Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRQNIA4)

• DOT Name: BAG family molecular chaperone regulator 1 (BAG1)
• Synonyms: BAG-1; Bcl-2-associated athanogene 1
• Gene Name: BAG1
• Related Disease:
  Acute myelogenous leukaemia
  Bipolar disorder
  Estrogen-receptor positive breast cancer
  Melanoma
  Neoplasm
  Advanced cancer
  Alzheimer disease
  Autism spectrum disorder
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Carcinoma of esophagus
  Colon cancer
  Colon carcinoma
  Colorectal adenoma
  Colorectal neoplasm
  Depression
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  Invasive ductal breast carcinoma
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Osteosarcoma
  Parkinson disease
  Prostate neoplasm
  Squamous cell carcinoma
  Breast neoplasm
  Gastric cancer
  Invasive breast carcinoma
  Adenocarcinoma
  B-cell neoplasm
  Bipolar I disorder
  Colorectal carcinoma
  Glioblastoma multiforme
  Glioma
  Metastatic malignant neoplasm
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Psychotic disorder
  Stomach cancer
• UniProt ID: BAG1_HUMAN
• PDB ID: 1HX1; 1WXV; 3FZF; 3FZH; 3FZK; 3FZL; 3FZM; 3LDQ; 3M3Z; 5AQF; 5AQG; 5AQH; 5AQI; 5AQJ; 5AQK; 5AQL; 5AQM; 5AQN; 5AQO; 5AQP; 5AQQ; 5AQR; 5AQS; 5AQT; 5AQU; 5AQV
• Pfam ID: PF02179 ; PF00240
• Sequence:
  MAQRGGARRPRGDRERLGSRLRALRPGREPRQSEPPAQRGPPPSGRPPARSTASGHDRPT
  RGAAAGARRPRMKKKTRRRSTRSEELTRSEELTLSEEATWSEEATQSEEATQGEEMNRSQ
  EVTRDEESTRSEEVTREEMAAAGLTVTVTHSNEKHDLHVTSQQGSSEPVVQDLAQVVEEV
  IGVPQSFQKLIFKGKSLKEMETPLSALGIQDGCRVMLIGKKNSPQEEVELKKLKHLEKSV
  EKIADQLEELNKELTGIQQGFLPKDLQAEALCKLDRRVKATIEQFMKILEEIDTLILPEN
  FKDSRLKRKGLVKKVQAFLAECDTVEQNICQETERLQSTNFALAE
• Function: Co-chaperone for HSP70 and HSC70 chaperone proteins. Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate-binding domain (SBD) of HSPA8/HSC70. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli. Involved in the STUB1-mediated proteasomal degradation of ESR1 in response to age-related circulating estradiol (17-beta-estradiol/E2) decline, thereby promotes neuronal apoptosis in response to ischemic reperfusion injury.
• Tissue Specificity: Isoform 4 is the most abundantly expressed isoform. It is ubiquitously expressed throughout most tissues, except the liver, colon, breast and uterine myometrium. Isoform 1 is expressed in the ovary and testis. Isoform 4 is expressed in several types of tumor cell lines, and at consistently high levels in leukemia and lymphoma cell lines. Isoform 1 is expressed in the prostate, breast and leukemia cell lines. Isoform 3 is the least abundant isoform in tumor cell lines (at protein level).
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway: Regulation of HSF1-mediated heat shock response (R-HSA-3371453)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Bipolar disorder	DISAM7J2	Definitive	Biomarker	[2]
Estrogen-receptor positive breast cancer	DIS1H502	Definitive	Altered Expression	[3]
Melanoma	DIS1RRCY	Definitive	Biomarker	[4]
Neoplasm	DISZKGEW	Definitive	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[7]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[3]
Carcinoma	DISH9F1N	Strong	Altered Expression	[9]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Colorectal adenoma	DISTSVHM	Strong	Biomarker	[8]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[12]
Depression	DIS3XJ69	Strong	Biomarker	[13]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[15]
Invasive ductal breast carcinoma	DIS43J58	Strong	Biomarker	[16]
leukaemia	DISS7D1V	Strong	Biomarker	[17]
Leukemia	DISNAKFL	Strong	Biomarker	[17]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[18]
Lung cancer	DISCM4YA	Strong	Altered Expression	[19]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[19]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[19]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[8]
Parkinson disease	DISQVHKL	Strong	Biomarker	[20]
Prostate neoplasm	DISHDKGQ	Strong	Genetic Variation	[21]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[22]
Breast neoplasm	DISNGJLM	moderate	Altered Expression	[23]
Gastric cancer	DISXGOUK	moderate	Biomarker	[24]
Invasive breast carcinoma	DISANYTW	moderate	Altered Expression	[25]
Adenocarcinoma	DIS3IHTY	Disputed	Altered Expression	[26]
B-cell neoplasm	DISVY326	Limited	Biomarker	[19]
Bipolar I disorder	DISD09EH	Limited	Genetic Variation	[27]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[28]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[29]
Glioma	DIS5RPEH	Limited	Altered Expression	[29]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[16]
Pancreatic cancer	DISJC981	Limited	Biomarker	[30]
Prostate cancer	DISF190Y	Limited	Biomarker	[31]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[31]
Psychotic disorder	DIS4UQOT	Limited	Genetic Variation	[27]
Stomach cancer	DISKIJSX	Limited	Biomarker	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of BAG family molecular chaperone regulator 1 (BAG1).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[34]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[35]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[36]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[37]
Selenium	DM25CGV	Approved	Selenium increases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[38]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[39]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[40]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[41]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[43]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol decreases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[44]
UCN-01	DMUNJZB	Phase 2	UCN-01 decreases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[46]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[47]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[48]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[49]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of BAG family molecular chaperone regulator 1 (BAG1).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fenretinide	DMRD5SP	Phase 3	Fenretinide affects the localization of BAG family molecular chaperone regulator 1 (BAG1).	[42]

References

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