PSMC1 proteasome 26S subunit, ATPase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PSMC1provided by HGNC
Official Full Name: proteasome 26S subunit, ATPase 1provided by HGNC
Primary source: HGNC:HGNC:9547
See related: Ensembl:ENSG00000100764 MIM:602706; AllianceGenome:HGNC:9547
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: S4; p56; RPT2; P26S4; NEDGTH
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. This subunit and a 20S core alpha subunit interact specifically with the hepatitis B virus X protein, a protein critical to viral replication. This subunit also interacts with the adenovirus E1A protein and this interaction alters the activity of the proteasome. Finally, this subunit interacts with ataxin-7, suggesting a role for the proteasome in the development of spinocerebellar ataxia type 7, a progressive neurodegenerative disorder. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in testis (RPKM 27.5), fat (RPKM 23.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q32.11

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (90256553..90275429)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (84478491..84499697)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (90722897..90741773)

Chromosome 14 - NC_000014.9 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?

PSMC1 variant causes a novel neurological syndrome.
Title: PSMC1 variant causes a novel neurological syndrome.
Low expression of TCP1 (T-Complex 1) and PSMC1 (Proteasome 26S subunit, ATPase 1) in heterotopic ossification during ankylosing spondylitis.
Title: Low expression of TCP1 (T-Complex 1) and PSMC1 (Proteasome 26S subunit, ATPase 1) in heterotopic ossification during ankylosing spondylitis.
14q32.11 microdeletion including CALM1, TTC7B, PSMC1, and RPS6KA5: A new potential cause of developmental and language delay in three unrelated patients.
Title: 14q32.11 microdeletion including CALM1, TTC7B, PSMC1, and RPS6KA5: A new potential cause of developmental and language delay in three unrelated patients.
P26s4 Associates with the C-Terminal Region of TOPORS.
Title: TOPORS, a Dual E3 Ubiquitin and Sumo1 Ligase, Interacts with 26 S Protease Regulatory Subunit 4, Encoded by the PSMC1 Gene.
Our results suggest that there is no association between variations or haplotypes in the PSMC1 gene and Parkinson's disease
Title: PSMC1 Gene in Parkinson's Disease.
Caspase-3 cleaves specific 19 S proteasome subunits in skeletal muscle stimulating proteasome activity
Title: Caspase-3 cleaves specific 19 S proteasome subunits in skeletal muscle stimulating proteasome activity.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Psmc1 conditional knock-out mice demonstrate that 26S proteasomal dysfunction is sufficient to trigger neurodegenerative disease.
Title: Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies.
Hepatocytes dying because of inhibition of proteasome function produce massive quantities of the proinflammatory chemokine IL-8, possibly resulting in neutrophil infiltration, increased inflammation, and liver injury.
Title: Inhibition of proteasome function leads to NF-kappaB-independent IL-8 expression in human hepatocytes.

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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

Associated conditions

Description	Tests
Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss MedGen: C5774229 OMIM: 620071 GeneReviews: Not available	not available

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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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
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

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

SGC34848 (e-PCR)
- UniSTS:48951

A009W30 (e-PCR)
- UniSTS:62440

G32920 (e-PCR)
- UniSTS:117498

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 RNA binding	HDA 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 protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
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

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 4

Names: 26S protease regulatory subunit 4; 26S proteasome AAA-ATPase subunit RPT2; proteasome (prosome, macropain) 26S subunit, ATPase, 1; proteasome 26S ATPase subunit 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.

Genomic

NG_046999.2 RefSeqGene

Range

5002..23878

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001330212.2 → NP_001317141.1 26S proteasome regulatory subunit 4 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' structure, resulting in the use of a downstream start codon, compared to variant 1. The encoded isoform (b) has a shorter N-terminus compared to isoform a.

Source sequence(s)

AL161662, AL355074, BQ574737

Consensus CDS

CCDS81837.1

UniProtKB/TrEMBL

Q53HB3

Related

ENSP00000445147.2, ENST00000543772.2

Conserved Domains (1) summary

PTZ00361
Location:1 → 367

PTZ00361; 26 proteosome regulatory subunit 4-like protein; Provisional
NM_002802.3 → NP_002793.2 26S proteasome regulatory subunit 4 isoform a

See identical proteins and their annotated locations for NP_002793.2

Status: REVIEWED

Description

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

Source sequence(s)

AL161662, AL355074

Consensus CDS

CCDS32139.1

UniProtKB/Swiss-Prot

B4DR63, P49014, P62191, Q03527, Q6IAW0, Q6NW36, Q96AZ3

UniProtKB/TrEMBL

Q53HB3, Q53XL8

Related

ENSP00000261303.8, ENST00000261303.13

Conserved Domains (1) summary

PTZ00361
Location:1 → 440

PTZ00361; 26 proteosome regulatory subunit 4-like protein; Provisional