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    PDIA3 protein disulfide isomerase family A member 3 [ Homo sapiens (human) ]

    Gene ID: 2923, updated on 28-Oct-2024

    Summary

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    Official Symbol
    PDIA3provided by HGNC
    Official Full Name
    protein disulfide isomerase family A member 3provided by HGNC
    Primary source
    HGNC:HGNC:4606
    See related
    Ensembl:ENSG00000167004 MIM:602046; AllianceGenome:HGNC:4606
    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
    P58; ER60; ERp57; ERp60; ERp61; GRP57; GRP58; PI-PLC; HsT17083; HEL-S-269; HEL-S-93n
    Summary
    This gene encodes a protein of the endoplasmic reticulum that interacts with lectin chaperones calreticulin and calnexin to modulate folding of newly synthesized glycoproteins. The protein was once thought to be a phospholipase; however, it has been demonstrated that the protein actually has protein disulfide isomerase activity. It is thought that complexes of lectins and this protein mediate protein folding by promoting formation of disulfide bonds in their glycoprotein substrates. This protein also functions as a molecular chaperone that prevents the formation of protein aggregates. [provided by RefSeq, Dec 2016]
    Expression
    Ubiquitous expression in thyroid (RPKM 333.0), prostate (RPKM 175.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PDIA3 in Genome Data Viewer
    Location:
    15q15.3
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (43746438..43773278)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (41553795..41580638)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (44038636..44065476)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9318 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9319 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9320 Neighboring gene RNA, U6 small nuclear 354, pseudogene Neighboring gene CATSPER2 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6387 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9321 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9322 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:44068605-44069133 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6388 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9324 Neighboring gene elongation factor for RNA polymerase II 3 Neighboring gene small EDRK-rich factor 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9325 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:44081221-44081720 Neighboring gene SERF2-C15orf63 readthrough Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:44084013-44085212 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:44085666-44086519 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:44087241-44087742 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:44087743-44088242 Neighboring gene microRNA 1282 Neighboring gene serine incorporator 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:44091515-44092215 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:44092216-44092916

    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 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. ERp57 is present in STAT3-DNA complexes. Eufemi M, et al. Biochem Biophys Res Commun, 2004 Oct 29. PMID 15451439
    2. ER-60 (PDIA3) is highly expressed in a newly established serous ovarian cancer cell line, YDOV-139. Chay D, et al. Int J Oncol, 2010 Aug. PMID 20596667
    3. Upregulation of ERp57 promotes clear cell renal cell carcinoma progression by initiating a STAT3/ILF3 feedback loop. Liu Y, et al. J Exp Clin Cancer Res, 2019 Oct 30. PMID 31747963, Free PMC Article
    4. Mutation in protein disulfide isomerase A3 causes neurodevelopmental defects by disturbing endoplasmic reticulum proteostasis. Bilches Medinas D, et al. EMBO J, 2022 Dec 17. PMID 34904718, Free PMC Article
    5. Characterisation of a multimeric protein complex associated with ERp57 within the nucleus in paclitaxel-sensitive and -resistant epithelial ovarian cancer cells: the involvement of specific conformational states of beta-actin. Cicchillitti L, et al. Int J Oncol, 2010 Aug. PMID 20596672

    See all (387) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. PDIA3 driven STAT3/PD-1 signaling promotes M2 TAM polarization and aggravates colorectal cancer progression.
      Title: PDIA3 driven STAT3/PD-1 signaling promotes M2 TAM polarization and aggravates colorectal cancer progression.
    2. CircPDIA3/miR-449a/XBP1 feedback loop curbs pyroptosis by inhibiting palmitoylation of the GSDME-C domain to induce chemoresistance of colorectal cancer.
      Title: CircPDIA3/miR-449a/XBP1 feedback loop curbs pyroptosis by inhibiting palmitoylation of the GSDME-C domain to induce chemoresistance of colorectal cancer.
    3. Single-cell analysis identified PDIA3 as regulator of malignant characteristics and macrophage function in human cancers.
      Title: Single-cell analysis identified PDIA3 as regulator of malignant characteristics and macrophage function in human cancers.
    4. PDIA3 inhibits mitochondrial respiratory function in brain endothelial cells and C. elegans through STAT3 signaling and decreases survival after OGD.
      Title: PDIA3 inhibits mitochondrial respiratory function in brain endothelial cells and C. elegans through STAT3 signaling and decreases survival after OGD.
    5. Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation.
      Title: Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation.
    6. PDIA3 modulates genomic response to 1,25-dihydroxyvitamin D3 in squamous cell carcinoma of the skin.
      Title: PDIA3 modulates genomic response to 1,25-dihydroxyvitamin D(3) in squamous cell carcinoma of the skin.
    7. Interaction with ERp57 is required for progranulin protection against Type 2 Gaucher disease.
      Title: Interaction with ERp57 is required for progranulin protection against Type 2 Gaucher disease.
    8. PDIA3 Expression Is Altered in the Limbic Brain Regions of Triple-Transgenic Mouse Model of Alzheimer's Disease.
      Title: PDIA3 Expression Is Altered in the Limbic Brain Regions of Triple-Transgenic Mouse Model of Alzheimer's Disease.
    9. Protein disulfide isomerase A3 activity promotes extracellular accumulation of proteins relevant to basal breast cancer outcomes in human MDA-MB-A231 breast cancer cells.
      Title: Protein disulfide isomerase A3 activity promotes extracellular accumulation of proteins relevant to basal breast cancer outcomes in human MDA-MB-A231 breast cancer cells.
    10. Calreticulin and PDIA3, two markers of endoplasmic reticulum stress, are associated with metabolic alterations and insulin resistance in pediatric obesity: A pilot study.
      Title: Calreticulin and PDIA3, two markers of endoplasmic reticulum stress, are associated with metabolic alterations and insulin resistance in pediatric obesity: A pilot study.
    Submit: New GeneRIF Correction See all GeneRIFs (140)

