Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYD2TR1)

• DOT Name: Calreticulin (CALR)
• Synonyms: CRP55; Calregulin; Endoplasmic reticulum resident protein 60; ERp60; HACBP; grp60
• Gene Name: CALR
• UniProt ID: CALR_HUMAN
• PDB ID: 2CLR; 3DOW; 3POS; 3POW; 5LK5; 5V90; 6ENY; 7QPD; 8TZO; 8TZR
• Pfam ID: PF00262
• Sequence:
  MLLSVPLLLGLLGLAVAEPAVYFKEQFLDGDGWTSRWIESKHKSDFGKFVLSSGKFYGDE
  EKDKGLQTSQDARFYALSASFEPFSNKGQTLVVQFTVKHEQNIDCGGGYVKLFPNSLDQT
  DMHGDSEYNIMFGPDICGPGTKKVHVIFNYKGKNVLINKDIRCKDDEFTHLYTLIVRPDN
  TYEVKIDNSQVESGSLEDDWDFLPPKKIKDPDASKPEDWDERAKIDDPTDSKPEDWDKPE
  HIPDPDAKKPEDWDEEMDGEWEPPVIQNPEYKGEWKPRQIDNPDYKGTWIHPEIDNPEYS
  PDPSIYAYDNFGVLGLDLWQVKSGTIFDNFLITNDEAYAEEFGNETWGVTKAAEKQMKDK
  QDEEQRLKEEEEDKKRKEEEEAEDKEDDEDKDEDEEDEEDKEEDEEEDVPGQAKDEL
• Function: Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER. Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export. Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis. Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and might participate in the block to polyspermy.
• KEGG Pathway:
  Protein processing in endoplasmic reticulum (hsa04141)
  Phagosome (hsa04145)
  Efferocytosis (hsa04148)
  Antigen processing and presentation (hsa04612)
  Chagas disease (hsa05142)
  Human cytomegalovirus infection (hsa05163)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
• Reactome Pathway:
  Assembly of Viral Components at the Budding Site (R-HSA-168316)
  Scavenging by Class A Receptors (R-HSA-3000480)
  Scavenging by Class F Receptors (R-HSA-3000484)
  ATF6 (ATF6-alpha) activates chaperone genes (R-HSA-381183)
  Calnexin/calreticulin cycle (R-HSA-901042)
  Antigen Presentation (R-HSA-983170)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Calreticulin (CALR) affects the response to substance of Methotrexate.	[32]

36 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 Calreticulin (CALR).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Calreticulin (CALR).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Calreticulin (CALR).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Calreticulin (CALR).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Calreticulin (CALR).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Calreticulin (CALR).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Calreticulin (CALR).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Calreticulin (CALR).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Calreticulin (CALR).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Calreticulin (CALR).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Calreticulin (CALR).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Calreticulin (CALR).	[12]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Calreticulin (CALR).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Calreticulin (CALR).	[13]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Calreticulin (CALR).	[14]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Calreticulin (CALR).	[15]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Calreticulin (CALR).	[16]
Etretinate	DM2CZFA	Approved	Etretinate increases the expression of Calreticulin (CALR).	[17]
Gallium nitrate	DMF9O6B	Approved	Gallium nitrate decreases the expression of Calreticulin (CALR).	[18]
Dutasteride	DMQ4TJK	Approved	Dutasteride decreases the expression of Calreticulin (CALR).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Calreticulin (CALR).	[19]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Calreticulin (CALR).	[20]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Calreticulin (CALR).	[21]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine increases the expression of Calreticulin (CALR).	[13]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Calreticulin (CALR).	[22]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Calreticulin (CALR).	[12]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate decreases the expression of Calreticulin (CALR).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Calreticulin (CALR).	[24]
Clioquinol	DM746BZ	Withdrawn from market	Clioquinol decreases the expression of Calreticulin (CALR).	[25]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Calreticulin (CALR).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Calreticulin (CALR).	[27]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Calreticulin (CALR).	[28]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Calreticulin (CALR).	[29]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Calreticulin (CALR).	[30]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID decreases the expression of Calreticulin (CALR).	[20]
L-Serine	DM6WPIS	Investigative	L-Serine increases the expression of Calreticulin (CALR).	[31]

References

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