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    PDIA4 protein disulfide isomerase family A member 4 [ Homo sapiens (human) ]

    Gene ID: 9601, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PDIA4provided by HGNC
    Official Full Name
    protein disulfide isomerase family A member 4provided by HGNC
    Primary source
    HGNC:HGNC:30167
    See related
    Ensembl:ENSG00000155660 MIM:620018; AllianceGenome:HGNC:30167
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ERP70; ERP72; ERp-72
    Summary
    This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, three catalytically active thioredoxin (TRX) domains, two TRX-like domains and a C-terminal ER-retention sequence. This protein, when bound to cyclophilin B, enhances the rate of immunoglobulin G intermolecular disulfide bonding and antibody assembly. [provided by RefSeq, Dec 2016]
    Expression
    Broad expression in thyroid (RPKM 166.5), liver (RPKM 67.6) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PDIA4 in Genome Data Viewer
    Location:
    7q36.1
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (149003051..149028505, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (150185192..150210630, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (148700143..148725597, complement)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18740 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:148684478-148684978 Neighboring gene gastric carcinoma proliferation enhancing transcript 1 Neighboring gene RNA, Ro60-associated Y1 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:148709903-148710069 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26805 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26806 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26807 Neighboring gene NANOG hESC enhancer GRCh37_chr7:148720643-148721222 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:148724717-148725311 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:148725312-148725905 Neighboring gene RNA, U6 small nuclear 650, pseudogene Neighboring gene MPRA-validated peak6833 silencer Neighboring gene cytochrome c oxidase subunit 6B1 pseudogene 1

    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. Potential Anti-tumor Properties of PDIA4 in Lung Adenocarcinoma. Kim HJ, et al. Anticancer Res, 2024 Oct. PMID 39348977
    2. Protein disulfide-isomerase A4 confers glioblastoma angiogenesis promotion capacity and resistance to anti-angiogenic therapy. Tu Z, et al. J Exp Clin Cancer Res, 2023 Mar 30. PMID 36997943, Free PMC Article
    3. PDIA4 confers resistance to ferroptosis via induction of ATF4/SLC7A11 in renal cell carcinoma. Kang L, et al. Cell Death Dis, 2023 Mar 11. PMID 36906674, Free PMC Article
    4. Human deoxycytidine kinase. Sequence of cDNA clones and analysis of expression in cell lines with and without enzyme activity. Huang SH, et al. J Biol Chem, 1989 Sep 5. PMID 2549034
    5. PDIA4, a new endoplasmic reticulum stress protein, modulates insulin resistance and inflammation in skeletal muscle. Lee CH, et al. Front Endocrinol (Lausanne), 2022. PMID 36619574, Free PMC Article

    See all (185) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Potential Anti-tumor Properties of PDIA4 in Lung Adenocarcinoma.
      Title: Potential Anti-tumor Properties of PDIA4 in Lung Adenocarcinoma.
    2. Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival.
      Title: Protein Disulfide Isomerase 4 Is an Essential Regulator of Endothelial Function and Survival.
    3. PDIA4 Is a Host Factor Important for Lymphocytic Choriomeningitis Virus Infection.
      Title: PDIA4 Is a Host Factor Important for Lymphocytic Choriomeningitis Virus Infection.
    4. Protein disulfide isomerase family member 4 promotes triple-negative breast cancer tumorigenesis and radiotherapy resistance through JNK pathway.
      Title: Protein disulfide isomerase family member 4 promotes triple-negative breast cancer tumorigenesis and radiotherapy resistance through JNK pathway.
    5. LncRNA FAM225B Regulates PDIA4-Mediated Ovarian Cancer Cell Invasion and Migration via Modulating Transcription Factor DDX17.
      Title: LncRNA FAM225B Regulates PDIA4-Mediated Ovarian Cancer Cell Invasion and Migration via Modulating Transcription Factor DDX17.
    6. Protein disulfide-isomerase A4 confers glioblastoma angiogenesis promotion capacity and resistance to anti-angiogenic therapy.
      Title: Protein disulfide-isomerase A4 confers glioblastoma angiogenesis promotion capacity and resistance to anti-angiogenic therapy.
    7. PDIA4 confers resistance to ferroptosis via induction of ATF4/SLC7A11 in renal cell carcinoma.
      Title: PDIA4 confers resistance to ferroptosis via induction of ATF4/SLC7A11 in renal cell carcinoma.
    8. CircPDIA4 Induces Gastric Cancer Progression by Promoting ERK1/2 Activation and Enhancing Biogenesis of Oncogenic circRNAs.
      Title: CircPDIA4 Induces Gastric Cancer Progression by Promoting ERK1/2 Activation and Enhancing Biogenesis of Oncogenic circRNAs.
    9. PDIA4, a new endoplasmic reticulum stress protein, modulates insulin resistance and inflammation in skeletal muscle.
      Title: PDIA4, a new endoplasmic reticulum stress protein, modulates insulin resistance and inflammation in skeletal muscle.
    10. PDIA4, a novel ER stress chaperone, modulates adiponectin expression and inflammation in adipose tissue.
      Title: PDIA4, a novel ER stress chaperone, modulates adiponectin expression and inflammation in adipose tissue.
    Submit: New GeneRIF Correction See all GeneRIFs (22)

