Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA6OR6C)

• DOT Name: L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (AASDHPPT)
• Synonyms: EC 2.7.8.7; 4'-phosphopantetheinyl transferase; Alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase; AASD-PPT; LYS5 ortholog
• Gene Name: AASDHPPT
• Related Disease:
  Advanced cancer
  Carpenter syndrome
  Factor IX deficiency
• UniProt ID: ADPPT_HUMAN
• PDB ID: 2BYD; 2C43; 2CG5
• EC Number: 2.7.8.7
• Pfam ID: PF01648
• Sequence:
  MVFPAKRFCLVPSMEGVRWAFSCGTWLPSRAEWLLAVRSIQPEEKERIGQFVFARDAKAA
  MAGRLMIRKLVAEKLNIPWNHIRLQRTAKGKPVLAKDSSNPYPNFNFNISHQGDYAVLAA
  EPELQVGIDIMKTSFPGRGSIPEFFHIMKRKFTNKEWETIRSFKDEWTQLDMFYRNWALK
  ESFIKAIGVGLGFELQRLEFDLSPLNLDIGQVYKETRLFLDGEEEKEWAFEESKIDEHHF
  VAVALRKPDGSRHQDVPSQDDSKPTQRQFTILNFNDLMSSAVPMTPEDPSFWDCFCFTEE
  IPIRNGTKS
• Function: Catalyzes the post-translational modification of target proteins by phosphopantetheine. Can transfer the 4'-phosphopantetheine moiety from coenzyme A, regardless of whether the CoA is presented in the free thiol form or as an acetyl thioester, to a serine residue of a broad range of acceptors including the acyl carrier domain of FASN.
• Tissue Specificity: Detected in heart, skeletal muscle, placenta, testis, brain, pancreas, liver and kidney.
• KEGG Pathway:
  Pantothe.te and CoA biosynthesis (hsa00770)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Vitamin B5 (pantothenate) metabolism (R-HSA-199220)
• BioCyc Pathway: MetaCyc:HS14278-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Carpenter syndrome	DISU690E	Strong	Genetic Variation	[2]
Factor IX deficiency	DISHN9SC	moderate	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (AASDHPPT).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (AASDHPPT).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (AASDHPPT).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (AASDHPPT).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (AASDHPPT).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (AASDHPPT).	[9]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (AASDHPPT).	[10]

References

• [1] A polysaccharide from Antrodia cinnamomea mycelia exerts antitumor activity through blocking of TOP1/TDP1-mediated DNA repair pathway.Int J Biol Macromol. 2018 Dec;120(Pt B):1551-1560. doi: 10.1016/j.ijbiomac.2018.09.162. Epub 2018 Sep 26.
• [2] Acrocephalopolysyndactyly type II--Carpenter syndrome: clinical spectrum and an attempt at unification with Goodman and Summit syndromes.Am J Med Genet. 1987 Oct;28(2):311-24. doi: 10.1002/ajmg.1320280208.
• [3] Lysine 5 and phenylalanine 9 of the factor IX omega-loop interact with phosphatidylserine in a membrane-mimetic environment.Biochemistry. 2004 Dec 14;43(49):15367-78. doi: 10.1021/bi049107f.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.