PSMD4_HUMAN
ID PSMD4_HUMAN Reviewed; 377 AA.
AC P55036; D3DV16; Q5VWC5; Q9NS92;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=26S proteasome non-ATPase regulatory subunit 4;
DE AltName: Full=26S proteasome regulatory subunit RPN10;
DE AltName: Full=26S proteasome regulatory subunit S5A;
DE AltName: Full=Antisecretory factor 1;
DE Short=AF;
DE Short=ASF;
DE AltName: Full=Multiubiquitin chain-binding protein;
GN Name=PSMD4; Synonyms=MCB1;
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], AND PROTEIN SEQUENCE OF 63-75 AND 130-140.
RC TISSUE=Pituitary;
RX PubMed=7657640; DOI=10.1074/jbc.270.35.20615;
RA Johansson E., Loennroth I., Lange S., Jonson I., Jennische E.,
RA Loennroth C.;
RT "Molecular cloning and expression of a pituitary gland protein modulating
RT intestinal fluid secretion.";
RL J. Biol. Chem. 270:20615-20620(1995).
RN [2]
RP SEQUENCE REVISION.
RA Loennroth I.;
RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=8641424; DOI=10.1016/0014-5793(96)00101-9;
RA Ferrell K., Deveraux Q., van Nocker S., Rechsteiner M.;
RT "Molecular cloning and expression of a multiubiquitin chain binding subunit
RT of the human 26S protease.";
RL FEBS Lett. 381:143-148(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RC TISSUE=Fetal brain;
RX PubMed=10921894; DOI=10.1093/emboj/19.15.4144;
RA Kawahara H., Kasahara M., Nishiyama A., Ohsumi K., Goto T., Kishimoto T.,
RA Saeki Y., Yokosawa H., Shimbara N., Murata S., Chiba T., Suzuki K.,
RA Tanaka K.;
RT "Developmentally regulated, alternative splicing of the Rpn10 gene
RT generates multiple forms of 26S proteasomes.";
RL EMBO J. 19:4144-4153(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver, and Lung;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 70-377.
RC TISSUE=Brain;
RA Fraser P.E., Levesque G., Rogaeva E.A., Yu G., St George-Hyslop P.H.;
RT "Proteolysis of presenilin 1 is associated with the 26S proteasome and is
RT altered in Alzheimer's disease.";
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP CHARACTERIZATION.
RX PubMed=3524692; DOI=10.1016/0304-4165(86)90144-3;
RA Loennroth I., Lange S.;
RT "Purification and characterization of the antisecretory factor: a protein
RT in the central nervous system and in the gut which inhibits intestinal
RT hypersecretion induced by cholera toxin.";
RL Biochim. Biophys. Acta 883:138-144(1986).
RN [10]
RP FUNCTION.
RX PubMed=1317798; DOI=10.1111/j.1432-1033.1992.tb16961.x;
RA Kanayama H.O., Tamura T., Ugai S., Kagawa S., Tanahashi N., Yoshimura T.,
RA Tanaka K., Ichihara A.;
RT "Demonstration that a human 26S proteolytic complex consists of a
RT proteasome and multiple associated protein components and hydrolyzes ATP
RT and ubiquitin-ligated proteins by closely linked mechanisms.";
RL Eur. J. Biochem. 206:567-578(1992).
RN [11]
RP POLYUBIQUITIN BINDING SITES.
RX PubMed=9488668; DOI=10.1074/jbc.273.10.5461;
RA Young P., Deveraux Q., Beal R.E., Pickart C.M., Rechsteiner M.;
RT "Characterization of two polyubiquitin binding sites in the 26 S protease
RT subunit 5a.";
RL J. Biol. Chem. 273:5461-5467(1998).
RN [12]
RP INTERACTION WITH NUB1.
RX PubMed=11585840; DOI=10.1074/jbc.m108636200;
RA Kamitani T., Kito K., Fukuda-Kamitani T., Yeh E.T.H.;
RT "Targeting of NEDD8 and its conjugates for proteasomal degradation by
RT NUB1.";
RL J. Biol. Chem. 276:46655-46660(2001).
RN [13]
RP INTERACTION WITH UBQLN1.
