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Protein

26S proteasome non-ATPase regulatory subunit 4

Gene

PSMD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.2 Publications

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-1169091 Activation of NF-kappaB in B cells
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1236974 ER-Phagosome pathway
R-HSA-1236978 Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1
R-HSA-174154 APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-180534 Vpu mediated degradation of CD4
R-HSA-180585 Vif-mediated degradation of APOBEC3G
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-202424 Downstream TCR signaling
R-HSA-211733 Regulation of activated PAK-2p34 by proteasome mediated degradation
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-349425 Autodegradation of the E3 ubiquitin ligase COP1
R-HSA-350562 Regulation of ornithine decarboxylase (ODC)
R-HSA-382556 ABC-family proteins mediated transport
R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-4641257 Degradation of AXIN
R-HSA-4641258 Degradation of DVL
R-HSA-5358346 Hedgehog ligand biogenesis
R-HSA-5362768 Hh mutants that don't undergo autocatalytic processing are degraded by ERAD
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5610780 Degradation of GLI1 by the proteasome
R-HSA-5610783 Degradation of GLI2 by the proteasome
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome
R-HSA-5632684 Hedgehog 'on' state
R-HSA-5658442 Regulation of RAS by GAPs
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway
R-HSA-5676590 NIK-->noncanonical NF-kB signaling
R-HSA-5678895 Defective CFTR causes cystic fibrosis
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-5689603 UCH proteinases
R-HSA-5689880 Ub-specific processing proteases
R-HSA-68827 CDT1 association with the CDC6:ORC:origin complex
R-HSA-68949 Orc1 removal from chromatin
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6
R-HSA-69229 Ubiquitin-dependent degradation of Cyclin D1
R-HSA-69481 G2/M Checkpoints
R-HSA-69601 Ubiquitin Mediated Degradation of Phosphorylated Cdc25A
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint
R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-8941858 Regulation of RUNX3 expression and activity
R-HSA-8948751 Regulation of PTEN stability and activity
R-HSA-8951664 Neddylation
R-HSA-9010553 Regulation of expression of SLITs and ROBOs
R-HSA-9020702 Interleukin-1 signaling
R-HSA-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
Antisecretory factor 1
Short name:
AF
Short name:
ASF
Multiubiquitin chain-binding protein
Gene namesi
Name:PSMD4
Synonyms:MCB1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000159352.15
HGNCiHGNC:9561 PSMD4
MIMi601648 gene
neXtProtiNX_P55036

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi5710
OpenTargetsiENSG00000159352
PharmGKBiPA33907

Chemistry databases

ChEMBLiCHEMBL2364701

Polymorphism and mutation databases

BioMutaiPSMD4
DMDMi1709796

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001738281 – 37726S proteasome non-ATPase regulatory subunit 4Add BLAST377

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki122Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei250PhosphothreonineBy similarity1
Modified residuei253PhosphothreonineBy similarity1
Modified residuei256PhosphoserineBy similarity1
Modified residuei266PhosphoserineCombined sources1
Modified residuei358PhosphoserineCombined sources1
Modified residuei361PhosphoserineCombined sources1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP55036
MaxQBiP55036
PaxDbiP55036
PeptideAtlasiP55036
PRIDEiP55036
ProteomicsDBi56762
56763 [P55036-2]

PTM databases

iPTMnetiP55036
PhosphoSitePlusiP55036

Expressioni

Gene expression databases

BgeeiENSG00000159352
CleanExiHS_PSMD4
ExpressionAtlasiP55036 baseline and differential
GenevisibleiP55036 HS

Organism-specific databases

HPAiCAB047300
HPA038807
HPA039252

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:27428775, PubMed:27342858). Interacts with NUB1 (PubMed:11585840). Interacts with SQSTM1 (PubMed:15340068). Interacts with UBQLN4 (PubMed:15280365). Interacts with UBE3A (PubMed:22645313). Interacts with UBQLN1 (via ubiquitin-like domain) (PubMed:15147878).9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111683, 186 interactors
CORUMiP55036
DIPiDIP-38189N
IntActiP55036, 92 interactors
MINTiP55036
STRINGi9606.ENSP00000357879

Structurei

Secondary structure

1377
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi201 – 203Combined sources3
Beta strandi205 – 208Combined sources4
Helixi210 – 212Combined sources3
Helixi214 – 244Combined sources31
Beta strandi245 – 249Combined sources5
Beta strandi268 – 270Combined sources3
Beta strandi273 – 275Combined sources3
Helixi278 – 294Combined sources17
Beta strandi296 – 300Combined sources5
Beta strandi302 – 304Combined sources3

3D structure databases

ProteinModelPortaliP55036
SMRiP55036
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55036

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 UBQLN11 PublicationAdd BLAST66
Regioni216 – 220Essential for ubiquitin-binding5
Regioni287 – 291Essential for ubiquitin-binding5

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.2 Publications

Sequence similaritiesi

Belongs to the proteasome subunit S5A family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2884 Eukaryota
COG5148 LUCA
GeneTreeiENSGT00530000064050
HOGENOMiHOG000165630
HOVERGENiHBG000425
InParanoidiP55036
KOiK03029
PhylomeDBiP55036
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
IPR036465 vWFA_dom_sf
PANTHERiPTHR10223:SF6 PTHR10223:SF6, 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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform Rpn10A (identifier: P55036-1) [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
TGTEDSDDAL LKMTISQQEF GRTGLPDLSS MTEEEQIAYA MQMSLQGAEF
310 320 330 340 350
GQAESADIDA SSAMDTSEPA KEEDDYDVMQ DPEFLQSVLE NLPGVDPNNE
360 370
AIRNAMGSLA SQATKDGKKD KKEEDKK
Length:377
Mass (Da):40,737
Last modified:October 1, 1996 - v1
Checksum:iEC712EC4DB1CE9AB
GO
Isoform Rpn10E (identifier: P55036-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     255-268: DSDDALLKMTISQQ → GERGGIRSPGTAGC
     269-377: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:268
Mass (Da):28,612
Checksum:i6640BF4CD5C91C6E
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005291255 – 268DSDDA…TISQQ → GERGGIRSPGTAGC in isoform Rpn10E. CuratedAdd BLAST14
Alternative sequenceiVSP_005292269 – 377Missing in isoform Rpn10E. CuratedAdd BLAST109

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U51007 mRNA Translation: AAC50433.1
U24704 mRNA Translation: AAB54057.1
AB033605 mRNA Translation: BAA97581.1
AL391069 Genomic DNA No translation available.
AL592424 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW53457.1
CH471121 Genomic DNA Translation: EAW53458.1
BC002365 mRNA Translation: AAH02365.1
BC072008 mRNA Translation: AAH72008.1
U72664 mRNA Translation: AAB68598.1
CCDSiCCDS991.1 [P55036-1]
PIRiS63671
RefSeqiNP_002801.1, NM_002810.2 [P55036-1]
UniGeneiHs.505059

Genome annotation databases

EnsembliENST00000368884; ENSP00000357879; ENSG00000159352 [P55036-1]
GeneIDi5710
KEGGihsa:5710
UCSCiuc001exl.4 human [P55036-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPSMD4_HUMAN
AccessioniPrimary (citable) accession number: P55036
Secondary accession number(s): D3DV16, Q5VWC5, Q9NS92
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 18, 2018
This is version 190 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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