Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5CQPZY)

• DOT Name: Acetyl-CoA carboxylase 1 (ACACA)
• Synonyms: ACC1; EC 6.4.1.2; Acetyl-Coenzyme A carboxylase alpha; ACC-alpha
• Gene Name: ACACA
• Related Disease:
  Non-alcoholic fatty liver disease
  Anorexia nervosa cachexia
  Anxiety
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiac failure
  Cardiovascular disease
  Coeliac disease
  Colorectal carcinoma
  Congestive heart failure
  Fatty liver disease
  Glioblastoma multiforme
  Hepatitis C virus infection
  Hepatocellular carcinoma
  High blood pressure
  Leukemia
  Lung cancer
  Lung carcinoma
  Major depressive disorder
  Mesothelioma
  Neoplasm
  Obesity
  Parkinson disease
  Polycystic ovarian syndrome
  Prostate cancer
  Systemic lupus erythematosus
  Tuberculosis
  Acute myelogenous leukaemia
  Adrenocortical carcinoma
  Gastric cancer
  Non-insulin dependent diabetes
  Prostate carcinoma
  Stomach cancer
  Acute myocardial infarction
  Anxiety disorder
  Aplasia cutis congenita
  Bipolar disorder
  Chronic graft versus host disease
  Chronic kidney disease
  Coronary heart disease
  Corpus callosum, agenesis of
  Inflammatory bowel disease
  Malignant pleural mesothelioma
  Metabolic disorder
  Non-small-cell lung cancer
  Type-1/2 diabetes
• UniProt ID: ACACA_HUMAN
• PDB ID: 2YL2; 3COJ; 4ASI; 6G2D; 6G2H; 6G2I
• EC Number: 6.4.1.2
• Pfam ID: PF08326 ; PF21385 ; PF02785 ; PF00289 ; PF00364 ; PF01039 ; PF02786
• Sequence:
  MDEPSPLAQPLELNQHSRFIIGSVSEDNSEDEISNLVKLDLLEEKEGSLSPASVGSDTLS
  DLGISSLQDGLALHIRSSMSGLHLVKQGRDRKKIDSQRDFTVASPAEFVTRFGGNKVIEK
  VLIANNGIAAVKCMRSIRRWSYEMFRNERAIRFVVMVTPEDLKANAEYIKMADHYVPVPG
  GPNNNNYANVELILDIAKRIPVQAVWAGWGHASENPKLPELLLKNGIAFMGPPSQAMWAL
  GDKIASSIVAQTAGIPTLPWSGSGLRVDWQENDFSKRILNVPQELYEKGYVKDVDDGLQA
  AEEVGYPVMIKASEGGGGKGIRKVNNADDFPNLFRQVQAEVPGSPIFVMRLAKQSRHLEV
  QILADQYGNAISLFGRDCSVQRRHQKIIEEAPATIATPAVFEHMEQCAVKLAKMVGYVSA
  GTVEYLYSQDGSFYFLELNPRLQVEHPCTEMVADVNLPAAQLQIAMGIPLYRIKDIRMMY
  GVSPWGDSPIDFEDSAHVPCPRGHVIAARITSENPDEGFKPSSGTVQELNFRSNKNVWGY
  FSVAAAGGLHEFADSQFGHCFSWGENREEAISNMVVALKELSIRGDFRTTVEYLIKLLET
