Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXLIBD7)

• DOT Name: Phosphatidylserine synthase 1 (PTDSS1)
• Synonyms: PSS-1; PtdSer synthase 1; EC 2.7.8.29; Serine-exchange enzyme I
• Gene Name: PTDSS1
• Related Disease:
  Lenz-Majewski hyperostotic dwarfism
  Alzheimer disease
  Autism
  Lateral meningocele syndrome
  Limb-mammary syndrome
  Aortic disorder
  Aortic valve stenosis
  Dental enamel hypoplasia
• UniProt ID: PTSS1_HUMAN
• EC Number: 2.7.8.29
• Pfam ID: PF03034
• Sequence:
  MASCVGSRTLSKDDVNYKMHFRMINEQQVEDITIDFFYRPHTITLLSFTIVSLMYFAFTR
  DDSVPEDNIWRGILSVIFFFLIISVLAFPNGPFTRPHPALWRMVFGLSVLYFLFLVFLLF
  LNFEQVKSLMYWLDPNLRYATREADVMEYAVNCHVITWERIISHFDIFAFGHFWGWAMKA
  LLIRSYGLCWTISITWELTELFFMHLLPNFAECWWDQVILDILLCNGGGIWLGMVVCRFL
  EMRTYHWASFKDIHTTTGKIKRAVLQFTPASWTYVRWFDPKSSFQRVAGVYLFMIIWQLT
  ELNTFFLKHIFVFQASHPLSWGRILFIGGITAPTVRQYYAYLTDTQCKRVGTQCWVFGVI
  GFLEAIVCIKFGQDLFSKTQILYVVLWLLCVAFTTFLCLYGMIWYAEHYGHREKTYSECE
  DGTYSPEISWHHRKGTKGSEDSPPKHAGNNESHSSRRRNRHSKSKVTNGVGKK
• Function: Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine. Catalyzes mainly the conversion of phosphatidylcholine. Also converts, in vitro and to a lesser extent, phosphatidylethanolamine.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of PS (R-HSA-1483101)
• BioCyc Pathway: MetaCyc:HS08129-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lenz-Majewski hyperostotic dwarfism	DIS174EL	Definitive	Autosomal dominant	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Autism	DISV4V1Z	Strong	Genetic Variation	[3]
Lateral meningocele syndrome	DISG74RP	Strong	Genetic Variation	[4]
Limb-mammary syndrome	DIS7H4FP	Strong	Genetic Variation	[4]
Aortic disorder	DISKXISV	moderate	Biomarker	[5]
Aortic valve stenosis	DISW7AQ9	moderate	Biomarker	[5]
Dental enamel hypoplasia	DISN6ZMR	Limited	Biomarker	[6]

3 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 Phosphatidylserine synthase 1 (PTDSS1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Phosphatidylserine synthase 1 (PTDSS1).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Phosphatidylserine synthase 1 (PTDSS1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosphatidylserine synthase 1 (PTDSS1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Phosphatidylserine synthase 1 (PTDSS1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphatidylserine synthase 1 (PTDSS1).	[10]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Phosphatidylserine synthase 1 (PTDSS1).	[12]

References

• [1] Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome. Nat Genet. 2014 Jan;46(1):70-6. doi: 10.1038/ng.2829. Epub 2013 Nov 17.
• [2] Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer's disease during lifespan.Lett Appl Microbiol. 2018 Jun;66(6):464-471. doi: 10.1111/lam.12882. Epub 2018 Apr 16.
• [3] RYR2, PTDSS1 and AREG genes are implicated in a Lebanese population-based study of copy number variation in autism.Sci Rep. 2016 Jan 8;6:19088. doi: 10.1038/srep19088.
• [4] Lenz-Majewski syndrome in a patient from Egypt.Am J Med Genet A. 2019 Oct;179(10):2039-2042. doi: 10.1002/ajmg.a.61327. Epub 2019 Aug 12.
• [5] Three-dimensional thoracic aorta principal strain analysis from routine ECG-gated computerized tomography: feasibility in patients undergoing transcatheter aortic valve replacement.BMC Cardiovasc Disord. 2018 May 2;18(1):76. doi: 10.1186/s12872-018-0818-0.
• [6] Lenz-Majewski syndrome: Report of a case with novel mutation inPTDSS1 gene.Eur J Med Genet. 2015 Aug;58(8):392-9. doi: 10.1016/j.ejmg.2015.06.002. Epub 2015 Jun 24.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] 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.
• [11] 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.
• [12] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.