Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ7AP04)

• DOT Name: Centromere-associated protein E (CENPE)
• Synonyms: Centromere protein E; CENP-E; Kinesin-7; Kinesin-related protein CENPE
• Gene Name: CENPE
• Related Disease:
  Seckel syndrome
  Autosomal recessive primary microcephaly
  Microcephaly 13, primary, autosomal recessive
• UniProt ID: CENPE_HUMAN
• PDB ID: 1T5C; 5JVP; 6M4I; 8HFH; 8OWI
• Pfam ID: PF00225
• Sequence:
  MAEEGAVAVCVRVRPLNSREESLGETAQVYWKTDNNVIYQVDGSKSFNFDRVFHGNETTK
  NVYEEIAAPIIDSAIQGYNGTIFAYGQTASGKTYTMMGSEDHLGVIPRAIHDIFQKIKKF
  PDREFLLRVSYMEIYNETITDLLCGTQKMKPLIIREDVNRNVYVADLTEEVVYTSEMALK
  WITKGEKSRHYGETKMNQRSSRSHTIFRMILESREKGEPSNCEGSVKVSHLNLVDLAGSE
  RAAQTGAAGVRLKEGCNINRSLFILGQVIKKLSDGQVGGFINYRDSKLTRILQNSLGGNA
  KTRIICTITPVSFDETLTALQFASTAKYMKNTPYVNEVSTDEALLKRYRKEIMDLKKQLE
  EVSLETRAQAMEKDQLAQLLEEKDLLQKVQNEKIENLTRMLVTSSSLTLQQELKAKRKRR
  VTWCLGKINKMKNSNYADQFNIPTNITTKTHKLSINLLREIDESVCSESDVFSNTLDTLS
  EIEWNPATKLLNQENIESELNSLRADYDNLVLDYEQLRTEKEEMELKLKEKNDLDEFEAL
  ERKTKKDQEMQLIHEISNLKNLVKHAEVYNQDLENELSSKVELLREKEDQIKKLQEYIDS
  QKLENIKMDLSYSLESIEDPKQMKQTLFDAETVALDAKRESAFLRSENLELKEKMKELAT
  TYKQMENDIQLYQSQLEAKKKMQVDLEKELQSAFNEITKLTSLIDGKVPKDLLCNLELEG
  KITDLQKELNKEVEENEALREEVILLSELKSLPSEVERLRKEIQDKSEELHIITSEKDKL
  FSEVVHKESRVQGLLEEIGKTKDDLATTQSNYKSTDQEFQNFKTLHMDFEQKYKMVLEEN
  ERMNQEIVNLSKEAQKFDSSLGALKTELSYKTQELQEKTREVQERLNEMEQLKEQLENRD
  STLQTVEREKTLITEKLQQTLEEVKTLTQEKDDLKQLQESLQIERDQLKSDIHDTVNMNI
  DTQEQLRNALESLKQHQETINTLKSKISEEVSRNLHMEENTGETKDEFQQKMVGIDKKQD
  LEAKNTQTLTADVKDNEIIEQQRKIFSLIQEKNELQQMLESVIAEKEQLKTDLKENIEMT
  IENQEELRLLGDELKKQQEIVAQEKNHAIKKEGELSRTCDRLAEVEEKLKEKSQQLQEKQ
  QQLLNVQEEMSEMQKKINEIENLKNELKNKELTLEHMETERLELAQKLNENYEEVKSITK
  ERKVLKELQKSFETERDHLRGYIREIEATGLQTKEELKIAHIHLKEHQETIDELRRSVSE
  KTAQIINTQDLEKSHTKLQEEIPVLHEEQELLPNVKEVSETQETMNELELLTEQSTTKDS
  TTLARIEMERLRLNEKFQESQEEIKSLTKERDNLKTIKEALEVKHDQLKEHIRETLAKIQ
  ESQSKQEQSLNMKEKDNETTKIVSEMEQFKPKDSALLRIEIEMLGLSKRLQESHDEMKSV
  AKEKDDLQRLQEVLQSESDQLKENIKEIVAKHLETEEELKVAHCCLKEQEETINELRVNL
  SEKETEISTIQKQLEAINDKLQNKIQEIYEKEEQFNIKQISEVQEKVNELKQFKEHRKAK
  DSALQSIESKMLELTNRLQESQEEIQIMIKEKEEMKRVQEALQIERDQLKENTKEIVAKM
  KESQEKEYQFLKMTAVNETQEKMCEIEHLKEQFETQKLNLENIETENIRLTQILHENLEE
  MRSVTKERDDLRSVEETLKVERDQLKENLRETITRDLEKQEELKIVHMHLKEHQETIDKL
  RGIVSEKTNEISNMQKDLEHSNDALKAQDLKIQEELRIAHMHLKEQQETIDKLRGIVSEK
  TDKLSNMQKDLENSNAKLQEKIQELKANEHQLITLKKDVNETQKKVSEMEQLKKQIKDQS
  LTLSKLEIENLNLAQKLHENLEEMKSVMKERDNLRRVEETLKLERDQLKESLQETKARDL
  EIQQELKTARMLSKEHKETVDKLREKISEKTIQISDIQKDLDKSKDELQKKIQELQKKEL
  QLLRVKEDVNMSHKKINEMEQLKKQFEAQNLSMQSVRMDNFQLTKKLHESLEEIRIVAKE
  RDELRRIKESLKMERDQFIATLREMIARDRQNHQVKPEKRLLSDGQQHLTESLREKCSRI
  KELLKRYSEMDDHYECLNRLSLDLEKEIEFQKELSMRVKANLSLPYLQTKHIEKLFTANQ
  RCSMEFHRIMKKLKYVLSYVTKIKEEQHESINKFEMDFIDEVEKQKELLIKIQHLQQDCD
  VPSRELRDLKLNQNMDLHIEEILKDFSESEFPSIKTEFQQVLSNRKEMTQFLEEWLNTRF
  DIEKLKNGIQKENDRICQVNNFFNNRIIAIMNESTEFEERSATISKEWEQDLKSLKEKNE
  KLFKNYQTLKTSLASGAQVNPTTQDNKNPHVTSRATQLTTEKIRELENSLHEAKESAMHK
  ESKIIKMQKELEVTNDIIAKLQAKVHESNKCLEKTKETIQVLQDKVALGAKPYKEEIEDL
  KMKLVKIDLEKMKNAKEFEKEISATKATVEYQKEVIRLLRENLRRSQQAQDTSVISEHTD
  PQPSNKPLTCGGGSGIVQNTKALILKSEHIRLEKEISKLKQQNEQLIKQKNELLSNNQHL
  SNEVKTWKERTLKREAHKQVTCENSPKSPKVTGTASKKKQITPSQCKERNLQDPVPKESP
  KSCFFDSRSKSLPSPHPVRYFDNSSLGLCPEVQNAGAESVDSQPGPWHASSGKDVPECKT
  Q
• Function: Microtubule plus-end-directed kinetochore motor which plays an important role in chromosome congression, microtubule-kinetochore conjugation and spindle assembly checkpoint activation. Drives chromosome congression (alignment of chromosomes at the spindle equator resulting in the formation of the metaphase plate) by mediating the lateral sliding of polar chromosomes along spindle microtubules towards the spindle equator and by aiding the establishment and maintenance of connections between kinetochores and spindle microtubules. The transport of pole-proximal chromosomes towards the spindle equator is favored by microtubule tracks that are detyrosinated. Acts as a processive bi-directional tracker of dynamic microtubule tips; after chromosomes have congressed, continues to play an active role at kinetochores, enhancing their links with dynamic microtubule ends. Suppresses chromosome congression in NDC80-depleted cells and contributes positively to congression only when microtubules are stabilized. Plays an important role in the formation of stable attachments between kinetochores and spindle microtubules The stabilization of kinetochore-microtubule attachment also requires CENPE-dependent localization of other proteins to the kinetochore including BUB1B, MAD1 and MAD2. Plays a role in spindle assembly checkpoint activation (SAC) via its interaction with BUB1B resulting in the activation of its kinase activity, which is important for activating SAC. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss.
