Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6O0V51)

• DOT Name: Pyruvate carboxylase, mitochondrial (PC)
• Synonyms: EC 6.4.1.1; Pyruvic carboxylase; PCB
• Gene Name: PC
• Related Disease:
  Autism
  Beta-thalassemia major
  Myocardial infarction
  Pyruvate carboxylase deficiency disease
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  B-cell neoplasm
  Bipolar depression
  Bipolar disorder
  Bronchopulmonary dysplasia
  Cardiovascular disease
  Cervical cancer
  Cervical carcinoma
  Coagulation defect
  Colitis
  Disseminated intravascular coagulation
  Hepatocellular carcinoma
  Hereditary antithrombin deficiency
  Hyperglycemia
  Inflammatory bowel disease
  Inherited thrombophilia
  Lactic acidosis
  Liver cirrhosis
  Lung cancer
  Lupus
  Multiple sclerosis
  Neoplasm
  Nephropathy
  Non-small-cell lung cancer
  Systemic lupus erythematosus
  Thrombophilia
  Thyroid gland papillary carcinoma
  Tuberculosis
  Venous thromboembolism
  Burkitt lymphoma
  High blood pressure
  Pyruvate carboxylase deficiency, benign type
  Pyruvate carboxylase deficiency, infantile form
  Pyruvate carboxylase deficiency, severe neonatal type
  Breast cancer
  Breast carcinoma
  Hypoglycemia
  Intellectual disability
  Lung squamous cell carcinoma
  Obesity
  Type-1/2 diabetes
• UniProt ID: PYC_HUMAN
• PDB ID: 3BG3; 3BG9; 7WTA; 7WTB; 7WTC; 7WTD; 7WTE
• EC Number: 6.4.1.1
• Pfam ID: PF02785 ; PF00289 ; PF00364 ; PF02786 ; PF00682 ; PF02436
• Sequence:
  MLKFRTVHGGLRLLGIRRTSTAPAASPNVRRLEYKPIKKVMVANRGEIAIRVFRACTELG
  IRTVAIYSEQDTGQMHRQKADEAYLIGRGLAPVQAYLHIPDIIKVAKENNVDAVHPGYGF
  LSERADFAQACQDAGVRFIGPSPEVVRKMGDKVEARAIAIAAGVPVVPGTDAPITSLHEA
  HEFSNTYGFPIIFKAAYGGGGRGMRVVHSYEELEENYTRAYSEALAAFGNGALFVEKFIE
  KPRHIEVQILGDQYGNILHLYERDCSIQRRHQKVVEIAPAAHLDPQLRTRLTSDSVKLAK
  QVGYENAGTVEFLVDRHGKHYFIEVNSRLQVEHTVTEEITDVDLVHAQIHVAEGRSLPDL
  GLRQENIRINGCAIQCRVTTEDPARSFQPDTGRIEVFRSGEGMGIRLDNASAFQGAVISP
  HYDSLLVKVIAHGKDHPTAATKMSRALAEFRVRGVKTNIAFLQNVLNNQQFLAGTVDTQF
  IDENPELFQLRPAQNRAQKLLHYLGHVMVNGPTTPIPVKASPSPTDPVVPAVPIGPPPAG
  FRDILLREGPEGFARAVRNHPGLLLMDTTFRDAHQSLLATRVRTHDLKKIAPYVAHNFSK
  LFSMENWGGATFDVAMRFLYECPWRRLQELRELIPNIPFQMLLRGANAVGYTNYPDNVVF
  KFCEVAKENGMDVFRVFDSLNYLPNMLLGMEAAGSAGGVVEAAISYTGDVADPSRTKYSL
  QYYMGLAEELVRAGTHILCIKDMAGLLKPTACTMLVSSLRDRFPDLPLHIHTHDTSGAGV
  AAMLACAQAGADVVDVAADSMSGMTSQPSMGALVACTRGTPLDTEVPMERVFDYSEYWEG
  ARGLYAAFDCTATMKSGNSDVYENEIPGGQYTNLHFQAHSMGLGSKFKEVKKAYVEANQM
  LGDLIKVTPSSKIVGDLAQFMVQNGLSRAEAEAQAEELSFPRSVVEFLQGYIGVPHGGFP
  EPFRSKVLKDLPRVEGRPGASLPPLDLQALEKELVDRHGEEVTPEDVLSAAMYPDVFAHF
  KDFTATFGPLDSLNTRLFLQGPKIAEEFEVELERGKTLHIKALAVSDLNRAGQRQVFFEL
  NGQLRSILVKDTQAMKEMHFHPKALKDVKGQIGAPMPGKVIDIKVVAGAKVAKGQPLCVL
  SAMKMETVVTSPMEGTVRKVHVTKDMTLEGDDLILEIE
• Function: Pyruvate carboxylase catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. Catalyzes in a tissue specific manner, the initial reactions of glucose (liver, kidney) and lipid (adipose tissue, liver, brain) synthesis from pyruvate.
• KEGG Pathway:
  Citrate cycle (TCA cycle) (hsa00020)
  Pyruvate metabolism (hsa00620)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway:
  Defective HLCS causes multiple carboxylase deficiency (R-HSA-3371599)
  Gluconeogenesis (R-HSA-70263)
  Biotin transport and metabolism (R-HSA-196780)
• BioCyc Pathway: MetaCyc:HS10697-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Definitive	Genetic Variation	[1]
Beta-thalassemia major	DISW06BV	Definitive	Biomarker	[2]
Myocardial infarction	DIS655KI	Definitive	Altered Expression	[3]
Pyruvate carboxylase deficiency disease	DIS6000W	Definitive	Autosomal recessive	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
B-cell neoplasm	DISVY326	Strong	Posttranslational Modification	[8]
Bipolar depression	DISA75FU	Strong	Biomarker	[9]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[9]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Biomarker	[10]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[11]
