PSMD4_MOUSE
ID PSMD4_MOUSE Reviewed; 376 AA.
AC O35226; Q91V59; Q9JJM0; Q9JJM1; Q9JJM2; Q9JJM3;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 180.
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=Multiubiquitin chain-binding protein;
GN Name=Psmd4; Synonyms=Mcb1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9511739; DOI=10.1016/s0378-1119(97)00599-4;
RA Pusch W., Jaehner D., Ivell R.;
RT "Molecular cloning and testicular expression of the gene transcripts
RT encoding the murine multiubiquitin-chain-binding protein (Mcb1).";
RL Gene 207:19-24(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND ALTERNATIVE SPLICING.
RC STRAIN=129/SvJ; TISSUE=Embryo, and Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE (ISOFORM RPN10B).
RA Masumoto H., Lee H.-J., Tomioka M., Saido T.C.;
RT "Molecular cloning of a multiubiquitin chain binding subunit of mouse 26S
RT proteasome.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM RPN10B).
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-250, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [6]
RP IDENTIFICATION IN THE 19S PROTEASOME REGULATORY COMPLEX.
RX PubMed=16857966; DOI=10.1161/01.res.0000237386.98506.f7;
RA Gomes A.V., Zong C., Edmondson R.D., Li X., Stefani E., Zhang J.,
RA Jones R.C., Thyparambil S., Wang G.W., Qiao X., Bardag-Gorce F., Ping P.;
RT "Mapping the murine cardiac 26S proteasome complexes.";
RL Circ. Res. 99:362-371(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-250, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-250; THR-253 AND SER-256,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-250 AND SER-259 (ISOFORMS
RP RPN10B AND RPN10C), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:0000250|UniProtKB:P55036}.
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:16857966). Interacts with NUB1.
CC Interacts with SQSTM1. Interacts with UBQLN4. Interacts with UBE3A.
CC Interacts with UBQLN1 (via ubiquitin-like domain). Interacts with DDI2
CC (By similarity). {ECO:0000250|UniProtKB:P55036,
CC ECO:0000269|PubMed:16857966}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=Rpn10A;
CC IsoId=O35226-1; Sequence=Displayed;
CC Name=Rpn10B;
CC IsoId=O35226-2; Sequence=VSP_005293;
CC Name=Rpn10C;
CC IsoId=O35226-3; Sequence=VSP_005293, VSP_005294, VSP_005295;
CC Name=Rpn10D;
CC IsoId=O35226-4; Sequence=VSP_005296, VSP_005297;
CC Name=Rpn10E;
CC IsoId=O35226-5; Sequence=VSP_005298, VSP_005299;
CC -!- TISSUE SPECIFICITY: Isoform Rpn10A is ubiquitous whereas isoform Rpn10E
CC is mostly expressed in the embryonic brain.
CC -!- DEVELOPMENTAL STAGE: Isoform Rpn10E is expressed only in the embryos.
CC -!- DOMAIN: The 2 UIM motifs are involved in the binding to a multi-
CC ubiquitin chain in a cooperative way. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the proteasome subunit S5A family.
CC {ECO:0000305}.
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DR EMBL; AF013099; AAC53547.1; -; mRNA.
DR EMBL; AB029090; BAA97572.1; -; Genomic_DNA.
DR EMBL; AB029142; BAA97573.1; -; mRNA.
DR EMBL; AB029143; BAA97574.1; -; mRNA.
DR EMBL; AB029144; BAA97575.1; -; mRNA.
DR EMBL; AB029145; BAA97576.1; -; mRNA.
DR EMBL; AB029146; BAA97577.1; -; mRNA.
DR EMBL; AF175574; AAG09199.1; -; mRNA.
DR EMBL; BC009005; AAH09005.1; -; mRNA.
DR CCDS; CCDS38541.1; -. [O35226-1]
DR CCDS; CCDS71287.1; -. [O35226-2]
DR PIR; JC6535; JC6535.
DR RefSeq; NP_001268946.1; NM_001282017.1. [O35226-2]
DR RefSeq; NP_032977.1; NM_008951.2. [O35226-1]
DR AlphaFoldDB; O35226; -.
