Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBBBV70)

DOT Name Methylmalonyl-CoA mutase, mitochondrial (MMUT)
Synonyms MCM; EC 5.4.99.2; Methylmalonyl-CoA isomerase
Gene Name MMUT
Related Disease
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency ( )
Advanced cancer ( )
Alzheimer disease ( )
Breast cancer ( )
Cardiac failure ( )
Cervical cancer ( )
Cervical carcinoma ( )
Cervical Intraepithelial neoplasia ( )
Colon carcinoma ( )
Congestive heart failure ( )
Dilated cardiomyopathy 1A ( )
Familial Alzheimer disease ( )
Gastric cancer ( )
Glioma ( )
Lung cancer ( )
Lung carcinoma ( )
Medulloblastoma ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Obesity ( )
Retinoblastoma ( )
Stomach cancer ( )
Transitional cell carcinoma ( )
Urothelial carcinoma ( )
Bone osteosarcoma ( )
Cardiomyopathy ( )
Clear cell renal carcinoma ( )
Hepatocellular carcinoma ( )
Influenza ( )
Laryngeal squamous cell carcinoma ( )
Meningioma ( )
Metastatic malignant neoplasm ( )
Nasopharyngeal carcinoma ( )
Osteosarcoma ( )
Renal cell carcinoma ( )
Vitamin B12-unresponsive methylmalonic acidemia type mut- ( )
Vitamin B12-unresponsive methylmalonic acidemia type mut0 ( )
Colorectal carcinoma ( )
Type-1/2 diabetes ( )
Cutaneous squamous cell carcinoma ( )
Inborn error of metabolism ( )
Matthew-Wood syndrome ( )
Megalencephaly-capillary malformation-polymicrogyria syndrome ( )
Neuroblastoma ( )
Pancreatic ductal carcinoma ( )
Thyroid gland papillary carcinoma ( )
Thyroid gland undifferentiated (anaplastic) carcinoma ( )
UniProt ID
MUTA_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2XIJ; 2XIQ; 3BIC; 8DYJ; 8DYL
EC Number
5.4.99.2
Pfam ID
PF02310 ; PF01642
Sequence
MLRAKNQLFLLSPHYLRQVKESSGSRLIQQRLLHQQQPLHPEWAALAKKQLKGKNPEDLI
WHTPEGISIKPLYSKRDTMDLPEELPGVKPFTRGPYPTMYTFRPWTIRQYAGFSTVEESN
KFYKDNIKAGQQGLSVAFDLATHRGYDSDNPRVRGDVGMAGVAIDTVEDTKILFDGIPLE
KMSVSMTMNGAVIPVLANFIVTGEEQGVPKEKLTGTIQNDILKEFMVRNTYIFPPEPSMK
IIADIFEYTAKHMPKFNSISISGYHMQEAGADAILELAYTLADGLEYSRTGLQAGLTIDE
FAPRLSFFWGIGMNFYMEIAKMRAGRRLWAHLIEKMFQPKNSKSLLLRAHCQTSGWSLTE
QDPYNNIVRTAIEAMAAVFGGTQSLHTNSFDEALGLPTVKSARIARNTQIIIQEESGIPK
VADPWGGSYMMECLTNDVYDAALKLINEIEEMGGMAKAVAEGIPKLRIEECAARRQARID
SGSEVIVGVNKYQLEKEDAVEVLAIDNTSVRNRQIEKLKKIKSSRDQALAERCLAALTEC
AASGDGNILALAVDASRARCTVGEITDALKKVFGEHKANDRMVSGAYRQEFGESKEITSA
IKRVHKFMEREGRRPRLLVAKMGQDGHDRGAKVIATGFADLGFDVDIGPLFQTPREVAQQ
AVDADVHAVGISTLAAGHKTLVPELIKELNSLGRPDILVMCGGVIPPQDYEFLFEVGVSN
VFGPGTRIPKAAVQVLDDIEKCLEKKQQSV
Function
Catalyzes the reversible isomerization of methylmalonyl-CoA (MMCoA) (generated from branched-chain amino acid metabolism and degradation of dietary odd chain fatty acids and cholesterol) to succinyl-CoA (3-carboxypropionyl-CoA), a key intermediate of the tricarboxylic acid cycle.
KEGG Pathway
Valine, leucine and isoleucine degradation (hsa00280 )
Glyoxylate and dicarboxylate metabolism (hsa00630 )
Propanoate metabolism (hsa00640 )
Metabolic pathways (hsa01100 )
Carbon metabolism (hsa01200 )
Cobalamin transport and metabolism (hsa04980 )
Reactome Pathway
Defective MUT causes MMAM (R-HSA-3359478 )
Propionyl-CoA catabolism (R-HSA-71032 )
Cobalamin (Cbl) metabolism (R-HSA-9759218 )
Defective MMAA causes MMA, cblA type (R-HSA-3359475 )
BioCyc Pathway
MetaCyc:HS07322-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency DISFKMDJ Definitive Autosomal recessive [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Alzheimer disease DISF8S70 Strong Biomarker [3]
Breast cancer DIS7DPX1 Strong Biomarker [4]
Cardiac failure DISDC067 Strong Genetic Variation [5]
Cervical cancer DISFSHPF Strong Biomarker [6]
Cervical carcinoma DIST4S00 Strong Biomarker [6]
Cervical Intraepithelial neoplasia DISXP757 Strong Biomarker [7]
Colon carcinoma DISJYKUO Strong Biomarker [8]