    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 protein disulfide isomerase family A, member 3 (PDIA3) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120/MBL complex co-localizes with the ER marker ERp57 and the Golgi marker p230 at subcellular perinuclear compartments in neuronal cells PubMed
    env PDI is predominantly involved in HIV-1 entry and infection of the T cell line PM-1 and PHA-stimulated primary T lymphocytes, suggesting the preferential use of PDI relevant to the HIV-1 entry and establishment of virus reservoirs in resting CD4+ cells PubMed
    env The disulfide cross-linking interaction between gp120 and PDI is enhanced by CD4 protein PubMed
    env Protein-disulfide isomerase (PDI) cleaves disulfide bonds in recombinant HIV-1 envelope glycoprotein gp120, and gp120 bound to the surface receptor CD4 undergoes a disulfide reduction that is prevented by PDI inhibitors PubMed
    Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 interacts with PDIA3; predicted interaction to be within the endoplasmic reticulum and function as a thioredoxin reductase PubMed
    env HIV-1 gp160 is identified to have a physical interaction with protein disulfide isomerase family A, member 3 (PDIA3) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    env Treatment of trimeric HIV-1 rgp140 with protein disulfide isomerase yields monomers by disruption of the intermolecular disulfide bonds PubMed
    Envelope transmembrane glycoprotein gp41 env HIV-1 gp41 is identified to have a physical interaction with protein disulfide isomerase family A, member 3 (PDIA3) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of protein disulfide isomerase A3 (PDIA3) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed
    retropepsin gag-pol Positional proteomics analysis identifies the cleavage of human protein disulfide isomerase family A, member 3 (PDIA3) at amino acid residues 27-28 by the HIV-1 protease 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 cysteine-type endopeptidase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables disulfide oxidoreductase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables phospholipase C activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein disulfide isomerase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein-disulfide reductase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to interleukin-7 IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in extrinsic apoptotic signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in peptide antigen assembly with MHC class I protein complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in platelet aggregation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of extrinsic apoptotic signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein folding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein folding in endoplasmic reticulum TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in response to endoplasmic reticulum stress IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    part_of MHC class I peptide loading complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of Tapasin-ERp57 complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    is_active_in cell surface IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in endoplasmic reticulum IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in focal adhesion HDA PubMed 
    located_in melanosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleus HDA PubMed 
    located_in phagocytic vesicle TAS
    Traceable Author Statement
    more info
    		  
    located_in recycling endosome membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    protein disulfide-isomerase A3
    Names
    58 kDa glucose-regulated protein
    58 kDa microsomal protein
    ER protein 57
    ER protein 60
    disulfide isomerase ER-60
    endoplasmic reticulum P58
    endoplasmic reticulum resident protein 57
    endoplasmic reticulum resident protein 60
    epididymis secretory protein Li 269
    epididymis secretory sperm binding protein Li 93n
    glucose regulated protein, 58kDa
    phospholipase C-alpha
    protein disulfide isomerase-associated 3
    NP_005304.3

    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)

    1. NM_005313.5 → NP_005304.3  protein disulfide-isomerase A3 precursor

      See identical proteins and their annotated locations for NP_005304.3

      Status: REVIEWED

      Source sequence(s)
      AC018512, AI769725, BC014433, BE644608, BG826781, BM854408
      Consensus CDS
      CCDS10101.1
      UniProtKB/Swiss-Prot
      P30101, Q13453, Q14255, Q8IYF8, Q9UMU7
      UniProtKB/TrEMBL
      A0A8I5KT88, V9HVY3
      Related
      ENSP00000300289.5, ENST00000300289.10
      Conserved Domains (1) summary
      cl27119
      Location:25 → 487
      YbbN; Negative regulator of GroEL, contains thioredoxin-like and TPR-like domains [Posttranslational modification, protein turnover, chaperones]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      43746438..43773278
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      41553795..41580638
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P30101.4 GenPept UniProtKB/Swiss-Prot:P30101

    Gene LinkOut

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

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