC027228; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471136; EAW99163.1; -; Genomic_DNA.
DR EMBL; CH471136; EAW99164.1; -; Genomic_DNA.
DR EMBL; BC005361; AAH05361.1; -; mRNA.
DR EMBL; BC022445; AAH22445.1; -; mRNA.
DR EMBL; BC022817; AAH22817.2; -; mRNA.
DR EMBL; BC047667; AAH47667.1; -; mRNA.
DR EMBL; BC093069; AAH93069.1; -; mRNA.
DR CCDS; CCDS10303.1; -. [P25789-1]
DR CCDS; CCDS45319.1; -. [P25789-2]
DR PIR; S15972; SNHUC9.
DR RefSeq; NP_001096137.1; NM_001102667.2. [P25789-1]
DR RefSeq; NP_001096138.1; NM_001102668.2. [P25789-2]
DR RefSeq; NP_001317605.1; NM_001330676.1. [P25789-1]
DR RefSeq; NP_002780.1; NM_002789.5. [P25789-1]
DR PDB; 4R3O; X-ray; 2.60 A; C/Q=2-251.
DR PDB; 4R67; X-ray; 2.89 A; C/Q/e/s=2-251.
DR PDB; 5A0Q; EM; 3.50 A; C/Q=1-261.
DR PDB; 5GJQ; EM; 4.50 A; D/j=1-261.
DR PDB; 5GJR; EM; 3.50 A; D/j=1-261.
DR PDB; 5L4G; EM; 4.02 A; C/P=1-261.
DR PDB; 5LE5; X-ray; 1.80 A; B/P=1-261.
DR PDB; 5LEX; X-ray; 2.20 A; B/P=1-261.
DR PDB; 5LEY; X-ray; 1.90 A; B/P=1-261.
DR PDB; 5LEZ; X-ray; 2.19 A; B/P=1-261.
DR PDB; 5LF0; X-ray; 2.41 A; B/P=1-261.
DR PDB; 5LF1; X-ray; 2.00 A; B/P=1-261.
DR PDB; 5LF3; X-ray; 2.10 A; B/P=1-261.
DR PDB; 5LF4; X-ray; 1.99 A; B/P=1-261.
DR PDB; 5LF6; X-ray; 2.07 A; B/P=1-261.
DR PDB; 5LF7; X-ray; 2.00 A; B/P=1-261.
DR PDB; 5LN3; EM; 6.80 A; C=1-261.
DR PDB; 5M32; EM; 3.80 A; B/P=1-261.
DR PDB; 5T0C; EM; 3.80 A; AI/BI=2-261.
DR PDB; 5T0G; EM; 4.40 A; I=2-261.
DR PDB; 5T0H; EM; 6.80 A; I=2-261.
DR PDB; 5T0I; EM; 8.00 A; I=2-261.
DR PDB; 5T0J; EM; 8.00 A; I=2-261.
DR PDB; 5VFO; EM; 3.50 A; I/i=2-251.
DR PDB; 5VFP; EM; 4.20 A; I/i=2-251.
DR PDB; 5VFQ; EM; 4.20 A; I/i=2-251.
DR PDB; 5VFR; EM; 4.90 A; I/i=2-251.
DR PDB; 5VFS; EM; 3.60 A; I/i=2-251.
DR PDB; 5VFT; EM; 7.00 A; I/i=2-251.
DR PDB; 5VFU; EM; 5.80 A; I/i=2-251.
DR PDB; 6AVO; EM; 3.80 A; O/Z=1-261.
DR PDB; 6E5B; X-ray; 2.77 A; B/P=1-261.
DR PDB; 6KWY; EM; 2.72 A; B/P=1-261.
DR PDB; 6MSB; EM; 3.00 A; I/i=2-261.
DR PDB; 6MSD; EM; 3.20 A; I/i=2-261.
DR PDB; 6MSE; EM; 3.30 A; I/i=2-261.
DR PDB; 6MSG; EM; 3.50 A; I/i=2-261.
DR PDB; 6MSH; EM; 3.60 A; I/i=2-261.
DR PDB; 6MSJ; EM; 3.30 A; I/i=2-261.
DR PDB; 6MSK; EM; 3.20 A; I/i=2-261.
DR PDB; 6R70; EM; 3.50 A; B/P=2-249.
DR PDB; 6REY; EM; 3.00 A; C/Q=1-261.
DR PDB; 6RGQ; EM; 2.60 A; C/Q=1-261.
DR PDB; 6WJD; EM; 4.80 A; I/i=2-261.
DR PDB; 6WJN; EM; 5.70 A; I/i=2-251.
DR PDB; 6XMJ; EM; 3.00 A; C=2-251.
DR PDB; 7AWE; X-ray; 2.29 A; C/Q=2-257.
DR PDB; 7B12; X-ray; 2.43 A; C/Q=2-249.
DR PDB; 7LXV; EM; 3.40 A; B/P=1-261.
DR PDB; 7NHT; EM; 2.80 A; B=1-261.
DR PDB; 7PG9; EM; 3.70 A; C/Q=1-261.
DR PDB; 7V5G; EM; 4.47 A; Q/X=1-261.
