Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3ELHIJ)

• DOT Name: Thyroglobulin (TG)
• Synonyms: Tg
• Gene Name: TG
• Related Disease:
  Autoimmune disease
  Behcet disease
  Euthyroid goiter
  Adenoma
  Advanced cancer
  Anxiety disorder
  Ataxia-telangiectasia
  Autoimmune disease, susceptibility to, 6
  Carcinoma
  Coeliac disease
  Congenital hypothyroidism
  Depression
  Familial thyroid dyshormonogenesis 1
  Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors
  Herpes simplex infection
  Hyperthyroidism
  Medullary thyroid gland carcinoma
  Multinodular goiter
  Non-small-cell lung cancer
  Pendred syndrome
  Pituitary dwarfism
  Poorly differentiated thyroid gland carcinoma
  STAT3-related early-onset multisystem autoimmune disease
  Systemic lupus erythematosus
  Thyroid dyshormonogenesis 3
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Thyroiditis
  Type-1 diabetes
  Type-1/2 diabetes
  Vitiligo
  Endemic goiter
  Hypothyroidism
  Thyrotoxicosis
  Familial thyroid dyshormonogenesis
  Inflammatory bowel disease
  Adenocarcinoma
  Crohn disease
  Rheumatoid arthritis
  Trichorhinophalangeal syndrome type II
  Turner syndrome
• UniProt ID: THYG_HUMAN
• PDB ID: 6SCJ; 7B75
• Pfam ID: PF00135 ; PF07699 ; PF00086
• Sequence:
  MALVLEIFTLLASICWVSANIFEYQVDAQPLRPCELQRETAFLKQADYVPQCAEDGSFQT
  VQCQNDGRSCWCVGANGSEVLGSRQPGRPVACLSFCQLQKQQILLSGYINSTDTSYLPQC
  QDSGDYAPVQCDVQQVQCWCVDAEGMEVYGTRQLGRPKRCPRSCEIRNRRLLHGVGDKSP
  PQCSAEGEFMPVQCKFVNTTDMMIFDLVHSYNRFPDAFVTFSSFQRRFPEVSGYCHCADS
  QGRELAETGLELLLDEIYDTIFAGLDLPSTFTETTLYRILQRRFLAVQSVISGRFRCPTK
  CEVERFTATSFGHPYVPSCRRNGDYQAVQCQTEGPCWCVDAQGKEMHGTRQQGEPPSCAE
  GQSCASERQQALSRLYFGTSGYFSQHDLFSSPEKRWASPRVARFATSCPPTIKELFVDSG
  LLRPMVEGQSQQFSVSENLLKEAIRAIFPSRGLARLALQFTTNPKRLQQNLFGGKFLVNV
  GQFNLSGALGTRGTFNFSQFFQQLGLASFLNGGRQEDLAKPLSVGLDSNSSTGTPEAAKK
  DGTMNKPTVGSFGFEINLQENQNALKFLASLLELPEFLLFLQHAISVPEDVARDLGDVME
  TVLSSQTCEQTPERLFVPSCTTEGSYEDVQCFSGECWCVNSWGKELPGSRVRGGQPRCPT
  DCEKQRARMQSLMGSQPAGSTLFVPACTSEGHFLPVQCFNSECYCVDAEGQAIPGTRSAI
  GKPKKCPTPCQLQSEQAFLRTVQALLSNSSMLPTLSDTYIPQCSTDGQWRQVQCNGPPEQ
  VFELYQRWEAQNKGQDLTPAKLLVKIMSYREAASGNFSLFIQSLYEAGQQDVFPVLSQYP
  SLQDVPLAALEGKRPQPRENILLEPYLFWQILNGQLSQYPGSYSDFSTPLAHFDLRNCWC
  VDEAGQELEGMRSEPSKLPTCPGSCEEAKLRVLQFIRETEEIVSASNSSRFPLGESFLVA
  KGIRLRNEDLGLPPLFPPREAFAEQFLRGSDYAIRLAAQSTLSFYQRRRFSPDDSAGASA
