PDIA6 protein disulfide isomerase family A member 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PDIA6provided by HGNC
Official Full Name: protein disulfide isomerase family A member 6provided by HGNC
Primary source: HGNC:HGNC:30168
See related: Ensembl:ENSG00000143870 MIM:611099; AllianceGenome:HGNC:30168
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: P5; ERP5; TXNDC7
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, two catalytically active thioredoxin (TRX) domains, a TRX-like domain, and a C-terminal ER-retention sequence. This protein inhibits the aggregation of misfolded proteins and exhibits both isomerase and chaperone activity. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]
Expression: Ubiquitous expression in thyroid (RPKM 159.7), placenta (RPKM 70.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p25.1

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (10783391..10837712, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (10813390..10867711, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (10923517..10977838, complement)

Chromosome 2 - NC_000002.12 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?

The SOX2/PDIA6 axis mediates aerobic glycolysis to promote stemness in non-small cell lung cancer cells.
Title: The SOX2/PDIA6 axis mediates aerobic glycolysis to promote stemness in non-small cell lung cancer cells.
PDIA6, which is regulated by TRPM2-AS/miR-424-5p axis, promotes endometrial cancer progression via TGF-beta pathway.
Title: PDIA6, which is regulated by TRPM2-AS/miR-424-5p axis, promotes endometrial cancer progression via TGF-beta pathway.
Downregulated miR-181a alleviates H2O2-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts.
Title: Downregulated miR-181a alleviates H(2)O(2)-induced oxidative stress and cellular senescence by targeting PDIA6 in human foreskin fibroblasts.
Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis.
Title: Melanoma RBPome identification reveals PDIA6 as an unconventional RNA-binding protein involved in metastasis.
Biallelic loss of function variant in the unfolded protein response gene PDIA6 is associated with asphyxiating thoracic dystrophy and neonatal-onset diabetes.
Title: Biallelic loss of function variant in the unfolded protein response gene PDIA6 is associated with asphyxiating thoracic dystrophy and neonatal-onset diabetes.
Protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis.
Title: Protein disulfide isomerase family 6 promotes the imatinib-resistance of renal cell carcinoma by regulation of Wnt3a-Frizzled1 axis.
PDIA6 promotes pancreatic cancer progression and immune escape through CSN5-mediated deubiquitination of beta-catenin and PD-L1.
Title: PDIA6 promotes pancreatic cancer progression and immune escape through CSN5-mediated deubiquitination of β-catenin and PD-L1.
PDIA6 contributes to aerobic glycolysis and cancer progression in oral squamous cell carcinoma.
Title: PDIA6 contributes to aerobic glycolysis and cancer progression in oral squamous cell carcinoma.
One novel transcriptome-wide significant association from this study is the downregulation of PDIA6, which showed minimal evidence of association in the genome-wide association study (GWAS).
Title: Novel Insight Into the Etiology of Autism Spectrum Disorder Gained by Integrating Expression Data With Genome-wide Association Statistics.
The results of this study suggest that PDIA6 is an important component of EGFR-mediated migration and invasion of U87MG cells.
Title: PDIA6 regulation of ADAM17 shedding activity and EGFR-mediated migration and invasion of glioblastoma cells.

Submit: New GeneRIF Correction See all GeneRIFs (30)

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)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of protein disulfide isomerase family A, member 6 (PDIA6) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed

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 PDIA6; predicted interaction to be within the endoplasmic reticulum and function as a 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 6 (PDIA6) 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

SGC31703 (e-PCR)
- UniSTS:51040

RH11818 (e-PCR)
- UniSTS:53905

RH70399 (e-PCR)
- UniSTS:57524

WI-18107 (e-PCR)
- UniSTS:55990

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein disulfide isomerase activity	IEA Inferred from Electronic Annotation more info
enables protein-disulfide reductase 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 protein folding	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
located_in cytosol	IDA Inferred from Direct Assay more info
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
located_in endoplasmic reticulum	TAS Traceable Author Statement more info	PubMed
part_of endoplasmic reticulum chaperone complex	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in endoplasmic reticulum-Golgi intermediate compartment	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in melanosome	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: protein disulfide-isomerase A6

Names: ER protein 5; endoplasmic reticulum protein 5; epididymis secretory sperm binding protein; protein disulfide isomerase P5; protein disulfide isomerase-associated 6; protein disulfide isomerase-related protein; thioredoxin domain containing 7 (protein disulfide isomerase); thioredoxin domain-containing protein 7

NP_001269633.1

EC 5.3.4.1

NP_001269634.1

EC 5.3.4.1

NP_001269635.1

EC 5.3.4.1

NP_001269636.1

EC 5.3.4.1

NP_005733.1

EC 5.3.4.1

XP_011508610.1

EC 5.3.4.1

XP_054196066.1

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_001282704.2 → NP_001269633.1 protein disulfide-isomerase A6 isoform a

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AC092687, AK127433, BM511594

Consensus CDS

CCDS62854.1

UniProtKB/Swiss-Prot

Q15084

Related

ENSP00000385385.2, ENST00000404371.6

Conserved Domains (2) summary

cd02983
Location:327 → 456

P5_C; P5 family, C-terminal redox inactive TRX-like domain; P5 is a protein disulfide isomerase (PDI)-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is ...

cd03001
Location:78 → 180

PDI_a_P5; PDIa family, P5 subfamily; composed of eukaryotic proteins similar to human P5, a PDI-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is located in the ...
NM_001282705.2 → NP_001269634.1 protein disulfide-isomerase A6 isoform b

Status: VALIDATED

Description

Transcript Variant: This variant (2) contains alternate 5' exon structure and it thus differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (b) has a distinct N-terminus and is shorter than isoform a.

