Target Information
| Target General Information | Top | |||||
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| Target ID |
T59537
(Former ID: TTDR01062)
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| Target Name |
Membrane-associated kinase (PKMYT1)
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| Synonyms |
Myt1 kinase; Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase; MYT1
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| Gene Name |
PKMYT1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation. May be involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect. May be a downstream target of Notch signaling pathway during eye development. Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
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| Sequence |
MLERPPALAMPMPTEGTPPPLSGTPIPVPAYFRHAEPGFSLKRPRGLSRSLPPPPPAKGS
IPISRLFPPRTPGWHQLQPRRVSFRGEASETLQSPGYDPSRPESFFQQSFQRLSRLGHGS YGEVFKVRSKEDGRLYAVKRSMSPFRGPKDRARKLAEVGSHEKVGQHPCCVRLEQAWEEG GILYLQTELCGPSLQQHCEAWGASLPEAQVWGYLRDTLLALAHLHSQGLVHLDVKPANIF LGPRGRCKLGDFGLLVELGTAGAGEVQEGDPRYMAPELLQGSYGTAADVFSLGLTILEVA CNMELPHGGEGWQQLRQGYLPPEFTAGLSSELRSVLVMMLEPDPKLRATAEALLALPVLR QPRAWGVLWCMAAEALSRGWALWQALLALLCWLWHGLAHPASWLQPLGPPATPPGSPPCS LLLDSSLSSNWDDDSLGPSLSPEAVLARTVGSTSTPRSRCTPRDALDLSDINSEPPRGSF PSFEPRNLLSLFEDTLDPT Click to Show/Hide
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| 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: Bosutinib | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF HUMAN MYT1 KINASE DOMAIN IN COMPLEX WITH BOSUTINIB | PDB:5VCY | ||||
| Method | X-ray diffraction | Resolution | 1.56 Å | Mutation | No | [2] |
| PDB Sequence |
DLGTENLYFQ
-2 LQPRRVSFRG86 EASETLQSPG96 YDPSRPESFF106 QQSFQRLSRL116 GHGSYGEVFK 126 VRSKEDGRLY136 AVKRSMSPFR146 GPKDRARKLA156 EVGSHEKVGQ166 HPCCVRLEQA 176 WEEGGILYLQ186 TELCGPSLQQ196 HCEAWGASLP206 EAQVWGYLRD216 TLLALAHLHS 226 QGLVHLDVKP236 ANIFLGPRGR246 CKLGDFGLLV256 ELGTAGAGEV266 QEGDPRYMAP 276 ELLQGSYGTA286 ADVFSLGLTI296 LEVACNMELP306 HGGEGWQQLR316 QGYLPPEFTA 326 GLSSELRSVL336 VMMLEPDPKL346 RATAEALLAL356 PVLRQP
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SER114
4.935
LEU116
2.510
GLY117
3.564
VAL124
2.503
PHE125
4.699
LYS126
4.260
ALA137
2.477
VAL138
2.455
LYS139
2.352
GLU157
3.005
HIS161
4.250
VAL171
2.762
LEU185
2.260
GLN186
3.094
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| Ligand Name: Dasatinib | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF HUMAN MYT1 KINASE DOMAIN IN COMPLEX WITH Dasatinib | PDB:5VCV | ||||
| Method | X-ray diffraction | Resolution | 1.92 Å | Mutation | No | [2] |
| PDB Sequence |
MHQLQPRRVS
83 FRGEASETLQ93 SPGYDPSRPE103 SFFQQSFQRL113 SRLGHGSYGE123 VFKVRSKEDG 133 RLYAVKRSMS143 PFRGPKDRAR153 KLAEVGSHEK163 VGQHPCCVRL173 EQAWEEGGIL 183 YLQTELCGPS193 LQQHCEAWGA203 SLPEAQVWGY213 LRDTLLALAH223 LHSQGLVHLD 233 VKPANIFLGP243 RGRCKLGDFG253 LLVELGAGAG264 EVQEGDPRYM274 APELLQGSYG 284 TAADVFSLGL294 TILEVACNME304 LPHGGEGWQQ314 LRQGYLPPEF324 TAGLSSELRS 334 VLVMMLEPDP344 KLRATAEALL354 ALPVLRQ
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LEU116
2.472
GLY117
3.769
VAL124
2.566
LYS126
4.724
ALA137
2.752
VAL138
3.090
LYS139
2.338
GLU157
2.617
HIS161
3.336
VAL171
3.185
LEU185
2.532
GLN186
3.936
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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 Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
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 Pathway Affiliation
Biological Network Descriptors
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Cell cycle | hsa04110 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Oocyte meiosis | hsa04114 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Progesterone-mediated oocyte maturation | hsa04914 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Degree | 6 | Degree centrality | 6.45E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 2.06E-01 | Radiality | 1.36E+01 | Clustering coefficient | 1.00E+00 |
| Neighborhood connectivity | 7.77E+01 | Topological coefficient | 4.41E-01 | Eccentricity | 12 |
| 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 | ||||||
| References | Top | |||||
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| REF 1 | Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. | |||||
| REF 2 | Structural Basis of Wee Kinases Functionality and Inactivation by Diverse Small Molecule Inhibitors. J Med Chem. 2017 Sep 28;60(18):7863-7875. | |||||
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