Details of Drug Off-Target (DOT)

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

• DOT Name: Protein disulfide-isomerase (P4HB)
• Synonyms: PDI; EC 5.3.4.1; Cellular thyroid hormone-binding protein; Prolyl 4-hydroxylase subunit beta; p55
• Gene Name: P4HB
• Related Disease:
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Amyotrophic lateral sclerosis
  Bacterial infection
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Classic Hodgkin lymphoma
  Cole-Carpenter syndrome 1
  Depression
  Glioma
  Hepatocellular carcinoma
  Huntington disease
  Myocardial ischemia
  Neuroblastoma
  Non-small-cell lung cancer
  Osteogenesis imperfecta
  Pneumonia
  Prostate cancer
  Prostate neoplasm
  Rheumatoid arthritis
  Schizophrenia
  Spinocerebellar ataxia type 17
  Stroke
  Tuberculosis
  Type-1/2 diabetes
  Visceral leishmaniasis
  Carcinoma
  Colon cancer
  Colon carcinoma
  Gastric cancer
  Obesity
  Cole-Carpenter syndrome
  Osteogenesis imperfecta type 1
  Plasma cell myeloma
  Acute myelogenous leukaemia
  Arteriosclerosis
  Atherosclerosis
  Colorectal carcinoma
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Non-insulin dependent diabetes
  Osteoporosis
  Ovarian cancer
  Ovarian neoplasm
  Stomach cancer
  Systemic sclerosis
• UniProt ID: PDIA1_HUMAN
• PDB ID: 1BJX; 1MEK; 1X5C; 2BJX; 2K18; 3BJ5; 3UEM; 4EKZ; 4EL1; 4JU5; 6I7S; 7ZSC; 8EOJ
• EC Number: 5.3.4.1
• Pfam ID: PF00085 ; PF13848
• Sequence:
  MLRRALLCLAVAALVRADAPEEEDHVLVLRKSNFAEALAAHKYLLVEFYAPWCGHCKALA
  PEYAKAAGKLKAEGSEIRLAKVDATEESDLAQQYGVRGYPTIKFFRNGDTASPKEYTAGR
  EADDIVNWLKKRTGPAATTLPDGAAAESLVESSEVAVIGFFKDVESDSAKQFLQAAEAID
  DIPFGITSNSDVFSKYQLDKDGVVLFKKFDEGRNNFEGEVTKENLLDFIKHNQLPLVIEF
  TEQTAPKIFGGEIKTHILLFLPKSVSDYDGKLSNFKTAAESFKGKILFIFIDSDHTDNQR
  ILEFFGLKKEECPAVRLITLEEEMTKYKPESEELTAERITEFCHRFLEGKIKPHLMSQEL
  PEDWDKQPVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENI
  VIAKMDSTANEVEAVKVHSFPTLKFFPASADRTVIDYNGERTLDGFKKFLESGGQDGAGD
  DDDLEDLEEAEEPDMEEDDDQKAVKDEL
• Function: This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  Insulin processing (R-HSA-264876)
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Hedgehog ligand biogenesis (R-HSA-5358346)
  VLDL assembly (R-HSA-8866423)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Chylomicron assembly (R-HSA-8963888)
  LDL remodeling (R-HSA-8964041)
  Interleukin-12 signaling (R-HSA-9020591)
  Interleukin-23 signaling (R-HSA-9020933)
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
• BioCyc Pathway: MetaCyc:HS06845-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[4]
Bacterial infection	DIS5QJ9S	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[8]
Cole-Carpenter syndrome 1	DIS33I78	Strong	Autosomal dominant	[9]
Depression	DIS3XJ69	Strong	Genetic Variation	[10]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Huntington disease	DISQPLA4	Strong	Altered Expression	[13]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[14]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[16]
Osteogenesis imperfecta	DIS7XQSD	Strong	Biomarker	[17]
Pneumonia	DIS8EF3M	Strong	Altered Expression	[18]
Prostate cancer	DISF190Y	Strong	Biomarker	[19]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[19]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[20]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[21]
Spinocerebellar ataxia type 17	DISJXO7P	Strong	Biomarker	[22]
Stroke	DISX6UHX	Strong	Biomarker	[23]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[24]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[25]
Visceral leishmaniasis	DISTKEYK	Strong	Biomarker	[26]
Carcinoma	DISH9F1N	moderate	Altered Expression	[27]
Colon cancer	DISVC52G	moderate	Biomarker	[28]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[28]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[29]
Obesity	DIS47Y1K	moderate	Biomarker	[30]
Cole-Carpenter syndrome	DISTWF6O	Supportive	Autosomal dominant	[9]
Osteogenesis imperfecta type 1	DISPEDS3	Supportive	Autosomal dominant	[31]
Plasma cell myeloma	DIS0DFZ0	Disputed	Biomarker	[32]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[33]
