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    PSMD4 proteasome 26S subunit ubiquitin receptor, non-ATPase 4 [ Homo sapiens (human) ]

    Gene ID: 5710, updated on 5-May-2024

    Summary

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    Official Symbol
    PSMD4provided by HGNC
    Official Full Name
    proteasome 26S subunit ubiquitin receptor, non-ATPase 4provided by HGNC
    Primary source
    HGNC:HGNC:9561
    See related
    Ensembl:ENSG00000159352 MIM:601648; AllianceGenome:HGNC:9561
    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
    AF; ASF; S5A; AF-1; MCB1; Rpn10; pUB-R5
    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. Pseudogenes have been identified on chromosomes 10 and 21. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis (RPKM 64.3), placenta (RPKM 46.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PSMD4 in Genome Data Viewer
    Location:
    1q21.3
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (151254734..151267479)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (150378457..150391195)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (151227210..151239955)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1710 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1711 Neighboring gene vacuolar protein sorting 72 homolog Neighboring gene uncharacterized LOC124904419 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1712 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1713 Neighboring gene phosphatidylinositol-4-phosphate 5-kinase type 1 alpha Neighboring gene ReSE screen-validated silencer GRCh37_chr1:151183035-151183192 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:151183741-151184733 Neighboring gene MPRA-validated peak410 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1714 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1316 Neighboring gene Sharpr-MPRA regulatory region 10214 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:151253738-151254622 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:151254623-151255508 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1717 Neighboring gene ZNF687 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:151261481-151262132 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:151262133-151262782 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:151262783-151263433 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:151266030-151267013 Neighboring gene zinc finger protein 687 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:151267014-151267998 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:151267999-151268981 Neighboring gene phosphatidylinositol 4-kinase beta Neighboring gene RNA, 7SL, cytoplasmic 444, pseudogene

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. Upregulation of Rpn10 promotes tumor progression via activation of the NF-κB pathway in clear cell renal cell carcinoma. Huang T, et al. Acta Biochim Biophys Sin (Shanghai), 2021 Jul 28. PMID 34133712
    2. The role of endogenous Antisecretory Factor (AF) in the treatment of Ménière's Disease: A two-year follow-up study. Preliminary results. Viola P, et al. Am J Otolaryngol, 2020 Nov-Dec. PMID 32829060
    3. PSMD4 regulates the malignancy of esophageal cancer cells by suppressing endoplasmic reticulum stress. Ma AG, et al. Kaohsiung J Med Sci, 2019 Oct. PMID 31162820
    4. Inhibition of PSMD4 blocks the tumorigenesis of hepatocellular carcinoma. Cai MJ, et al. Gene, 2019 Jun 20. PMID 30930224
    5. Low levels of anti-secretory factor in placenta are associated with preterm birth and inflammation. Gustafsson AM, et al. Acta Obstet Gynecol Scand, 2018 Mar. PMID 29265188