  ESFQMNRIDTGWLDRLIAEKVQAERPDTMLGVVCGALHVADVSLRNSVSNFLHSLERGQV
  LPAHTLLNTVDVELIYEGVKYVLKVTRQSPNSYVVIMNGSCVEVDVHRLSDGGLLLSYDG
  SSYTTYMKEEVDRYRITIGNKTCVFEKENDPSVMRSPSAGKLIQYIVEDGGHVFAGQCYA
  EIEVMKMVMTLTAVESGCIHYVKRPGAALDPGCVLAKMQLDNPSKVQQAELHTGSLPRIQ
  STALRGEKLHRVFHYVLDNLVNVMNGYCLPDPFFSSKVKDWVERLMKTLRDPSLPLLELQ
  DIMTSVSGRIPPNVEKSIKKEMAQYASNITSVLCQFPSQQIANILDSHAATLNRKSEREV
  FFMNTQSIVQLVQRYRSGIRGHMKAVVMDLLRQYLRVETQFQNGHYDKCVFALREENKSD
  MNTVLNYIFSHAQVTKKNLLVTMLIDQLCGRDPTLTDELLNILTELTQLSKTTNAKVALR
  ARQVLIASHLPSYELRHNQVESIFLSAIDMYGHQFCIENLQKLILSETSIFDVLPNFFYH
  SNQVVRMAALEVYVRRAYIAYELNSVQHRQLKDNTCVVEFQFMLPTSHPNRGNIPTLNRM
  SFSSNLNHYGMTHVASVSDVLLDNSFTPPCQRMGGMVSFRTFEDFVRIFDEVMGCFSDSP
  PQSPTFPEAGHTSLYDEDKVPRDEPIHILNVAIKTDCDIEDDRLAAMFREFTQQNKATLV
  DHGIRRLTFLVAQKDFRKQVNYEVDRRFHREFPKFFTFRARDKFEEDRIYRHLEPALAFQ
  LELNRMRNFDLTAIPCANHKMHLYLGAAKVEVGTEVTDYRFFVRAIIRHSDLVTKEASFE
  YLQNEGERLLLEAMDELEVAFNNTNVRTDCNHIFLNFVPTVIMDPSKIEESVRSMVMRYG
  SRLWKLRVLQAELKINIRLTPTGKAIPIRLFLTNESGYYLDISLYKEVTDSRTAQIMFQA
  YGDKQGPLHGMLINTPYVTKDLLQSKRFQAQSLGTTYIYDIPEMFRQSLIKLWESMSTQA
  FLPSPPLPSDMLTYTELVLDDQGQLVHMNRLPGGNEIGMVAWKMTFKSPEYPEGRDIIVI
  GNDITYRIGSFGPQEDLLFLRASELARAEGIPRIYVSANSGARIGLAEEIRHMFHVAWVD
  PEDPYKGYRYLYLTPQDYKRVSALNSVHCEHVEDEGESRYKITDIIGKEEGIGPENLRGS
  GMIAGESSLAYNEIITISLVTCRAIGIGAYLVRLGQRTIQVENSHLILTGAGALNKVLGR
  EVYTSNNQLGGIQIMHNNGVTHCTVCDDFEGVFTVLHWLSYMPKSVHSSVPLLNSKDPID
  RIIEFVPTKTPYDPRWMLAGRPHPTQKGQWLSGFFDYGSFSEIMQPWAQTVVVGRARLGG
  IPVGVVAVETRTVELSIPADPANLDSEAKIIQQAGQVWFPDSAFKTYQAIKDFNREGLPL
  MVFANWRGFSGGMKDMYDQVLKFGAYIVDGLRECCQPVLVYIPPQAELRGGSWVVIDSSI
  NPRHMEMYADRESRGSVLEPEGTVEIKFRRKDLVKTMRRVDPVYIHLAERLGTPELSTAE
  RKELENKLKEREEFLIPIYHQVAVQFADLHDTPGRMQEKGVISDILDWKTSRTFFYWRLR
  RLLLEDLVKKKIHNANPELTDGQIQAMLRRWFVEVEGTVKAYVWDNNKDLAEWLEKQLTE
  EDGVHSVIEENIKCISRDYVLKQIRSLVQANPEVAMDSIIHMTQHISPTQRAEVIRILST
  MDSPST
• Function: Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis. This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA.
• Tissue Specificity: Expressed in brain, placenta, skeletal muscle, renal, pancreatic and adipose tissues; expressed at low level in pulmonary tissue; not detected in the liver.
