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Protein

26S proteasome non-ATPase regulatory subunit 4

Gene

Psmd4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMD4 acts as an ubiquitin receptor subunit through ubiquitin-interacting motifs and selects ubiquitin-conjugates for destruction. Displays a preferred selectivity for longer polyubiquitin chains.By similarity

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-MMU-1169091. Activation of NF-kappaB in B cells.
R-MMU-1234176. Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
R-MMU-1236978. Cross-presentation of soluble exogenous antigens (endosomes).
R-MMU-174084. Autodegradation of Cdh1 by Cdh1:APC/C.
R-MMU-174113. SCF-beta-TrCP mediated degradation of Emi1.
R-MMU-174154. APC/C:Cdc20 mediated degradation of Securin.
R-MMU-174178. APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1.
R-MMU-174184. Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
R-MMU-187577. SCF(Skp2)-mediated degradation of p27/p21.
R-MMU-195253. Degradation of beta-catenin by the destruction complex.
R-MMU-202424. Downstream TCR signaling.
R-MMU-2467813. Separation of Sister Chromatids.
R-MMU-2871837. FCERI mediated NF-kB activation.
R-MMU-349425. Autodegradation of the E3 ubiquitin ligase COP1.
R-MMU-350562. Regulation of ornithine decarboxylase (ODC).
R-MMU-382556. ABC-family proteins mediated transport.
R-MMU-446652. Interleukin-1 family signaling.
R-MMU-450408. AUF1 (hnRNP D0) binds and destabilizes mRNA.
R-MMU-4608870. Asymmetric localization of PCP proteins.
R-MMU-4641257. Degradation of AXIN.
R-MMU-4641258. Degradation of DVL.
R-MMU-5358346. Hedgehog ligand biogenesis.
R-MMU-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-MMU-5607764. CLEC7A (Dectin-1) signaling.
R-MMU-5610780. Degradation of GLI1 by the proteasome.
R-MMU-5610785. GLI3 is processed to GLI3R by the proteasome.
R-MMU-5632684. Hedgehog 'on' state.
R-MMU-5658442. Regulation of RAS by GAPs.
R-MMU-5668541. TNFR2 non-canonical NF-kB pathway.
R-MMU-5676590. NIK-->noncanonical NF-kB signaling.
R-MMU-5687128. MAPK6/MAPK4 signaling.
R-MMU-5689603. UCH proteinases.
R-MMU-5689880. Ub-specific processing proteases.
R-MMU-68827. CDT1 association with the CDC6:ORC:origin complex.
R-MMU-68949. Orc1 removal from chromatin.
R-MMU-69017. CDK-mediated phosphorylation and removal of Cdc6.
R-MMU-69229. Ubiquitin-dependent degradation of Cyclin D1.
R-MMU-69481. G2/M Checkpoints.
R-MMU-69601. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
R-MMU-8852276. The role of GTSE1 in G2/M progression after G2 checkpoint.
R-MMU-8854050. FBXL7 down-regulates AURKA during mitotic entry and in early mitosis.
R-MMU-8939236. RUNX1 regulates transcription of genes involved in differentiation of HSCs.
R-MMU-8941858. Regulation of RUNX3 expression and activity.
R-MMU-8948751. Regulation of PTEN stability and activity.
R-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Names & Taxonomyi

Protein namesi
Recommended name:
26S proteasome non-ATPase regulatory subunit 4
Alternative name(s):
26S proteasome regulatory subunit RPN10
26S proteasome regulatory subunit S5A
Multiubiquitin chain-binding protein
Gene namesi
Name:Psmd4
Synonyms:Mcb1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1201670. Psmd4.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Proteasome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001738291 – 37626S proteasome non-ATPase regulatory subunit 4Add BLAST376

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki122Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei250PhosphothreonineCombined sources1
Modified residuei253PhosphothreonineCombined sources1
Modified residuei256PhosphoserineCombined sources1
Modified residuei360PhosphoserineBy similarity1
Isoform Rpn10B (identifier: O35226-2)
Modified residuei250PhosphothreonineCombined sources1
Modified residuei259PhosphoserineCombined sources1
Isoform Rpn10C (identifier: O35226-3)
Modified residuei250PhosphothreonineCombined sources1
Modified residuei259PhosphoserineCombined sources1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO35226.
MaxQBiO35226.
PaxDbiO35226.
PeptideAtlasiO35226.
PRIDEiO35226.