    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

    EBI GWAS Catalog

    Description
    Hundreds of variants clustered in genomic loci and biological pathways affect human height.
    EBI GWAS Catalog

    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 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 PDIA4; predicted interaction to be within the endoplasmic reticulum and function as thioredoxin reductase PubMed
    env Treatment of trimeric HIV-1 rgp140 with protein disulfide isomerase yields monomers by disruption of the intermolecular disulfide bonds PubMed
    Pol gag-pol HIV-1 Pol is identified to have a physical interaction with protein disulfide isomerase family A, member 4 (PDIA4) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    integrase gag-pol HIV-1 IN is identified to have a physical interaction with protein disulfide isomerase family A, member 4 (PDIA4) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses 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 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 isomerase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein-disulfide reductase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in chaperone-mediated protein folding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein folding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein secretion 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
    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 lumen IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in melanosome IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    protein disulfide-isomerase A4
    Names
    ER protein 70
    ER protein 72
    endoplasmic reticulum resident protein 70
    endoplasmic reticulum resident protein 72
    protein disulfide isomerase related protein (calcium-binding protein, intestinal-related)
    protein disulfide isomerase-associated 4
    testicular tissue protein Li 137
    NP_001358173.1
    NP_001358174.1
    NP_004902.1

    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.

    mRNA and Protein(s)

    1. NM_001371244.1 → NP_001358173.1  protein disulfide-isomerase A4 isoform 1 precursor

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC093743
      Consensus CDS
      CCDS94226.1
      UniProtKB/TrEMBL
      A0A499FI48, C9JMN9
      Related
      ENSP00000286091.5, ENST00000286091.9
      Conserved Domains (2) summary
      TIGR01126
      Location:67 → 168
      pdi_dom; protein disulfide-isomerase domain
      TIGR01130
      Location:177 → 641
      ER_PDI_fam; protein disulfide isomerase, eukaryotic

    2. NM_001371245.1 → NP_001358174.1  protein disulfide-isomerase A4 isoform 3 precursor

      Status: VALIDATED

      Source sequence(s)
      AC093743
      UniProtKB/TrEMBL
      C9JMN9
      Conserved Domains (2) summary
      TIGR01130
      Location:63 → 617
      ER_PDI_fam; protein disulfide isomerase, eukaryotic
      cl00388
      Location:179 → 211
      Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

    3. NM_004911.5 → NP_004902.1  protein disulfide-isomerase A4 isofrom 2 precursor

      See identical proteins and their annotated locations for NP_004902.1

      Status: VALIDATED

      Source sequence(s)
      AU139362, BC000425, BC001928, CX871856
      Consensus CDS
      CCDS5893.1
      UniProtKB/Swiss-Prot
      A8K4K6, P13667, Q549T6
      UniProtKB/TrEMBL
      A0A090N8Y2, C9JMN9
      Related
      ENSP00000499129.1, ENST00000652332.1
      Conserved Domains (2) summary
      TIGR01126
      Location:67 → 168
      pdi_dom; protein disulfide-isomerase domain
      TIGR01130
      Location:177 → 640
      ER_PDI_fam; protein disulfide isomerase, eukaryotic

    RNA

    1. NR_163905.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC093743

    2. NR_163906.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC093743

    3. NR_163907.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC093743

    4. NR_163908.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC093743

    5. NR_163909.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC093743

    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_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      149003051..149028505 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      150185192..150210630 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P13667.2 GenPept UniProtKB/Swiss-Prot:P13667

    Gene LinkOut

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

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