PSMC5 proteasome 26S subunit, ATPase 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PSMC5provided by HGNC
Official Full Name: proteasome 26S subunit, ATPase 5provided by HGNC
Primary source: HGNC:HGNC:9552
See related: Ensembl:ENSG00000087191 MIM:601681; AllianceGenome:HGNC:9552
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: S8; p45; RPT6; SUG1; SUG-1; TBP10; TRIP1; p45/SUG
Summary: The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes one of the ATPase subunits, a member of the triple-A family of ATPases which have a chaperone-like activity. In addition to participation in proteasome functions, this subunit may participate in transcriptional regulation since it has been shown to interact with the thyroid hormone receptor and retinoid X receptor-alpha. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]
Expression: Ubiquitous expression in kidney (RPKM 58.1), brain (RPKM 54.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q23.3

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (63827431..63832019)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (64697992..64702868)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (61904791..61909379)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Identification of a quality-control factor that monitors failures during proteasome assembly.
Title: Identification of a quality-control factor that monitors failures during proteasome assembly.
Hypoxia-induced increase in Sug1 leads to poor post-transplantation survival of allogeneic mesenchymal stem cells.
Title: Hypoxia-induced increase in Sug1 leads to poor post-transplantation survival of allogeneic mesenchymal stem cells.
autoinflammation-associated H443P nlrc4 mutant is altered in interaction with SUG1 and ubiquitinated proteins, triggering constitutive caspase-8-mediated cell death dependent on FADD but independent of Ser(533) phosphorylation.
Title: A Disease-associated Mutant of NLRC4 Shows Enhanced Interaction with SUG1 Leading to Constitutive FADD-dependent Caspase-8 Activation and Cell Death.
results demonstrate that PSMC5 is a new and important player involved in regulating ERK1/2 signal transmission through the remodeling of Shoc2 scaffold complex in a spatially-defined manner.
Title: Spatial control of Shoc2-scaffold-mediated ERK1/2 signaling requires remodeling activity of the ATPase PSMC5.
Our data suggest that PSMC5 facilitates the damaging effects of radiation in radiation-responsive H460 cancer cells and therefore may serve as a prognostic indicator for radiotherapy and molecular targeted therapy in lung cancer patients.
Title: Radiosensitizing effect of PSMC5, a 19S proteasome ATPase, in H460 lung cancer cells.
XopJ has protease activity to specifically degrade RPT6.
Title: The Xanthomonas campestris type III effector XopJ proteolytically degrades proteasome subunit RPT6.
TRIP-1 regulates fibroblast acquisition of phenotype and function associated with myofibroblasts.
Title: TRIP-1 via AKT modulation drives lung fibroblast/myofibroblast trans-differentiation.
gamma-aminobutyric acidB receptor proteasomal degradation is mediated by the interaction of the GABAB2 C terminus with the proteasomal ATPase Rtp6 and regulated by neuronal activity
Title: Proteasomal degradation of γ-aminobutyric acidB receptors is mediated by the interaction of the GABAB2 C terminus with the proteasomal ATPase Rtp6 and regulated by neuronal activity.
Rpt6 interacts directly with CKIP-1 and promotes the turnover of Smurf1.
Title: CKIP-1 couples Smurf1 ubiquitin ligase with Rpt6 subunit of proteasome to promote substrate degradation.
Sug1 plays a critical role in transcription of MHC class I, and the MHC class II-like molecules, HLA-DM and HLA-DO.
Title: Role of Sug1, a 19S proteasome ATPase, in the transcription of MHC I and the atypical MHC II molecules, HLA-DM and HLA-DO.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of proteasome (prosome, macropain) 26S subunit, ATPase, 5 (PSMC5) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat slightly enhances the activity of the purified 26 S proteasome	PubMed
	tat	Amino acids Lys51, Arg52, and Asp67 of HIV-1 Tat represent the proteasome binding site of Tat, and Tat amino acids 37-72 are necessary for proteasomal interaction and suppression of 11 S regulator-mediated antigen presentation	PubMed
	tat	HIV-1 Tat inhibits the peptidase activity of the 20 S proteasome and interferes with the formation of the 20 S proteasome-11 S regulator complex	PubMed
	tat	HIV-1 Tat binds to the alpha2, alpha4, alpha6, alpha7, beta1, beta2, beta3, beta5, beta6, beta7, LMP7/beta5i, and MECL1/beta2i subunits of the proteasome 20 S core structure and can inhibit cellular proteasome function	PubMed
	tat	TBP10 (SUG1) is a homolog of TBP1, a component of the 26S proteasome and a transcriptional activator that interacts with HIV-1 Tat to specifically inhibit Tat-mediated transactivation of the HIV-1 LTR promoter	PubMed
Vif	vif	HIV-1 Vif binds to the cellular cytidine deaminase APOBEC3G and targets it for degradation through an interaction with the proteasome, thereby inhibiting APOBEC3G mediated restriction of HIV-1 replication	PubMed
integrase	gag-pol	Proteasomal degradation of HIV-1 integrase in mammalian cells occurs by the N-end rule pathway	PubMed
matrix	gag	HIV-1 MA downregulates PSMC5 gene expression in HepG2 cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH36133 (e-PCR)
- UniSTS:37130

