Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAG4LPL)

• DOT Name: 52 kDa repressor of the inhibitor of the protein kinase (THAP12)
• Synonyms: p52rIPK; 58 kDa interferon-induced protein kinase-interacting protein; p58IPK-interacting protein; Death-associated protein 4; THAP domain-containing protein 0; THAP domain-containing protein 12
• Gene Name: THAP12
• Related Disease: Neoplasm
• UniProt ID: P52K_HUMAN
• Pfam ID: PF05699 ; PF14291 ; PF05485
• Sequence:
  MPNFCAAPNCTRKSTQSDLAFFRFPRDPARCQKWVENCRRADLEDKTPDQLNKHYRLCAK
  HFETSMICRTSPYRTVLRDNAIPTIFDLTSHLNNPHSRHRKRIKELSEDEIRTLKQKKID
  ETSEQEQKHKETNNSNAQNPSEEEGEGQDEDILPLTLEEKENKEYLKSLFEILILMGKQN
  IPLDGHEADEIPEGLFTPDNFQALLECRINSGEEVLRKRFETTAVNTLFCSKTQQRQMLE
  ICESCIREETLREVRDSHFFSIITDDVVDIAGEEHLPVLVRFVDESHNLREEFIGFLPYE
  ADAEILAVKFHTMITEKWGLNMEYCRGQAYIVSSGFSSKMKVVASRLLEKYPQAIYTLCS
  SCALNMWLAKSVPVMGVSVALGTIEEVCSFFHRSPQLLLELDNVISVLFQNSKERGKELK
  EICHSQWTGRHDAFEILVELLQALVLCLDGINSDTNIRWNNYIAGRAFVLCSAVSDFDFI
  VTIVVLKNVLSFTRAFGKNLQGQTSDVFFAAGSLTAVLHSLNEVMENIEVYHEFWFEEAT
  NLATKLDIQMKLPGKFRRAHQGNLESQLTSESYYKETLSVPTVEHIIQELKDIFSEQHLK
  ALKCLSLVPSVMGQLKFNTSEEHHADMYRSDLPNPDTLSAELHCWRIKWKHRGKDIELPS
  TIYEALHLPDIKFFPNVYALLKVLCILPVMKVENERYENGRKRLKAYLRNTLTDQRSSNL
  ALLNINFDIKHDLDLMVDTYIKLYTSKSELPTDNSETVENT
• Function: Upstream regulator of interferon-induced serine/threonine protein kinase R (PKR). May block the PKR-inhibitory function of DNAJC3, resulting in restoration of kinase activity and suppression of cell growth.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Genetic Variation	[1]

3 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 52 kDa repressor of the inhibitor of the protein kinase (THAP12).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 52 kDa repressor of the inhibitor of the protein kinase (THAP12).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 52 kDa repressor of the inhibitor of the protein kinase (THAP12).	[4]

References

• [1] Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer.Cancer Res. 2016 Apr 1;76(7):1714-23. doi: 10.1158/0008-5472.CAN-15-0338. Epub 2016 Feb 8.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.