RX PubMed=15147878; DOI=10.1016/j.febslet.2004.04.031;
RA Ko H.S., Uehara T., Tsuruma K., Nomura Y.;
RT "Ubiquilin interacts with ubiquitylated proteins and proteasome through its
RT ubiquitin-associated and ubiquitin-like domains.";
RL FEBS Lett. 566:110-114(2004).
RN [14]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [15]
RP INTERACTION WITH UBQLN4.
RX PubMed=15280365; DOI=10.1074/jbc.m406284200;
RA Riley B.E., Xu Y., Zoghbi H.Y., Orr H.T.;
RT "The effects of the polyglutamine repeat protein ataxin-1 on the UbL-UBA
RT protein A1Up.";
RL J. Biol. Chem. 279:42290-42301(2004).
RN [16]
RP INTERACTION WITH SQSTM1.
RX PubMed=15340068; DOI=10.1128/mcb.24.18.8055-8068.2004;
RA Seibenhener M.L., Babu J.R., Geetha T., Wong H.C., Krishna N.R.,
RA Wooten M.W.;
RT "Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in
RT ubiquitin proteasome degradation.";
RL Mol. Cell. Biol. 24:8055-8068(2004).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-358 AND SER-361, AND
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 26S
RT proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, 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 [21]
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP INTERACTION WITH UBE3A.
RX PubMed=22645313; DOI=10.1128/mcb.00201-12;
RA Martinez-Noel G., Galligan J.T., Sowa M.E., Arndt V., Overton T.M.,
RA Harper J.W., Howley P.M.;
RT "Identification and proteomic analysis of distinct UBE3A/E6AP protein
RT complexes.";
RL Mol. Cell. Biol. 32:3095-3106(2012).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-266; SER-358 AND SER-361, AND
RP IDENTIFICATION BY 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 [26]
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 [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-122, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [28]
RP INTERACTION WITH DDI2.
RX PubMed=29290612; DOI=10.1016/j.molcel.2017.11.035;
RA Kottemann M.C., Conti B.A., Lach F.P., Smogorzewska A.;
RT "Removal of RTF2 from Stalled Replisomes Promotes Maintenance of Genome
RT Integrity.";
RL Mol. Cell 69:24-35.E5(2018).
RN [29]
RP STRUCTURE BY NMR OF 263-306 IN COMPLEX WITH HR23A UBIQUITIN-LIKE DOMAIN.
RX PubMed=12970176; DOI=10.1093/emboj/cdg467;
RA Mueller T.D., Feigon J.;
RT "Structural determinants for the binding of ubiquitin-like domains to the
RT proteasome.";
RL EMBO J. 22:4634-4645(2003).
RN [30]
RP STRUCTURE BY NMR OF 260-307 IN COMPLEX WITH HR23B UBIQUITIN-LIKE DOMAIN.
RX PubMed=14585839; DOI=10.1074/jbc.m309448200;
RA Fujiwara K., Tenno T., Sugasawa K., Jee J.-G., Ohki I., Kojima C.,
RA Tochio H., Hiroaki H., Hanaoka F., Shirakawa M.;
RT "Structure of the ubiquitin-interacting motif of S5a bound to the
RT ubiquitin-like domain of HR23B.";
RL J. Biol. Chem. 279:4760-4767(2004).
RN [31]
RP STRUCTURE BY NMR OF 192-306, FUNCTION, AND DOMAIN.
RX PubMed=15826667; DOI=10.1016/j.jmb.2005.03.007;
RA Wang Q., Young P., Walters K.J.;
RT "Structure of S5a bound to monoubiquitin provides a model for polyubiquitin
RT recognition.";
RL J. Mol. Biol. 348:727-739(2005).
RN [32]
RP STRUCTURE BY NMR OF 196-306, AND DOMAIN.
RX PubMed=19683493; DOI=10.1016/j.molcel.2009.06.010;
RA Zhang N., Wang Q., Ehlinger A., Randles L., Lary J.W., Kang Y.,
RA Haririnia A., Storaska A.J., Cole J.L., Fushman D., Walters K.J.;
RT "Structure of the s5a:k48-linked diubiquitin complex and its interactions
RT with rpn13.";
RL Mol. Cell 35:280-290(2009).
RN [33]
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 [34]
RP STRUCTURE BY ELECTRON MICROSCOPY (4.50 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).
CC -!- FUNCTION: Component of the 26S proteasome, a multiprotein complex
CC involved in the ATP-dependent degradation of ubiquitinated proteins.
