Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHPQ0Q3)

• DOT Name: Protein disulfide-isomerase A3 (PDIA3)
• Synonyms: EC 5.3.4.1; 58 kDa glucose-regulated protein; 58 kDa microsomal protein; p58; Disulfide isomerase ER-60; Endoplasmic reticulum resident protein 57; ER protein 57; ERp57; Endoplasmic reticulum resident protein 60; ER protein 60; ERp60
• Gene Name: PDIA3
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Myelodysplastic syndrome
  Spinocerebellar ataxia type 17
  Acute myelogenous leukaemia
  Amyotrophic lateral sclerosis
  Asthma
  Benign neoplasm
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Endometriosis
  Epithelial ovarian cancer
  Fatty liver disease
  Gastric cancer
  Gastric neoplasm
  Glioblastoma multiforme
  Glioma
  Hepatitis B virus infection
  Hepatitis C virus infection
  Irritable bowel syndrome
  Liver cirrhosis
  Major depressive disorder
  Melanoma
  Non-alcoholic fatty liver disease
  Non-small-cell lung cancer
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Post-traumatic stress disorder
  Prostate carcinoma
  Prostate neoplasm
  Pulmonary hypertension
  Renal fibrosis
  Squamous cell carcinoma
  Stomach cancer
  Influenza
  Acute coronary syndrome
  Adenocarcinoma
  Clear cell renal carcinoma
  Hepatocellular carcinoma
  Neuroblastoma
  Prostate cancer
  Rheumatoid arthritis
• UniProt ID: PDIA3_HUMAN
• PDB ID: 2ALB; 2DMM; 2H8L; 3F8U; 6ENY; 7QNG; 7QPD
• EC Number: 5.3.4.1
• Pfam ID: PF00085 ; PF13848
• Sequence:
  MRLRRLALFPGVALLLAAARLAAASDVLELTDDNFESRISDTGSAGLMLVEFFAPWCGHC
  KRLAPEYEAAATRLKGIVPLAKVDCTANTNTCNKYGVSGYPTLKIFRDGEEAGAYDGPRT
  ADGIVSHLKKQAGPASVPLRTEEEFKKFISDKDASIVGFFDDSFSEAHSEFLKAASNLRD
  NYRFAHTNVESLVNEYDDNGEGIILFRPSHLTNKFEDKTVAYTEQKMTSGKIKKFIQENI
  FGICPHMTEDNKDLIQGKDLLIAYYDVDYEKNAKGSNYWRNRVMMVAKKFLDAGHKLNFA
  VASRKTFSHELSDFGLESTAGEIPVVAIRTAKGEKFVMQEEFSRDGKALERFLQDYFDGN
  LKRYLKSEPIPESNDGPVKVVVAENFDEIVNNENKDVLIEFYAPWCGHCKNLEPKYKELG
  EKLSKDPNIVIAKMDATANDVPSPYEVRGFPTIYFSPANKKLNPKKYEGGRELSDFISYL
  QREATNPPVIQEEKPKKKKKAQEDL
• Function: Protein disulfide isomerase that catalyzes the formation, isomerization, and reduction or oxidation of disulfide bonds in client proteins and functions as a protein folding chaperone. Core component of the major histocompatibility complex class I (MHC I) peptide loading complex where it functions as an essential folding chaperone for TAPBP. Through TAPBP, assists the dynamic assembly of the MHC I complex with high affinity antigens in the endoplasmic reticulum. Therefore, plays a crucial role in the presentation of antigens to cytotoxic T cells in adaptive immunity.
• Tissue Specificity: Detected in the flagellum and head region of spermatozoa (at protein level) . Expressed in liver, stomach and colon (at protein level). Expressed in gastric parietal cells and chief cells (at protein level) .
• KEGG Pathway:
  Protein processing in endoplasmic reticulum (hsa04141)
  Antigen processing and presentation (hsa04612)
  Human cytomegalovirus infection (hsa05163)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
• Reactome Pathway:
  Calnexin/calreticulin cycle (R-HSA-901042)
  Antigen Presentation (R-HSA-983170)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Definitive	Altered Expression	[1]
Cervical carcinoma	DIST4S00	Definitive	Altered Expression	[1]
Myelodysplastic syndrome	DISYHNUI	Definitive	Biomarker	[2]
Spinocerebellar ataxia type 17	DISJXO7P	Definitive	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[5]
Asthma	DISW9QNS	Strong	Biomarker	[6]
Benign neoplasm	DISDUXAD	Strong	Therapeutic	[7]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[8]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[8]
Carcinoma	DISH9F1N	Strong	Posttranslational Modification	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[10]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[11]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[11]
Endometriosis	DISX1AG8	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[13]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[16]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[17]
Glioma	DIS5RPEH	Strong	Altered Expression	[18]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[19]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[20]
Irritable bowel syndrome	DIS27206	Strong	ModifyingMutation	[21]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[22]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[23]
Melanoma	DIS1RRCY	Strong	Altered Expression	[24]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[25]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[26]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[13]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[13]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[27]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[28]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[29]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[30]
Pulmonary hypertension	DIS1RSP5	Strong	Biomarker	[31]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[32]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[33]
Stomach cancer	DISKIJSX	Strong	Biomarker	[15]
Influenza	DIS3PNU3	moderate	Biomarker	[34]
Acute coronary syndrome	DIS7DYEW	Limited	Biomarker	[35]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[36]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[37]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[38]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[39]
Prostate cancer	DISF190Y	Limited	Biomarker	[29]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[40]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Protein disulfide-isomerase A3 (PDIA3) affects the response to substance of Cisplatin.	[69]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein disulfide-isomerase A3 (PDIA3).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein disulfide-isomerase A3 (PDIA3).	[61]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein disulfide-isomerase A3 (PDIA3).	[62]

26 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[42]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[43]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein disulfide-isomerase A3 (PDIA3).	[44]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein disulfide-isomerase A3 (PDIA3).	[45]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[46]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein disulfide-isomerase A3 (PDIA3).	[47]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein disulfide-isomerase A3 (PDIA3).	[48]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[49]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein disulfide-isomerase A3 (PDIA3).	[50]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein disulfide-isomerase A3 (PDIA3).	[51]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Protein disulfide-isomerase A3 (PDIA3).	[52]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Protein disulfide-isomerase A3 (PDIA3).	[53]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Protein disulfide-isomerase A3 (PDIA3).	[53]
Dopamine	DMPGUCF	Approved	Dopamine decreases the expression of Protein disulfide-isomerase A3 (PDIA3).	[54]
Etretinate	DM2CZFA	Approved	Etretinate decreases the expression of Protein disulfide-isomerase A3 (PDIA3).	[55]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[56]
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the expression of Protein disulfide-isomerase A3 (PDIA3).	[57]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[58]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[59]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein disulfide-isomerase A3 (PDIA3).	[63]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[64]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[65]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Protein disulfide-isomerase A3 (PDIA3).	[66]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Protein disulfide-isomerase A3 (PDIA3).	[68]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal affects the binding of Protein disulfide-isomerase A3 (PDIA3).	[67]

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