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Symbol PDIA3 contributors: mct/pgu - updated : 03-06-2016
HGNC name protein disulfide isomerase family A, member 3
HGNC id 4606
Location 15q15.3      Physical location : 44.038.589 - 44.064.803
Synonym name
  • oxidoreductase ERp57 protein isomerase A3
  • thiol oxidoreductase
  • glucose regulated protein, 58kDa
  • endoplasmic reticulum P58
  • Synonym symbol(s) GRP58, ERp57, ERp60, ERp61, GRP57, HsT17083, P58, PI-PLC
    TYPE functioning gene
    STRUCTURE 26.21 kb     13 Exon(s)
    MAPPING cloned Y linked   status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 3060 - 505 - 2008 18039656
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
     liver   highly
    Endocrinepancreas   highly
    Respiratorylung   highly
    Visualeyeanterior segmentcornea  
    cell lineage
    cell lines
    at STAGE
    physiological period pregnancy
    Text placenta
  • 24 AAs at the N-terminal hydrophobic region targeting GRP58 to ER for synthesis at the ER membrane and translocation into the ER lumen
  • two thioredoxin domains bearing the catalytic site for PDI (protein disulfide isomerase) activity
  • other domains of homology with PDI
  • three major protease-sensitive regions, the first of which was located between residues 120 and 150, the second between 201 and 215
  • and the third between 313 and 341
  • putative nuclear localization (NLS) and ER retention signals (overlapping NLS and ER retention signal sequences regulate nuclear localization and ER retention)
  • conjugated FlavoP
    intraspecies homolog to protein disulfide isomerase
  • cysteine type endopeptidase family
  • PDI family
  • CATEGORY chaperone/stress , enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • cholesterol enriched microdomains (rafts)
  • localized in the cytosol, endoplasmic reticulum (ER) and nucleus
  • mainly localized in the endoplasmic reticulum
  • basic FUNCTION
  • oxidoreductase that, in conjunction with calnexin and calreticulin, assists disulfide bond formation in folding glycoproteins
  • controlling the folding of proteins
  • involved in protein-nucleus import, protein-ER retention, electron transport, signal transduction
  • functioning in the endoplasmic reticulum together with the lectins calreticulin and calnexin to achieve folding of newly synthesized glycoproteins
  • may be involved in the redox regulation of components during assembly and peptide loading
  • . may be functioning as thiol-dependent oxidoreductase (Adikesavan 2008)
  • play a role in gamete fusion and regulation of transcription factors APEX1
  • chaperone for the signal transducer and activator of transcription (STAT) signaling in which STAT3 protein function in the cytoplasm as complexes with novel accessory scaffolding protein
  • catalyze the isomerization of non-native disulfide bonds formed in glycoproteins with unstructured disulfide-rich domains (Jessop 2009)
  • participates in the nuclear import and degradation of RARA in Sertoli cells
  • may act as a molecular chaperone that alters the protein conformation of RARA for its delivery to the nucleus and, then with time, accompanies RARA to the ER for RARA ubiquitination and proteasome-mediated ERAD
  • is involved in the assembly of MTOR and positively regulates MTOR signaling at the cytosol and the cytosolic side of the ER
  • participation in signal transduction from the cell surface, in regulatory processes taking place in the nucleus, and in multimeric protein complexes involved in DNA repair
  • by ER luminal interaction with STIM1, has a modulatory role in capacitative Ca(2+) entry
  • forms disulfide bonds in glycoproteins in the endoplasmic reticulum and is expressed on the platelet surface
  • glycoprotein-specific PDIA3, is required for platelet aggregation, hemostasis, and thrombosis
  • of particular interest given its potential role in regulating chemosensitivity of cancer cells
  • acts in concert with calreticulin and calnexin in the folding of glycoproteins destined to the plasma membrane or to be secreted
  • participates in the regulation of calcium homeostasis, and is a potent regulator of mitochondrial calcium homeostasis
  • CELLULAR PROCESS protein, post translation
    text modification
    signaling signal transduction
    a component
  • component of rafts/microdomains
  • forms a mixed disulfide with the MHC class I-specific chaperone tapasin, and this dimeric conjugate edits the peptide repertoire bound by MHC class I molecules
    small molecule
  • consisting and interacting with calnexin and calreticulin for the folding and quality control of newly synthesized glycoproteins in ER
  • MHC class I molecules,leading unfolding molecule to targeting and degradation
  • physically associated with the calnexin cycle to catalyze isomerization reactions with most of its substrates
  • PDIA3 appeared to be a negative effector of SLC28A2 function, whereas ALDOB flux modulated SLC28A2 activity via a mechanism involving acquisition of higher affinity for its substrates
  • interaction of TMTC3 with PDIA3, a molecule resident in the endoplasmic reticulum (ER)
  • interacts with the ER luminal domain of STIM1, with this interaction involving two conserved cysteine residues, C(49) and C(56)
  • acts as disulfide isomerase, oxidoreductase and chaperone, in concert with the lectins calreticulin (CRT) and calnexin
  • PLAA is required for 1alpha,25-dihydroxyvitamin D3 dependent rapid activation of protein kinase C via PDIA3
  • bound specifically to the GDP-bound form of RALA, but not the GTP-bound form
  • PDIA3 regulates RALA signalling by acting as a redox-sensitive guanine-nucleotide dissociation inhibitor (RALGDS inhibitor)
  • interacts with DNA fragments in melanoma cells and is potentially involved in the transcriptional regulation of its target genes
  • functions as a pasma membrane receptor for 1alpha,25(OH)2D3 (both the chaperone functional domains and the subcellular location of PDIA3 control rapid membrane responses to 1alpha,25(OH)2D3)
  • can regulate the expression of the mitochondrial calcium uniporter (MCU) and modulate mitochondrial calcium uptake
  • PLAA is located in caveolae, where it interacts with PDIA3 and CAV1 to initiate rapid signaling via CAMK2A, CAMK2B
  • PSIP1 is not an inhibitor of apoptosis but rather an antagonist of oxidative stress-induced necrosis, and its overexpression in Prostate carcinoma leads to PDIA3 upregulation
  • cell surface trafficking of P4HB, PDIA3, and PDIA6 is dependent on KDELR1, which travels in a dynamic manner to the cell surface
  • cell & other
    Other glucose regulated
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in serous ovarian cancer
    tumoral     --over  
    of PDIA3, LYAR, NOP14, NCALD and MTSS1 genes in the ovarian cancer with poor prognosis
    Variant & Polymorphism
    Candidate gene
  • alterations in PDIA3/PDIA6 expression levels may be involved in the breast carcinogenic process and should be further investigated as a marker of aggressiveness
  • Therapy target