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 27-MAR-2024, entry version 227. 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; P13569: CFTR; NbExp=13; IntAct=EBI-359318, EBI-349854; 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}. 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; 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 PDB; 7QXN; EM; 3.70 A; b=1-377. DR PDB; 7QXP; EM; 3.60 A; b=1-377. DR PDB; 7QXU; EM; 4.30 A; b=1-377. DR PDB; 7QXW; EM; 4.10 A; b=1-377. DR PDB; 7QXX; EM; 4.40 A; b=1-377. DR PDB; 7QY7; EM; 4.70 A; b=1-377. DR PDB; 7QYA; EM; 4.80 A; b=1-377. DR PDB; 7QYB; EM; 4.10 A; b=1-377. DR PDB; 7W37; EM; 3.00 A; b=1-377. DR PDB; 7W38; EM; 3.10 A; b=1-377. DR PDB; 7W39; EM; 3.20 A; b=1-377. DR PDB; 7W3A; EM; 3.50 A; b=1-377. DR PDB; 7W3B; EM; 3.60 A; b=1-377. DR PDB; 7W3C; EM; 3.40 A; b=1-377. DR PDB; 7W3F; EM; 3.30 A; b=1-377. DR PDB; 7W3G; EM; 3.20 A; b=1-377. DR PDB; 7W3H; EM; 3.20 A; b=1-377. DR PDB; 7W3I; EM; 3.50 A; b=1-377. DR PDB; 7W3J; EM; 3.50 A; b=1-377. DR PDB; 7W3K; EM; 3.60 A; b=1-377. DR PDB; 7W3M; EM; 3.50 A; b=1-377. DR PDB; 8CVT; EM; 3.00 A; b=1-377. 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 PDBsum; 7QXN; -. DR PDBsum; 7QXP; -. DR PDBsum; 7QXU; -. DR PDBsum; 7QXW; -. DR PDBsum; 7QXX; -. DR PDBsum; 7QY7; -. DR PDBsum; 7QYA; -. DR PDBsum; 7QYB; -. DR PDBsum; 7W37; -. DR PDBsum; 7W38; -. DR PDBsum; 7W39; -. DR PDBsum; 7W3A; -. DR PDBsum; 7W3B; -. DR PDBsum; 7W3C; -. DR PDBsum; 7W3F; -. DR PDBsum; 7W3G; -. DR PDBsum; 7W3H; -. DR PDBsum; 7W3I; -. DR PDBsum; 7W3J; -. DR PDBsum; 7W3K; -. DR PDBsum; 7W3M; -. DR PDBsum; 8CVT; -. DR AlphaFoldDB; P55036; -. DR BMRB; P55036; -. DR EMDB; EMD-14201; -. DR EMDB; EMD-14202; -. DR EMDB; EMD-14203; -. DR EMDB; EMD-14204; -. DR EMDB; EMD-14205; -. DR EMDB; EMD-14209; -. DR EMDB; EMD-14210; -. DR EMDB; EMD-14211; -. DR EMDB; EMD-8672; -. DR EMDB; EMD-8674; -. DR EMDB; EMD-8675; -. DR EMDB; EMD-8676; -. DR EMDB; EMD-8684; -. DR SMR; P55036; -. DR BioGRID; 111683; 371. DR ComplexPortal; CPX-5993; 26S Proteasome complex. DR CORUM; P55036; -. DR DIP; DIP-38189N; -. DR IntAct; P55036; 126. DR MINT; P55036; -. DR STRING; 9606.ENSP00000357876; -. 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; 9606-ENSP00000357879; -. DR PeptideAtlas; P55036; -. DR ProteomicsDB; 56762; -. [P55036-1] DR ProteomicsDB; 56763; -. [P55036-2] DR Pumba; P55036; -. DR Antibodypedia; 20322; 482 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 AGR; HGNC:9561; -. 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; QMSMQDQ; -. DR OrthoDB; 169547at2759; -. 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-9824272; Somitogenesis. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; P55036; -. DR SIGNOR; P55036; -. DR BioGRID-ORCS; 5710; 758 hits in 1176 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 208 other cell types or tissues. DR ExpressionAtlas; P55036; baseline and differential. 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:0060090; F:molecular adaptor activity; EXP:DisProt. 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 CDD; cd22297; PSMD4_RAZUL; 1. DR CDD; cd01452; VWA_26S_proteasome_subunit; 1. DR DisProt; DP01192; -. DR Gene3D; 6.10.250.380; -; 1. DR Gene3D; 6.10.300.40; -; 1. DR Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 1. DR InterPro; IPR049590; PSMD4_RAZUL-like. DR InterPro; IPR003903; UIM_dom. DR InterPro; IPR002035; VWF_A. DR InterPro; IPR036465; vWFA_dom_sf. DR PANTHER; PTHR10223; 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 4; 1. DR PANTHER; PTHR10223:SF0; 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 4; 1. DR Pfam; PF02809; UIM; 2. DR Pfam; PF13519; VWA_2; 1. DR SMART; SM00726; UIM; 2. DR SMART; SM00327; VWA; 1. DR SUPFAM; SSF53300; vWA-like; 1. DR PROSITE; PS50330; UIM; 2. DR PROSITE; PS50234; VWFA; 1. DR Genevisible; P55036; HS. 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 //