Source sequence(s)

AC092687, AK127433, AK131234, BM511594

Consensus CDS

CCDS62855.1

UniProtKB/Swiss-Prot

Q15084

Related

ENSP00000384459.2, ENST00000404824.2

Conserved Domains (2) summary

cd02983
Location:323 → 452

P5_C; P5 family, C-terminal redox inactive TRX-like domain; P5 is a protein disulfide isomerase (PDI)-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is ...

cd03001
Location:74 → 176

PDI_a_P5; PDIa family, P5 subfamily; composed of eukaryotic proteins similar to human P5, a PDI-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is located in the ...
NM_001282706.2 → NP_001269635.1 protein disulfide-isomerase A6 isoform c

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks a portion of the 5' UTR and 5' coding region, and uses a downstream in-frame translational start codon, compared to variant 1. The encoded isoform (c) is shorter at the N-terminus, compared to isoform a.

Source sequence(s)

AC092687, AK127433, AK297547, BM511594

Consensus CDS

CCDS62853.1

UniProtKB/Swiss-Prot

Q15084

Related

ENSP00000371024.4, ENST00000381611.8

Conserved Domains (3) summary

cd02983
Location:280 → 409

P5_C; P5 family, C-terminal redox inactive TRX-like domain; P5 is a protein disulfide isomerase (PDI)-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is ...

cd03001
Location:31 → 133

PDI_a_P5; PDIa family, P5 subfamily; composed of eukaryotic proteins similar to human P5, a PDI-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is located in the ...

TIGR01130
Location:30 → 267

ER_PDI_fam; protein disulfide isomerase, eukaryotic
NM_001282707.2 → NP_001269636.1 protein disulfide-isomerase A6 isoform e precursor

See identical proteins and their annotated locations for NP_001269636.1

Status: VALIDATED

Description

Transcript Variant: This variant (5) contains alternate 5' exon structure and it thus differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (e) has a distinct N-terminus and is shorter than isoform a.

Source sequence(s)

AK127433, AK294347, BM511594, HY166449

Consensus CDS

CCDS62852.1

UniProtKB/Swiss-Prot

Q15084

Related

ENSP00000438778.1, ENST00000540494.5

Conserved Domains (3) summary

cd02983
Location:272 → 401

P5_C; P5 family, C-terminal redox inactive TRX-like domain; P5 is a protein disulfide isomerase (PDI)-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is ...

cd03001
Location:23 → 125

PDI_a_P5; PDIa family, P5 subfamily; composed of eukaryotic proteins similar to human P5, a PDI-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is located in the ...

TIGR01130
Location:22 → 259

ER_PDI_fam; protein disulfide isomerase, eukaryotic
NM_005742.4 → NP_005733.1 protein disulfide-isomerase A6 isoform d precursor

See identical proteins and their annotated locations for NP_005733.1

Status: VALIDATED

Description

Transcript Variant: This variant (4) contains alternate 5' exon structure and it thus differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (d) has a distinct N-terminus and is shorter than isoform a.

Source sequence(s)

AK127433, BC001312, BM511594

Consensus CDS

CCDS1675.1

UniProtKB/Swiss-Prot

B3KY95, B5MCQ5, B7Z254, B7Z4M8, F8WA83, Q15084, Q53RC7, Q6ZSH5, Q99778

UniProtKB/TrEMBL

A0A384NPU5

Related

ENSP00000272227.4, ENST00000272227.8

Conserved Domains (2) summary

cd02983
Location:275 → 404

P5_C; P5 family, C-terminal redox inactive TRX-like domain; P5 is a protein disulfide isomerase (PDI)-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is ...

cd03001
Location:26 → 128

PDI_a_P5; PDIa family, P5 subfamily; composed of eukaryotic proteins similar to human P5, a PDI-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is located in the ...

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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

10783391..10837712 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011510308.2 → XP_011508610.1 protein disulfide-isomerase A6 isoform X1

Conserved Domains (3) summary

cd02983
Location:275 → 385

P5_C; P5 family, C-terminal redox inactive TRX-like domain; P5 is a protein disulfide isomerase (PDI)-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is ...

cd03001
Location:26 → 128

PDI_a_P5; PDIa family, P5 subfamily; composed of eukaryotic proteins similar to human P5, a PDI-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is located in the ...

TIGR01130
Location:25 → 262

ER_PDI_fam; protein disulfide isomerase, eukaryotic