Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4FJEAR)

DOT Name Thyroid receptor-interacting protein 11 (TRIP11)
Synonyms TR-interacting protein 11; TRIP-11; Clonal evolution-related gene on chromosome 14 protein; Golgi-associated microtubule-binding protein 210; GMAP-210; Trip230
Gene Name TRIP11
Related Disease
Achondrogenesis type IA ( )
Achondrogenesis ( )
Kidney cancer ( )
Neoplasm ( )
Odontochondrodysplasia ( )
Renal carcinoma ( )
Renal cell carcinoma ( )
Retinoblastoma ( )
Fetal growth restriction ( )
Acute myelogenous leukaemia ( )
Enterovirus infection ( )
Lymphoid neoplasm ( )
UniProt ID
TRIPB_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSSWLGGLGSGLGQSLGQVGGSLASLTGQISNFTKDMLMEGTEEVEAELPDSRTKEIEAI
HAILRSENERLKKLCTDLEEKHEASEIQIKQQSTSYRNQLQQKEVEISHLKARQIALQDQ
LLKLQSAAQSVPSGAGVPATTASSSFAYGISHHPSAFHDDDMDFGDIISSQQEINRLSNE
VSRLESEVGHWRHIAQTSKAQGTDNSDQSEICKLQNIIKELKQNRSQEIDDHQHEMSVLQ
NAHQQKLTEISRRHREELSDYEERIEELENLLQQGGSGVIETDLSKIYEMQKTIQVLQIE
KVESTKKMEQLEDKIKDINKKLSSAENDRDILRREQEQLNVEKRQIMEECENLKLECSKL
QPSAVKQSDTMTEKERILAQSASVEEVFRLQQALSDAENEIMRLSSLNQDNSLAEDNLKL
KMRIEVLEKEKSLLSQEKEELQMSLLKLNNEYEVIKSTATRDISLDSELHDLRLNLEAKE
QELNQSISEKETLIAEIEELDRQNQEATKHMILIKDQLSKQQNEGDSIISKLKQDLNDEK
KRVHQLEDDKMDITKELDVQKEKLIQSEVALNDLHLTKQKLEDKVENLVDQLNKSQESNV
SIQKENLELKEHIRQNEEELSRIRNELMQSLNQDSNSNFKDTLLKEREAEVRNLKQNLSE
LEQLNENLKKVAFDVKMENEKLVLACEDVRHQLEECLAGNNQLSLEKNTIVETLKMEKGE
IEAELCWAKKRLLEEANKYEKTIEELSNARNLNTSALQLEHEHLIKLNQKKDMEIAELKK
NIEQMDTDHKETKDVLSSSLEEQKQLTQLINKKEIFIEKLKERSSKLQEELDKYSQALRK
NEILRQTIEEKDRSLGSMKEENNHLQEELERLREEQSRTAPVADPKTLDSVTELASEVSQ
LNTIKEHLEEEIKHHQKIIEDQNQSKMQLLQSLQEQKKEMDEFRYQHEQMNATHTQLFLE
KDEEIKSLQKTIEQIKTQLHEERQDIQTDNSDIFQETKVQSLNIENGSEKHDLSKAETER
LVKGIKERELEIKLLNEKNISLTKQIDQLSKDEVGKLTQIIQQKDLEIQALHARISSTSH
TQDVVYLQQQLQAYAMEREKVFAVLNEKTRENSHLKTEYHKMMDIVAAKEAALIKLQDEN
KKLSTRFESSGQDMFRETIQNLSRIIREKDIEIDALSQKCQTLLAVLQTSSTGNEAGGVN
SNQFEELLQERDKLKQQVKKMEEWKQQVMTTVQNMQHESAQLQEELHQLQAQVLVDSDNN
SKLQVDYTGLIQSYEQNETKLKNFGQELAQVQHSIGQLCNTKDLLLGKLDIISPQLSSAS
LLTPQSAECLRASKSEVLSESSELLQQELEELRKSLQEKDATIRTLQENNHRLSDSIAAT
SELERKEHEQTDSEIKQLKEKQDVLQKLLKEKDLLIKAKSDQLLSSNENFTNKVNENELL
RQAVTNLKERILILEMDIGKLKGENEKIVETYRGKETEYQALQETNMKFSMMLREKEFEC
HSMKEKALAFEQLLKEKEQGKTGELNQLLNAVKSMQEKTVVFQQERDQVMLALKQKQMEN
TALQNEVQRLRDKEFRSNQELERLRNHLLESEDSYTREALAAEDREAKLRKKVTVLEEKL
VSSSNAMENASHQASVQVESLQEQLNVVSKQRDETALQLSVSQEQVKQYALSLANLQMVL
EHFQQEEKAMYSAELEKQKQLIAEWKKNAENLEGKVISLQECLDEANAALDSASRLTEQL
DVKEEQIEELKRQNELRQEMLDDVQKKLMSLANSSEGKVDKVLMRNLFIGHFHTPKNQRH
EVLRLMGSILGVRREEMEQLFHDDQGGVTRWMTGWLGGGSKSVPNTPLRPNQQSVVNSSF
SELFVKFLETESHPSIPPPKLSVHDMKPLDSPGRRKRDTNAPESFKDTAESRSGRRTDVN
PFLAPRSAAVPLINPAGLGPGGPGHLLLKPISDVLPTFTPLPALPDNSAGVVLKDLLKQ
Function
Is a membrane tether required for vesicle tethering to Golgi. Has an essential role in the maintenance of Golgi structure and function. It is required for efficient anterograde and retrograde trafficking in the early secretory pathway, functioning at both the ER-to-Golgi intermediate compartment (ERGIC) and Golgi complex. Binds the ligand binding domain of the thyroid receptor (THRB) in the presence of triiodothyronine and enhances THRB-modulated transcription.
Tissue Specificity
Highly expressed in pancreas, muscle, heart, testis, peripheral blood leukocytes, and in several leukemia cell lines. Detected at intermediate levels in placenta and kidney, and at low levels in brain and lung. Isoform 1 and isoform 2 are expressed in articular chondrocytes .
Reactome Pathway
Intra-Golgi traffic (R-HSA-6811438 )
Signaling by FLT3 fusion proteins (R-HSA-9703465 )
Intraflagellar transport (R-HSA-5620924 )