Arteriosclerosis	DISK5QGC	Limited	Genetic Variation	[34]
Atherosclerosis	DISMN9J3	Limited	Genetic Variation	[34]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[35]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[36]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[37]
Osteoporosis	DISF2JE0	Limited	Altered Expression	[38]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[36]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[36]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[29]
Systemic sclerosis	DISF44L6	Limited	Biomarker	[39]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Protein disulfide-isomerase (P4HB) affects the response to substance of Methotrexate.	[66]
Sulforaphane	DMQY3L0	Investigative	Protein disulfide-isomerase (P4HB) affects the binding of Sulforaphane.	[67]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein disulfide-isomerase (P4HB).	[40]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein disulfide-isomerase (P4HB).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein disulfide-isomerase (P4HB).	[42]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Protein disulfide-isomerase (P4HB).	[43]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein disulfide-isomerase (P4HB).	[44]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein disulfide-isomerase (P4HB).	[45]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein disulfide-isomerase (P4HB).	[46]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Protein disulfide-isomerase (P4HB).	[47]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein disulfide-isomerase (P4HB).	[48]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein disulfide-isomerase (P4HB).	[49]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Protein disulfide-isomerase (P4HB).	[50]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Protein disulfide-isomerase (P4HB).	[51]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Protein disulfide-isomerase (P4HB).	[52]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Protein disulfide-isomerase (P4HB).	[52]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Protein disulfide-isomerase (P4HB).	[53]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Protein disulfide-isomerase (P4HB).	[52]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Protein disulfide-isomerase (P4HB).	[54]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Protein disulfide-isomerase (P4HB).	[55]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Protein disulfide-isomerase (P4HB).	[52]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Protein disulfide-isomerase (P4HB).	[52]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Protein disulfide-isomerase (P4HB).	[56]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Protein disulfide-isomerase (P4HB).	[57]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Protein disulfide-isomerase (P4HB).	[57]
Etretinate	DM2CZFA	Approved	Etretinate increases the expression of Protein disulfide-isomerase (P4HB).	[58]
Allopurinol	DMLPAOB	Approved	Allopurinol decreases the expression of Protein disulfide-isomerase (P4HB).	[52]
Indinavir	DM0T3YH	Approved	Indinavir increases the expression of Protein disulfide-isomerase (P4HB).	[52]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Protein disulfide-isomerase (P4HB).	[59]
ME-344	DM6JN19	Phase 1/2	ME-344 increases the expression of Protein disulfide-isomerase (P4HB).	[61]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein disulfide-isomerase (P4HB).	[41]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein disulfide-isomerase (P4HB).	[62]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein disulfide-isomerase (P4HB).	[63]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Protein disulfide-isomerase (P4HB).	[64]
L-Serine	DM6WPIS	Investigative	L-Serine increases the expression of Protein disulfide-isomerase (P4HB).	[65]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Protein disulfide-isomerase (P4HB).	[60]

References

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