Congestive heart failure DIS32MEA Strong Genetic Variation [5]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Biomarker [9]
Familial Alzheimer disease DISE75U4 Strong Biomarker [10]
Gastric cancer DISXGOUK Strong Genetic Variation [11]
Glioma DIS5RPEH Strong Biomarker [12]
Lung cancer DISCM4YA Strong Biomarker [13]
Lung carcinoma DISTR26C Strong Biomarker [13]
Medulloblastoma DISZD2ZL Strong Biomarker [14]
Neoplasm DISZKGEW Strong Genetic Variation [15]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [16]
Obesity DIS47Y1K Strong Biomarker [17]
Retinoblastoma DISVPNPB Strong Biomarker [18]
Stomach cancer DISKIJSX Strong Genetic Variation [11]
Transitional cell carcinoma DISWVVDR Strong Biomarker [19]
Urothelial carcinoma DISRTNTN Strong Biomarker [19]
Bone osteosarcoma DIST1004 moderate Altered Expression [20]
Cardiomyopathy DISUPZRG moderate Biomarker [21]
Clear cell renal carcinoma DISBXRFJ moderate Biomarker [22]
Hepatocellular carcinoma DIS0J828 moderate Biomarker [23]
Influenza DIS3PNU3 moderate Genetic Variation [24]
Laryngeal squamous cell carcinoma DIS9UUVF moderate Altered Expression [25]
Meningioma DISPT4TG moderate Biomarker [26]
Metastatic malignant neoplasm DIS86UK6 moderate Biomarker [22]
Nasopharyngeal carcinoma DISAOTQ0 moderate Biomarker [27]
Osteosarcoma DISLQ7E2 moderate Altered Expression [20]
Renal cell carcinoma DISQZ2X8 moderate Biomarker [22]
Vitamin B12-unresponsive methylmalonic acidemia type mut- DISMWLB2 Supportive Autosomal recessive [28]
Vitamin B12-unresponsive methylmalonic acidemia type mut0 DISZR2TF Supportive Autosomal recessive [29]
Colorectal carcinoma DIS5PYL0 Disputed Genetic Variation [30]
Type-1/2 diabetes DISIUHAP Disputed Biomarker [31]
Cutaneous squamous cell carcinoma DIS3LXUG Limited Biomarker [32]
Inborn error of metabolism DISO5FAY Limited Biomarker [33]
Matthew-Wood syndrome DISA7HR7 Limited Biomarker [34]
Megalencephaly-capillary malformation-polymicrogyria syndrome DISAHLVO Limited Biomarker [35]
Neuroblastoma DISVZBI4 Limited Altered Expression [36]
Pancreatic ductal carcinoma DIS26F9Q Limited Biomarker [34]
Thyroid gland papillary carcinoma DIS48YMM Limited Biomarker [37]
Thyroid gland undifferentiated (anaplastic) carcinoma DISYBB1W Limited Altered Expression [38]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [39]
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18 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [40]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [41]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [42]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [43]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [44]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [45]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [46]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [47]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [48]
Selenium DM25CGV Approved Selenium decreases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [49]
Zidovudine DM4KI7O Approved Zidovudine increases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [44]
Gentamicin DMKINJO Approved Gentamicin affects the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [50]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [51]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [52]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [53]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [54]
G418 DMKTJBU Investigative G418 affects the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [50]
PMEA DMBKVJY Investigative PMEA increases the expression of Methylmalonyl-CoA mutase, mitochondrial (MMUT). [44]
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⏷ Show the Full List of 18 Drug(s)

References

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