RH36220 (e-PCR)
- UniSTS:37131

MARC_4113-4114:991938380:3 (e-PCR)
- UniSTS:231072

MARC_4113-4114:996679383:1 (e-PCR)
- UniSTS:231072

PMC113761P5 (e-PCR)
- UniSTS:270256

SGC30177 (e-PCR)
- UniSTS:12005

D17S1654 (e-PCR)
- UniSTS:153831

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables general transcription initiation factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables proteasome-activating activity	IBA Inferred from Biological aspect of Ancestor more info
enables proteasome-activating activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables proteasome-activating activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables thyrotropin-releasing hormone receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription factor binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in negative regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of programmed cell death	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of proteasomal protein catabolic process	IC Inferred by Curator more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in blood microparticle	HDA more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	HDA more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of proteasome accessory complex	ISS Inferred from Sequence or Structural Similarity more info
part_of proteasome complex	IDA Inferred from Direct Assay more info	PubMed
part_of proteasome complex	NAS Non-traceable Author Statement more info	PubMed
part_of proteasome regulatory particle, base subcomplex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: 26S proteasome regulatory subunit 8

Names: 26S protease regulatory subunit 8; 26S proteasome AAA-ATPase subunit RPT6; MSUG1 protein; Tat-binding protein homolog 10; proteasome (prosome, macropain) 26S subunit, ATPase, 5; proteasome 26S ATPase subunit 5; proteasome subunit p45; testicular tissue protein Li 149; thyroid hormone receptor-interacting protein 1; thyroid receptor interactor 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001199163.2 → NP_001186092.1 26S proteasome regulatory subunit 8 isoform 2

See identical proteins and their annotated locations for NP_001186092.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

BC001932, DA056321

Consensus CDS

CCDS56043.1

UniProtKB/TrEMBL

A0A994J6V8

Related

ENSP00000364970.4, ENST00000375812.8

Conserved Domains (1) summary

COG1222
Location:1 → 396

RPT1; ATP-dependent 26S proteasome regulatory subunit [Posttranslational modification, protein turnover, chaperones]
NM_002805.6 → NP_002796.4 26S proteasome regulatory subunit 8 isoform 1

See identical proteins and their annotated locations for NP_002796.4

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

BC001932, BP209525

Consensus CDS

CCDS11645.1

UniProtKB/Swiss-Prot

A8K3Z3, A8K763, O35051, O43208, P47210, P52915, P52916, P62195

UniProtKB/TrEMBL

A0A140VJS3, A0A994J6V8

Related

ENSP00000310572.6, ENST00000310144.11

Conserved Domains (1) summary

COG1222
Location:4 → 404

RPT1; ATP-dependent 26S proteasome regulatory subunit [Posttranslational modification, protein turnover, chaperones]