Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZNXYS2)

• DOT Name: Prohibitin 1 (PHB1)
• Gene Name: PHB1
• UniProt ID: PHB1_HUMAN
• Pfam ID: PF01145
• Sequence:
  MAAKVFESIGKFGLALAVAGGVVNSALYNVDAGHRAVIFDRFRGVQDIVVGEGTHFLIPW
  VQKPIIFDCRSRPRNVPVITGSKDLQNVNITLRILFRPVASQLPRIFTSIGEDYDERVLP
  SITTEILKSVVARFDAGELITQRELVSRQVSDDLTERAATFGLILDDVSLTHLTFGKEFT
  EAVEAKQVAQQEAERARFVVEKAEQQKKAAIISAEGDSKAAELIANSLATAGDGLIELRK
  LEAAEDIAYQLSRSRNITYLPAGQSVLLQLPQ
• Function: Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors in the nucleus. Plays a role in adipose tissue and glucose homeostasis in a sex-specific manner. Contributes to pulmonary vascular remodeling by accelerating proliferation of pulmonary arterial smooth muscle cells; In the mitochondria, together with PHB2, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as a chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner. Regulates mitochondrial respiration activity playing a role in cellular aging. The prohibitin complex plays a role of mitophagy receptor involved in targeting mitochondria for autophagic degradation. Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6 ; In the nucleus, acts as a transcription coregulator, enhances promoter binding by TP53, a transcription factor it activates, but reduces the promoter binding by E2F1, a transcription factor it represses. Interacts with STAT3 to affect IL17 secretion in T-helper Th17 cells ; In the plasma membrane, cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates. Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation.
• Tissue Specificity: Widely expressed in different tissues.
• Reactome Pathway:
  Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946)
  Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955)
  Processing of SMDT1 (R-HSA-8949664)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  RAF activation (R-HSA-5673000)

Molecular Interaction Atlas (MIA) of This DOT

29 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 Prohibitin 1 (PHB1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Prohibitin 1 (PHB1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Prohibitin 1 (PHB1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Prohibitin 1 (PHB1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Prohibitin 1 (PHB1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Prohibitin 1 (PHB1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prohibitin 1 (PHB1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Prohibitin 1 (PHB1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Prohibitin 1 (PHB1).	[3]
Marinol	DM70IK5	Approved	Marinol increases the expression of Prohibitin 1 (PHB1).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Prohibitin 1 (PHB1).	[10]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Prohibitin 1 (PHB1).	[11]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Prohibitin 1 (PHB1).	[12]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Prohibitin 1 (PHB1).	[13]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Prohibitin 1 (PHB1).	[14]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Prohibitin 1 (PHB1).	[15]
Dopamine	DMPGUCF	Approved	Dopamine increases the expression of Prohibitin 1 (PHB1).	[16]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Prohibitin 1 (PHB1).	[17]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Prohibitin 1 (PHB1).	[18]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Prohibitin 1 (PHB1).	[19]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Prohibitin 1 (PHB1).	[21]
CLIK-148	DM0BHL8	Preclinical	CLIK-148 increases the expression of Prohibitin 1 (PHB1).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Prohibitin 1 (PHB1).	[23]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Prohibitin 1 (PHB1).	[24]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Prohibitin 1 (PHB1).	[25]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Prohibitin 1 (PHB1).	[8]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Prohibitin 1 (PHB1).	[26]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the expression of Prohibitin 1 (PHB1).	[27]
Flavone	DMEQH6J	Investigative	Flavone decreases the expression of Prohibitin 1 (PHB1).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Prohibitin 1 (PHB1).	[20]

References

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