DR SMR; O35226; -.
DR BioGRID; 202431; 64.
DR IntAct; O35226; 23.
DR MINT; O35226; -.
DR STRING; 10090.ENSMUSP00000071589; -.
DR iPTMnet; O35226; -.
DR PhosphoSitePlus; O35226; -.
DR SwissPalm; O35226; -.
DR REPRODUCTION-2DPAGE; IPI00345779; -.
DR EPD; O35226; -.
DR jPOST; O35226; -.
DR MaxQB; O35226; -.
DR PaxDb; O35226; -.
DR PeptideAtlas; O35226; -.
DR PRIDE; O35226; -.
DR ProteomicsDB; 291698; -. [O35226-1]
DR ProteomicsDB; 291699; -. [O35226-2]
DR ProteomicsDB; 291700; -. [O35226-3]
DR ProteomicsDB; 291701; -. [O35226-4]
DR ProteomicsDB; 291702; -. [O35226-5]
DR Antibodypedia; 20322; 444 antibodies from 37 providers.
DR DNASU; 19185; -.
DR Ensembl; ENSMUST00000071664; ENSMUSP00000071589; ENSMUSG00000005625. [O35226-2]
DR Ensembl; ENSMUST00000107237; ENSMUSP00000102857; ENSMUSG00000005625. [O35226-1]
DR Ensembl; ENSMUST00000117355; ENSMUSP00000113554; ENSMUSG00000005625. [O35226-3]
DR GeneID; 19185; -.
DR KEGG; mmu:19185; -.
DR UCSC; uc008qhr.2; mouse. [O35226-1]
DR UCSC; uc008qht.2; mouse. [O35226-3]
DR UCSC; uc008qhu.2; mouse. [O35226-4]
DR UCSC; uc008qhv.2; mouse. [O35226-5]
DR CTD; 5710; -.
DR MGI; MGI:1201670; Psmd4.
DR VEuPathDB; HostDB:ENSMUSG00000005625; -.
DR eggNOG; KOG2884; Eukaryota.
DR GeneTree; ENSGT00530000064050; -.
DR HOGENOM; CLU_033293_0_1_1; -.
DR InParanoid; O35226; -.
DR OMA; IQGEDGM; -.
DR PhylomeDB; O35226; -.
DR TreeFam; TF106232; -.
DR Reactome; R-MMU-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-MMU-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-MMU-1236978; Cross-presentation of soluble exogenous antigens (endosomes).
DR Reactome; R-MMU-174084; Autodegradation of Cdh1 by Cdh1:APC/C.
DR Reactome; R-MMU-174154; APC/C:Cdc20 mediated degradation of Securin.
DR Reactome; R-MMU-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
DR Reactome; R-MMU-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR Reactome; R-MMU-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-MMU-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-2467813; Separation of Sister Chromatids.
DR Reactome; R-MMU-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-MMU-349425; Autodegradation of the E3 ubiquitin ligase COP1.
DR Reactome; R-MMU-350562; Regulation of ornithine decarboxylase (ODC).
DR Reactome; R-MMU-382556; ABC-family proteins mediated transport.
DR Reactome; R-MMU-450408; AUF1 (hnRNP D0) binds and destabilizes mRNA.
DR Reactome; R-MMU-4608870; Asymmetric localization of PCP proteins.
DR Reactome; R-MMU-4641257; Degradation of AXIN.
DR Reactome; R-MMU-4641258; Degradation of DVL.
DR Reactome; R-MMU-5358346; Hedgehog ligand biogenesis.
DR Reactome; R-MMU-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-MMU-5610780; Degradation of GLI1 by the proteasome.
DR Reactome; R-MMU-5610785; GLI3 is processed to GLI3R by the proteasome.
DR Reactome; R-MMU-5632684; Hedgehog 'on' state.
DR Reactome; R-MMU-5658442; Regulation of RAS by GAPs.
DR Reactome; R-MMU-5668541; TNFR2 non-canonical NF-kB pathway.