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Achondrogenesis type IA DISQS0N4 Definitive Autosomal recessive [1]
Achondrogenesis DISCBQB8 Strong Genetic Variation [2]
Kidney cancer DISBIPKM Strong Biomarker [3]
Neoplasm DISZKGEW Strong Altered Expression [3]
Odontochondrodysplasia DIS7OXG7 Strong Genetic Variation [2]
Renal carcinoma DISER9XT Strong Biomarker [3]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [3]
Retinoblastoma DISVPNPB Strong Biomarker [4]
Fetal growth restriction DIS5WEJ5 moderate Genetic Variation [5]
Acute myelogenous leukaemia DISCSPTN Limited Biomarker [6]
Enterovirus infection DISH2UDP Limited Genetic Variation [7]
Lymphoid neoplasm DIS9S8BC Limited Genetic Variation [8]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Thyroid receptor-interacting protein 11 (TRIP11). [9]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Thyroid receptor-interacting protein 11 (TRIP11). [10]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Thyroid receptor-interacting protein 11 (TRIP11). [11]
Nicotine DMWX5CO Approved Nicotine increases the expression of Thyroid receptor-interacting protein 11 (TRIP11). [12]
Clorgyline DMCEUJD Approved Clorgyline increases the expression of Thyroid receptor-interacting protein 11 (TRIP11). [13]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Thyroid receptor-interacting protein 11 (TRIP11). [15]
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⏷ Show the Full List of 6 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Thyroid receptor-interacting protein 11 (TRIP11). [14]
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References

1 Lethal skeletal dysplasia in mice and humans lacking the golgin GMAP-210. N Engl J Med. 2010 Jan 21;362(3):206-16. doi: 10.1056/NEJMoa0900158.
2 Hypomorphic mutations of TRIP11 cause odontochondrodysplasia.JCI Insight. 2019 Feb 7;4(3):e124701. doi: 10.1172/jci.insight.124701.
3 The significance of TRIP11 and T3 signalling pathway in renal cancer progression and survival of patients.Endokrynol Pol. 2017;68(6):631-641. doi: 10.5603/EP.a2017.0052. Epub 2017 Oct 12.
4 Thyroid hormone, T3-dependent phosphorylation and translocation of Trip230 from the Golgi complex to the nucleus.Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4443-8. doi: 10.1073/pnas.96.8.4443.
5 The phenotype range of achondrogenesis 1A.Am J Med Genet A. 2013 Oct;161A(10):2554-8. doi: 10.1002/ajmg.a.36106. Epub 2013 Aug 16.
6 Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution.Blood. 1997 Dec 1;90(11):4271-7.
7 A novel enterovirus species identified from severe diarrheal goats.PLoS One. 2017 Apr 4;12(4):e0174600. doi: 10.1371/journal.pone.0174600. eCollection 2017.
8 A novel TRIP11-FLT3 fusion in a patient with a myeloid/lymphoid neoplasm with eosinophilia.Cancer Genet. 2017 Oct;216-217:10-15. doi: 10.1016/j.cancergen.2017.05.001. Epub 2017 May 10.
9 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
10 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
11 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
12 Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
13 Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
14 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
15 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.