Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZYJ8VN)

• DOT Name: Lysine-specific demethylase 3A (KDM3A)
• Synonyms: EC 1.14.11.65; JmjC domain-containing histone demethylation protein 2A; Jumonji domain-containing protein 1A; -dimethyl-L-lysine(9) demethylase 3A
• Gene Name: KDM3A
• UniProt ID: KDM3A_HUMAN
• EC Number: 1.14.11.65
• Pfam ID: PF02373
• Sequence:
  MVLTLGESWPVLVGRRFLSLSAADGSDGSHDSWDVERVAEWPWLSGTIRAVSHTDVTKKD
  LKVCVEFDGESWRKRRWIEVYSLLRRAFLVEHNLVLAERKSPEISERIVQWPAITYKPLL
  DKAGLGSITSVRFLGDQQRVFLSKDLLKPIQDVNSLRLSLTDNQIVSKEFQALIVKHLDE
  SHLLKGDKNLVGSEVKIYSLDPSTQWFSATVINGNPASKTLQVNCEEIPALKIVDPSLIH
  VEVVHDNLVTCGNSARIGAVKRKSSENNGTLVSKQAKSCSEASPSMCPVQSVPTTVFKEI
  LLGCTAATPPSKDPRQQSTPQAANSPPNLGAKIPQGCHKQSLPEEISSCLNTKSEALRTK
  PDVCKAGLLSKSSQIGTGDLKILTEPKGSCTQPKTNTDQENRLESVPQALTGLPKECLPT
  KASSKAELEIANPPELQKHLEHAPSPSDVSNAPEVKAGVNSDSPNNCSGKKVEPSALACR
  SQNLKESSVKVDNESCCSRSNNKIQNAPSRKSVLTDPAKLKKLQQSGEAFVQDDSCVNIV
  AQLPKCRECRLDSLRKDKEQQKDSPVFCRFFHFRRLQFNKHGVLRVEGFLTPNKYDNEAI
  GLWLPLTKNVVGIDLDTAKYILANIGDHFCQMVISEKEAMSTIEPHRQVAWKRAVKGVRE
  MCDVCDTTIFNLHWVCPRCGFGVCVDCYRMKRKNCQQGAAYKTFSWLKCVKSQIHEPENL
  MPTQIIPGKALYDVGDIVHSVRAKWGIKANCPCSNRQFKLFSKPASKEDLKQTSLAGEKP
  TLGAVLQQNPSVLEPAAVGGEAASKPAGSMKPACPASTSPLNWLADLTSGNVNKENKEKQ
  PTMPILKNEIKCLPPLPPLSKSSTVLHTFNSTILTPVSNNNSGFLRNLLNSSTGKTENGL
  KNTPKILDDIFASLVQNKTTSDLSKRPQGLTIKPSILGFDTPHYWLCDNRLLCLQDPNNK
  SNWNVFRECWKQGQPVMVSGVHHKLNSELWKPESFRKEFGEQEVDLVNCRTNEIITGATV
  GDFWDGFEDVPNRLKNEKEPMVLKLKDWPPGEDFRDMMPSRFDDLMANIPLPEYTRRDGK
  LNLASRLPNYFVRPDLGPKMYNAYGLITPEDRKYGTTNLHLDVSDAANVMVYVGIPKGQC
  EQEEEVLKTIQDGDSDELTIKRFIEGKEKPGALWHIYAAKDTEKIREFLKKVSEEQGQEN
  PADHDPIHDQSWYLDRSLRKRLHQEYGVQGWAIVQFLGDVVFIPAGAPHQVHNLYSCIKV
  AEDFVSPEHVKHCFWLTQEFRYLSQTHTNHEDKLQVKNVIYHAVKDAVAMLKASESSFGK
  P
• Function: Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Preferentially demethylates mono- and dimethylated H3 'Lys-9' residue, with a preference for dimethylated residue, while it has weak or no activity on trimethylated H3 'Lys-9'. Demethylation of Lys residue generates formaldehyde and succinate. Involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes, resulting in H3 'Lys-9' demethylation and transcriptional activation. Involved in spermatogenesis by regulating expression of target genes such as PRM1 and TNP1 which are required for packaging and condensation of sperm chromatin. Involved in obesity resistance through regulation of metabolic genes such as PPARA and UCP1.
• KEGG Pathway: Thermogenesis (hsa04714)
• Reactome Pathway:
  NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux (R-HSA-9029569)
  HDMs demethylate histones (R-HSA-3214842)
• BioCyc Pathway: MetaCyc:ENSG00000115548-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

30 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 Lysine-specific demethylase 3A (KDM3A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Lysine-specific demethylase 3A (KDM3A).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lysine-specific demethylase 3A (KDM3A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lysine-specific demethylase 3A (KDM3A).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Lysine-specific demethylase 3A (KDM3A).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Lysine-specific demethylase 3A (KDM3A).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Lysine-specific demethylase 3A (KDM3A).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Lysine-specific demethylase 3A (KDM3A).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Lysine-specific demethylase 3A (KDM3A).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Lysine-specific demethylase 3A (KDM3A).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Lysine-specific demethylase 3A (KDM3A).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Lysine-specific demethylase 3A (KDM3A).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Lysine-specific demethylase 3A (KDM3A).	[9]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Lysine-specific demethylase 3A (KDM3A).	[6]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Lysine-specific demethylase 3A (KDM3A).	[6]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Lysine-specific demethylase 3A (KDM3A).	[6]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Lysine-specific demethylase 3A (KDM3A).	[12]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Lysine-specific demethylase 3A (KDM3A).	[12]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil decreases the expression of Lysine-specific demethylase 3A (KDM3A).	[6]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the expression of Lysine-specific demethylase 3A (KDM3A).	[13]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of Lysine-specific demethylase 3A (KDM3A).	[14]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Lysine-specific demethylase 3A (KDM3A).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Lysine-specific demethylase 3A (KDM3A).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Lysine-specific demethylase 3A (KDM3A).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Lysine-specific demethylase 3A (KDM3A).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Lysine-specific demethylase 3A (KDM3A).	[20]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Lysine-specific demethylase 3A (KDM3A).	[21]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Lysine-specific demethylase 3A (KDM3A).	[22]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Lysine-specific demethylase 3A (KDM3A).	[23]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Lysine-specific demethylase 3A (KDM3A).	[24]

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 Lysine-specific demethylase 3A (KDM3A).	[18]

References

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