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Protein

26S proteasome non-ATPase regulatory subunit 12

Gene

PSMD12

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.1 Publication

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-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-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 12
Alternative name(s):
26S proteasome regulatory subunit RPN5
26S proteasome regulatory subunit p55
Gene namesi
Name:PSMD12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000197170.9
HGNCiHGNC:9557 PSMD12
MIMi604450 gene
neXtProtiNX_O00232

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

Involvement in diseasei

Stankiewicz-Isidor syndrome (STISS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, behavioral disorders, mild dysmorphism, ophthalmologic anomalies, feeding difficulties, deafness, and variable congenital malformations of the cardiac and/or urogenital systems.
See also OMIM:617516

Keywords - Diseasei

Mental retardation

Organism-specific databases

DisGeNETi5718
MalaCardsiPSMD12
MIMi617516 phenotype
OpenTargetsiENSG00000197170
PharmGKBiPA33903

Chemistry databases

ChEMBLiCHEMBL2364701

Polymorphism and mutation databases

BioMutaiPSMD12

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001738612 – 45626S proteasome non-ATPase regulatory subunit 12Add BLAST455

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Cross-linki92Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki92Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei221N6-acetyllysineCombined sources1
Modified residuei368N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiO00232
MaxQBiO00232
PaxDbiO00232
PeptideAtlasiO00232
PRIDEiO00232
ProteomicsDBi47797
47798 [O00232-2]

PTM databases

iPTMnetiO00232
PhosphoSitePlusiO00232
SwissPalmiO00232

Expressioni

Gene expression databases

BgeeiENSG00000197170
CleanExiHS_PSMD12
ExpressionAtlasiO00232 baseline and differential
GenevisibleiO00232 HS

Organism-specific databases

HPAiHPA023119

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 PSMD12, a base containing 6 ATPases and few additional components.2 Publications

Protein-protein interaction databases

BioGridi111690, 112 interactors
CORUMiO00232
DIPiDIP-27549N
IntActiO00232, 30 interactors
MINTiO00232
STRINGi9606.ENSP00000348442

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5GJQelectron microscopy4.50P1-456[»]
5GJRelectron microscopy3.503/P1-456[»]
5L4Kelectron microscopy4.50P1-456[»]
5LN3electron microscopy6.80P1-456[»]
5M32electron microscopy3.80k1-456[»]
5T0Celectron microscopy3.80AW/BW1-456[»]
5T0Gelectron microscopy4.40W1-456[»]
5T0Helectron microscopy6.80W1-456[»]
5T0Ielectron microscopy8.00W1-456[»]
5T0Jelectron microscopy8.00W1-456[»]
5VGZelectron microscopy3.70W1-456[»]
5VHFelectron microscopy5.70W1-456[»]
5VHHelectron microscopy6.10W1-456[»]
5VHIelectron microscopy6.80W1-456[»]
5VHSelectron microscopy8.80W1-456[»]
ProteinModelPortaliO00232
SMRiO00232
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini242 – 420PCIPROSITE-ProRule annotationAdd BLAST179

Sequence similaritiesi

Belongs to the proteasome subunit p55 family.Curated

Phylogenomic databases

eggNOGiKOG1498 Eukaryota
COG5071 LUCA
GeneTreeiENSGT00730000111110
HOGENOMiHOG000194265
HOVERGENiHBG053739
InParanoidiO00232
KOiK03035
OMAiKQAITKM
OrthoDBiEOG091G06CB
PhylomeDBiO00232
TreeFamiTF105721

Family and domain databases

Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR000717 PCI_dom
IPR035297 PSMD12
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PANTHERiPTHR10855:SF1 PTHR10855:SF1, 1 hit
PfamiView protein in Pfam
PF01399 PCI, 1 hit
SMARTiView protein in SMART
SM00088 PINT, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
PROSITEiView protein in PROSITE
PS50250 PCI, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: O00232-1) [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
MADGGSERAD GRIVKMEVDY SATVDQRLPE CAKLAKEGRL QEVIETLLSL
60 70 80 90 100
EKQTRTASDM VSTSRILVAV VKMCYEAKEW DLLNENIMLL SKRRSQLKQA
110 120 130 140 150
VAKMVQQCCT YVEEITDLPI KLRLIDTLRM VTEGKIYVEI ERARLTKTLA
160 170 180 190 200
TIKEQNGDVK EAASILQELQ VETYGSMEKK ERVEFILEQM RLCLAVKDYI
210 220 230 240 250
RTQIISKKIN TKFFQEENTE KLKLKYYNLM IQLDQHEGSY LSICKHYRAI
260 270 280 290 300
YDTPCIQAES EKWQQALKSV VLYVILAPFD NEQSDLVHRI SGDKKLEEIP
310 320 330 340 350
KYKDLLKLFT TMELMRWSTL VEDYGMELRK GSLESPATDV FGSTEEGEKR
360 370 380 390 400
WKDLKNRVVE HNIRIMAKYY TRITMKRMAQ LLDLSVDESE AFLSNLVVNK
410 420 430 440 450
TIFAKVDRLA GIINFQRPKD PNNLLNDWSQ KLNSLMSLVN KTTHLIAKEE

MIHNLQ
Length:456
Mass (Da):52,904
Last modified:January 23, 2007 - v3
Checksum:i97D0BDBDB0C96195
GO
Isoform 2 (identifier: O00232-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     37-56: Missing.

Note: No experimental confirmation available.
Show »
Length:436
Mass (Da):50,579
Checksum:i01DCBC0BF3EC3718
GO

Sequence cautioni

The sequence AAH65826 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti300P → S in BAD96399 (Ref. 3) Curated1
Sequence conflicti398V → D in BAD96399 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051558358V → A. Corresponds to variant dbSNP:rs2230680Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04271837 – 56Missing in isoform 2. 1 PublicationAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB003103 mRNA Translation: BAA19749.1
AK091198 mRNA Translation: BAG52303.1
AK222679 mRNA Translation: BAD96399.1
AC110921 Genomic DNA No translation available.
CH471099 Genomic DNA Translation: EAW89028.1
BC019062 mRNA Translation: AAH19062.1
BC065826 mRNA Translation: AAH65826.1 Different initiation.
CCDSiCCDS11669.1 [O00232-1]
CCDS11670.1 [O00232-2]
PIRiPC6501 JC6523
RefSeqiNP_001303270.1, NM_001316341.1
NP_002807.1, NM_002816.4 [O00232-1]
NP_777360.1, NM_174871.3 [O00232-2]
UniGeneiHs.4295
Hs.592689

Genome annotation databases

EnsembliENST00000356126; ENSP00000348442; ENSG00000197170 [O00232-1]
ENST00000357146; ENSP00000349667; ENSG00000197170 [O00232-2]
GeneIDi5718
KEGGihsa:5718
UCSCiuc002jfy.4 human [O00232-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPSD12_HUMAN
AccessioniPrimary (citable) accession number: O00232
Secondary accession number(s): A6NP15, Q53HA2, Q6P053
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 15, 2002
Last sequence update: January 23, 2007
Last modified: June 20, 2018
This is version 168 of the entry and version 3 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 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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