General Information of Drug Off-Target (DOT) (ID: OTG6CYJ0)

DOT Name TOG array regulator of axonemal microtubules protein 1 (TOGARAM1)
Synonyms Crescerin-1; Protein FAM179B
Gene Name TOGARAM1
Related Disease
Advanced cancer ( )
Glioma ( )
Joubert syndrome 37 ( )
Neoplasm ( )
Non-hodgkin lymphoma ( )
Ciliopathy ( )
UniProt ID
TGRM1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF21040
Sequence
MAAAPSALLLLPPFPVLSTYRLQSRSRPSAPETDDSRVGGIMRGEKNYYFRGAAGDHGSC
PTTTSPLASALLMPSEAVSSSWSESGGGLSGGDEEDTRLLQLLRTARDPSEAFQALQAAL
PRRGGRLGFPRRKEALYRALGRVLVEGGSDEKRLCLQLLSDVLRGQGEAGQLEEAFSLAL
LPQLVVSLREENPALRKDALQILHICLKRSPGEVLRTLIQQGLESTDARLRASTALLLPI
LLTTEDLLLGLDLTEVIISLARKLGDQETEEESETAFSALQQIGERLGQDRFQSYISRLP
SALRRHYNRRLESQFGSQVPYYLELEASGFPEDPLPCAVTLSNSNLKFGIIPQELHSRLL
DQEDYKNRTQAVEELKQVLGKFNPSSTPHSSLVGFISLLYNLLDDSNFKVVHGTLEVLHL
LVIRLGEQVQQFLGPVIAASVKVLADNKLVIKQEYMKIFLKLMKEVGPQQVLCLLLEHLK
HKHSRVREEVVNICICSLLTYPSEDFDLPKLSFDLAPALVDSKRRVRQAALEAFAVLASS
MGSGKTSILFKAVDTVELQDNGDGVMNAVQARLARKTLPRLTEQGFVEYAVLMPSSAGGR
SNHLAHGADTDWLLAGNRTQSAHCHCGDHVRDSMHIYGSYSPTICTRRVLSAGKGKNKLP
WENEQPGIMGENQTSTSKDIEQFSTYDFIPSAKLKLSQGMPVNDDLCFSRKRVSRNLFQN
SRDFNPDCLPLCAAGTTGTHQTNLSGKCAQLGFSQICGKTGSVGSDLQFLGTTSSHQEKV
YASLNFGSKTQQTFGSQTECTSSNGQNPSPGAYILPSYPVSSPRTSPKHTSPLIISPKKS
QDNSVNFSNSWPLKSFEGLSKPSPQKKLVSQKSSDPTGRNHGENSQEKPPVQLTPALVRS
PSSRRGLNGTKPVPPIPRGISLLPDKADLSTVGHKKKEPDDIWKCEKDSLPIDLSELNFK
DKDLDQEEMHSSLRSLRNSAAKKRAKLSGSTSDLESPDSAMKLDLTMDSPSLSSSPNINS
YSESGVYSQESLTSSLSTTPQGKRIMSDIFPTFGSKPCPTRLSSAKKKISHIAEQSPSAG
SSSNPQQISSFDFTTTKALSEDSVVVVGKGVFGSLSSAPATCSQSVISSVENGDTFSIKQ
SIEPPSGIYGRSVQQNISSYLDVENEKDAKVSISKSTYNKMRQKRKEEKELFHNKDCEKK
EKNSWERMRHTGTEKMASESETPTGAISQYKERMPSVTHSPEIMDLSELRPFSKPEIALT
EALRLLADEDWEKKIEGLNFIRCLAAFHSEILNTKLHETNFAVVQEVKNLRSGVSRAAVV
CLSDLFTYLKKSMDQELDTTVKVLLHKAGESNTFIREDVDKALRAMVNNVTPARAVVSLI
NGGQRYYGRKMLFFMMCHPNFEKMLEKYVPSKDLPYIKDSVRNLQQKGLGEIPLDTPSAK
GRRSHTGSVGNTRSSSVSRDAFNSAERAVTEVREVTRKSVPRNSLESAEYLKLITGLLNA
KDFRDRINGIKQLLSDTENNQDLVVGNIVKIFDAFKSRLHDSNSKVNLVALETMHKMIPL
LRDHLSPIINMLIPAIVDNNLNSKNPGIYAAATNVVQALSQHVDNYLLLQPFCTKAQFLN
GKAKQDMTEKLADIVTELYQRKPHATEQKVLVVLWHLLGNMTNSGSLPGAGGNIRTATAK
LSKALFAQMGQNLLNQAASQPPHIKKSLEELLDMTILNEL
Function
Involved in ciliogenesis. It is required for appropriate acetylation and polyglutamylation of ciliary microtubules, and regulation of cilium length. Interacts with microtubules and promotes microtubule polymerization via its HEAT repeat domains, especially those in TOG region 2 and 4.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Genetic Variation [1]
Glioma DIS5RPEH Strong Genetic Variation [2]
Joubert syndrome 37 DIS5AGN8 Strong Autosomal recessive [3]
Neoplasm DISZKGEW Strong Biomarker [4]
Non-hodgkin lymphoma DISS2Y8A Strong Genetic Variation [1]
Ciliopathy DIS10G4I Limited Autosomal recessive [5]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of TOG array regulator of axonemal microtubules protein 1 (TOGARAM1). [6]
------------------------------------------------------------------------------------
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 TOG array regulator of axonemal microtubules protein 1 (TOGARAM1). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of TOG array regulator of axonemal microtubules protein 1 (TOGARAM1). [8]
Demecolcine DMCZQGK Approved Demecolcine increases the expression of TOG array regulator of axonemal microtubules protein 1 (TOGARAM1). [9]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of TOG array regulator of axonemal microtubules protein 1 (TOGARAM1). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of TOG array regulator of axonemal microtubules protein 1 (TOGARAM1). [11]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of TOG array regulator of axonemal microtubules protein 1 (TOGARAM1). [12]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 Drug(s)

References

1 A polymorphism at the microRNA binding site in the 3' untranslated region of C14orf101 is associated with non-Hodgkin lymphoma overall survival.Cancer Genet. 2014 Apr;207(4):141-6. doi: 10.1016/j.cancergen.2014.03.007. Epub 2014 Mar 22.
2 GOLGA7 rs11337, a Polymorphism at the MicroRNA Binding Site, Is Associated with Glioma Prognosis.Mol Ther Nucleic Acids. 2019 Dec 6;18:56-65. doi: 10.1016/j.omtn.2019.08.006. Epub 2019 Aug 14.
3 Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome. J Clin Invest. 2020 Aug 3;130(8):4423-4439. doi: 10.1172/JCI131656.
4 TOG-tubulin binding specificity promotes microtubule dynamics and mitotic spindle formation.J Cell Biol. 2017 Jun 5;216(6):1641-1657. doi: 10.1083/jcb.201610090. Epub 2017 May 16.
5 Biallelic mutations in the TOGARAM1 gene cause a novel primary ciliopathy. J Med Genet. 2021 Aug;58(8):526-533. doi: 10.1136/jmedgenet-2020-106833. Epub 2020 Aug 3.
6 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
7 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.
8 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
9 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
10 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
11 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
12 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.