Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUXQS0N)

• DOT Name: Phosphatidylserine synthase 2 (PTDSS2)
• Synonyms: PSS-2; PtdSer synthase 2; EC 2.7.8.29; Serine-exchange enzyme II
• Gene Name: PTDSS2
• UniProt ID: PTSS2_HUMAN
• EC Number: 2.7.8.29
• Pfam ID: PF03034
• Sequence:
  MRRGERRDAGGPRPESPVPAGRASLEEPPDGPSAGQATGPGEGRRSTESEVYDDGTNTFF
  WRAHTLTVLFILTCTLGYVTLLEETPQDTAYNTKRGIVASILVFLCFGVTQAKDGPFSRP
  HPAYWRFWLCVSVVYELFLIFILFQTVQDGRQFLKYVDPKLGVPLPERDYGGNCLIYDPD
  NETDPFHNIWDKLDGFVPAHFLGWYLKTLMIRDWWMCMIISVMFEFLEYSLEHQLPNFSE
  CWWDHWIMDVLVCNGLGIYCGMKTLEWLSLKTYKWQGLWNIPTYKGKMKRIAFQFTPYSW
  VRFEWKPASSLRRWLAVCGIILVFLLAELNTFYLKFVLWMPPEHYLVLLRLVFFVNVGGV
  AMREIYDFMDDPKPHKKLGPQAWLVAAITATELLIVVKYDPHTLTLSLPFYISQCWTLGS
  VLALTWTVWRFFLRDITLRYKETRWQKWQNKDDQGSTVGNGDQHPLGLDEDLLGPGVAEG
  EGAPTPN
• Function: Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine. Catalyzes the conversion of phosphatatidylethanolamine and does not act on phosphatidylcholine. Can utilize both phosphatidylethanolamine (PE) plasmalogen and diacyl PE as substrate and the latter is six times better utilized, indicating the importance of an ester linkage at the sn-1 position. Although it shows no sn-1 fatty acyl preference, exhibits significant preference towards docosahexaenoic acid (22:6n-3) compared with 18:1 or 20:4 at the sn-2 position.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of PS (R-HSA-1483101)
• BioCyc Pathway: MetaCyc:HS10846-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphatidylserine synthase 2 (PTDSS2).	[1]

3 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 Phosphatidylserine synthase 2 (PTDSS2).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Phosphatidylserine synthase 2 (PTDSS2).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Phosphatidylserine synthase 2 (PTDSS2).	[4]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] 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.
• [3] 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.
• [4] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.