    See all (343) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. PSMD4 drives progression of hepatocellular carcinoma via Akt/COX2 pathway and p53 inhibition.
      Title: PSMD4 drives progression of hepatocellular carcinoma via Akt/COX2 pathway and p53 inhibition.
    2. Upregulation of Rpn10 promotes tumor progression via activation of the NF-kappaB pathway in clear cell renal cell carcinoma.
      Title: Upregulation of Rpn10 promotes tumor progression via activation of the NF-κB pathway in clear cell renal cell carcinoma.
    3. The role of endogenous Antisecretory Factor (AF) in the treatment of Meniere's Disease: A two-year follow-up study. Preliminary results.
      Title: The role of endogenous Antisecretory Factor (AF) in the treatment of Ménière's Disease: A two-year follow-up study. Preliminary results.
    4. E6AP/UBE3A is distinguished from other E3 ligases by having a 12 nM binding site at the proteasome contributed by substrate receptor hRpn10/PSMD4/S5a.
      Title: Structure of E3 ligase E6AP with a proteasome-binding site provided by substrate receptor hRpn10.
    5. Data shows upregulation of PSMD4 promoted the progression of esophageal cancer mainly by reducing ERS-induced cell apoptosis.
      Title: PSMD4 regulates the malignancy of esophageal cancer cells by suppressing endoplasmic reticulum stress.
    6. UBQLN2 UBL is fine-tuned for the hRpn10 UIM-1 site.
      Title: Structure of hRpn10 Bound to UBQLN2 UBL Illustrates Basis for Complementarity between Shuttle Factors and Substrates at the Proteasome.
    7. Rpn10 directly promoted PTEN degradation.
      Title: Rpn10 promotes tumor progression by regulating hypoxia-inducible factor 1 alpha through the PTEN/Akt signaling pathway in hepatocellular carcinoma.
    8. Two Angelman syndrome point mutations of UBE3A that affect the AZUL domain show an impaired ability to bind PSMD4.
      Title: Angelman syndrome-associated point mutations in the Zn(2+)-binding N-terminal (AZUL) domain of UBE3A ubiquitin ligase inhibit binding to the proteasome.
    9. Findings indicated PSMD4 as a subunit of 26S proteasome exerts as an oncogene during tumor development of hepatocellular carcinoma.
      Title: Inhibition of PSMD4 blocks the tumorigenesis of hepatocellular carcinoma.
    10. Preterm delivery is associated with low levels of anti-secretory factor in placenta. Inflammation, a potential trigger of preterm birth, is more pronounced in the preterm placenta and inversely related to the placental level of anti-secretory factor.
      Title: Low levels of anti-secretory factor in placenta are associated with preterm birth and inflammation.
    Submit: New GeneRIF Correction See all GeneRIFs (41)

    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)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of proteasome (prosome, macropain) 26S subunit, non-ATPase, 4 (PSMD4) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells 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
    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

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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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

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding HDA PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables molecular adaptor activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables polyubiquitin modification-dependent protein binding 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 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
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    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, base subcomplex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    26S proteasome non-ATPase regulatory subunit 4
    Names
    26S proteasome regulatory subunit S5A
    S5a/antisecretory factor protein
    angiocidin
    antisecretory factor 1
    multiubiquitin chain-binding protein
    proteasome (prosome, macropain) 26S subunit, non-ATPase, 4
    proteasome 26S subunit, non-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.

    Genomic

    1. NG_029700.1 RefSeqGene

      Range
      5014..17759
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001330692.2 → NP_001317621.1  26S proteasome non-ATPase regulatory subunit 4 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AL391069, AL592424
      Consensus CDS
      CCDS81375.1
      UniProtKB/TrEMBL
      Q5VWC4
      Related
      ENSP00000357876.4, ENST00000368881.8
      Conserved Domains (2) summary
      cd01452
      Location:1 → 187
      VWA_26S_proteasome_subunit; 26S proteasome plays a major role in eukaryotic protein breakdown, especially for ubiquitin-tagged proteins. It is an ATP-dependent protease responsible for the bulk of non-lysosomal proteolysis in eukaryotes, often using covalent modification of ...
      cd22297
      Location:323 → 366
      PSMD4_RAZUL; RAZUL (Rpn10 AZUL-binding) domain of 26S proteasome non-ATPase regulatory subunit 4 (PSMD4) and similar proteins

    2. NM_002810.4 → NP_002801.1  26S proteasome non-ATPase regulatory subunit 4 isoform 2

      See identical proteins and their annotated locations for NP_002801.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice junction compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AL391069, U24704
      Consensus CDS
      CCDS991.1
      UniProtKB/Swiss-Prot
      D3DV16, P55036, Q5VWC5, Q9NS92
      Related
      ENSP00000357879.4, ENST00000368884.8
      Conserved Domains (2) summary
      cd01452
      Location:1 → 187
      VWA_26S_proteasome_subunit; 26S proteasome plays a major role in eukaryotic protein breakdown, especially for ubiquitin-tagged proteins. It is an ATP-dependent protease responsible for the bulk of non-lysosomal proteolysis in eukaryotes, often using covalent modification of ...
      cd22297
      Location:320 → 363
      PSMD4_RAZUL; RAZUL (Rpn10 AZUL-binding) domain of 26S proteasome non-ATPase regulatory subunit 4 (PSMD4) and similar proteins

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      151254734..151267479
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      150378457..150391195
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_153822.2: Suppressed sequence

      Description
      NM_153822.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P55036.1 GenPept UniProtKB/Swiss-Prot:P55036

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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