DR PDB; 7V5M; EM; 3.88 A; C/Q=1-261.
DR PDBsum; 4R3O; -.
DR PDBsum; 4R67; -.
DR PDBsum; 5A0Q; -.
DR PDBsum; 5GJQ; -.
DR PDBsum; 5GJR; -.
DR PDBsum; 5L4G; -.
DR PDBsum; 5LE5; -.
DR PDBsum; 5LEX; -.
DR PDBsum; 5LEY; -.
DR PDBsum; 5LEZ; -.
DR PDBsum; 5LF0; -.
DR PDBsum; 5LF1; -.
DR PDBsum; 5LF3; -.
DR PDBsum; 5LF4; -.
DR PDBsum; 5LF6; -.
DR PDBsum; 5LF7; -.
DR PDBsum; 5LN3; -.
DR PDBsum; 5M32; -.
DR PDBsum; 5T0C; -.
DR PDBsum; 5T0G; -.
DR PDBsum; 5T0H; -.
DR PDBsum; 5T0I; -.
DR PDBsum; 5T0J; -.
DR PDBsum; 5VFO; -.
DR PDBsum; 5VFP; -.
DR PDBsum; 5VFQ; -.
DR PDBsum; 5VFR; -.
DR PDBsum; 5VFS; -.
DR PDBsum; 5VFT; -.
DR PDBsum; 5VFU; -.
DR PDBsum; 6AVO; -.
DR PDBsum; 6E5B; -.
DR PDBsum; 6KWY; -.
DR PDBsum; 6MSB; -.
DR PDBsum; 6MSD; -.
DR PDBsum; 6MSE; -.
DR PDBsum; 6MSG; -.
DR PDBsum; 6MSH; -.
DR PDBsum; 6MSJ; -.
DR PDBsum; 6MSK; -.
DR PDBsum; 6R70; -.
DR PDBsum; 6REY; -.
DR PDBsum; 6RGQ; -.
DR PDBsum; 6WJD; -.
DR PDBsum; 6WJN; -.
DR PDBsum; 6XMJ; -.
DR PDBsum; 7AWE; -.
DR PDBsum; 7B12; -.
DR PDBsum; 7LXV; -.
DR PDBsum; 7NHT; -.
DR PDBsum; 7PG9; -.
DR PDBsum; 7V5G; -.
DR PDBsum; 7V5M; -.
DR AlphaFoldDB; P25789; -.
DR SMR; P25789; -.
DR BioGRID; 111658; 185.
DR ComplexPortal; CPX-5993; 26S Proteasome complex.
DR CORUM; P25789; -.
DR DIP; DIP-29365N; -.
DR IntAct; P25789; 64.
DR MINT; P25789; -.
DR STRING; 9606.ENSP00000044462; -.
DR BindingDB; P25789; -.
DR ChEMBL; CHEMBL2364701; -.
DR ChEMBL; CHEMBL3831201; -.
DR DrugBank; DB08515; (3AR,6R,6AS)-6-((S)-((S)-CYCLOHEX-2-ENYL)(HYDROXY)METHYL)-6A-METHYL-4-OXO-HEXAHYDRO-2H-FURO[3,2-C]PYRROLE-6-CARBALDEHYDE.
DR MEROPS; T01.973; -.
DR GlyGen; P25789; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P25789; -.
DR MetOSite; P25789; -.
DR PhosphoSitePlus; P25789; -.
DR SwissPalm; P25789; -.
DR BioMuta; PSMA4; -.
DR DMDM; 130861; -.
DR UCD-2DPAGE; P25789; -.
DR EPD; P25789; -.
DR jPOST; P25789; -.
DR MassIVE; P25789; -.
DR MaxQB; P25789; -.
DR PaxDb; P25789; -.
DR PeptideAtlas; P25789; -.
DR PRIDE; P25789; -.
DR ProteomicsDB; 54292; -. [P25789-1]
DR ProteomicsDB; 54293; -. [P25789-2]
DR TopDownProteomics; P25789-1; -. [P25789-1]
DR Antibodypedia; 27657; 341 antibodies from 36 providers.
DR DNASU; 5685; -.
DR Ensembl; ENST00000044462.12; ENSP00000044462.7; ENSG00000041357.16. [P25789-1]
DR Ensembl; ENST00000413382.6; ENSP00000402118.2; ENSG00000041357.16. [P25789-2]
DR Ensembl; ENST00000559082.5; ENSP00000453887.1; ENSG00000041357.16. [P25789-1]
DR GeneID; 5685; -.
DR KEGG; hsa:5685; -.
DR MANE-Select; ENST00000044462.12; ENSP00000044462.7; NM_002789.6; NP_002780.1.
DR UCSC; uc002bdu.5; human. [P25789-1]
DR CTD; 5685; -.
DR DisGeNET; 5685; -.
DR GeneCards; PSMA4; -.
DR HGNC; HGNC:9533; PSMA4.
DR HPA; ENSG00000041357; Low tissue specificity.
DR MIM; 176846; gene.
DR neXtProt; NX_P25789; -.
DR OpenTargets; ENSG00000041357; -.
