PSME1 proteasome activator subunit 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PSME1provided by HGNC
Official Full Name: proteasome activator subunit 1provided by HGNC
Primary source: HGNC:HGNC:9568
See related: Ensembl:ENSG00000092010 MIM:600654; AllianceGenome:HGNC:9568
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: PA28A; IFI5111; REGalpha; PA28alpha; HEL-S-129m
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. The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. Three subunits (alpha, beta and gamma) of the 11S regulator have been identified. This gene encodes the alpha subunit of the 11S regulator, one of the two 11S subunits that is induced by gamma-interferon. Three alpha and three beta subunits combine to form a heterohexameric ring. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Expression: Ubiquitous expression in lymph node (RPKM 102.3), spleen (RPKM 98.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q12

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (24136194..24138962)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (18334505..18337273)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (24605403..24608171)

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?

Downregulation of PA28alpha induces proteasome remodeling and results in resistance to proteasome inhibitors in multiple myeloma.
Title: Downregulation of PA28α induces proteasome remodeling and results in resistance to proteasome inhibitors in multiple myeloma.
Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks.
Title: Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks.
Such a modulation of proteasome activity is explained, at least in part, by the circadian expression of both Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and the proteasome activator PA28ab
Title: Circadian modulation of proteasome activity and accumulation of oxidized protein in human embryonic kidney HEK 293 cells and primary dermal fibroblasts.
Results show that PA28alpha was found to be overexpressed in oral squamous cell carcinoma cell lines and tumor tissues. High expression of PA28alpha was significantly associated with recurrence and poorer overall survival.
Title: Overexpression of proteasomal activator PA28α serves as a prognostic factor in oral squamous cell carcinoma.
Constitutive expression of PA28 and ERAP1 in melanoma cells indicate that both interfere with MART-1(26-35) epitope generation even in the absence of IFN-gamma
Title: The proteasome immunosubunits, PA28 and ER-aminopeptidase 1 protect melanoma cells from efficient MART-126-35 -specific T-cell recognition.
PA28 is a tumor marker and a potential target for therapeutic intervention in prostate cancer.
Title: Proteasome activator complex PA28 identified as an accessible target in prostate cancer by in vivo selection of human antibodies.
Reduction in ATP levels triggers immunoproteasome activation by the 11S (PA28) regulator during early antiviral response mediated by IFNbeta in mouse pancreatic beta-cells.
Title: Reduction in ATP levels triggers immunoproteasome activation by the 11S (PA28) regulator during early antiviral response mediated by IFNβ in mouse pancreatic β-cells.
the first evidence of a novel ovarian cancer-specific marker
Title: The C-terminal fragment of the immunoproteasome PA28S (Reg alpha) as an early diagnosis and tumor-relapse biomarker: evidence from mass spectrometry profiling.
bortezomib-adapted HL-60 cells showed increased expression and proteasome association of the 11S proteasome activator
Title: Characterization of the ubiquitin-proteasome system in bortezomib-adapted cells.
the 11S proteasome activator complex, Reg alpha fragment, may have a role in ovarian cancer
Title: Specific MALDI imaging and profiling for biomarker hunting and validation: fragment of the 11S proteasome activator complex, Reg alpha fragment, is a new potential ovary cancer biomarker.

Submit: New GeneRIF Correction See all GeneRIFs (14)

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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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
capsid	gag	HIV-1 CA downregulates PA28beta and the beta2i subunit of the immunoproteasome complex in a dendritic cell line (JAWS II), whereas in primary dendritic cells, PA28alpha, beta2i, and beta5i are downregulated by CA	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

RH78603 (e-PCR)
- UniSTS:73309

RH75843 (e-PCR)
- UniSTS:91113

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables endopeptidase activator 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 antigen processing and presentation of exogenous antigen	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of G1/S transition of mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of proteasomal protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	TAS Traceable Author Statement more info
part_of proteasome activator complex	IEA Inferred from Electronic Annotation more info
part_of proteasome complex	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: proteasome activator complex subunit 1

Names: 11S regulator complex subunit alpha; 29-kD MCP activator subunit; IGUP I-5111; activator of multicatalytic protease subunit 1; epididymis secretory sperm binding protein Li 129m; interferon gamma up-regulated I-5111 protein; interferon-gamma IEF SSP 5111; interferon-gamma-inducible protein 5111; proteasome (prosome, macropain) activator subunit 1 (PA28 alpha)

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_001281528.2 → NP_001268457.1 proteasome activator complex subunit 1 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 3, which has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

BJ993879, BM981616, BU192084

Consensus CDS

CCDS61415.1

UniProtKB/TrEMBL

Q6FHU3

Related

ENSP00000453976.1, ENST00000561435.5

Conserved Domains (2) summary

pfam02251
Location:10 → 67

PA28_alpha; Proteasome activator pa28 alpha subunit

pfam02252
Location:103 → 223

PA28_beta; Proteasome activator pa28 beta subunit
NM_001281529.2 → NP_001268458.1 proteasome activator complex subunit 1 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. It encodes isoform 4 which is shorter compared to isoform 1.

Source sequence(s)

AI445328, BJ993879, BM470561, BM981616

UniProtKB/TrEMBL

Q6FHU3

Conserved Domains (2) summary

pfam02251
Location:10 → 67

PA28_alpha; Proteasome activator pa28 alpha subunit

pfam02252
Location:106 → 234

PA28_beta; Proteasome activator pa28 beta subunit
NM_006263.4 → NP_006254.1 proteasome activator complex subunit 1 isoform 1

See identical proteins and their annotated locations for NP_006254.1

Status: REVIEWED

Description

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

Source sequence(s)

BM981616, L07633

Consensus CDS

CCDS9612.1

UniProtKB/Swiss-Prot

A6NJG9, H0YNE3, Q06323, Q6IBM2, Q9UEF4

UniProtKB/TrEMBL

A0A0K0K1L8, Q6FHU3

Related

ENSP00000206451.6, ENST00000206451.11

Conserved Domains (2) summary

pfam02251
Location:8 → 68

PA28_alpha; Proteasome activator pa28 alpha subunit

pfam02252
Location:104 → 246

PA28_beta; Proteasome activator pa28 beta subunit
NM_176783.3 → NP_788955.1 proteasome activator complex subunit 1 isoform 2

See identical proteins and their annotated locations for NP_788955.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 3' structure, and thus differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (3) has a distinct and longer C-terminus, compared to isoform 1.

Source sequence(s)

BJ993879, BM981616, BQ060125, BX248293

Consensus CDS

CCDS41930.1

UniProtKB/TrEMBL

Q6FHU3

Related

ENSP00000372155.3, ENST00000382708.7

Conserved Domains (2) summary

pfam02251
Location:10 → 67

PA28_alpha; Proteasome activator pa28 alpha subunit

pfam02252
Location:106 → 223

PA28_beta; Proteasome activator pa28 beta subunit