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Protein

26S proteasome non-ATPase regulatory subunit 4

Gene

PSMD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Binds and presumably selects ubiquitin-conjugates for destruction. Displays selectivity for longer polyubiquitin chains. Modulates intestinal fluid secretion.

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • poly(A) RNA binding Source: UniProtKB
  • polyubiquitin binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
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-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-5687128. MAPK6/MAPK4 signaling.
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-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

HGNCiHGNC:9561. PSMD4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Proteasome

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA33907.

Polymorphism and mutation databases

BioMutaiPSMD4.
DMDMi1709796.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 37737726S proteasome non-ATPase regulatory subunit 4PRO_0000173828Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei250 – 2501PhosphothreonineBy similarity
Modified residuei253 – 2531PhosphothreonineBy similarity
Modified residuei256 – 2561PhosphoserineBy similarity
Modified residuei266 – 2661PhosphoserineCombined sources
Modified residuei358 – 3581PhosphoserineCombined sources
Modified residuei361 – 3611PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP55036.
MaxQBiP55036.
PaxDbiP55036.
PeptideAtlasiP55036.
PRIDEiP55036.

PTM databases

iPTMnetiP55036.
PhosphoSiteiP55036.

Expressioni

Gene expression databases

BgeeiENSG00000159352.
CleanExiHS_PSMD4.
ExpressionAtlasiP55036. baseline and differential.
GenevisibleiP55036. HS.

Organism-specific databases

HPAiCAB047300.
HPA038807.
HPA039252.

Interactioni

Subunit structurei

The 26S proteasome is composed of a core protease, known as the 20S proteasome, capped at one or both ends by the 19S regulatory complex (RC). The RC is composed of at least 18 different subunits in two subcomplexes, the base and the lid, which form the portions proximal and distal to the 20S proteolytic core, respectively (By similarity). Directly interacts with NUB1. Interacts with SQSTM1. Interacts with UBQLN4. Interacts with UBE3A. Interacts with UBQLN1 (via ubiquitin-like domain).By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-359318,EBI-359318
ADRM1Q161864EBI-359318,EBI-954387
DSK2P485102EBI-359318,EBI-6174From a different organism.
DSK2BQ9SII83EBI-359318,EBI-4433040From a different organism.
Pax3P246103EBI-359318,EBI-1208116From a different organism.
PSMC1P621912EBI-359318,EBI-357598
PSMD2Q132003EBI-359318,EBI-357648
RAD23AP547253EBI-359318,EBI-746453
RAD23AQ84L323EBI-359318,EBI-6394924From a different organism.
RAD23BP5472712EBI-359318,EBI-954531
Rbck1Q629213EBI-359318,EBI-7266339From a different organism.
SCHIP1Q9P0W52EBI-359318,EBI-1397509
UBCP0CG488EBI-359318,EBI-3390054
UBQLN1Q9UMX06EBI-359318,EBI-741480
UBQLN2Q9UHD93EBI-359318,EBI-947187
UCHL5Q9Y5K55EBI-359318,EBI-1051183

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • polyubiquitin binding Source: GO_Central

Protein-protein interaction databases

BioGridi111683. 175 interactions.
DIPiDIP-38189N.
IntActiP55036. 80 interactions.
MINTiMINT-105366.
STRINGi9606.ENSP00000357879.

Structurei

Secondary structure

1
377
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi201 – 2033Combined sources
Beta strandi205 – 2084Combined sources
Helixi210 – 2123Combined sources
Helixi214 – 24431Combined sources
Beta strandi245 – 2495Combined sources
Beta strandi268 – 2703Combined sources
Beta strandi273 – 2753Combined sources
Helixi278 – 29417Combined sources
Beta strandi296 – 3005Combined sources
Beta strandi302 – 3043Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1P9CNMR-A263-307[»]
1P9DNMR-S263-307[»]
1UELNMR-B263-307[»]
1YX4NMR-A196-306[»]
1YX5NMR-A192-306[»]
1YX6NMR-A196-306[»]
2KDENMR-A196-306[»]
2KDFNMR-A196-306[»]
ProteinModelPortaliP55036.
SMRiP55036. Positions 1-306.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP55036.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini5 – 188184VWFAPROSITE-ProRule annotationAdd
BLAST
Domaini211 – 23020UIM 1PROSITE-ProRule annotationAdd
BLAST
Domaini282 – 30120UIM 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni197 – 26266Interaction with UBQLN11 PublicationAdd
BLAST
Regioni216 – 2205Essential for ubiquitin-binding
Regioni287 – 2915Essential for ubiquitin-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi238 – 2469Poly-Ala

