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

Gene ID: 9601, updated on 7-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (149003051..149028505, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (150185192..150210630, complement)
105.20220307 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. 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
  2. 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
  3. 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
  4. High expression of PDIA4 promotes malignant cell behavior and predicts reduced survival in cervical cancer. Xing F, et al. Oncol Rep, 2022 Oct. PMID 36082822, Free PMC Article
  5. Circulating protein disulfide isomerase family member 4 is associated with type 2 diabetes mellitus, insulin sensitivity, and obesity. Su SC, et al. Acta Diabetol, 2022 Aug. PMID 35460376

See all (150) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. PDIA4 Is a Host Factor Important for Lymphocytic Choriomeningitis Virus Infection.
    Title: PDIA4 Is a Host Factor Important for Lymphocytic Choriomeningitis Virus Infection.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. High expression of PDIA4 promotes malignant cell behavior and predicts reduced survival in cervical cancer.
    Title: High expression of PDIA4 promotes malignant cell behavior and predicts reduced survival in cervical cancer.
  10. Circulating protein disulfide isomerase family member 4 is associated with type 2 diabetes mellitus, insulin sensitivity, and obesity.
    Title: Circulating protein disulfide isomerase family member 4 is associated with type 2 diabetes mellitus, insulin sensitivity, and obesity.
Submit: New GeneRIF Correction See all GeneRIFs (20)

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)

Genotypes

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_2023_10

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

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