  LLRSGPYMPQCDAFGSWEPVQCHAGTGHCWCVDEKGGFIPGSLTARSLQIPQCPTTCEKS
  RTSGLLSSWKQARSQENPSPKDLFVPACLETGEYARLQASGAGTWCVDPASGEELRPGSS
  SSAQCPSLCNVLKSGVLSRRVSPGYVPACRAEDGGFSPVQCDQAQGSCWCVMDSGEEVPG
  TRVTGGQPACESPRCPLPFNASEVVGGTILCETISGPTGSAMQQCQLLCRQGSWSVFPPG
  PLICSLESGRWESQLPQPRACQRPQLWQTIQTQGHFQLQLPPGKMCSADYADLLQTFQVF
  ILDELTARGFCQIQVKTFGTLVSIPVCNNSSVQVGCLTRERLGVNVTWKSRLEDIPVASL
  PDLHDIERALVGKDLLGRFTDLIQSGSFQLHLDSKTFPAETIRFLQGDHFGTSPRTWFGC
  SEGFYQVLTSEASQDGLGCVKCPEGSYSQDEECIPCPVGFYQEQAGSLACVPCPVGRTTI
  SAGAFSQTHCVTDCQRNEAGLQCDQNGQYRASQKDRGSGKAFCVDGEGRRLPWWETEAPL
  EDSQCLMMQKFEKVPESKVIFDANAPVAVRSKVPDSEFPVMQCLTDCTEDEACSFFTVST
  TEPEISCDFYAWTSDNVACMTSDQKRDALGNSKATSFGSLRCQVKVRSHGQDSPAVYLKK
  GQGSTTTLQKRFEPTGFQNMLSGLYNPIVFSASGANLTDAHLFCLLACDRDLCCDGFVLT
  QVQGGAIICGLLSSPSVLLCNVKDWMDPSEAWANATCPGVTYDQESHQVILRLGDQEFIK
  SLTPLEGTQDTFTNFQQVYLWKDSDMGSRPESMGCRKDTVPRPASPTEAGLTTELFSPVD
  LNQVIVNGNQSLSSQKHWLFKHLFSAQQANLWCLSRCVQEHSFCQLAEITESASLYFTCT
  LYPEAQVCDDIMESNAQGCRLILPQMPKALFRKKVILEDKVKNFYTRLPFQKLMGISIRN
  KVPMSEKSISNGFFECERRCDADPCCTGFGFLNVSQLKGGEVTCLTLNSLGIQMCSEENG
  GAWRILDCGSPDIEVHTYPFGWYQKPIAQNNAPSFCPLVVLPSLTEKVSLDSWQSLALSS
  VVVDPSIRHFDVAHVSTAATSNFSAVRDLCLSECSQHEACLITTLQTQPGAVRCMFYADT
  QSCTHSLQGQNCRLLLREEATHIYRKPGISLLSYEASVPSVPISTHGRLLGRSQAIQVGT
  SWKQVDQFLGVPYAAPPLAERRFQAPEPLNWTGSWDASKPRASCWQPGTRTSTSPGVSED
  CLYLNVFIPQNVAPNASVLVFFHNTMDREESEGWPAIDGSFLAAVGNLIVVTASYRVGVF
  GFLSSGSGEVSGNWGLLDQVAALTWVQTHIRGFGGDPRRVSLAADRGGADVASIHLLTAR
  ATNSQLFRRAVLMGGSALSPAAVISHERAQQQAIALAKEVSCPMSSSQEVVSCLRQKPAN
  VLNDAQTKLLAVSGPFHYWGPVIDGHFLREPPARALKRSLWVEVDLLIGSSQDDGLINRA
  KAVKQFEESRGRTSSKTAFYQALQNSLGGEDSDARVEAAATWYYSLEHSTDDYASFSRAL
  ENATRDYFIICPIIDMASAWAKRARGNVFMYHAPENYGHGSLELLADVQFALGLPFYPAY
  EGQFSLEEKSLSLKIMQYFSHFIRSGNPNYPYEFSRKVPTFATPWPDFVPRAGGENYKEF
  SELLPNRQGLKKADCSFWSKYISSLKTSADGAKGGQSAESEEEELTAGSGLREDLLSLQE
  PGSKTYSK
• Function: Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3). The synthesis of T3 and T4 involves iodination of selected tyrosine residues of TG/thyroglobulin followed by their oxidative coupling in the thyroid follicle lumen. Following TG re-internalization and lysosomal-mediated proteolysis, T3 and T4 are released from the polypeptide backbone leading to their secretion into the bloodstream. One dimer produces 7 thyroid hormone molecules.