Domaini

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

Sequence similaritiesi

Belongs to the proteasome subunit S5A family.Curated
Contains 2 UIM (ubiquitin-interacting motif) domains.PROSITE-ProRule annotation
Contains 1 VWFA domain.PROSITE-ProRule annotation

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.
InterProiIPR027040. Proteasome_su_Rpn10.
IPR003903. UIM_dom.
IPR002035. VWF_A.
[Graphical view]
PANTHERiPTHR10223. PTHR10223. 1 hit.
PfamiPF02809. UIM. 2 hits.
PF13519. VWA_2. 1 hit.
[Graphical view]
SMARTiSM00726. UIM. 2 hits.
SM00327. VWA. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
PROSITEiPS50330. UIM. 2 hits.
PS50234. VWFA. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei255 – 26814DSDDA…TISQQ → GERGGIRSPGTAGC in isoform Rpn10E. CuratedVSP_005291Add
BLAST
Alternative sequencei269 – 377109Missing in isoform Rpn10E. CuratedVSP_005292Add
BLAST

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, AL592424 Genomic DNA. Translation: CAH70329.1.
AL592424, AL391069 Genomic DNA. Translation: CAI16390.1.
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

Cross-referencesi

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, AL592424 Genomic DNA. Translation: CAH70329.1.
AL592424, AL391069 Genomic DNA. Translation: CAI16390.1.
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1P9CNMR-A263-307[»]
1P9DNMR-S263-307[»]
1UELNMR-B263-307[»]
1YX4NMR-A196-306[»]
1YX5NMR-A192-306[»]
1YX6NMR-A196-306[»]
2KDENMR-A196-306[»]
2KDFNMR-A196-306[»]
ProteinModelPortaliP55036.
SMRiP55036. Positions 1-306.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111683. 175 interactions.
DIPiDIP-38189N.
IntActiP55036. 80 interactions.
MINTiMINT-105366.
STRINGi9606.ENSP00000357879.

PTM databases

iPTMnetiP55036.
PhosphoSiteiP55036.

Polymorphism and mutation databases

BioMutaiPSMD4.
DMDMi1709796.

Proteomic databases

EPDiP55036.
MaxQBiP55036.
PaxDbiP55036.
PeptideAtlasiP55036.
PRIDEiP55036.

Protocols and materials databases

DNASUi5710.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5710.
GeneCardsiPSMD4.
HGNCiHGNC:9561. PSMD4.
HPAiCAB047300.
HPA038807.
HPA039252.
MIMi601648. gene.
neXtProtiNX_P55036.
PharmGKBiPA33907.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2884. Eukaryota.
COG5148. LUCA.
GeneTreeiENSGT00530000064050.
HOGENOMiHOG000165630.
HOVERGENiHBG000425.
InParanoidiP55036.
KOiK03029.
PhylomeDBiP55036.
TreeFamiTF106232.

Enzyme and pathway databases

ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
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-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-5687128. MAPK6/MAPK4 signaling.
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-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiPSMD4. human.
EvolutionaryTraceiP55036.
GeneWikiiPSMD4.
GenomeRNAii5710.
PROiP55036.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000159352.
CleanExiHS_PSMD4.
ExpressionAtlasiP55036. baseline and differential.
GenevisibleiP55036. HS.

Family and domain databases

Gene3Di3.40.50.410. 1 hit.
InterProiIPR027040. Proteasome_su_Rpn10.
IPR003903. UIM_dom.
IPR002035. VWF_A.
[Graphical view]
PANTHERiPTHR10223. PTHR10223. 1 hit.
PfamiPF02809. UIM. 2 hits.
PF13519. VWA_2. 1 hit.
[Graphical view]
SMARTiSM00726. UIM. 2 hits.
SM00327. VWA. 1 hit.
[Graphical view]
SUPFAMiSSF53300. SSF53300. 1 hit.
PROSITEiPS50330. UIM. 2 hits.
PS50234. VWFA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPSMD4_HUMAN
AccessioniPrimary (citable) accession number: P55036
Secondary accession number(s): D3DV16, Q5VWC5, Q9NS92
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 7, 2016
This is version 171 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.