PSMD2 proteasome 26S subunit ubiquitin receptor, non-ATPase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PSMD2provided by HGNC
Official Full Name: proteasome 26S subunit ubiquitin receptor, non-ATPase 2provided by HGNC
Primary source: HGNC:HGNC:9559
See related: Ensembl:ENSG00000175166 MIM:606223; AllianceGenome:HGNC:9559
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: S2; P97; RPN1; TRAP2
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 non-ATPase subunits of the 19S regulator lid. In addition to participation in proteasome function, this subunit may also participate in the TNF signalling pathway since it interacts with the tumor necrosis factor type 1 receptor. A pseudogene has been identified on chromosome 1. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]
Expression: Ubiquitous expression in testis (RPKM 64.5), brain (RPKM 40.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q27.1

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (184299241..184309050)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (187108522..187118326)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (184017029..184026838)

Chromosome 3 - NC_000003.12 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?

DNAJA4 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma via PSMD2-mediated MYH9 degradation.
Title: DNAJA4 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma via PSMD2-mediated MYH9 degradation.
Proteasomal Degradation of TRAF2 Mediates Mitochondrial Dysfunction in Doxorubicin-Cardiomyopathy.
Title: Proteasomal Degradation of TRAF2 Mediates Mitochondrial Dysfunction in Doxorubicin-Cardiomyopathy.
Diverse Ras-related GTPase DIRAS2, downregulated by PSMD2 in a proteasome-mediated way, inhibits colorectal cancer proliferation by blocking NF-kappaB signaling.
Title: Diverse Ras-related GTPase DIRAS2, downregulated by PSMD2 in a proteasome-mediated way, inhibits colorectal cancer proliferation by blocking NF-κB signaling.
TRAF2 Knockdown in Nasopharyngeal Carcinoma Induced Cell Cycle Arrest and Enhanced the Sensitivity to Radiotherapy.
Title: TRAF2 Knockdown in Nasopharyngeal Carcinoma Induced Cell Cycle Arrest and Enhanced the Sensitivity to Radiotherapy.
The authors demonstrate that PSMD1 and PSMD2 promote the proliferation of HepG2 cells via facilitating cellular lipid droplet accumulation.
Title: PSMD1 and PSMD2 regulate HepG2 cell proliferation and apoptosis via modulating cellular lipid droplet metabolism.
Asporin (ASPN) interacts with proteasome 26S subunit non-ATPase 2 (PSMD2) and promotes the proliferation of gastric cancer (GC) cells.
Title: Asporin promotes cell proliferation via interacting with PSMD2 in gastric cancer.
Study found that PSMD2 was markedly upregulated in breast cancer. High PSMD2 expression was significantly correlated with poor prognosis. PSMD2 knockdown inhibited cell proliferation and arrested cell cycle at G0/G1 phase in vitro, as well as suppressed tumor growth in vivo. Mechanically, PSMD2 physically interacted with p21 and p27 and mediated their ubiquitin-proteasome degradation with the cooperation of USP14.
Title: PSMD2 regulates breast cancer cell proliferation and cell cycle progression by modulating p21 and p27 proteasomal degradation.
By recruiting the 26S proteasome and the ubiquitin-selective ATPase p97 to arsenite-induced stress granules, ZFAND1 ensures their timely clearance and prevents their aberration.
Title: ZFAND1 Recruits p97 and the 26S Proteasome to Promote the Clearance of Arsenite-Induced Stress Granules.
the high-resolution solution structure of the UBL domain of human UBLCP1 and its interaction with Rpn1
Title: Solution structure and Rpn1 interaction of the UBL domain of human RNA polymerase II C-terminal domain phosphatase.
Results suggest that PSMD2 may be a good molecular target candidate.
Title: Proteasomal non-catalytic subunit PSMD2 as a potential therapeutic target in association with various clinicopathologic features in lung adenocarcinomas.

Submit: New GeneRIF Correction See all GeneRIFs (15)

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
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Nef	nef	Tandem affinity purification and mass spectrometry analysis identify 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify 26S proteasome non-ATPase regulatory subunit 2 (PSMD2), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Tat	tat	Expression of HIV-1 Tat upregulates the abundance of proteasome (prosome, macropain) 26S subunit, non-ATPase, 2 (PSMD2) in the nucleoli of Jurkat T-cells	PubMed
	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
Vpr	vpr	Pull-down analysis shows that S2 and S5a, two components of the 19S subunit of the 26S proteasome, interact with HIV-1 Vpr	PubMed
integrase	gag-pol	Proteasomal degradation of HIV-1 integrase in mammalian cells occurs by the N-end rule pathway	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

RH70376 (e-PCR)
- UniSTS:73065

T03659 (e-PCR)
- UniSTS:14455

G62053 (e-PCR)
- UniSTS:139161

RH65279 (e-PCR)
- UniSTS:84197

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables enzyme regulator activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
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 regulation of protein catabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in ficolin-1-rich granule lumen	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
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	TAS Traceable Author Statement more info	PubMed
part_of proteasome regulatory particle, base subcomplex	IBA Inferred from Biological aspect of Ancestor more info
is_active_in proteasome storage granule	IBA Inferred from Biological aspect of Ancestor more info
located_in secretory granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: 26S proteasome non-ATPase regulatory subunit 2

Names: 55.11 protein; TNFR-associated protein 2; proteasome (prosome, macropain) 26S subunit, non-ATPase, 2; proteasome 26S subunit, non-ATPase 2; protein 55.11; tumor necrosis factor type 1 receptor-associated protein 2

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_001278708.2 → NP_001265637.1 26S proteasome non-ATPase regulatory subunit 2 isoform 2

See identical proteins and their annotated locations for NP_001265637.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and the 5' coding region and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform 2, which is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AK301759, AK302177, BC002997

Consensus CDS

CCDS63853.1

UniProtKB/TrEMBL

B4DM22

Related

ENSP00000416028.1, ENST00000439383.5

Conserved Domains (1) summary

cl28113
Location:4 → 776

PC_rep; Proteasome/cyclosome repeat
NM_001278709.2 → NP_001265638.1 26S proteasome non-ATPase regulatory subunit 2 isoform 3

See identical proteins and their annotated locations for NP_001265638.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and the 5' coding region and initiates translation at an alternate start codon, compared to variant 1. It encodes isoform 3, which has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AK301759, AK302177, BC002997

Consensus CDS

CCDS63854.1

UniProtKB/TrEMBL

B4DM22

Related

ENSP00000402618.1, ENST00000435761.5

Conserved Domains (1) summary

COG5110
Location:3 → 747

RPN1; 26S proteasome regulatory complex component [Posttranslational modification, protein turnover, chaperones]
NM_002808.5 → NP_002799.3 26S proteasome non-ATPase regulatory subunit 2 isoform 1

See identical proteins and their annotated locations for NP_002799.3

Status: REVIEWED

Description

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

Source sequence(s)

BC002997, HY006627

Consensus CDS

CCDS3258.1

UniProtKB/Swiss-Prot

B4DX07, B4DXY1, E7EW34, E9PCS3, Q12932, Q13200, Q15321, Q53XQ4, Q96I12

UniProtKB/TrEMBL

Q59EG8

Related

ENSP00000310129.4, ENST00000310118.9

Conserved Domains (1) summary

COG5110
Location:26 → 906

RPN1; 26S proteasome regulatory complex component [Posttranslational modification, protein turnover, chaperones]