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Protein

Proteasome activator complex subunit 3

Gene

PSME3

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

Functioni

Subunit of the 11S REG-gamma (also called PA28-gamma) proteasome regulator, a doughnut-shaped homoheptamer which associates with the proteasome. 11S REG-gamma activates the trypsin-like catalytic subunit of the proteasome but inhibits the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. Facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. May also be involved in cell cycle regulation. Mediates CCAR2 and CHEK2-dependent SIRT1 inhibition (PubMed:25361978).7 Publications

GO - Molecular functioni

  • endopeptidase activator activity Source: UniProtKB
  • identical protein binding Source: IntAct
  • MDM2/MDM4 family protein binding Source: UniProtKB
  • p53 binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processApoptosis, Cell cycle

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:
Proteasome activator complex subunit 3
Alternative name(s):
11S regulator complex subunit gamma
Short name:
REG-gamma
Activator of multicatalytic protease subunit 3
Ki nuclear autoantigen
Proteasome activator 28 subunit gamma
Short name:
PA28g
Short name:
PA28gamma
Gene namesi
Name:PSME3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000131467.10
HGNCiHGNC:9570 PSME3
MIMi605129 gene
neXtProtiNX_P61289

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

Cytoplasm, Nucleus, Proteasome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi188K → E, D, A, C, N, Q, H, F, S, I or P: Assembles into less stable hexamers/heptamers and therefore impairs specificity of activation of trypsin-like subunits of the proteasome. 1 Publication1

Organism-specific databases

DisGeNETi10197
OpenTargetsiENSG00000131467
PharmGKBiPA33916

Polymorphism and mutation databases

BioMutaiPSME3
DMDMi47117724

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001617892 – 254Proteasome activator complex subunit 3Add BLAST253

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei17PhosphoserineCombined sources1
Modified residuei24PhosphoserineCombined sources1
Modified residuei195N6-acetyllysine; by P300/CBP1 Publication1
Modified residuei247Phosphoserine; by CHEK21 Publication1

Post-translational modificationi

Phosphorylated by MAP3K3 (By similarity). Phosphorylation at Ser-247 promotes its association with CCAR2.By similarity1 Publication
Acetylation at the major site Lys-195 is important for oligomerization and ability to degrade its target substrates. Deacetylated by SIRT1.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP61289
PaxDbiP61289
PeptideAtlasiP61289
PRIDEiP61289

PTM databases

iPTMnetiP61289
PhosphoSitePlusiP61289
SwissPalmiP61289

Miscellaneous databases

PMAP-CutDBiP61289

Expressioni

Inductioni

Up-regulated in thyroid carcinoma cells.1 Publication

Gene expression databases

BgeeiENSG00000131467
CleanExiHS_PSME3
ExpressionAtlasiP61289 baseline and differential
GenevisibleiP61289 HS

Organism-specific databases

HPAiCAB008388
HPA012510

Interactioni

Subunit structurei

Homoheptamer; the stability of the heptamer is essential for the specific activation of the trypsine-like subunit and inhibition of the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits of the proteasome. Interacts with p53/TP53 and MDM2. Interacts with MAP3K3 (By similarity). Associates with the proteasome. Interacts with human cytomegalovirus UL27. Interacts with CCAR2.By similarity8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • MDM2/MDM4 family protein binding Source: UniProtKB
  • p53 binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115492, 181 interactors
CORUMiP61289
IntActiP61289, 86 interactors
MINTiP61289
STRINGi9606.ENSP00000293362

Structurei

3D structure databases

ProteinModelPortaliP61289
SMRiP61289
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The C-terminal sequences affect heptamer stability and proteasome affinity.1 Publication

Sequence similaritiesi

Belongs to the PA28 family.Curated

Phylogenomic databases

eggNOGiKOG4470 Eukaryota
ENOG410XQVX LUCA
GeneTreeiENSGT00510000046374
HOVERGENiHBG053745
InParanoidiP61289
KOiK06698
OMAiPCNKPLC
OrthoDBiEOG091G0GX7
PhylomeDBiP61289
TreeFamiTF106236

