Details of Drug Off-Target (DOT)

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
• 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]

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]

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]

References

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