Target Information
| Target General Information | Top | |||||
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| Target ID |
T39486
(Former ID: TTDI03164)
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| Target Name |
Dual-specificity tyrosine-phosphorylation regulated kinase 2 (DYRK2)
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| Synonyms |
Dual specificity tyrosine-phosphorylation-regulated kinase 2
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| Gene Name |
DYRK2
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| Target Type |
Patented-recorded target
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[1] | ||||
| Function |
Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.12.1
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| Sequence |
MLTRKPSAAAPAAYPTGRGGDSAVRQLQASPGLGAGATRSGVGTGPPSPIALPPLRASNA
AAAAHTIGGSKHTMNDHLHVGSHAHGQIQVQQLFEDNSNKRTVLTTQPNGLTTVGKTGLP VVPERQLDSIHRRQGSSTSLKSMEGMGKVKATPMTPEQAMKQYMQKLTAFEHHEIFSYPE IYFLGLNAKKRQGMTGGPNNGGYDDDQGSYVQVPHDHVAYRYEVLKVIGKGSFGQVVKAY DHKVHQHVALKMVRNEKRFHRQAAEEIRILEHLRKQDKDNTMNVIHMLENFTFRNHICMT FELLSMNLYELIKKNKFQGFSLPLVRKFAHSILQCLDALHKNRIIHCDLKPENILLKQQG RSGIKVIDFGSSCYEHQRVYTYIQSRFYRAPEVILGARYGMPIDMWSLGCILAELLTGYP LLPGEDEGDQLACMIELLGMPSQKLLDASKRAKNFVSSKGYPRYCTVTTLSDGSVVLNGG RSRRGKLRGPPESREWGNALKGCDDPLFLDFLKQCLEWDPAVRMTPGQALRHPWLRRRLP KPPTGEKTSVKRITESTGAITSISKLPPPSSSASKLRTNLAQMTDANGNIQQRTVLPKLV S Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| 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: Curcumin | Ligand Info | |||||
| Structure Description | Human DYRK2 bound to Curcumin | PDB:6HDR | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [3] |
| PDB Sequence |
HHHSGVDLGT
65 ENLYFQSMGK75 VKATPMTPEQ85 AMKQYMQKLT95 AFEHHEIFSY105 PEIYFLGLNA 115 KKRQGMTGGP125 NNGGYDDDQG135 SYVQVPHDHV145 AYRYEVLKVI155 GKGSFGQVVK 165 AYDHKVHQHV175 ALKMVRNEKR185 FHRQAAEEIR195 ILEHLRKQDK205 DNTMNVIHML 215 ENFTFRNHIC225 MTFELLSMNL235 YELIKKNKFQ245 GFSLPLVRKF255 AHSILQCLDA 265 LHKNRIIHCD275 LKPENILLKQ285 QGRSGIKVID295 FGSSCYEHQR305 VYTIQSRFYR 316 APEVILGARY326 GMPIDMWSLG336 CILAELLTGY346 PLLPGEDEGD356 QLACMIELLG 366 MPSQKLLDAS376 KRAKNFVSKG387 YPRYCTVTTL397 SDVVLNGGRS409 RRGKLRGPPE 419 SREWGNALKG429 CDDPLFLDFL439 KQCLEWDPAV449 RMTPGQALRH459 PWLR |
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LYS153
3.465
ILE155
3.494
PHE160
3.661
VAL163
4.019
LYS165
4.598
ALA176
3.431
LYS178
2.920
GLU193
2.385
LEU197
4.882
ILE212
3.683
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| Ligand Name: DTD | Ligand Info | |||||
| Structure Description | Human DYRK2 bound to Curcumin | PDB:6HDR | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [3] |
| PDB Sequence |
HHHSGVDLGT
65 ENLYFQSMGK75 VKATPMTPEQ85 AMKQYMQKLT95 AFEHHEIFSY105 PEIYFLGLNA 115 KKRQGMTGGP125 NNGGYDDDQG135 SYVQVPHDHV145 AYRYEVLKVI155 GKGSFGQVVK 165 AYDHKVHQHV175 ALKMVRNEKR185 FHRQAAEEIR195 ILEHLRKQDK205 DNTMNVIHML 215 ENFTFRNHIC225 MTFELLSMNL235 YELIKKNKFQ245 GFSLPLVRKF255 AHSILQCLDA 265 LHKNRIIHCD275 LKPENILLKQ285 QGRSGIKVID295 FGSSCYEHQR305 VYTIQSRFYR 316 APEVILGARY326 GMPIDMWSLG336 CILAELLTGY346 PLLPGEDEGD356 QLACMIELLG 366 MPSQKLLDAS376 KRAKNFVSKG387 YPRYCTVTTL397 SDVVLNGGRS409 RRGKLRGPPE 419 SREWGNALKG429 CDDPLFLDFL439 KQCLEWDPAV449 RMTPGQALRH459 PWLR |
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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).
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
Biological Network Descriptors
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| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.70E-01 | Radiality | 1.27E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.10E+01 | Topological coefficient | 1.00E+00 | 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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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors: a survey of recent patent literature.Expert Opin Ther Pat. 2017 Nov;27(11):1183-1199. | |||||
| REF 2 | Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing. J Med Chem. 2011 Jun 23;54(12):4172-86. | |||||
| REF 3 | DYRK2 bound to Curcumin | |||||
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