• KEGG Pathway:
  Fatty acid biosynthesis (hsa00061)
  Pyruvate metabolism (hsa00620)
  Propanoate metabolism (hsa00640)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  AMPK sig.ling pathway (hsa04152)
  Insulin sig.ling pathway (hsa04910)
  Glucagon sig.ling pathway (hsa04922)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway:
  Biotin transport and metabolism (R-HSA-196780)
  Carnitine metabolism (R-HSA-200425)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Defective HLCS causes multiple carboxylase deficiency (R-HSA-3371599)
  Fatty acyl-CoA biosynthesis (R-HSA-75105)
  ChREBP activates metabolic gene expression (R-HSA-163765)
• BioCyc Pathway: MetaCyc:HS05598-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
Non-alcoholic fatty liver disease	DISDG1NL	Definitive	Altered Expression	[1]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Biomarker	[2]
Anxiety	DISIJDBA	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[7]
Coeliac disease	DISIY60C	Strong	Genetic Variation	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[9]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[10]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[13]
High blood pressure	DISY2OHH	Strong	Biomarker	[14]
Leukemia	DISNAKFL	Strong	Genetic Variation	[15]
Lung cancer	DISCM4YA	Strong	Posttranslational Modification	[16]
Lung carcinoma	DISTR26C	Strong	Posttranslational Modification	[16]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[17]
Mesothelioma	DISKWK9M	Strong	Altered Expression	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Obesity	DIS47Y1K	Strong	Biomarker	[20]
Parkinson disease	DISQVHKL	Strong	Biomarker	[21]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[22]
Prostate cancer	DISF190Y	Strong	Altered Expression	[23]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[24]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[25]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[26]
Adrenocortical carcinoma	DISZF4HX	moderate	Biomarker	[27]
Gastric cancer	DISXGOUK	moderate	Genetic Variation	[28]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Genetic Variation	[7]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[29]
Stomach cancer	DISKIJSX	moderate	Genetic Variation	[28]
Acute myocardial infarction	DISE3HTG	Limited	Genetic Variation	[30]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[3]
Aplasia cutis congenita	DISMDAYM	Limited	Posttranslational Modification	[31]
Bipolar disorder	DISAM7J2	Limited	Altered Expression	[32]
Chronic graft versus host disease	DIS1MM9J	Limited	Biomarker	[33]
Chronic kidney disease	DISW82R7	Limited	Genetic Variation	[34]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[35]
Corpus callosum, agenesis of	DISO9P40	Limited	Posttranslational Modification	[31]
Inflammatory bowel disease	DISGN23E	Limited	Biomarker	[36]
Malignant pleural mesothelioma	DIST2R60	Limited	Biomarker	[37]
Metabolic disorder	DIS71G5H	Limited	Biomarker	[13]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[38]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[39]

39 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 Acetyl-CoA carboxylase 1 (ACACA).	[40]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[42]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[43]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[44]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[45]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[46]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[48]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Acetyl-CoA carboxylase 1 (ACACA).	[49]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Acetyl-CoA carboxylase 1 (ACACA).	[50]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[51]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[52]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[54]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[55]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[56]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[57]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[58]
Zidovudine	DM4KI7O	Approved	Zidovudine affects the expression of Acetyl-CoA carboxylase 1 (ACACA).	[59]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[56]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[60]
Glucosamine	DM4ZLFD	Approved	Glucosamine increases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[62]
Orlistat	DMRJSP8	Approved	Orlistat decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[63]
OPC-34712	DMHG57U	Approved	OPC-34712 decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[66]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[67]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[68]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[71]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[75]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[77]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[78]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[79]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[80]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[81]
Oleic acid	DM54O1Z	Investigative	Oleic acid increases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[82]
Dorsomorphin	DMKYXJW	Investigative	Dorsomorphin decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[80]
T0901317	DMZQVDI	Investigative	T0901317 decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[83]
CITCO	DM0N634	Investigative	CITCO increases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[85]
Ganoderic acid A	DM42EVG	Investigative	Ganoderic acid A decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[86]
Raffinose	DMVHDOS	Investigative	Raffinose decreases the expression of Acetyl-CoA carboxylase 1 (ACACA).	[87]

14 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 Acetyl-CoA carboxylase 1 (ACACA).	[47]
Ethanol	DMDRQZU	Approved	Ethanol decreases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[53]
Sertraline	DM0FB1J	Approved	Sertraline increases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[61]
Crizotinib	DM4F29C	Approved	Crizotinib increases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[64]
Nilotinib	DM7HXWT	Approved	Nilotinib increases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[64]
Nicotinamide	DMUPE07	Approved	Nicotinamide decreases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[65]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[69]
Curcumin	DMQPH29	Phase 3	Curcumin increases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[70]
URSOLIC ACID	DM4SOAW	Phase 2	URSOLIC ACID increases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[72]
Beta-caryophyllene	DM7583A	Phase 2	Beta-caryophyllene increases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[73]
TAK-114	DMTXE19	Phase 1	TAK-114 increases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[74]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[76]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[46]
OXYRESVERATROL	DMN7S4L	Investigative	OXYRESVERATROL increases the phosphorylation of Acetyl-CoA carboxylase 1 (ACACA).	[84]

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