Target Information
| Target General Information | Top | |||||
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| Target ID |
T14945
(Former ID: TTDC00064)
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| Target Name |
Centromeric protein E (CENPE)
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| Synonyms |
Centromere-associated protein E; CENPE; CENP-E
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| Gene Name |
CENPE
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| Target Type |
Literature-reported target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
Essential for the maintenance of chromosomal stability through efficient stabilization of microtubule capture at kinetochores. Plays a key role in the movement of chromosomes toward the metaphase plate during mitosis. Is a slow plus end- directed motor whose activity is essential for metaphase chromosome alignment. Couples chromosome position to microtubule depolymerizing activity. The highly processive microtubule- dependent motor activity of CENPE servesto power chromosome congression and provides a flexible, motile tether linking kinetochores to dynamic spindle microtubules. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss. Required for the efficient recruitment of BUBR1, MAD1 and MAD2 to attached and newly unattached kinetochores. Stimulates mammalian BUBR1 kinase activity. Accumulates just before mitosis at the G2 phase of the cell cycle.
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| BioChemical Class |
TRAFAC class myosin-kinesin ATPase
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| UniProt ID | ||||||
| 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 Click to Show/Hide
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| HIT2.0 ID | T13E59 | |||||
| Drugs and Modes of Action | Top | |||||
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| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | GSK-923295 | Drug Info | Terminated | Solid tumour/cancer | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | GSK-923295 | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | Structure of CENP-E motor domain at 1.9 angstrom resolution | PDB:6M4I | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [3] |
| PDB Sequence |
EGAVAVCVRV
13 RPLNAQVYWK32 TDNNVIYQVD42 GSKSFNFDRV52 FHGNETTKNV62 YEEIAAPIID 72 SAIQGYNGTI82 FAYGQTASGK92 TYTMMGSEDH102 LGVIPRAIHD112 IFQKIKKFPD 122 REFLLRVSYM132 EIYNETITDL142 LCGTQKMKPL152 IIREDVNNVY163 VADLTEEVVY 173 TSEMALKWIT183 KGEKSRHYNQ198 RSSRSHTIFR208 MILESREKGS225 VKVSHLNLVD 235 LAGSERAALK253 EGCNINRSLF263 ILGQVIKKLS273 DGQVGGFINY283 RDSKLTRILQ 293 NSLGGNPKTR303 IICTITPVSF313 DETLTALQFA323 STAKYMKNTP333 YVNEVS |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Pipes | Ligand Info | |||||
| Structure Description | Crystal structure of the motor domain of human kinetochore protein CENP-E | PDB:1T5C | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [4] |
| PDB Sequence |
EGAVAVCVRV
13 RPLNSREESL23 GETAQVYWKT33 DNNVIYQVDG43 SKSFNFDRVF53 HGNETTKNVY 63 EEIAAPIIDS73 AIQGYNGTIF83 AYGQTASGKT93 YTMMGSEDHL103 GVIPRAIHDI 113 FQKIKKFPDR123 EFLLRVSYME133 IYNETITDLL143 CGTQKMKPLI153 IREDVNRNVY 163 VADLTEEVVY173 TSEMALKWIT183 KGEKSRHYGE193 TKMNQRSSRS203 HTIFRMILES 213 REKGSVKVSH230 LNLVDLAGSE240 RAARLKEGCN257 INRSLFILGQ267 VIKKLSDGQV 277 GGFINYRDSK287 LTRILQNSLG297 GNAKTRIICT307 ITPVSFDETL317 TALQFASTAK 327 YMKNTPYVNE337 VS
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Degree | 34 | Degree centrality | 3.65E-03 | Betweenness centrality | 1.02E-04 |
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| Closeness centrality | 2.17E-01 | Radiality | 1.38E+01 | Clustering coefficient | 6.19E-01 |
| Neighborhood connectivity | 4.09E+01 | Topological coefficient | 1.55E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | PLK1 signaling events | |||||
| Reactome | [+] 6 Reactome Pathways | + | ||||
| 1 | MHC class II antigen presentation | |||||
| 2 | Separation of Sister Chromatids | |||||
| 3 | Resolution of Sister Chromatid Cohesion | |||||
| 4 | RHO GTPases Activate Formins | |||||
| 5 | Mitotic Prometaphase | |||||
| 6 | Kinesins | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Mitotic Metaphase and Anaphase | |||||
| 2 | MHC class II antigen presentation | |||||
| 3 | Mitotic Prometaphase | |||||
| 4 | Kinesins | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Cytokinetics Announces Non-Clinical Trial Data Presented at 2007 AACR Annual Meeting. Cytokinetics, Incorporated. 2007. | |||||
| REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026868) | |||||
| REF 3 | Structure and comparison of the motor domain ofcentromere-associated protein E. doi:10.1107/S2059798321000176. | |||||
| REF 4 | Crystal structure of the motor domain of the human kinetochore protein CENP-E. J Mol Biol. 2004 Jul 23;340(5):1107-16. | |||||
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