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

Summary

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

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_000007.14 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?

Potential Anti-tumor Properties of PDIA4 in Lung Adenocarcinoma.
Title: Potential Anti-tumor Properties of PDIA4 in Lung Adenocarcinoma.
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.
PDIA4 Is a Host Factor Important for Lymphocytic Choriomeningitis Virus Infection.
Title: PDIA4 Is a Host Factor Important for Lymphocytic Choriomeningitis Virus Infection.
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.
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.
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.
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.
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.
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.
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 EBI GWAS CatalogPubMed

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D7S2640 (e-PCR)
- UniSTS:72704

RH12856 (e-PCR)
- UniSTS:22

RH16208 (e-PCR)
- UniSTS:26959

RH47225 (e-PCR)
- UniSTS:23771

G27935 (e-PCR)
- UniSTS:30965

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	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

EC 5.3.4.1

NP_001358174.1

EC 5.3.4.1

NP_004902.1

EC 5.3.4.1

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)

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
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
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