2D gel databases

REPRODUCTION-2DPAGEiIPI00345779.

PTM databases

iPTMnetiO35226.
PhosphoSitePlusiO35226.
SwissPalmiO35226.

Expressioni

Tissue specificityi

Isoform Rpn10A is ubiquitous whereas isoform Rpn10E is mostly expressed in the embryonic brain.

Developmental stagei

Isoform Rpn10E is expressed only in the embryos.

Gene expression databases

BgeeiENSMUSG00000005625.
ExpressionAtlasiO35226. baseline and differential.
GenevisibleiO35226. MM.

Interactioni

Subunit structurei

Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD4 (PubMed:16857966). Interacts with NUB1. Interacts with SQSTM1. Interacts with UBQLN4. Interacts with UBE3A. Interacts with UBQLN1 (via ubiquitin-like domain).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202431. 4 interactors.
IntActiO35226. 22 interactors.
MINTiMINT-2841145.
STRINGi10090.ENSMUSP00000102857.

Structurei

3D structure databases

ProteinModelPortaliO35226.
SMRiO35226.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 188VWFAPROSITE-ProRule annotationAdd BLAST184
Domaini211 – 230UIM 1PROSITE-ProRule annotationAdd BLAST20
Domaini282 – 301UIM 2PROSITE-ProRule annotationAdd BLAST20

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni197 – 262Interaction with UBQLN1By similarityAdd BLAST66

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi238 – 246Poly-Ala9

Domaini

The 2 UIM motifs are involved in the binding to a multi-ubiquitin chain in a cooperative way.By similarity

Sequence similaritiesi

Belongs to the proteasome subunit S5A family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2884. Eukaryota.
COG5148. LUCA.
GeneTreeiENSGT00530000064050.
HOGENOMiHOG000165630.
HOVERGENiHBG000425.
InParanoidiO35226.
KOiK03029.
OMAiMGGKGPE.
PhylomeDBiO35226.
TreeFamiTF106232.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiView protein in InterPro
IPR027040. Proteasome_su_Rpn10.
IPR003903. UIM_dom.
IPR002035. VWF_A.
PANTHERiPTHR10223. PTHR10223. 1 hit.
PfamiView protein in Pfam
PF02809. UIM. 2 hits.
PF13519. VWA_2. 1 hit.
SMARTiView protein in SMART
SM00726. UIM. 2 hits.
SM00327. VWA. 1 hit.
SUPFAMiSSF53300. SSF53300. 1 hit.
PROSITEiView protein in PROSITE
PS50330. UIM. 2 hits.
PS50234. VWFA. 1 hit.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Rpn10A (identifier: O35226-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVLESTMVCV DNSEYMRNGD FLPTRLQAQQ DAVNIVCHSK TRSNPENNVG
60 70 80 90 100
LITLANDCEV LTTLTPDTGR ILSKLHTVQP KGKITFCTGI RVAHLALKHR
110 120 130 140 150
QGKNHKMRII AFVGSPVEDN EKDLVKLAKR LKKEKVNVDI INFGEEEVNT
160 170 180 190 200
EKLTAFVNTL NGKDGTGSHL VTVPPGPSLA DALISSPILA GEGGAMLGLG
210 220 230 240 250
ASDFEFGVDP SADPELALAL RVSMEEQRQR QEEEARRAAA ASAAEAGIAT
260 270 280 290 300
PGTEDSDDAL LKMTINQQEF GRPGLPDLSS MTEEEQIAYA MQMSLQGTEF
310 320 330 340 350
SQESADMDAS SAMDTSDPVK EEDDYDVMQD PEFLQSVLEN LPGVDPNNAA
360 370
IRSVMGALAS QATKDGKNDK KEEEKK
Length:376
Mass (Da):40,704
Last modified:January 1, 1998 - v1
Checksum:i732AC02B56760EAA
GO
Isoform Rpn10B (identifier: O35226-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     254-254: E → EGER

Show »
Length:379
Mass (Da):41,046
Checksum:i9D3DC705FACF4AEE
GO
Isoform Rpn10C (identifier: O35226-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     254-254: E → EGER
     321-365: EEDDYDVMQD...GALASQATKD → VRASSEALTQ...KGLGATEGNT
     366-376: Missing.

