PSMC4 proteasome 26S subunit, ATPase 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PSMC4provided by HGNC
Official Full Name: proteasome 26S subunit, ATPase 4provided by HGNC
Primary source: HGNC:HGNC:9551
See related: Ensembl:ENSG00000013275 MIM:602707; AllianceGenome:HGNC:9551
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: S6; RPT3; TBP7; TBP-7; MIP224
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. This gene encodes a member of the triple-A family of ATPases that is a component of the 19S regulatory subunit and plays a role in 26S proteasome assembly. The encoded protein interacts with gankyrin, a liver oncoprotein, and may also play a role in Parkinson's disease through interactions with synphilin-1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]
Expression: Ubiquitous expression in thyroid (RPKM 29.3), brain (RPKM 25.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.2

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (39971165..39981764)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (42791375..42801971)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (40477072..40487671)

Chromosome 19 - NC_000019.10 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
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?

PSMC4 promotes prostate carcinoma progression by regulating the CBX3-EGFR-PI3K-AKT-mTOR pathway.
Title: PSMC4 promotes prostate carcinoma progression by regulating the CBX3-EGFR-PI3K-AKT-mTOR pathway.
This study demonstrated that particular distribution for HSC70 and PSMC4 in the cytoplasm and accumulation within Lewy body in the dopaminergic neurons of the substantia nigra in Parkinson patients.
Title: Differential Alterations in Metabolism and Proteolysis-Related Proteins in Human Parkinson's Disease Substantia Nigra.
Structural mechanism for nucleotide-driven remodeling of RPT3 and its homologs in the activated human 26S proteasome has been reported.
Title: Structural mechanism for nucleotide-driven remodeling of the AAA-ATPase unfoldase in the activated human 26S proteasome.
Site-specific Rpt3 phosphorylation by DYRK2 controls cell proliferation and tumorigenesis in breast neoplasms.
Title: Site-specific proteasome phosphorylation controls cell proliferation and tumorigenesis.
Saquinavir-NO inhibits activation of S6 protein in androgen-dependent prostate cancer cells.
Title: Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL.
The proposed TRAP1 network has an impact in vivo, as it is conserved in human colorectal cancers, is controlled by ER-localized TRAP1 interacting with TBP7 and provides a novel model of the ER-mitochondria crosstalk.
Title: TRAP1 and the proteasome regulatory particle TBP7/Rpt3 interact in the endoplasmic reticulum and control cellular ubiquitination of specific mitochondrial proteins.
C terminus of Rpt3, an ATPase subunit of PA700 (19 S) regulatory complex, is essential for 26 S proteasome assembly but not for activation
Title: The C terminus of Rpt3, an ATPase subunit of PA700 (19 S) regulatory complex, is essential for 26 S proteasome assembly but not for activation.
An insertion/deletion variant in intron 5 of the S6 ATPase gene was more frequent in German Parkinson's disease patients compared to controls
Title: A comprehensive genetic study of the proteasomal subunit S6 ATPase in German Parkinson's disease patients.
interacts with gankyrin through C-terminal 78 amino acids
Title: Gankyrin is an ankyrin-repeat oncoprotein that interacts with CDK4 kinase and the S6 ATPase of the 26 S proteasome.
a novel specific interaction of synphilin-1 with the regulatory proteasomal protein S6 ATPase (tbp7) in aggresome-like intracytoplasmic inclusions
Title: The proteasomal subunit S6 ATPase is a novel synphilin-1 interacting protein--implications for Parkinson's disease.

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Phenotypes

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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, 4 (PSMC4) 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	TBP7 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
retropepsin	gag-pol	Positional proteomics analysis identifies the cleavage of human proteasome (prosome, macropain) 26S subunit, ATPase, 4 (PSMC4) at amino acid residues 7-8 by the HIV-1 protease	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH98237 (e-PCR)
- UniSTS:92540

STS-T26522 (e-PCR)
- UniSTS:69583

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 proteasome-activating activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in blastocyst development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of proteasomal protein catabolic process	IEA Inferred from Electronic Annotation more info
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	NAS Non-traceable Author Statement more info	PubMed
involved_in proteolysis	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	HDA 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 6B

Names: 26S protease regulatory subunit 6B; 26S proteasome AAA-ATPase subunit RPT3; MB67-interacting protein; Tat-binding protein 7; protease 26S subunit 6; proteasome (prosome, macropain) 26S subunit, ATPase, 4

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_006503.4 → NP_006494.1 26S proteasome regulatory subunit 6B isoform 1

See identical proteins and their annotated locations for NP_006494.1

Status: REVIEWED

Description

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

Source sequence(s)

AC007842, AK313183

Consensus CDS

CCDS12547.1

UniProtKB/Swiss-Prot

P43686, Q96FV5, Q9UBM3, Q9UEX3

UniProtKB/TrEMBL

A8K2M0

Related

ENSP00000157812.1, ENST00000157812.7

Conserved Domains (1) summary

PTZ00454
Location:34 → 418

PTZ00454; 26S protease regulatory subunit 6B-like protein; Provisional
NM_153001.3 → NP_694546.1 26S proteasome regulatory subunit 6B isoform 2

See identical proteins and their annotated locations for NP_694546.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AC007842, BC010396, BI828251

Consensus CDS

CCDS46076.1

UniProtKB/Swiss-Prot

P43686

Related

ENSP00000413869.1, ENST00000455878.2

Conserved Domains (1) summary

PTZ00454
Location:33 → 387

PTZ00454; 26S protease regulatory subunit 6B-like protein; Provisional