DR PharmGKB; PA33878; -.
DR VEuPathDB; HostDB:ENSG00000041357; -.
DR eggNOG; KOG0178; Eukaryota.
DR GeneTree; ENSGT00550000074827; -.
DR InParanoid; P25789; -.
DR OMA; YVLNDNM; -.
DR OrthoDB; 1222564at2759; -.
DR PhylomeDB; P25789; -.
DR TreeFam; TF106209; -.
DR BRENDA; 3.4.25.1; 2681.
DR PathwayCommons; P25789; -.
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-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; P25789; -.
DR SIGNOR; P25789; -.
DR BioGRID-ORCS; 5685; 774 hits in 1053 CRISPR screens.
DR ChiTaRS; PSMA4; human.
DR GeneWiki; PSMA4; -.
DR GenomeRNAi; 5685; -.
DR Pharos; P25789; Tbio.
DR PRO; PR:P25789; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P25789; protein.
DR Bgee; ENSG00000041357; Expressed in monocyte and 202 other tissues.
DR ExpressionAtlas; P25789; baseline and differential.
DR Genevisible; P25789; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0000502; C:proteasome complex; IDA:UniProtKB.
DR GO; GO:0005839; C:proteasome core complex; IDA:UniProtKB.
DR GO; GO:0019773; C:proteasome core complex, alpha-subunit complex; IDA:UniProtKB.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IBA:GO_Central.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IC:ComplexPortal.
DR Gene3D; 3.60.20.10; -; 1.
DR InterPro; IPR029055; Ntn_hydrolases_N.
DR InterPro; IPR023332; Proteasome_alpha-type.
DR InterPro; IPR000426; Proteasome_asu_N.
DR InterPro; IPR016050; Proteasome_bsu_CS.
DR InterPro; IPR001353; Proteasome_sua/b.
DR InterPro; IPR034647; Proteasome_subunit_alpha4.
DR PANTHER; PTHR11599:SF13; PTHR11599:SF13; 1.
DR Pfam; PF00227; Proteasome; 1.
DR Pfam; PF10584; Proteasome_A_N; 1.
DR SMART; SM00948; Proteasome_A_N; 1.
DR SUPFAM; SSF56235; SSF56235; 1.
DR PROSITE; PS00388; PROTEASOME_ALPHA_1; 1.
DR PROSITE; PS51475; PROTEASOME_ALPHA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Host-virus interaction; Nucleus; Phosphoprotein;
KW Proteasome; Reference proteome.
FT CHAIN 1..261
FT /note="Proteasome subunit alpha type-4"
FT /id="PRO_0000124103"
FT REGION 240..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 75
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17323924"
FT MOD_RES 127
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 173
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 176
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..71
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043102"
FT TURN 3..5
FT /evidence="ECO:0007829|PDB:5LE5"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:5VFO"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:7AWE"
FT HELIX 19..29
FT /evidence="ECO:0007829|PDB:5LE5"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:5LE5"
FT STRAND 42..48
FT /evidence="ECO:0007829|PDB:5LE5"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:6KWY"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:5LE5"
FT STRAND 72..78
FT /evidence="ECO:0007829|PDB:5LE5"
FT HELIX 80..101
FT /evidence="ECO:0007829|PDB:5LE5"
FT HELIX 107..123
FT /evidence="ECO:0007829|PDB:5LE5"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:5LE5"
FT STRAND 132..140
FT /evidence="ECO:0007829|PDB:5LE5"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:5LE5"
FT STRAND 144..150
FT /evidence="ECO:0007829|PDB:5LE5"
FT TURN 152..154
FT /evidence="ECO:0007829|PDB:6E5B"
FT STRAND 156..165
FT /evidence="ECO:0007829|PDB:5LE5"
FT HELIX 168..178
FT /evidence="ECO:0007829|PDB:5LE5"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:5LE5"
FT HELIX 186..200
FT /evidence="ECO:0007829|PDB:5LE5"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:5LE5"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:5LE5"
FT STRAND 211..219
FT /evidence="ECO:0007829|PDB:5LE5"
FT STRAND 222..227
FT /evidence="ECO:0007829|PDB:5LE5"
FT HELIX 230..246
FT /evidence="ECO:0007829|PDB:5LE5"
FT HELIX 249..252
FT /evidence="ECO:0007829|PDB:7AWE"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:7AWE"
SQ SEQUENCE 261 AA; 29484 MW; 7867422B1B31F3B9 CRC64;
MSRRYDSRTT IFSPEGRLYQ VEYAMEAIGH AGTCLGILAN DGVLLAAERR NIHKLLDEVF
FSEKIYKLNE DMACSVAGIT SDANVLTNEL RLIAQRYLLQ YQEPIPCEQL VTALCDIKQA
YTQFGGKRPF GVSLLYIGWD KHYGFQLYQS DPSGNYGGWK ATCIGNNSAA AVSMLKQDYK
EGEMTLKSAL ALAIKVLNKT MDVSKLSAEK VEIATLTREN GKTVIRVLKQ KEVEQLIKKH
EEEEAKAERE KKEKEQKEKD K
