Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

26S proteasome non-ATPase regulatory subunit 14

Gene

PSMD14

Organism
Homo sapiens (Human)
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. The PSMD14 subunit is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains within the complex. Plays a role in response to double-strand breaks (DSBs): acts as a regulator of non-homologous end joining (NHEJ) by cleaving 'Lys-63'-linked polyubiquitin, thereby promoting retention of JMJD2A/KDM4A on chromatin and restricting TP53BP1 accumulation. Also involved in homologous recombination repair by promoting RAD51 loading.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi113Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi115Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi126Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

  • endopeptidase activator activity Source: UniProtKB
  • Lys63-specific deubiquitinase activity Source: Reactome
  • metal ion binding Source: UniProtKB-KW
  • metallopeptidase activity Source: UniProtKB
  • proteasome binding Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processDNA damage, DNA repair, Ubl conjugation pathway
LigandMetal-binding, Zinc

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-446652. Interleukin-1 family signaling.
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-5689901. Metalloprotease DUBs.
R-HSA-6798695. Neutrophil degranulation.
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-8941858. Regulation of RUNX3 expression and activity.
R-HSA-8948751. Regulation of PTEN stability and activity.
R-HSA-8951664. Neddylation.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Names & Taxonomyi

Protein namesi
Recommended name:
26S proteasome non-ATPase regulatory subunit 14 (EC:3.4.19.-)
Alternative name(s):
26S proteasome regulatory subunit RPN11
26S proteasome-associated PAD1 homolog 1
Gene namesi
Name:PSMD14
Synonyms:POH1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000115233.11.
HGNCiHGNC:16889. PSMD14.

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi113 – 115HSH → ASA: Abolishes ubiquitin thioesterase activity, leading to prevent maintenance of JMJD2A/KDM4A on chromatin. 1 Publication3

Organism-specific databases

DisGeNETi10213.
OpenTargetsiENSG00000115233.
PharmGKBiPA134957776.

Chemistry databases

ChEMBLiCHEMBL2007629.

Polymorphism and mutation databases

BioMutaiPSMD14.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002139521 – 31026S proteasome non-ATPase regulatory subunit 14Add BLAST310

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei150PhosphoserineCombined sources1
Modified residuei224PhosphoserineCombined sources1
Modified residuei266PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO00487.
MaxQBiO00487.
PaxDbiO00487.
PeptideAtlasiO00487.
PRIDEiO00487.
TopDownProteomicsiO00487.

2D gel databases

OGPiO00487.
REPRODUCTION-2DPAGEiIPI00024821.

PTM databases

iPTMnetiO00487.
PhosphoSitePlusiO00487.
SwissPalmiO00487.

Expressioni

Tissue specificityi

Widely expressed. Highest levels in heart and skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000115233.
CleanExiHS_PSMD14.
ExpressionAtlasiO00487. baseline and differential.
GenevisibleiO00487. HS.

Organism-specific databases

HPAiHPA002114.
HPA003828.

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 including PSMD4, a base containing 6 ATPases and few additional components (PubMed:27428775, PubMed:27342858). Within the complex, PSMD4 interacts with subunit PSMD7 through their respective MPN domain. Interacts with TXNL1 (PubMed:19349277).4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • proteasome binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115508. 113 interactors.
CORUMiO00487.
IntActiO00487. 67 interactors.
MINTiMINT-5003743.
STRINGi9606.ENSP00000386541.

Chemistry databases

BindingDBiO00487.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5GJQelectron microscopy4.50V1-310[»]
5GJRelectron microscopy3.509/V1-310[»]
5L4Kelectron microscopy4.50V1-310[»]
5LN3electron microscopy6.80V1-310[»]
5M32electron microscopy3.80q1-310[»]
5T0Celectron microscopy3.80Ac/Bc1-310[»]
5T0Gelectron microscopy4.40c2-310[»]
5T0Helectron microscopy6.80c2-310[»]
5T0Ielectron microscopy8.00c2-310[»]
5T0Jelectron microscopy8.00c2-310[»]
5VGZelectron microscopy3.70c24-310[»]
5VHFelectron microscopy5.70c24-310[»]
5VHHelectron microscopy6.10c24-310[»]
5VHIelectron microscopy6.80c24-310[»]
5VHSelectron microscopy8.80c24-310[»]
ProteinModelPortaliO00487.
SMRiO00487.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 166MPNPROSITE-ProRule annotationAdd BLAST136

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi113 – 126JAMM motifPROSITE-ProRule annotationAdd BLAST14

Sequence similaritiesi

Belongs to the peptidase M67A family. PSMD14 subfamily.Curated

Phylogenomic databases

eggNOGiKOG1555. Eukaryota.
COG1310. LUCA.
GeneTreeiENSGT00730000111116.
HOGENOMiHOG000183690.
HOVERGENiHBG053742.
InParanoidiO00487.
KOiK03030.
OMAiQTGRPET.
OrthoDBiEOG091G0CMC.
PhylomeDBiO00487.
TreeFamiTF105748.

Family and domain databases

InterProiView protein in InterPro
IPR000555. JAMM/MPN+_dom.
IPR035299. PSMD14.
IPR024969. Rpn11/EIF3F_C.
PANTHERiPTHR10410:SF13. PTHR10410:SF13. 1 hit.
PfamiView protein in Pfam
PF01398. JAB. 1 hit.
PF13012. MitMem_reg. 1 hit.
SMARTiView protein in SMART
SM00232. JAB_MPN. 1 hit.
PROSITEiView protein in PROSITE
PS50249. MPN. 1 hit.

Sequencei

Sequence statusi: Complete.

O00487-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDRLLRLGGG MPGLGQGPPT DAPAVDTAEQ VYISSLALLK MLKHGRAGVP
60 70 80 90 100
MEVMGLMLGE FVDDYTVRVI DVFAMPQSGT GVSVEAVDPV FQAKMLDMLK
110 120 130 140 150
QTGRPEMVVG WYHSHPGFGC WLSGVDINTQ QSFEALSERA VAVVVDPIQS
160 170 180 190 200
VKGKVVIDAF RLINANMMVL GHEPRQTTSN LGHLNKPSIQ ALIHGLNRHY
210 220 230 240 250
YSITINYRKN ELEQKMLLNL HKKSWMEGLT LQDYSEHCKH NESVVKEMLE
260 270 280 290 300
LAKNYNKAVE EEDKMTPEQL AIKNVGKQDP KRHLEEHVDV LMTSNIVQCL
310
AAMLDTVVFK
Length:310
Mass (Da):34,577
Last modified:July 1, 1997 - v1
Checksum:i18ACE876C7682039
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U86782 mRNA. Translation: AAC51866.1.
AK055128 mRNA. Translation: BAG51474.1.
CH471058 Genomic DNA. Translation: EAX11370.1.
BC066336 mRNA. Translation: AAH66336.1.
CCDSiCCDS46437.1.
RefSeqiNP_005796.1. NM_005805.5.
UniGeneiHs.740477.

Genome annotation databases

EnsembliENST00000409682; ENSP00000386541; ENSG00000115233.
GeneIDi10213.
KEGGihsa:10213.
UCSCiuc002ubu.4. human.

Similar proteinsi

Entry informationi

Entry nameiPSDE_HUMAN
AccessioniPrimary (citable) accession number: O00487
Secondary accession number(s): B3KNW2, O00176
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: July 1, 1997
Last modified: October 25, 2017
This is version 162 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 2
    Human chromosome 2: 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. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families