CC This complex plays a key role in the maintenance of protein homeostasis
CC by removing misfolded or damaged proteins, which could impair cellular
CC functions, and by removing proteins whose functions are no longer
CC required. Therefore, the proteasome participates in numerous cellular
CC processes, including cell cycle progression, apoptosis, or DNA damage
CC repair. PSMD4 acts as an ubiquitin receptor subunit through ubiquitin-
CC interacting motifs and selects ubiquitin-conjugates for destruction.
CC Displays a preferred selectivity for longer polyubiquitin chains.
CC {ECO:0000269|PubMed:1317798, ECO:0000269|PubMed:15826667}.
CC -!- SUBUNIT: Component of the 19S proteasome regulatory particle complex.
CC The 26S proteasome consists of a 20S core particle (CP) and two 19S
CC regulatory subunits (RP). The regulatory particle is made of a lid
CC composed of 9 subunits, a base containing 6 ATPases and few additional
CC components including PSMD4 (PubMed:27428775, PubMed:27342858).
CC Interacts with NUB1 (PubMed:11585840). Interacts with SQSTM1
CC (PubMed:15340068). Interacts with UBQLN4 (PubMed:15280365). Interacts
CC with UBE3A (PubMed:22645313). Interacts with UBQLN1 (via ubiquitin-like
CC domain) (PubMed:15147878). Interacts with DDI2 (PubMed:29290612).
CC {ECO:0000269|PubMed:11585840, ECO:0000269|PubMed:12970176,
CC ECO:0000269|PubMed:14585839, ECO:0000269|PubMed:15147878,
CC ECO:0000269|PubMed:15280365, ECO:0000269|PubMed:15340068,
CC ECO:0000269|PubMed:22645313, ECO:0000269|PubMed:27342858,
CC ECO:0000269|PubMed:27428775, ECO:0000269|PubMed:29290612}.
CC -!- INTERACTION:
CC P55036; Q16186: ADRM1; NbExp=5; IntAct=EBI-359318, EBI-954387;
CC P55036; P42858: HTT; NbExp=5; IntAct=EBI-359318, EBI-466029;
CC P55036; P28066: PSMA5; NbExp=2; IntAct=EBI-359318, EBI-355475;
CC P55036; P62191: PSMC1; NbExp=2; IntAct=EBI-359318, EBI-357598;
CC P55036; P62195: PSMC5; NbExp=2; IntAct=EBI-359318, EBI-357745;
CC P55036; O00232: PSMD12; NbExp=2; IntAct=EBI-359318, EBI-359733;
CC P55036; Q13200: PSMD2; NbExp=3; IntAct=EBI-359318, EBI-357648;
CC P55036; P55036: PSMD4; NbExp=3; IntAct=EBI-359318, EBI-359318;
CC P55036; P54725: RAD23A; NbExp=15; IntAct=EBI-359318, EBI-746453;
CC P55036; P54727: RAD23B; NbExp=11; IntAct=EBI-359318, EBI-954531;
CC P55036; P0DPB3: SCHIP1; NbExp=2; IntAct=EBI-359318, EBI-1397509;
CC P55036; Q9BYB0: SHANK3; NbExp=2; IntAct=EBI-359318, EBI-1752330;
CC P55036; Q9NUJ3: TCP11L1; NbExp=5; IntAct=EBI-359318, EBI-2555179;
CC P55036; P0CG48: UBC; NbExp=4; IntAct=EBI-359318, EBI-3390054;
CC P55036; Q05086: UBE3A; NbExp=3; IntAct=EBI-359318, EBI-954357;
CC P55036; Q05086-2: UBE3A; NbExp=3; IntAct=EBI-359318, EBI-10175863;
CC P55036; Q9UMX0: UBQLN1; NbExp=4; IntAct=EBI-359318, EBI-741480;
CC P55036; Q9Y5K5: UCHL5; NbExp=5; IntAct=EBI-359318, EBI-1051183;
CC P55036; P24610: Pax3; Xeno; NbExp=3; IntAct=EBI-359318, EBI-1208116;
CC P55036; Q62921: Rbck1; Xeno; NbExp=3; IntAct=EBI-359318, EBI-7266339;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=Rpn10A;
CC IsoId=P55036-1; Sequence=Displayed;
CC Name=Rpn10E;
CC IsoId=P55036-2; Sequence=VSP_005291, VSP_005292;
CC -!- DOMAIN: The 2 UIM motifs are involved in the binding to a multi-
CC ubiquitin chain in a cooperative way. {ECO:0000269|PubMed:15826667,
CC ECO:0000269|PubMed:19683493}.