Family and domain databases

Gene3Di1.20.120.180, 1 hit
1.20.5.120, 1 hit
InterProiView protein in InterPro
IPR003186 PA28_C
IPR036997 PA28_C_sf
IPR036996 PA28_N_sf
IPR009077 Proteasome_activ_PA28
IPR003185 Proteasome_activ_PA28_N
IPR036252 Proteasome_activ_sf
PANTHERiPTHR10660 PTHR10660, 1 hit
PfamiView protein in Pfam
PF02251 PA28_alpha, 1 hit
PF02252 PA28_beta, 1 hit
SUPFAMiSSF47216 SSF47216, 2 hits

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P61289-1) [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
MASLLKVDQE VKLKVDSFRE RITSEAEDLV ANFFPKKLLE LDSFLKEPIL
60 70 80 90 100
NIHDLTQIHS DMNLPVPDPI LLTNSHDGLD GPTYKKRRLD ECEEAFQGTK
110 120 130 140 150
VFVMPNGMLK SNQQLVDIIE KVKPEIRLLI EKCNTVKMWV QLLIPRIEDG
160 170 180 190 200
NNFGVSIQEE TVAELRTVES EAASYLDQIS RYYITRAKLV SKIAKYPHVE
210 220 230 240 250
DYRRTVTEID EKEYISLRLI ISELRNQYVT LHDMILKNIE KIKRPRSSNA

ETLY
Length:254
Mass (Da):29,506
Last modified:May 10, 2004 - v1
Checksum:i116FAB47D60A26C0
GO
Isoform 2 (identifier: P61289-2) [UniParc] [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     135-135: T → TPSGKGPHICFDLQ

Show »
Length:267
Mass (Da):30,887
Checksum:i76E7E6ECCC65589F
GO
Isoform 3 (identifier: P61289-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: MASLLKVDQEVKL → MEKWILKKIKYLQSGGLSASYYSY

Note: No experimental confirmation. Gene prediction based on EST data.
Show »
Length:265
Mass (Da):30,890
Checksum:iEC200E4F73756C82
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25E → K in AAB60335 (PubMed:7951316).Curated1
Sequence conflicti94E → K in AAA93227 (PubMed:7545954).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0550471 – 13MASLL…QEVKL → MEKWILKKIKYLQSGGLSAS YYSY in isoform 3. CuratedAdd BLAST13
Alternative sequenceiVSP_004516135T → TPSGKGPHICFDLQ in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U11292 mRNA Translation: AAB60335.1
BT019386 mRNA Translation: AAV38193.1
AK292618 mRNA Translation: BAF85307.1
AK074999 mRNA Translation: BAG52046.1
AC016889 Genomic DNA No translation available.
CH471152 Genomic DNA Translation: EAW60893.1
BC001423 mRNA Translation: AAH01423.1
BC002684 mRNA Translation: AAH02684.1
BC008020 mRNA Translation: AAH08020.1
U25756 Genomic DNA Translation: AAA93227.1
CCDSiCCDS11442.1 [P61289-2]
CCDS45689.1
CCDS59290.1 [P61289-3]
PIRiI38702 A60537
RefSeqiNP_005780.2, NM_005789.3 [P61289-1]
NP_789839.1, NM_176863.2 [P61289-2]
UniGeneiHs.152978

Genome annotation databases

EnsembliENST00000293362; ENSP00000293362; ENSG00000131467 [P61289-2]
ENST00000441946; ENSP00000409487; ENSG00000131467 [P61289-3]
ENST00000590720; ENSP00000466794; ENSG00000131467 [P61289-1]
GeneIDi10197
KEGGihsa:10197
UCSCiuc002ibq.5 human

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPSME3_HUMAN
AccessioniPrimary (citable) accession number: P61289
Secondary accession number(s): A8K9A3
, O35563, P97373, Q12920, Q13172, Q9BQD9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: May 23, 2018
This is version 153 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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. SIMILARITY comments
    Index of protein domains and families

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