Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ2AEW0)

• DOT Name: Dual oxidase 1 (DUOX1)
• Synonyms: EC 1.11.1.-; EC 1.6.3.1; Large NOX 1; Long NOX 1; NADPH thyroid oxidase 1; Thyroid oxidase 1
• Gene Name: DUOX1
• Related Disease:
  Advanced cancer
  Amyloidosis
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Cerebral infarction
  Congenital hypothyroidism
  Congestive heart failure
  Diabetic kidney disease
  Epilepsy
  Graves disease
  Hyperglycemia
  Inflammatory bowel disease
  Liver cancer
  Lung cancer
  Lupus
  Metabolic disorder
  Neoplasm
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
  Psoriasis
  Stroke
  Systemic lupus erythematosus
  Systemic sclerosis
  Thyroid tumor
  Tuberculosis
  Vascular disease
  Chronic obstructive pulmonary disease
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  High blood pressure
  Lung carcinoma
  Type-1 diabetes
  Prostate cancer
  Prostate carcinoma
  Abdominal aortic aneurysm
  Adenocarcinoma
  Adult glioblastoma
  Chronic granulomatous disease
  Coronary atherosclerosis
  Coronary heart disease
  Gastric cancer
  Glioblastoma multiforme
  Lung neoplasm
  Myocardial infarction
  Stomach cancer
  Thyroid gland papillary carcinoma
• UniProt ID: DUOX1_HUMAN
• PDB ID: 7D3E; 7D3F
• EC Number: 1.11.1.-; 1.6.3.1
• Pfam ID: PF03098 ; PF00036 ; PF13499 ; PF08022 ; PF01794 ; PF08030
• Sequence:
  MGFCLALAWTLLVGAWTPLGAQNPISWEVQRFDGWYNNLMEHRWGSKGSRLQRLVPASYA
  DGVYQPLGEPHLPNPRDLSNTISRGPAGLASLRNRTVLGVFFGYHVLSDLVSVETPGCPA
  EFLNIRIPPGDPMFDPDQRGDVVLPFQRSRWDPETGRSPSNPRDPANQVTGWLDGSAIYG
  SSHSWSDALRSFSRGQLASGPDPAFPRDSQNPLLMWAAPDPATGQNGPRGLYAFGAERGN
  REPFLQALGLLWFRYHNLWAQRLARQHPDWEDEELFQHARKRVIATYQNIAVYEWLPSFL
  QKTLPEYTGYRPFLDPSISSEFVAASEQFLSTMVPPGVYMRNASCHFQGVINRNSSVSRA
  LRVCNSYWSREHPSLQSAEDVDALLLGMASQIAEREDHVLVEDVRDFWPGPLKFSRTDHL
  ASCLQRGRDLGLPSYTKARAALGLSPITRWQDINPALSRSNDTVLEATAALYNQDLSWLE
  LLPGGLLESHRDPGPLFSTIVLEQFVRLRDGDRYWFENTRNGLFSKKEIEEIRNTTLQDV
  LVAVINIDPSALQPNVFVWHKGDPCPQPRQLSTEGLPACAPSVVRDYFEGSGFGFGVTIG
  TLCCFPLVSLLSAWIVARLRMRNFKRLQGQDRQSIVSEKLVGGMEALEWQGHKEPCRPVL
  VYLQPGQIRVVDGRLTVLRTIQLQPPQKVNFVLSSNRGRRTLLLKIPKEYDLVLLFNLEE
  ERQALVENLRGALKESGLSIQEWELREQELMRAAVTREQRRHLLETFFRHLFSQVLDINQ
  ADAGTLPLDSSQKVREALTCELSRAEFAESLGLKPQDMFVESMFSLADKDGNGYLSFREF
  LDILVVFMKGSPEEKSRLMFRMYDFDGNGLISKDEFIRMLRSFIEISNNCLSKAQLAEVV
  ESMFRESGFQDKEELTWEDFHFMLRDHNSELRFTQLCVKGVEVPEVIKDLCRRASYISQD
  MICPSPRVSARCSRSDIETELTPQRLQCPMDTDPPQEIRRRFGKKVTSFQPLLFTEAHRE
  KFQRSCLHQTVQQFKRFIENYRRHIGCVAVFYAIAGGLFLERAYYYAFAAHHTGITDTTR
  VGIILSRGTAASISFMFSYILLTMCRNLITFLRETFLNRYVPFDAAVDFHRLIASTAIVL
  TVLHSVGHVVNVYLFSISPLSVLSCLFPGLFHDDGSELPQKYYWWFFQTVPGLTGVVLLL
  ILAIMYVFASHHFRRRSFRGFWLTHHLYILLYVLLIIHGSFALIQLPRFHIFFLVPAIIY
  GGDKLVSLSRKKVEISVVKAELLPSGVTHLRFQRPQGFEYKSGQWVRIACLALGTTEYHP
  FTLTSAPHEDTLSLHIRAAGPWTTRLREIYSAPTGDRCARYPKLYLDGPFGEGHQEWHKF
  EVSVLVGGGIGVTPFASILKDLVFKSSVSCQVFCKKIYFIWVTRTQRQFEWLADIIREVE
  ENDHQDLVSVHIYITQLAEKFDLRTTMLYICERHFQKVLNRSLFTGLRSITHFGRPPFEP
  FFNSLQEVHPQVRKIGVFSCGPPGMTKNVEKACQLINRQDRTHFSHHYENF
• Function: Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain.
• Tissue Specificity: Expressed in thyrocytes and tracheal surface epithelial cells (at protein level). Expressed in thyroid, trachea, bronchium, and to a lower extent, in placenta, testis, prostate, pancreas and heart.
• KEGG Pathway: Thyroid hormone synthesis (hsa04918)
