Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMZD4PW)

• DOT Name: Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2)
• Synonyms: EC 6.2.1.5; ATP-specific succinyl-CoA synthetase subunit beta; A-SCS; Succinyl-CoA synthetase beta-A chain; SCS-betaA
• Gene Name: SUCLA2
• Related Disease:
  Epilepsy
  Leigh syndrome
  Age-related macular degeneration
  Alzheimer disease 3
  Arteriosclerosis
  Atherosclerosis
  Aural atresia, congenital
  Cardiac failure
  Cognitive impairment
  Congestive heart failure
  Creutzfeldt Jacob disease
  Crohn disease
  Dementia
  Depression
  Helminth infection
  Herpes simplex infection
  Leukopenia
  Methylmalonic acidemia
  Mitochondrial DNA depletion syndrome
  Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria
  Mitochondrial encephalomyopathy
  Movement disorder
  Neuroblastoma
  Non-insulin dependent diabetes
  Obesity
  Parkinson disease
  Retinoblastoma
  Trichohepatoenteric syndrome
  Tuberculosis
  Vascular dementia
  Dystonia
  Frontotemporal dementia
  Amyloidosis
  Erythropoietic protoporphyria
  Lactic acidosis
  Lewy body dementia
  Nervous system disease
  X-linked sideroblastic anemia 1
• UniProt ID: SUCB1_HUMAN
• PDB ID: 6G4Q
• EC Number: 6.2.1.5
• Pfam ID: PF08442 ; PF00549
• Sequence:
  MAASMFYGRLVAVATLRNHRPRTAQRAAAQVLGSSGLFNNHGLQVQQQQQRNLSLHEYMS
  MELLQEAGVSVPKGYVAKSPDEAYAIAKKLGSKDVVIKAQVLAGGRGKGTFESGLKGGVK
  IVFSPEEAKAVSSQMIGKKLFTKQTGEKGRICNQVLVCERKYPRREYYFAITMERSFQGP
  VLIGSSHGGVNIEDVAAESPEAIIKEPIDIEEGIKKEQALQLAQKMGFPPNIVESAAENM
  VKLYSLFLKYDATMIEINPMVEDSDGAVLCMDAKINFDSNSAYRQKKIFDLQDWTQEDER
  DKDAAKANLNYIGLDGNIGCLVNGAGLAMATMDIIKLHGGTPANFLDVGGGATVHQVTEA
  FKLITSDKKVLAILVNIFGGIMRCDVIAQGIVMAVKDLEIKIPVVVRLQGTRVDDAKALI
  ADSGLKILACDDLDEAARMVVKLSEIVTLAKQAHVDVKFQLPI
• Function: ATP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit.
• Tissue Specificity: Widely expressed. Not expressed in liver and lung.
• KEGG Pathway:
  Citrate cycle (TCA cycle) (hsa00020)
  Propanoate metabolism (hsa00640)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
• Reactome Pathway: Citric acid cycle (TCA cycle) (R-HSA-71403)
• BioCyc Pathway: MetaCyc:ENSG00000136143-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epilepsy	DISBB28L	Definitive	Genetic Variation	[1]
Leigh syndrome	DISWQU45	Definitive	Autosomal recessive	[2]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[3]
Alzheimer disease 3	DISVT69G	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[5]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[5]
Aural atresia, congenital	DISCP7UV	Strong	Biomarker	[6]
Cardiac failure	DISDC067	Strong	Biomarker	[7]
Cognitive impairment	DISH2ERD	Strong	Biomarker	[8]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[7]
Creutzfeldt Jacob disease	DISCB6RX	Strong	Biomarker	[9]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[10]
Dementia	DISXL1WY	Strong	Biomarker	[11]
Depression	DIS3XJ69	Strong	Biomarker	[12]
Helminth infection	DIS7CGKY	Strong	Altered Expression	[13]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[14]
Leukopenia	DISJMBMM	Strong	Genetic Variation	[10]
Methylmalonic acidemia	DISHY8VB	Strong	Genetic Variation	[15]
Mitochondrial DNA depletion syndrome	DISIGZSM	Strong	Altered Expression	[16]
Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria	DIS57FI7	Strong	Autosomal recessive	[17]
Mitochondrial encephalomyopathy	DISA6PTN	Strong	Genetic Variation	[18]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[19]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[20]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[21]
Obesity	DIS47Y1K	Strong	Biomarker	[22]
Parkinson disease	DISQVHKL	Strong	Biomarker	[23]
Retinoblastoma	DISVPNPB	Strong	Genetic Variation	[24]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[25]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[26]
Vascular dementia	DISVO82H	Strong	Altered Expression	[27]
Dystonia	DISJLFGW	moderate	Biomarker	[28]
Frontotemporal dementia	DISKYHXL	moderate	Biomarker	[29]
Amyloidosis	DISHTAI2	Limited	Biomarker	[30]
Erythropoietic protoporphyria	DISH4BY0	Limited	Genetic Variation	[31]
Lactic acidosis	DISZI1ZK	Limited	Altered Expression	[32]
Lewy body dementia	DISAE66J	Limited	Biomarker	[33]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[34]
X-linked sideroblastic anemia 1	DISWBQC7	Limited	Genetic Variation	[31]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2) affects the response to substance of Paclitaxel.	[45]
Vinblastine	DM5TVS3	Approved	Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2) affects the response to substance of Vinblastine.	[45]

8 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 Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2).	[39]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2).	[43]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2).	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Succinate--CoA ligase subunit beta, mitochondrial (SUCLA2).	[42]

References

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