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Protein

26S proteasome regulatory subunit 8

Gene

PSMC5

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. PSMC5 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi190 – 197ATPSequence analysis8

GO - Molecular functioni

  • ATPase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • proteasome-activating ATPase activity Source: GO_Central
  • TBP-class protein binding Source: GO_Central
  • thyrotropin-releasing hormone receptor binding Source: UniProtKB
  • transcription factor binding Source: GO_Central

GO - Biological processi

Keywordsi

LigandATP-binding, Nucleotide-binding

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 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-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-8941858. Regulation of RUNX3 expression and activity.
R-HSA-8951664. Neddylation.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Names & Taxonomyi

Protein namesi
Recommended name:
26S proteasome regulatory subunit 8
Alternative name(s):
26S proteasome AAA-ATPase subunit RPT6
Proteasome 26S subunit ATPase 5
Proteasome subunit p45
Thyroid hormone receptor-interacting protein 1
Short name:
TRIP1
p45/SUG
Gene namesi
Name:PSMC5
Synonyms:SUG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:9552. PSMC5.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytoplasmic vesicle Source: UniProtKB
  • cytosol Source: Reactome
  • cytosolic proteasome complex Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • inclusion body Source: Ensembl
  • membrane Source: UniProtKB
  • nuclear proteasome complex Source: GO_Central
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • postsynapse Source: Ensembl
  • proteasome accessory complex Source: UniProtKB
  • proteasome complex Source: UniProtKB
  • proteasome regulatory particle, base subcomplex Source: GO_Central

Keywords - Cellular componenti

Cytoplasm, Nucleus, Proteasome

Pathology & Biotechi

Organism-specific databases

DisGeNETi5705.
OpenTargetsiENSG00000087191.
PharmGKBiPA33897.

Chemistry databases

ChEMBLiCHEMBL2364701.

Polymorphism and mutation databases

BioMutaiPSMC5.
DMDMi49065819.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000847212 – 40626S proteasome regulatory subunit 8Add BLAST405

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei120PhosphoserineCombined sources1
Modified residuei222N6-acetyllysineCombined sources1
Isoform 2 (identifier: P62195-2)
Modified residuei1N-acetylmethionineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP62195.
MaxQBiP62195.
PaxDbiP62195.
PeptideAtlasiP62195.
PRIDEiP62195.

PTM databases

iPTMnetiP62195.
PhosphoSitePlusiP62195.
SwissPalmiP62195.

Expressioni

Gene expression databases

BgeeiENSG00000087191.
CleanExiHS_PSMC5.
ExpressionAtlasiP62195. baseline and differential.
GenevisibleiP62195. HS.

Organism-specific databases

HPAiHPA017871.
HPA064293.

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 including PSMC5 and few additional components (PubMed:27428775, PubMed:27342858). Component of a complex with USP49 and RUVBL1 (PubMed:23824326). Interacts with PRPF19. Interacts with TRIM5 (PubMed:22078707). Interacts with NDC80 (PubMed:9295362, PubMed:10409732). Interacts with PAAF1 (PubMed:15831487). Interacts, in vitro, with the thyroid hormone receptor (in a thyroid hormone T3-dependent manner) and with retinoid X receptor (RXR).By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • TBP-class protein binding Source: GO_Central
  • thyrotropin-releasing hormone receptor binding Source: UniProtKB
  • transcription factor binding Source: GO_Central

Protein-protein interaction databases

BioGridi111678. 221 interactors.
DIPiDIP-36645N.
IntActiP62195. 84 interactors.
MINTiMINT-5004394.
STRINGi9606.ENSP00000310572.

Structurei

Secondary structure

1406
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi322 – 333Combined sources12
Beta strandi336 – 338Combined sources3
Helixi344 – 349Combined sources6
Helixi356 – 372Combined sources17
Beta strandi376 – 378Combined sources3
Helixi380 – 391Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KRKNMR-A320-395[»]
3KW6X-ray2.10A318-395[»]
5GJQelectron microscopy4.50J1-406[»]
5GJRelectron microscopy3.50J/x1-406[»]
5L4Gelectron microscopy4.02J1-406[»]
5LN3electron microscopy6.80J1-406[»]
5T0Celectron microscopy3.80AC/BC1-406[»]
5T0Gelectron microscopy4.40C9-406[»]
5T0Helectron microscopy6.80C9-406[»]
5T0Ielectron microscopy8.00C9-406[»]
5T0Jelectron microscopy8.00C9-406[»]
ProteinModelPortaliP62195.
SMRiP62195.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP62195.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni186 – 406May mediate interaction with PRPF9By similarityAdd BLAST221

Sequence similaritiesi

Belongs to the AAA ATPase family.Curated

Phylogenomic databases

eggNOGiKOG0728. Eukaryota.
COG1222. LUCA.
GeneTreeiENSGT00550000074947.
HOGENOMiHOG000225143.
HOVERGENiHBG000109.
InParanoidiP62195.
KOiK03066.
OMAiHGNNQEA.
OrthoDBiEOG091G096W.
PhylomeDBiP62195.