• Reactome Pathway: Thyroxine biosynthesis (R-HSA-209968)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Amyloidosis	DISHTAI2	Strong	Altered Expression	[2]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[4]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[4]
Cardiac failure	DISDC067	Strong	Altered Expression	[5]
Cerebral infarction	DISR1WNP	Strong	Altered Expression	[6]
Congenital hypothyroidism	DISL5XVU	Strong	Biomarker	[7]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[5]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[8]
Epilepsy	DISBB28L	Strong	Altered Expression	[9]
Graves disease	DISU4KOQ	Strong	Biomarker	[10]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[11]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[12]
Liver cancer	DISDE4BI	Strong	Altered Expression	[4]
Lung cancer	DISCM4YA	Strong	Biomarker	[13]
Lupus	DISOKJWA	Strong	Biomarker	[14]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[16]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[17]
Psoriasis	DIS59VMN	Strong	Biomarker	[18]
Stroke	DISX6UHX	Strong	Biomarker	[11]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[14]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[19]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[20]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[21]
Vascular disease	DISVS67S	Strong	Altered Expression	[19]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Altered Expression	[22]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[23]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[24]
High blood pressure	DISY2OHH	moderate	Altered Expression	[25]
Lung carcinoma	DISTR26C	moderate	Biomarker	[26]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[27]
Prostate cancer	DISF190Y	Disputed	Biomarker	[28]
Prostate carcinoma	DISMJPLE	Disputed	Biomarker	[28]
Abdominal aortic aneurysm	DISD06OF	Limited	Biomarker	[29]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[30]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[28]
Chronic granulomatous disease	DIS9ZR24	Limited	Genetic Variation	[31]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[32]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[32]
Gastric cancer	DISXGOUK	Limited	Biomarker	[33]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[28]
Lung neoplasm	DISVARNB	Limited	Posttranslational Modification	[30]
Myocardial infarction	DIS655KI	Limited	Altered Expression	[34]
Stomach cancer	DISKIJSX	Limited	Biomarker	[33]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Dual oxidase 1 (DUOX1).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dual oxidase 1 (DUOX1).	[37]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Dual oxidase 1 (DUOX1).	[38]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Dual oxidase 1 (DUOX1).	[38]
Selenium	DM25CGV	Approved	Selenium increases the expression of Dual oxidase 1 (DUOX1).	[39]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Dual oxidase 1 (DUOX1).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Dual oxidase 1 (DUOX1).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Dual oxidase 1 (DUOX1).	[42]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Dual oxidase 1 (DUOX1).	[43]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Dual oxidase 1 (DUOX1).	[44]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Dual oxidase 1 (DUOX1).	[45]

References

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