General Information of Drug Off-Target (DOT) (ID: OTI2OOFN)

DOT Name Kinetochore-associated protein 1 (KNTC1)
Synonyms Rough deal homolog; HsROD; Rod; hRod
Gene Name KNTC1
Related Disease
Asthma ( )
Gastric cancer ( )
Stomach cancer ( )
Acute intermittent hepatic porphyria ( )
Advanced cancer ( )
Chagas disease ( )
Chromosomal disorder ( )
Esophageal squamous cell carcinoma ( )
MALT lymphoma ( )
Marginal zone lymphoma ( )
Myositis disease ( )
Retinitis pigmentosa ( )
Optic nerve disorder ( )
Disease of orbital part of eye adnexa ( )
Inflammation ( )
Lymphoproliferative syndrome ( )
Uveitis ( )
UniProt ID
KNTC1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7QPG
Pfam ID
PF10493
Sequence
MWNDIELLTNDDTGSGYLSVGSRKEHGTALYQVDLLVKISSEKASLNPKIQACSLSDGFI
IVADQSVILLDSICRSLQLHLVFDTEVDVVGLCQEGKFLLVGERSGNLHLIHVTSKQTLL
TNAFVQKANDENRRTYQNLVIEKDGSNEGTYYMLLLTYSGFFCITNLQLLKIQQAIENVD
FSTAKKLQGQIKSSFISTENYHTLGCLSLVAGDLASEVPVIIGGTGNCAFSKWEPDSSKK
GMTVKNLIDAEIIKGAKKFQLIDNLLFVLDTDNVLSLWDIYTLTPVWNWPSLHVEEFLLT
TEADSPSSVTWQGITNLKLIALTASANKKMKNLMVYSLPTMEILYSLEVSSVSSLVQTGI
STDTIYLLEGVCKNDPKLSEDSVSVLVLRCLTEALPENRLSRLLHKHRFAEAESFAIQFG
LDVELVYKVKSNHILEKLALSSVDASEQTEWQQLVDDAKENLHKIQDDEFVVNYCLKAQW
ITYETTQEMLNYAKTRLLKKEDKTALIYSDGLKEVLRAHAKLTTFYGAFGPEKFSGSSWI
EFLNNEDDLKDIFLQLKEGNLVCAQYLWLRHRANFESRFDVKMLESLLNSMSASVSLQKL
CPWFKNDVIPFVRRTVPEGQIILAKWLEQAARNLELTDKANWPENGLQLAEIFFTAEKTD
ELGLASSWHWISLKDYQNTEEVCQLRTLVNNLRELITLHRKYNCKLALSDFEKENTTTIV
FRMFDKVLAPELIPSILEKFIRVYMREHDLQEEELLLLYIEDLLNRCSSKSTSLFETAWE
AKAMAVIACLSDTDLIFDAVLKIMYAAVVPWSAAVEQLVKQHLEMDHPKVKLLQESYKLM
EMKKLLRGYGIREVNLLNKEIMRVVRYILKQDVPSSLEDALKVAQAFMLSDDEIYSLRII
DLIDREQGEDCLLLLKSLPPAEAEKTAERVIIWARLALQEEPDHSKEGKAWRMSVAKTSV
DILKILCDIQKDNLQKKDECEEMLKLFKEVASLQENFEVFLSFEDYSNSSLVADLREQHI
KAHEVAQAKHKPGSTPEPIAAEVRSPSMESKLHRQALALQMSKQELEAELTLRALKDGNI
KTALKKCSDLFKYHCNADTGKLLFLTCQKLCQMLADNVPVTVPVGLNLPSMIHDLASQAA
TICSPDFLLDALELCKHTLMAVELSRQCQMDDCGILMKASFGTHKDPYEEWSYSDFFSED
GIVLESQMVLPVIYELISSLVPLAESKRYPLESTSLPYCSLNEGDGLVLPVINSISALLQ
NLQESSQWELALRFVVGSFGTCLQHSVSNFMNATLSEKLFGETTLVKSRHVVMELKEKAV
IFIRENATTLLHKVFNCRLVDLDLALGYCTLLPQKDVFENLWKLIDKAWQNYDKILAISL
VGSELASLYQEIEMGLKFRELSTDAQWGIRLGKLGISFQPVFRQHFLTKKDLIKALVENI
DMDTSLILEYCSTFQLDCDAVLQLFIETLLHNTNAGQGQGDASMDSAKRRHPKLLAKALE
MVPLLTSTKDLVISLSGILHKLDPYDYEMIEVVLKVIERADEKITNININQALSILKHLK
SYRRISPPVDLEYQYMLEHVITLPSAAQTRLPFHLIFFGTAQNFWKILSTELSEESFPTL
LLISKLMKFSLDTLYVSTAKHVFEKKLKPKLLKLTQAKSSTLINKEITKITQTIESCLLS
IVNPEWAVAIAISLAQDIPEGSFKISALKFCLYLAERWLQNIPSQDEKREKAEALLKKLH
IQYRRSGTEAVLIAHKLNTEEYLRVIGKPAHLIVSLYEHPSINQRIQNSSGTDYPDIHAA
AKEIAEVNEINLEKVWDMLLEKWLCPSTKPGEKPSELFELQEDEALRRVQYLLLSRPIDY
SSRMLFVFATSTTTTLGMHQLTFAHRTRALQCLFYLADKETIESLFKKPIEEVKSYLRCI
TFLASFETLNIPITYELFCSSPKEGMIKGLWKNHSHESMAVRLVTELCLEYKIYDLQLWN
GLLQKLLGFNMIPYLRKVLKAISSIHSLWQVPYFSKAWQRVIQIPLLSASCPLSPDQLSD
CSESLIAVLECPVSGDLDLIGVARQYIQLELPAFALACLMLMPHSEKRHQQIKNFLGSCD
PQVILKQLEEHMNTGQLAGFSHQIRSLILNNIINKKEFGILAKTKYFQMLKMHAMNTNNI
TELVNYLANDLSLDEASVLITEYSKHCGKPVPPDTAPCEILKMFLSGLS
Function
Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex.
Tissue Specificity High expression in testis.
Reactome Pathway
Separation of Sister Chromatids (R-HSA-2467813 )
Resolution of Sister Chromatid Cohesion (R-HSA-2500257 )
RHO GTPases Activate Formins (R-HSA-5663220 )
Mitotic Prometaphase (R-HSA-68877 )
EML4 and NUDC in mitotic spindle formation (R-HSA-9648025 )
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444 )

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Asthma DISW9QNS Definitive Biomarker [1]
