Details of Drug Off-Target (DOT)

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

• DOT Name: Protein KRBA1 (KRBA1)
• Gene Name: KRBA1
• Related Disease: Major depressive disorder
• UniProt ID: KRBA1_HUMAN
• Pfam ID: PF15287
• Sequence:
  MRENYETLVSVGTAELLPLSAFLSPSEPGRAVGGGSHADEGQEPAGCGDPQGGQPRHSLH
  LTALVQLVKEIPEFLFGEVKGAMDSPESESRGASLDGERASPEAAAAREPCPLRGLLSCL
  PDGPTSQPHLATTPTDSSCSSGPTGDGVQGSPLPIKTADKPWPTRKEGPGALGGEPSPPT
  HSPSRRKSHRGQERGTSEAGISPGNSPLQGLINCLKEILVPGPRHPETSPSFLPPLPSLG
  TSRLTRADLGPGSPPWAVKTEAVSGDCPLQGLLHCLKELPEAQDRHPSPSGVGNRRLQEN
  PGAWKRGSGGPGYLLTPPPHPDLGAGGLLSVKMENSWVQSPPGPASCQPGRQPLSPSATG
  DTRGVPQPSWGPEAQAASASSSPLEALEACLKGIPPNGSSPSQLPPTSCSQNPQPGDSRS
  QKPELQPHRSHSEEATREPVLPLGLQSCVRDGPSRPLAPRGTPTSFSSSSSTDWDLDFGS
  PVGNQGQHPGKGSPPGSSPLQGLENCLKEIPVPVLRPAWPCSSAADRGPRRAEPRNWTAD
  KEGLRAEACESARLGQGRGEAPTRSLHLVSPQVFTSSCVPACHQRGFKDPGATRPGVWRW
  LPEGSAPKPSPLHCLESALRGILPVRPLRFACVGGPSPSPSPGSSSSFSGSEGEDPRPEP
  DLWKPLPQERDRLPSCKPPVPLSPCPGGTPAGSSGGSPGEDPRRTEPRYCSGLGAGTAQD
  PCPVSQLEKRPRVSEASRGLELGHGRPRVAAKTHERLLPQGPPELPSESPPPELPPPEAA
  PPVLPASSLQPPCHCGKPLQQELHSLGAALAEKLDRLATALAGLAQEVATMRTQVNRLGR
  RPQGPGPMGQASWMWTLPRGPRWAHGPGHRHLPYWRQKGPTRPKPKILRGQGESCRAGDL
  QGLSRGTARRARPLPPDAPPAEPPGLHCSSSQQLLSSTPSCHAAPPAHPLLAHTGGHQSP
  LPPLVPAALPLQGASPPAASADADVPTSGVAPDGIPERPKEPSSLLGGVQRALQEELWGG
  EHRDPRWGAH
• Tissue Specificity: Expressed in brain (cerebellum).
• Reactome Pathway: Generic Transcription Pathway (R-HSA-212436)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein KRBA1 (KRBA1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein KRBA1 (KRBA1).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein KRBA1 (KRBA1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein KRBA1 (KRBA1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein KRBA1 (KRBA1).	[4]

References

• [1] The PHF21B gene is associated with major depression and modulates the stress response.Mol Psychiatry. 2017 Jul;22(7):1015-1025. doi: 10.1038/mp.2016.174. Epub 2016 Oct 25.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [6] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.