Show »
Length:368
Mass (Da):39,590
Checksum:i1945E30F72EF6F3F
GO
Isoform Rpn10D (identifier: O35226-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     299-349: EFSQESADMD...NLPGVDPNNA → GGPWLGWQGL...QPWTHLIQSR
     350-376: Missing.

Show »
Length:349
Mass (Da):37,964
Checksum:iEE0CA045056F9A0F
GO
Isoform Rpn10E (identifier: O35226-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     255-260: DSDDAL → GERGGF
     261-376: Missing.

Show »
Length:260
Mass (Da):27,913
Checksum:iA715852C2CA04644
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005293254E → EGER in isoform Rpn10B and isoform Rpn10C. 1 Publication1
Alternative sequenceiVSP_005298255 – 260DSDDAL → GERGGF in isoform Rpn10E. Curated6
Alternative sequenceiVSP_005299261 – 376Missing in isoform Rpn10E. CuratedAdd BLAST116
Alternative sequenceiVSP_005296299 – 349EFSQE…DPNNA → GGPWLGWQGLDRVWGEELAL SGLLLSFPQSLAKNRLTWMP AQPWTHLIQSR in isoform Rpn10D. CuratedAdd BLAST51
Alternative sequenceiVSP_005294321 – 365EEDDY…QATKD → VRASSEALTQPSLTSPAFRS LSFWDQGLSSLAFHKKGLGA TEGNT in isoform Rpn10C. CuratedAdd BLAST45
Alternative sequenceiVSP_005297350 – 376Missing in isoform Rpn10D. CuratedAdd BLAST27
Alternative sequenceiVSP_005295366 – 376Missing in isoform Rpn10C. CuratedAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013099 mRNA. Translation: AAC53547.1.
AB029090 Genomic DNA. Translation: BAA97572.1.
AB029142 mRNA. Translation: BAA97573.1.
AB029143 mRNA. Translation: BAA97574.1.
AB029144 mRNA. Translation: BAA97575.1.
AB029145 mRNA. Translation: BAA97576.1.
AB029146 mRNA. Translation: BAA97577.1.
AF175574 mRNA. Translation: AAG09199.1.
BC009005 mRNA. Translation: AAH09005.1.
CCDSiCCDS38541.1. [O35226-1]
CCDS71287.1. [O35226-2]
PIRiJC6535.
RefSeqiNP_001268946.1. NM_001282017.1. [O35226-2]
NP_032977.1. NM_008951.2. [O35226-1]
UniGeneiMm.2261.

Genome annotation databases

EnsembliENSMUST00000071664; ENSMUSP00000071589; ENSMUSG00000005625. [O35226-2]
ENSMUST00000107237; ENSMUSP00000102857; ENSMUSG00000005625. [O35226-1]
ENSMUST00000117355; ENSMUSP00000113554; ENSMUSG00000005625. [O35226-3]
GeneIDi19185.
KEGGimmu:19185.
UCSCiuc008qhr.2. mouse. [O35226-1]
uc008qht.2. mouse. [O35226-3]
uc008qhu.2. mouse. [O35226-4]
uc008qhv.2. mouse. [O35226-5]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPSMD4_MOUSE
AccessioniPrimary (citable) accession number: O35226
Secondary accession number(s): Q91V59
, Q9JJM0, Q9JJM1, Q9JJM2, Q9JJM3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: January 1, 1998
Last modified: September 27, 2017
This is version 150 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families