Gastric cancer DISXGOUK Definitive Genetic Variation [2]
Stomach cancer DISKIJSX Definitive Genetic Variation [2]
Acute intermittent hepatic porphyria DIS80J7E Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Chagas disease DIS8KNVF Strong Biomarker [5]
Chromosomal disorder DISM5BB5 Strong Biomarker [6]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [4]
MALT lymphoma DIS1AVVE Strong Biomarker [7]
Marginal zone lymphoma DISLZ4AO Strong Biomarker [8]
Myositis disease DISCIXF0 Strong Biomarker [9]
Retinitis pigmentosa DISCGPY8 Strong Altered Expression [10]
Optic nerve disorder DISSOQM8 moderate Biomarker [11]
Disease of orbital part of eye adnexa DISGWPWX Limited Biomarker [12]
Inflammation DISJUQ5T Limited Biomarker [13]
Lymphoproliferative syndrome DISMVL8O Limited Biomarker [7]
Uveitis DISV0RYS Limited Biomarker [13]
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⏷ Show the Full List of 17 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Kinetochore-associated protein 1 (KNTC1). [14]
Arsenic DMTL2Y1 Approved Arsenic increases the methylation of Kinetochore-associated protein 1 (KNTC1). [20]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Kinetochore-associated protein 1 (KNTC1). [31]
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19 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Kinetochore-associated protein 1 (KNTC1). [15]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Kinetochore-associated protein 1 (KNTC1). [16]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Kinetochore-associated protein 1 (KNTC1). [17]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Kinetochore-associated protein 1 (KNTC1). [18]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Kinetochore-associated protein 1 (KNTC1). [19]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Kinetochore-associated protein 1 (KNTC1). [21]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Kinetochore-associated protein 1 (KNTC1). [21]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Kinetochore-associated protein 1 (KNTC1). [22]
Folic acid DMEMBJC Approved Folic acid affects the expression of Kinetochore-associated protein 1 (KNTC1). [23]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Kinetochore-associated protein 1 (KNTC1). [24]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Kinetochore-associated protein 1 (KNTC1). [25]
Dasatinib DMJV2EK Approved Dasatinib decreases the expression of Kinetochore-associated protein 1 (KNTC1). [26]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Kinetochore-associated protein 1 (KNTC1). [27]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Kinetochore-associated protein 1 (KNTC1). [28]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Kinetochore-associated protein 1 (KNTC1). [29]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Kinetochore-associated protein 1 (KNTC1). [30]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Kinetochore-associated protein 1 (KNTC1). [32]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Kinetochore-associated protein 1 (KNTC1). [33]
geraniol DMS3CBD Investigative geraniol decreases the expression of Kinetochore-associated protein 1 (KNTC1). [34]
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⏷ Show the Full List of 19 Drug(s)

References

1 Distinguishing IgG4-Related Ophthalmic Disease From Graves Orbitopathy.Ophthalmic Plast Reconstr Surg. 2019 Mar/Apr;35(2):170-176. doi: 10.1097/IOP.0000000000001201.