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[12]
Cervical carcinoma	DIST4S00	Strong	Genetic Variation	[12]
Coagulation defect	DIS9X3H6	Strong	Altered Expression	[13]
Colitis	DISAF7DD	Strong	Biomarker	[14]
Disseminated intravascular coagulation	DISCAVOZ	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
Hereditary antithrombin deficiency	DIS37I0W	Strong	Biomarker	[17]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[18]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[14]
Inherited thrombophilia	DISFG8KS	Strong	Genetic Variation	[19]
Lactic acidosis	DISZI1ZK	Strong	Biomarker	[20]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[21]
Lung cancer	DISCM4YA	Strong	Biomarker	[22]
Lupus	DISOKJWA	Strong	Biomarker	[23]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[24]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[12]
Nephropathy	DISXWP4P	Strong	Altered Expression	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[25]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[26]
Thrombophilia	DISQR7U7	Strong	Genetic Variation	[27]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[28]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[29]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[30]
Burkitt lymphoma	DIS9D5XU	moderate	Biomarker	[31]
High blood pressure	DISY2OHH	moderate	Altered Expression	[32]
Pyruvate carboxylase deficiency, benign type	DIS6UQA2	Supportive	Autosomal recessive	[33]
Pyruvate carboxylase deficiency, infantile form	DISAZN64	Supportive	Autosomal recessive	[33]
Pyruvate carboxylase deficiency, severe neonatal type	DIS2KKHU	Supportive	Autosomal recessive	[33]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[34]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[34]
Hypoglycemia	DISRCKR7	Limited	Biomarker	[35]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[36]
Lung squamous cell carcinoma	DISXPIBD	Limited	Genetic Variation	[37]
Obesity	DIS47Y1K	Limited	Biomarker	[38]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[25]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
D-glucose	DMMG2TO	Investigative	Pyruvate carboxylase, mitochondrial (PC) increases the oxidation of D-glucose.	[54]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Pyruvate carboxylase, mitochondrial (PC).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Pyruvate carboxylase, mitochondrial (PC).	[50]

13 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 Pyruvate carboxylase, mitochondrial (PC).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pyruvate carboxylase, mitochondrial (PC).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pyruvate carboxylase, mitochondrial (PC).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pyruvate carboxylase, mitochondrial (PC).	[43]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Pyruvate carboxylase, mitochondrial (PC).	[44]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Pyruvate carboxylase, mitochondrial (PC).	[45]
Selenium	DM25CGV	Approved	Selenium increases the expression of Pyruvate carboxylase, mitochondrial (PC).	[46]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Pyruvate carboxylase, mitochondrial (PC).	[47]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Pyruvate carboxylase, mitochondrial (PC).	[48]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Pyruvate carboxylase, mitochondrial (PC).	[49]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Pyruvate carboxylase, mitochondrial (PC).	[51]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Pyruvate carboxylase, mitochondrial (PC).	[52]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Pyruvate carboxylase, mitochondrial (PC).	[53]

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