CC -!- MISCELLANEOUS: [Isoform Rpn10E]: May be produced at very low levels due
CC to a premature stop codon in the mRNA, leading to nonsense-mediated
CC mRNA decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the proteasome subunit S5A family.
CC {ECO:0000305}.
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DR EMBL; U51007; AAC50433.1; -; mRNA.
DR EMBL; U24704; AAB54057.1; -; mRNA.
DR EMBL; AB033605; BAA97581.1; -; mRNA.
DR EMBL; AL391069; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL592424; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53457.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53458.1; -; Genomic_DNA.
DR EMBL; BC002365; AAH02365.1; -; mRNA.
DR EMBL; BC072008; AAH72008.1; -; mRNA.
DR EMBL; U72664; AAB68598.1; -; mRNA.
DR CCDS; CCDS991.1; -. [P55036-1]
DR PIR; S63671; S63671.
DR RefSeq; NP_002801.1; NM_002810.2. [P55036-1]
DR PDB; 1P9C; NMR; -; A=263-307.
DR PDB; 1P9D; NMR; -; S=263-307.
DR PDB; 1UEL; NMR; -; B=263-307.
DR PDB; 1YX4; NMR; -; A=196-306.
DR PDB; 1YX5; NMR; -; A=192-306.
DR PDB; 1YX6; NMR; -; A=196-306.
DR PDB; 2KDE; NMR; -; A=196-306.
DR PDB; 2KDF; NMR; -; A=196-306.
DR PDB; 5GJQ; EM; 4.50 A; W=1-377.
DR PDB; 5GJR; EM; 3.50 A; AA/W=1-377.
DR PDB; 5L4K; EM; 4.50 A; W=1-377.
DR PDB; 5LN3; EM; 6.80 A; W=1-377.
DR PDB; 5M32; EM; 3.80 A; p=1-377.
DR PDB; 5T0C; EM; 3.80 A; Ab/Bb=1-377.
DR PDB; 5T0G; EM; 4.40 A; b=1-377.
DR PDB; 5T0H; EM; 6.80 A; b=1-377.
DR PDB; 5T0I; EM; 8.00 A; b=1-377.
DR PDB; 5T0J; EM; 8.00 A; b=1-377.
DR PDB; 5VFP; EM; 4.20 A; b=1-191.
DR PDB; 5VFQ; EM; 4.20 A; b=1-191.
DR PDB; 5VFR; EM; 4.90 A; b=1-191.
DR PDB; 5VFS; EM; 3.60 A; b=1-191.
DR PDB; 5VFT; EM; 7.00 A; b=1-191.
DR PDB; 5VFU; EM; 5.80 A; b=1-191.
DR PDB; 5VGZ; EM; 3.70 A; b=1-191.
DR PDB; 5VHF; EM; 5.70 A; b=1-191.
DR PDB; 5VHH; EM; 6.10 A; b=1-191.
DR PDB; 5VHI; EM; 6.80 A; b=1-191.
DR PDB; 5VHS; EM; 8.80 A; b=1-191.
DR PDB; 6MSB; EM; 3.00 A; b=1-377.
DR PDB; 6MSD; EM; 3.20 A; b=1-377.
DR PDB; 6MSE; EM; 3.30 A; H/h=286-362.
DR PDB; 6MSG; EM; 3.50 A; b=1-377.
DR PDB; 6MSH; EM; 3.60 A; b=1-377.
DR PDB; 6MSJ; EM; 3.30 A; b=1-377.
DR PDB; 6MSK; EM; 3.20 A; b=1-377.
DR PDB; 6MUN; NMR; -; A=196-306.
DR PDB; 6U19; NMR; -; A=305-377.
DR PDB; 6WJD; EM; 4.80 A; b=1-377.
DR PDB; 6WJN; EM; 5.70 A; b=1-191.
DR PDBsum; 1P9C; -.
DR PDBsum; 1P9D; -.
DR PDBsum; 1UEL; -.
DR PDBsum; 1YX4; -.
DR PDBsum; 1YX5; -.