2 Novel somatic frameshift mutations of genes related to cell cycle and DNA damage response in gastric and colorectal cancers with microsatellite instability.Tumori. 2010 Nov-Dec;96(6):1004-9.
3 Frequency and distribution of CD4+CXCR5+ follicular B helper Tcells within involved tissues in IgG4related ophthalmic disease.Mol Med Rep. 2017 Dec;16(6):9512-9520. doi: 10.3892/mmr.2017.7780. Epub 2017 Oct 12.
4 shRNAmediated knockdown of KNTC1 suppresses cell viability and induces apoptosis in esophageal squamous cell carcinoma.Int J Oncol. 2019 Mar;54(3):1053-1060. doi: 10.3892/ijo.2019.4672. Epub 2019 Jan 3.
5 The genetic immunization with paraflagellar rod protein-2 fused to the HSP70 confers protection against late Trypanosoma cruzi infection.Vaccine. 2006 Nov 30;24(49-50):7046-55. doi: 10.1016/j.vaccine.2006.07.006. Epub 2006 Jul 21.
6 Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors.Genes Chromosomes Cancer. 1999 Jan;24(1):30-41.
7 Immunophenotypic profiles for distinguishing orbital mucosa-associated lymphoid tissue lymphoma from benign lymphoproliferative tumors.Jpn J Ophthalmol. 2017 Jul;61(4):354-360. doi: 10.1007/s10384-017-0513-1. Epub 2017 Apr 18.
8 Change of Serum IgG4 in Patients with Ocular Adnexal Marginal Zone B Cell Lymphoma Associated with IgG4-Related Ophthalmic Disease After Treatment.J Ocul Pharmacol Ther. 2017 Sep;33(7):543-548. doi: 10.1089/jop.2016.0175. Epub 2017 May 17.
9 Risk factors for extraophthalmic involvement and treatment outcomes in patients with IgG4-related ophthalmic disease.Br J Ophthalmol. 2018 Jun;102(6):736-741. doi: 10.1136/bjophthalmol-2017-310584. Epub 2017 Sep 28.
10 Small molecule Photoregulin3 prevents retinal degeneration in the Rho(P23H) mouse model of retinitis pigmentosa.Elife. 2017 Nov 17;6:e30577. doi: 10.7554/eLife.30577.
11 Magnetic resonance imaging indicator of the causes of optic neuropathy in IgG4-related ophthalmic disease.BMC Med Imaging. 2019 Jun 18;19(1):49. doi: 10.1186/s12880-019-0347-z.
12 IgG4-positive Cell Quantification Distinguishes Between Inflammatory and Noninflammatory Diseases of the Orbit.Appl Immunohistochem Mol Morphol. 2020 Jul;28(6):448-452. doi: 10.1097/PAI.0000000000000767.
13 IgG4-related disease in the eye and ocular adnexa.Curr Opin Ophthalmol. 2017 Nov;28(6):617-622. doi: 10.1097/ICU.0000000000000427.
14 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.
15 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.
16 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
17 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
18 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
19 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
20 Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
21 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
22 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
23 Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix. J Nutr Biochem. 2007 Aug;18(8):541-52. doi: 10.1016/j.jnutbio.2006.11.002. Epub 2007 Feb 22.
24 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
25 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
26 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
27 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
28 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
29 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
30 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.
31 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.
32 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
33 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
34 Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.