• KEGG Pathway: Motor proteins (hsa04814)
• Reactome Pathway:
  MHC class II antigen presentation (R-HSA-2132295)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Kinesins (R-HSA-983189)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Seckel syndrome	DISEVUBA	Supportive	Autosomal recessive	[1]
Autosomal recessive primary microcephaly	DIS29IE3	Limited	Autosomal recessive	[2]
Microcephaly 13, primary, autosomal recessive	DISXRGXJ	Limited	Autosomal recessive	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Centromere-associated protein E (CENPE).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Centromere-associated protein E (CENPE).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centromere-associated protein E (CENPE).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Centromere-associated protein E (CENPE).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Centromere-associated protein E (CENPE).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Centromere-associated protein E (CENPE).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Centromere-associated protein E (CENPE).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Centromere-associated protein E (CENPE).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Centromere-associated protein E (CENPE).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Centromere-associated protein E (CENPE).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Centromere-associated protein E (CENPE).	[14]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Centromere-associated protein E (CENPE).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Centromere-associated protein E (CENPE).	[16]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Centromere-associated protein E (CENPE).	[17]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Centromere-associated protein E (CENPE).	[18]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Centromere-associated protein E (CENPE).	[19]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Centromere-associated protein E (CENPE).	[20]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Centromere-associated protein E (CENPE).	[21]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Centromere-associated protein E (CENPE).	[22]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Centromere-associated protein E (CENPE).	[23]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Centromere-associated protein E (CENPE).	[24]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Centromere-associated protein E (CENPE).	[25]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Centromere-associated protein E (CENPE).	[26]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Centromere-associated protein E (CENPE).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Centromere-associated protein E (CENPE).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centromere-associated protein E (CENPE).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Centromere-associated protein E (CENPE).	[31]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Centromere-associated protein E (CENPE).	[32]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Centromere-associated protein E (CENPE).	[33]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Centromere-associated protein E (CENPE).	[34]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Centromere-associated protein E (CENPE).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Centromere-associated protein E (CENPE).	[30]

References

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