PDIA3

Protein identityUniProt · HPA

UniProt accession

P30101

Gene

PDIA3

Ensembl

ENSG00000167004

Chromosome

15

Canonical length

505 aa

Protein class

Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Transporters

Subcellular location

Endoplasmic reticulum

Secretome location

Intracellular and membrane

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

505 residues, UniProt reviewed canonical sequence.

>P30101|PDIA3
     1  MRLRRLALFP GVALLLAAAR LAAASDVLEL TDDNFESRIS DTGSAGLMLV EFFAPWCGHC
    61  KRLAPEYEAA ATRLKGIVPL AKVDCTANTN TCNKYGVSGY PTLKIFRDGE EAGAYDGPRT
   121  ADGIVSHLKK QAGPASVPLR TEEEFKKFIS DKDASIVGFF DDSFSEAHSE FLKAASNLRD
   181  NYRFAHTNVE SLVNEYDDNG EGIILFRPSH LTNKFEDKTV AYTEQKMTSG KIKKFIQENI
   241  FGICPHMTED NKDLIQGKDL LIAYYDVDYE KNAKGSNYWR NRVMMVAKKF LDAGHKLNFA
   301  VASRKTFSHE LSDFGLESTA GEIPVVAIRT AKGEKFVMQE EFSRDGKALE RFLQDYFDGN
   361  LKRYLKSEPI PESNDGPVKV VVAENFDEIV NNENKDVLIE FYAPWCGHCK NLEPKYKELG
   421  EKLSKDPNIV IAKMDATAND VPSPYEVRGF PTIYFSPANK KLNPKKYEGG RELSDFISYL
   481  QREATNPPVI QEEKPKKKKK AQEDL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PDIA3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

292 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PDIA3.

Disease | ImmuneIEDB

Conditions an epitope on PDIA3 was assayed in.

• autoimmune hepatitis B cell
• type 1 diabetes mellitus T cell

ReferencesPubMed · IEDB

Publications for PDIA3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.25

gnomAD pLI

1

gnomAD missense Z

0.68

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adaptive immune response
• cellular response to interleukin-7
• extrinsic apoptotic signaling pathway
• peptide antigen assembly with MHC class I protein complex
• platelet aggregation
• positive regulation of extrinsic apoptotic signaling pathway
• protein folding
• protein folding in endoplasmic reticulum
• response to endoplasmic reticulum stress

Molecular functions

• cysteine-type endopeptidase activity
• disulfide oxidoreductase activity
• identical protein binding
• lncRNA binding
• phospholipase C activity
• protein disulfide isomerase activity
• protein folding chaperone
• protein-disulfide reductase activity
• RNA binding

Cellular components

• cell surface
• endoplasmic reticulum
• endoplasmic reticulum lumen
• extracellular exosome
• extracellular space
• focal adhesion
• melanosome
• MHC class I peptide loading complex
• nucleus
• phagocytic vesicle
• recycling endosome membrane
• Tapasin-ERp57 complex

Protein domainsUniProt · Pfam · InterPro

• Protein disulfide-isomerase, thioredoxin-like domain
• Protein disulphide isomerase
• Thioredoxin domain
• Thioredoxin, conserved site
• Thioredoxin-like superfamily
• Thioredoxin
• Thioredoxin-like domain
• Protein disulfide-isomerase A3, first redox inactive TRX-like domain b

KeywordsUniProt

• Acetylation
• Adaptive immunity
• Disulfide bond
• Endoplasmic reticulum
• Immunity
• Isomerase
• Methylation
• Phosphoprotein
• Redox-active center
• Repeat
• Signal

InteractionsUniProt · HPA

Protein binding partners of PDIA3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ATP2A2
• CANX
• ERP27
• SERPINA2
• MZB1
• APP
• CALR
• CFTR
• CLU
• ERO1A
• TAP1