Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJHPHI5)

• DOT Name: Protein-cysteine N-palmitoyltransferase HHAT-like protein (HHATL)
• Synonyms: Glycerol uptake/transporter homolog; Hedgehog acyltransferase-like protein
• Gene Name: HHATL
• UniProt ID: HHATL_HUMAN
• Pfam ID: PF03062
• Sequence:
  MGIKTALPAAELGLYSLVLSGALAYAGRGLLEASQDGAHRKAFRESVRPGWEYIGRKMDV
  ADFEWVMWFTSFRNVIIFALSGHVLFAKLCTMVAPKLRSWMYAVYGALAVMGTMGPWYLL
  LLLGHCVGLYVASLLGQPWLCLGLGLASLASFKMDPLISWQSGFVTGTFDLQEVLFHGGS
  SFTVLRCTSFALESCAHPDRHYSLADLLKYNFYLPFFFFGPIMTFDRFHAQVSQVEPVRR
  EGELWHIRAQAGLSVVAIMAVDIFFHFFYILTIPSDLKFANRLPDSALAGLAYSNLVYDW
  VKAAVLFGVVNTVACLDHLDPPQPPKCITALYVFAETHFDRGINDWLCKYVYNHIGGEHS
  AVIPELAATVATFAITTLWLGPCDIVYLWSFLNCFGLNFELWMQKLAEWGPLARIEASLS
  VQMSRRVRALFGAMNFWAIIMYNLVSLNSLKFTELVARRLLLTGFPQTTLSILFVTYCGV
  QLVKERERTLALEEEQKQDKEKPE
• Function: Negatively regulates N-terminal palmitoylation of SHH by HHAT/SKN.
• Tissue Specificity: Heart-specific.
• KEGG Pathway: Hedgehog sig.ling pathway (hsa04340)

Molecular Interaction Atlas (MIA) of This DOT

3 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 Protein-cysteine N-palmitoyltransferase HHAT-like protein (HHATL).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein-cysteine N-palmitoyltransferase HHAT-like protein (HHATL).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein-cysteine N-palmitoyltransferase HHAT-like protein (HHATL).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein-cysteine N-palmitoyltransferase HHAT-like protein (HHATL).	[4]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] 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.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] 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.