DR PDBsum; 1YX6; -.
DR PDBsum; 2KDE; -.
DR PDBsum; 2KDF; -.
DR PDBsum; 5GJQ; -.
DR PDBsum; 5GJR; -.
DR PDBsum; 5L4K; -.
DR PDBsum; 5LN3; -.
DR PDBsum; 5M32; -.
DR PDBsum; 5T0C; -.
DR PDBsum; 5T0G; -.
DR PDBsum; 5T0H; -.
DR PDBsum; 5T0I; -.
DR PDBsum; 5T0J; -.
DR PDBsum; 5VFP; -.
DR PDBsum; 5VFQ; -.
DR PDBsum; 5VFR; -.
DR PDBsum; 5VFS; -.
DR PDBsum; 5VFT; -.
DR PDBsum; 5VFU; -.
DR PDBsum; 5VGZ; -.
DR PDBsum; 5VHF; -.
DR PDBsum; 5VHH; -.
DR PDBsum; 5VHI; -.
DR PDBsum; 5VHS; -.
DR PDBsum; 6MSB; -.
DR PDBsum; 6MSD; -.
DR PDBsum; 6MSE; -.
DR PDBsum; 6MSG; -.
DR PDBsum; 6MSH; -.
DR PDBsum; 6MSJ; -.
DR PDBsum; 6MSK; -.
DR PDBsum; 6MUN; -.
DR PDBsum; 6U19; -.
DR PDBsum; 6WJD; -.
DR PDBsum; 6WJN; -.
DR AlphaFoldDB; P55036; -.
DR BMRB; P55036; -.
DR SMR; P55036; -.
DR BioGRID; 111683; 318.
DR ComplexPortal; CPX-5993; 26S Proteasome complex.
DR CORUM; P55036; -.
DR DIP; DIP-38189N; -.
DR IntAct; P55036; 122.
DR MINT; P55036; -.
DR STRING; 9606.ENSP00000357879; -.
DR ChEMBL; CHEMBL2364701; -.
DR GlyGen; P55036; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P55036; -.
DR MetOSite; P55036; -.
DR PhosphoSitePlus; P55036; -.
DR BioMuta; PSMD4; -.
DR DMDM; 1709796; -.
DR EPD; P55036; -.
DR jPOST; P55036; -.
DR MassIVE; P55036; -.
DR MaxQB; P55036; -.
DR PaxDb; P55036; -.
DR PeptideAtlas; P55036; -.
DR PRIDE; P55036; -.
DR ProteomicsDB; 56762; -. [P55036-1]
DR ProteomicsDB; 56763; -. [P55036-2]
DR Antibodypedia; 20322; 444 antibodies from 37 providers.
DR CPTC; P55036; 3 antibodies.
DR DNASU; 5710; -.
DR Ensembl; ENST00000368884.8; ENSP00000357879.4; ENSG00000159352.16. [P55036-1]
DR GeneID; 5710; -.
DR KEGG; hsa:5710; -.
DR MANE-Select; ENST00000368884.8; ENSP00000357879.4; NM_002810.4; NP_002801.1.
DR UCSC; uc001exl.4; human. [P55036-1]
DR CTD; 5710; -.
DR DisGeNET; 5710; -.
DR GeneCards; PSMD4; -.
DR HGNC; HGNC:9561; PSMD4.
DR HPA; ENSG00000159352; Low tissue specificity.
DR MIM; 601648; gene.
DR neXtProt; NX_P55036; -.
DR OpenTargets; ENSG00000159352; -.
DR PharmGKB; PA33907; -.
DR VEuPathDB; HostDB:ENSG00000159352; -.
DR eggNOG; KOG2884; Eukaryota.
DR GeneTree; ENSGT00530000064050; -.
DR HOGENOM; CLU_033293_0_1_1; -.
DR InParanoid; P55036; -.
DR OMA; IQGEDGM; -.
DR PhylomeDB; P55036; -.
DR TreeFam; TF106232; -.
DR PathwayCommons; P55036; -.
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; P55036; -.
DR SIGNOR; P55036; -.
DR BioGRID-ORCS; 5710; 721 hits in 1093 CRISPR screens.
DR ChiTaRS; PSMD4; human.
DR EvolutionaryTrace; P55036; -.
DR GeneWiki; PSMD4; -.
DR GenomeRNAi; 5710; -.