• Tissue Specificity: Specifically expressed in the thyroid gland.
• KEGG Pathway:
  Thyroid hormone synthesis (hsa04918)
  Autoimmune thyroid disease (hsa05320)
• BioCyc Pathway: MetaCyc:ENSG00000042832-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Definitive	Biomarker	[1]
Behcet disease	DISSYMBS	Definitive	Biomarker	[2]
Euthyroid goiter	DISLRPYJ	Definitive	Genetic Variation	[3]
Adenoma	DIS78ZEV	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[6]
Ataxia-telangiectasia	DISP3EVR	Strong	Genetic Variation	[7]
Autoimmune disease, susceptibility to, 6	DISHNUXI	Strong	Genetic Variation	[8]
Carcinoma	DISH9F1N	Strong	Biomarker	[9]
Coeliac disease	DISIY60C	Strong	Biomarker	[10]
Congenital hypothyroidism	DISL5XVU	Strong	Genetic Variation	[11]
Depression	DIS3XJ69	Strong	Biomarker	[6]
Familial thyroid dyshormonogenesis 1	DISAXKZN	Strong	GermlineCausalMutation	[12]
Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors	DISVJILV	Strong	Genetic Variation	[13]
Herpes simplex infection	DISL1SAV	Strong	Altered Expression	[14]
Hyperthyroidism	DISX87ZH	Strong	Biomarker	[15]
Medullary thyroid gland carcinoma	DISHBL3K	Strong	Biomarker	[16]
Multinodular goiter	DISZQJH7	Strong	Biomarker	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Pendred syndrome	DISZ1MU8	Strong	Genetic Variation	[18]
Pituitary dwarfism	DISI019B	Strong	Biomarker	[19]
Poorly differentiated thyroid gland carcinoma	DISPBT1J	Strong	Altered Expression	[20]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	Strong	Genetic Variation	[8]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[21]
Thyroid dyshormonogenesis 3	DISGJDXU	Strong	Autosomal recessive	[22]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Altered Expression	[23]
Thyroiditis	DISTCV24	Strong	Biomarker	[24]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[25]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[26]
Vitiligo	DISR05SL	Strong	Genetic Variation	[27]
Endemic goiter	DISQ7HHE	moderate	Genetic Variation	[13]
Hypothyroidism	DISR0H6D	moderate	Genetic Variation	[28]
Thyrotoxicosis	DISWH7BV	moderate	Biomarker	[29]
Familial thyroid dyshormonogenesis	DISALTXN	Supportive	Autosomal recessive	[30]
Inflammatory bowel disease	DISGN23E	Disputed	Biomarker	[31]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[32]
Crohn disease	DIS2C5Q8	Limited	Biomarker	[33]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[34]
Trichorhinophalangeal syndrome type II	DISW4YZ1	Limited	Genetic Variation	[35]
Turner syndrome	DIS2035C	Limited	Biomarker	[36]

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 Thyroglobulin (TG).	[37]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Thyroglobulin (TG).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Thyroglobulin (TG).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Thyroglobulin (TG).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Thyroglobulin (TG).	[41]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Thyroglobulin (TG).	[42]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Thyroglobulin (TG).	[41]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Thyroglobulin (TG).	[44]
Efavirenz	DMC0GSJ	Approved	Efavirenz increases the expression of Thyroglobulin (TG).	[44]
Propylthiouracil	DM6D7N8	Approved	Propylthiouracil decreases the expression of Thyroglobulin (TG).	[45]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone decreases the expression of Thyroglobulin (TG).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Thyroglobulin (TG).	[47]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) increases the expression of Thyroglobulin (TG).	[48]
PGJ2	DMR2LTC	Investigative	PGJ2 increases the expression of Thyroglobulin (TG).	[48]
PGD2	DMYDW6J	Investigative	PGD2 increases the expression of Thyroglobulin (TG).	[48]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the secretion of Thyroglobulin (TG).	[43]

References

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