Family and domain databases

Gene3Di3.10.330.10. 1 hit.
InterProiView protein in InterPro
IPR005937. 26S_Psome_P45.
IPR003593. AAA+_ATPase.
IPR003959. ATPase_AAA_core.
IPR003960. ATPase_AAA_CS.
IPR029067. CDC48_domain_2-like.
IPR027417. P-loop_NTPase.
IPR035261. PSMC5.
PANTHERiPTHR23073:SF47. PTHR23073:SF47. 1 hit.
PfamiView protein in Pfam
PF00004. AAA. 1 hit.
SMARTiView protein in SMART
SM00382. AAA. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR01242. 26Sp45. 1 hit.
PROSITEiView protein in PROSITE
PS00674. AAA. 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: P62195-1) [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
MALDGPEQME LEEGKAGSGL RQYYLSKIEE LQLIVNDKSQ NLRRLQAQRN
60 70 80 90 100
ELNAKVRLLR EELQLLQEQG SYVGEVVRAM DKKKVLVKVH PEGKFVVDVD
110 120 130 140 150
KNIDINDVTP NCRVALRNDS YTLHKILPNK VDPLVSLMMV EKVPDSTYEM
160 170 180 190 200
IGGLDKQIKE IKEVIELPVK HPELFEALGI AQPKGVLLYG PPGTGKTLLA
210 220 230 240 250
RAVAHHTDCT FIRVSGSELV QKFIGEGARM VRELFVMARE HAPSIIFMDE
260 270 280 290 300
IDSIGSSRLE GGSGGDSEVQ RTMLELLNQL DGFEATKNIK VIMATNRIDI
310 320 330 340 350
LDSALLRPGR IDRKIEFPPP NEEARLDILK IHSRKMNLTR GINLRKIAEL
360 370 380 390 400
MPGASGAEVK GVCTEAGMYA LRERRVHVTQ EDFEMAVAKV MQKDSEKNMS

IKKLWK
Length:406
Mass (Da):45,626
Last modified:June 21, 2004 - v1
Checksum:i29C6410C4A85A7F7
GO
Isoform 2 (identifier: P62195-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: Missing.

Show »
Length:398
Mass (Da):44,784
Checksum:i450BB51DA8C9381D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti61E → R in BAA07919 (PubMed:7729537).Curated1
Sequence conflicti127 – 128LP → ML in AAB88187 (PubMed:9110174).Curated2
Sequence conflicti266D → S in AAC41735 (PubMed:7776974).Curated1
Sequence conflicti272T → Q in AAC41735 (PubMed:7776974).Curated1
Sequence conflicti300I → M in AAC41735 (PubMed:7776974).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03590160R → Q in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_048119258R → W. Corresponds to variant dbSNP:rs11543211Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0454411 – 8Missing in isoform 2. 1 Publication8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D44467 mRNA. Translation: BAA07919.1.
L38810 mRNA. Translation: AAC41735.1.
AK290758 mRNA. Translation: BAF83447.1.
AK291878 mRNA. Translation: BAF84567.1.
AC015651 Genomic DNA. No translation available.
CH471109 Genomic DNA. Translation: EAW94270.1.
CH471109 Genomic DNA. Translation: EAW94271.1.
CH471109 Genomic DNA. Translation: EAW94272.1.
BC001932 mRNA. Translation: AAH01932.1.
BC002367 mRNA. Translation: AAH02367.3.
AF035309 mRNA. Translation: AAB88187.1.
CCDSiCCDS11645.1. [P62195-1]
CCDS56043.1. [P62195-2]
PIRiS60343.
S65536.
RefSeqiNP_001186092.1. NM_001199163.1. [P62195-2]
NP_002796.4. NM_002805.5. [P62195-1]
UniGeneiHs.79387.

Genome annotation databases

EnsembliENST00000310144; ENSP00000310572; ENSG00000087191. [P62195-1]
ENST00000375812; ENSP00000364970; ENSG00000087191. [P62195-2]
ENST00000580864; ENSP00000462495; ENSG00000087191. [P62195-2]
ENST00000581882; ENSP00000463938; ENSG00000087191. [P62195-2]
GeneIDi5705.
KEGGihsa:5705.
UCSCiuc002jcb.4. human. [P62195-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPRS8_HUMAN
AccessioniPrimary (citable) accession number: P62195
Secondary accession number(s): A8K3Z3
, A8K763, O35051, O43208, P47210, P52915, P52916
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 21, 2004
Last sequence update: June 21, 2004
Last modified: August 30, 2017
This is version 146 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, 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