DR Pharos; P55036; Tbio.
DR PRO; PR:P55036; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P55036; protein.
DR Bgee; ENSG00000159352; Expressed in apex of heart and 206 other tissues.
DR ExpressionAtlas; P55036; baseline and differential.
DR Genevisible; P55036; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0022624; C:proteasome accessory complex; ISS:UniProtKB.
DR GO; GO:0000502; C:proteasome complex; IDA:UniProtKB.
DR GO; GO:0008540; C:proteasome regulatory particle, base subcomplex; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR DisProt; DP01192; -.
DR Gene3D; 3.40.50.410; -; 1.
DR InterPro; IPR003903; UIM_dom.
DR InterPro; IPR002035; VWF_A.
DR InterPro; IPR036465; vWFA_dom_sf.
DR Pfam; PF02809; UIM; 2.
DR Pfam; PF13519; VWA_2; 1.
DR SMART; SM00726; UIM; 2.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF53300; SSF53300; 1.
DR PROSITE; PS50330; UIM; 2.
DR PROSITE; PS50234; VWFA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Isopeptide bond; Phosphoprotein; Proteasome; Reference proteome; Repeat;
KW Ubl conjugation.
FT CHAIN 1..377
FT /note="26S proteasome non-ATPase regulatory subunit 4"
FT /id="PRO_0000173828"
FT DOMAIN 5..188
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT DOMAIN 211..230
FT /note="UIM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 282..301
FT /note="UIM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT REGION 197..262
FT /note="Interaction with UBQLN1"
FT /evidence="ECO:0000269|PubMed:15147878"
FT REGION 216..220
FT /note="Essential for ubiquitin-binding"
FT REGION 224..255
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 287..291
FT /note="Essential for ubiquitin-binding"
FT REGION 300..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 341..377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 225..239
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 250
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O35226"
FT MOD_RES 253
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O35226"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35226"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17323924,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17323924,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 122
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 255..268
FT /note="DSDDALLKMTISQQ -> GERGGIRSPGTAGC (in isoform
FT Rpn10E)"
FT /evidence="ECO:0000305"
FT /id="VSP_005291"
FT VAR_SEQ 269..377
FT /note="Missing (in isoform Rpn10E)"
FT /evidence="ECO:0000305"
FT /id="VSP_005292"
FT TURN 197..199
FT /evidence="ECO:0007829|PDB:6MUN"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:1YX4"
FT STRAND 205..208
FT /evidence="ECO:0007829|PDB:2KDE"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:1YX4"
FT HELIX 214..244
FT /evidence="ECO:0007829|PDB:1YX4"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:1YX4"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:1P9C"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:1P9C"
FT HELIX 278..294
FT /evidence="ECO:0007829|PDB:1P9C"
FT STRAND 296..300
FT /evidence="ECO:0007829|PDB:1P9C"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:2KDE"
FT TURN 309..313
FT /evidence="ECO:0007829|PDB:6U19"
FT HELIX 322..325
FT /evidence="ECO:0007829|PDB:6U19"
FT HELIX 328..330
FT /evidence="ECO:0007829|PDB:6U19"
FT HELIX 332..341
FT /evidence="ECO:0007829|PDB:6U19"
FT HELIX 350..363
FT /evidence="ECO:0007829|PDB:6U19"
SQ SEQUENCE 377 AA; 40737 MW; EC712EC4DB1CE9AB CRC64;
MVLESTMVCV DNSEYMRNGD FLPTRLQAQQ DAVNIVCHSK TRSNPENNVG LITLANDCEV
LTTLTPDTGR ILSKLHTVQP KGKITFCTGI RVAHLALKHR QGKNHKMRII AFVGSPVEDN
EKDLVKLAKR LKKEKVNVDI INFGEEEVNT EKLTAFVNTL NGKDGTGSHL VTVPPGPSLA
DALISSPILA GEGGAMLGLG ASDFEFGVDP SADPELALAL RVSMEEQRQR QEEEARRAAA
ASAAEAGIAT TGTEDSDDAL LKMTISQQEF GRTGLPDLSS MTEEEQIAYA MQMSLQGAEF
GQAESADIDA SSAMDTSEPA KEEDDYDVMQ DPEFLQSVLE NLPGVDPNNE AIRNAMGSLA
SQATKDGKKD KKEEDKK
