Details of Drug Off-Target (DOT)

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

• DOT Name: Corrinoid adenosyltransferase MMAB (MMAB)
• Synonyms: EC 2.5.1.-; ATP:co(I)rrinoid adenosyltransferase MMAB; Methylmalonic aciduria type B protein
• Gene Name: MMAB
• Related Disease:
  Methylmalonic aciduria, cblB type
  Advanced cancer
  Anxiety
  Depression
  Early-onset non-syndromic cataract
  Methylmalonic acidemia
  Mevalonate kinase deficiency
  Non-insulin dependent diabetes
  Triple negative breast cancer
  Vitamin B12-responsive methylmalonic acidemia
  Type-1 diabetes
  Type-1/2 diabetes
• UniProt ID: MMAB_HUMAN
• PDB ID: 2IDX; 6D5K; 6D5X; 7RUT; 7RUU; 7RUV
• EC Number: 2.5.1.-
• Pfam ID: PF01923
• Sequence:
  MAVCGLGSRLGLGSRLGLRGCFGAARLLYPRFQSRGPQGVEDGDRPQPSSKTPRIPKIYT
  KTGDKGFSSTFTGERRPKDDQVFEAVGTTDELSSAIGFALELVTEKGHTFAEELQKIQCT
  LQDVGSALATPCSSAREAHLKYTTFKAGPILELEQWIDKYTSQLPPLTAFILPSGGKISS
  ALHFCRAVCRRAERRVVPLVQMGETDANVAKFLNRLSDYLFTLARYAAMKEGNQEKIYMK
  NDPSAESEGL
• Function: Converts cob(I)alamin to adenosylcobalamin (adenosylcob(III)alamin), a coenzyme for methylmalonyl-CoA mutase, therefore participates in the final step of the vitamin B12 conversion. Generates adenosylcobalamin (AdoCbl) and directly delivers the cofactor to MUT in a transfer that is stimulated by ATP-binding to MMAB and gated by MMAA (Probable).
• Tissue Specificity: Expressed in liver and skeletal muscle.
• KEGG Pathway:
  Porphyrin metabolism (hsa00860)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
  Cobalamin transport and metabolism (hsa04980)
• Reactome Pathway:
  Cobalamin (Cbl) metabolism (R-HSA-9759218)
  Defective MMAB causes MMA, cblB type (R-HSA-3359471)
• BioCyc Pathway: MetaCyc:HS13779-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Methylmalonic aciduria, cblB type	DISXSKG7	Definitive	Autosomal recessive	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Anxiety	DISIJDBA	Strong	Genetic Variation	[3]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Early-onset non-syndromic cataract	DIS4VPS0	Strong	Genetic Variation	[5]
Methylmalonic acidemia	DISHY8VB	Strong	CausalMutation	[6]
Mevalonate kinase deficiency	DISSTRVK	Strong	Genetic Variation	[7]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[4]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[8]
Vitamin B12-responsive methylmalonic acidemia	DISXEKO2	Strong	Genetic Variation	[9]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[10]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[11]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[16]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[17]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[18]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[19]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[20]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[21]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[27]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Corrinoid adenosyltransferase MMAB (MMAB).	[28]

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 Corrinoid adenosyltransferase MMAB (MMAB).	[23]

References

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