DR Reactome; R-MMU-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-MMU-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-MMU-5689603; UCH proteinases.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-68867; Assembly of the pre-replicative complex.
DR Reactome; R-MMU-68949; Orc1 removal from chromatin.
DR Reactome; R-MMU-69017; CDK-mediated phosphorylation and removal of Cdc6.
DR Reactome; R-MMU-69481; G2/M Checkpoints.
DR Reactome; R-MMU-69601; Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
DR Reactome; R-MMU-75815; Ubiquitin-dependent degradation of Cyclin D.
DR Reactome; R-MMU-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint.
DR Reactome; R-MMU-8854050; FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
DR Reactome; R-MMU-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR Reactome; R-MMU-8939902; Regulation of RUNX2 expression and activity.
DR Reactome; R-MMU-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-MMU-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR Reactome; R-MMU-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-MMU-9762114; GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR BioGRID-ORCS; 19185; 30 hits in 72 CRISPR screens.
DR ChiTaRS; Psmd4; mouse.
DR PRO; PR:O35226; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; O35226; protein.
DR Bgee; ENSMUSG00000005625; Expressed in yolk sac and 257 other tissues.
DR ExpressionAtlas; O35226; baseline and differential.
DR Genevisible; O35226; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0022624; C:proteasome accessory complex; IDA:UniProtKB.
DR GO; GO:0000502; C:proteasome complex; ISO:MGI.
DR GO; GO:0008540; C:proteasome regulatory particle, base subcomplex; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
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 Alternative splicing; Isopeptide bond; Phosphoprotein; Proteasome;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..376
FT /note="26S proteasome non-ATPase regulatory subunit 4"
FT /id="PRO_0000173829"
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:0000250|UniProtKB:P55036"
FT REGION 224..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 355..376
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:0007744|PubMed:15345747,
FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:21183079"
FT MOD_RES 253
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55036"
FT CROSSLNK 122
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P55036"
FT VAR_SEQ 254
FT /note="E -> EGER (in isoform Rpn10B and isoform Rpn10C)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_005293"
FT VAR_SEQ 255..260
FT /note="DSDDAL -> GERGGF (in isoform Rpn10E)"
FT /evidence="ECO:0000305"
FT /id="VSP_005298"
FT VAR_SEQ 261..376
FT /note="Missing (in isoform Rpn10E)"
FT /evidence="ECO:0000305"
FT /id="VSP_005299"
FT VAR_SEQ 299..349
FT /note="EFSQESADMDASSAMDTSDPVKEEDDYDVMQDPEFLQSVLENLPGVDPNNA
FT -> GGPWLGWQGLDRVWGEELALSGLLLSFPQSLAKNRLTWMPAQPWTHLIQSR (in
FT isoform Rpn10D)"
FT /evidence="ECO:0000305"
FT /id="VSP_005296"
FT VAR_SEQ 321..365
FT /note="EEDDYDVMQDPEFLQSVLENLPGVDPNNAAIRSVMGALASQATKD -> VRA
FT SSEALTQPSLTSPAFRSLSFWDQGLSSLAFHKKGLGATEGNT (in isoform
FT Rpn10C)"
FT /evidence="ECO:0000305"
FT /id="VSP_005294"
FT VAR_SEQ 350..376
FT /note="Missing (in isoform Rpn10D)"
FT /evidence="ECO:0000305"
FT /id="VSP_005297"
FT VAR_SEQ 366..376
FT /note="Missing (in isoform Rpn10C)"
FT /evidence="ECO:0000305"
FT /id="VSP_005295"
FT MOD_RES O35226-2:250
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES O35226-2:259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES O35226-3:250
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES O35226-3:259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 376 AA; 40704 MW; 732AC02B56760EAA 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 PGTEDSDDAL LKMTINQQEF GRPGLPDLSS MTEEEQIAYA MQMSLQGTEF
SQESADMDAS SAMDTSDPVK EEDDYDVMQD PEFLQSVLEN LPGVDPNNAA IRSVMGALAS
QATKDGKNDK KEEEKK
