Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5NCAZN)

• DOT Name: Serine hydroxymethyltransferase, mitochondrial (SHMT2)
• Synonyms: SHMT; EC 2.1.2.1; Glycine hydroxymethyltransferase; Serine methylase
• Gene Name: SHMT2
• Related Disease:
  Hepatitis B virus infection
  Acute erythroid leukemia
  Anemia
  Autism
  Digestive system neoplasm
  Glioma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Intrahepatic cholangiocarcinoma
  Lung cancer
  Lung carcinoma
  Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities
  Non-hodgkin lymphoma
  Osteoarthritis
  Parkinson disease
  Carcinoma of liver and intrahepatic biliary tract
  Colon cancer
  Colon carcinoma
  Complex neurodevelopmental disorder
  Liver cancer
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Gastric cancer
  Neuroblastoma
  Non-small-cell lung cancer
  Stomach cancer
• UniProt ID: GLYM_HUMAN
• PDB ID: 4PVF; 5V7I; 5X3V; 6DK3; 6H3C; 6M5O; 6QVG; 6QVL; 6R8F; 7BYI; 8AQL; 8FJT; 8FJU; 8QI7; 8SSJ
• EC Number: 2.1.2.1
• Pfam ID: PF00464
• Sequence:
  MLYFSLFWAARPLQRCGQLVRMAIRAQHSNAAQTQTGEANRGWTGQESLSDSDPEMWELL
  QREKDRQCRGLELIASENFCSRAALEALGSCLNNKYSEGYPGKRYYGGAEVVDEIELLCQ
  RRALEAFDLDPAQWGVNVQPYSGSPANLAVYTALLQPHDRIMGLDLPDGGHLTHGYMSDV
  KRISATSIFFESMPYKLNPKTGLIDYNQLALTARLFRPRLIIAGTSAYARLIDYARMREV
  CDEVKAHLLADMAHISGLVAAKVIPSPFKHADIVTTTTHKTLRGARSGLIFYRKGVKAVD
  PKTGREIPYTFEDRINFAVFPSLQGGPHNHAIAAVAVALKQACTPMFREYSLQVLKNARA
  MADALLERGYSLVSGGTDNHLVLVDLRPKGLDGARAERVLELVSITANKNTCPGDRSAIT
  PGGLRLGAPALTSRQFREDDFRRVVDFIDEGVNIGLEVKSKTAKLQDFKSFLLKDSETSQ
  RLANLRQRVEQFARAFPMPGFDEH
• Function: Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis. Serine provides the major source of folate one-carbon in cells by catalyzing the transfer of one carbon from serine to tetrahydrofolate. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway via its role in glycine and tetrahydrofolate metabolism: thymidylate biosynthesis is required to prevent uracil accumulation in mtDNA. Also required for mitochondrial translation by producing 5,10-methylenetetrahydrofolate; 5,10-methylenetetrahydrofolate providing methyl donors to produce the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs. Associates with mitochondrial DNA. In addition to its role in mitochondria, also plays a role in the deubiquitination of target proteins as component of the BRISC complex: required for IFNAR1 deubiquitination by the BRISC complex.
• KEGG Pathway:
  Glycine, serine and threonine metabolism (hsa00260)
  Glyoxylate and dicarboxylate metabolism (hsa00630)
  One carbon pool by folate (hsa00670)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
  Biosynthesis of cofactors (hsa01240)
  Antifolate resistance (hsa01523)
• Reactome Pathway:
  RHOG GTPase cycle (R-HSA-9013408)
  Metabolism of folate and pterines (R-HSA-196757)
• BioCyc Pathway: MetaCyc:HS00049-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis B virus infection	DISLQ2XY	Definitive	Altered Expression	[1]
Acute erythroid leukemia	DISZFC1O	Strong	Biomarker	[2]
Anemia	DISTVL0C	Strong	Biomarker	[3]
Autism	DISV4V1Z	Strong	Genetic Variation	[4]
Digestive system neoplasm	DISPOJCT	Strong	Altered Expression	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[6]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[8]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[9]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[9]
Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities	DIS75JVJ	Strong	Autosomal recessive	[10]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[11]
Osteoarthritis	DIS05URM	Strong	Biomarker	[12]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[13]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[1]
Colon cancer	DISVC52G	moderate	Biomarker	[14]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[14]
Complex neurodevelopmental disorder	DISB9AFI	Moderate	Autosomal recessive	[15]
Liver cancer	DISDE4BI	moderate	Biomarker	[1]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[5]
Breast cancer	DIS7DPX1	Limited	Biomarker	[16]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[16]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[5]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[17]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[18]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[19]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[17]

22 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 hydroxymethyltransferase, mitochondrial (SHMT2).	[20]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[27]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[28]
Marinol	DM70IK5	Approved	Marinol affects the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[29]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[30]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[31]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[32]
Dopamine	DMPGUCF	Approved	Dopamine increases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[33]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin decreases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[37]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[39]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[40]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[41]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Serine hydroxymethyltransferase, mitochondrial (SHMT2).	[42]

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 hydroxymethyltransferase, mitochondrial (SHMT2).	[35]

References

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• [17] High Expression of Serine Hydroxymethyltransferase 2 Indicates Poor Prognosis of Gastric Cancer Patients.Med Sci Monit. 2019 Oct 3;25:7430-7438. doi: 10.12659/MSM.917435.
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