Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSZ1ZCL)

• DOT Name: Serine racemase (SRR)
• Synonyms: EC 5.1.1.18; D-serine ammonia-lyase; D-serine dehydratase; EC 4.3.1.18; L-serine ammonia-lyase; L-serine dehydratase; EC 4.3.1.17
• Gene Name: SRR
• UniProt ID: SRR_HUMAN
• PDB ID: 3L6B; 3L6R; 5X2L; 6SLH; 6ZSP; 6ZUJ; 7NBC; 7NBD; 7NBF; 7NBG; 7NBH
• EC Number: 4.3.1.17; 4.3.1.18; 5.1.1.18
• Pfam ID: PF00291
• Sequence:
  MCAQYCISFADVEKAHINIRDSIHLTPVLTSSILNQLTGRNLFFKCELFQKTGSFKIRGA
  LNAVRSLVPDALERKPKAVVTHSSGNHGQALTYAAKLEGIPAYIVVPQTAPDCKKLAIQA
  YGASIVYCEPSDESRENVAKRVTEETEGIMVHPNQEPAVIAGQGTIALEVLNQVPLVDAL
  VVPVGGGGMLAGIAITVKALKPSVKVYAAEPSNADDCYQSKLKGKLMPNLYPPETIADGV
  KSSIGLNTWPIIRDLVDDIFTVTEDEIKCATQLVWERMKLLIEPTAGVGVAAVLSQHFQT
  VSPEVKNICIVLSGGNVDLTSSITWVKQAERPASYQSVSV
• Function: Catalyzes the synthesis of D-serine from L-serine. D-serine is a key coagonist with glutamate at NMDA receptors. Has dehydratase activity towards both L-serine and D-serine.
• Tissue Specificity: Brain: expressed at high levels in hippocampus and corpus callosum, intermediate levels in substantia nigra and caudate, and low levels in amygdala, thalamus, and subthalamic nuclei. Expressed in heart, skeletal muscle, kidney and liver.
• KEGG Pathway:
  Glycine, serine and threonine metabolism (hsa00260)
  D-Amino acid metabolism (hsa00470)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Serine biosynthesis (R-HSA-977347)
• BioCyc Pathway: MetaCyc:HS09614-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Serine racemase (SRR).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine racemase (SRR).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine racemase (SRR).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Serine racemase (SRR).	[4]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Serine racemase (SRR).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Serine racemase (SRR).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Serine racemase (SRR).	[8]

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 Serine racemase (SRR).	[5]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] 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.
• [6] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.