Target Information
| Target General Information | Top | |||||
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| Target ID |
T01396
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| Target Name |
HUMAN microtubule affinity regulating kinase 2 (MARK2)
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| Synonyms |
Par-1b; Par1b; PAR1 homolog b; PAR1 homolog; MAP/microtubule affinity-regulating kinase 2; EMK-1; ELKL motif kinase 1
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| Gene Name |
MARK2
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| Function |
Human protein microtubule affinity regulating kinase 2 interacts with SARS-CoV-2 Orf9b protein with high significance, which indicates MARK2 as a potential therapeutic target.
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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 |
MSSARTPLPTLNERDTEQPTLGHLDSKPSSKSNMIRGRNSATSADEQPHIGNYRLLKTIG
KGNFAKVKLARHILTGKEVAVKIIDKTQLNSSSLQKLFREVRIMKVLNHPNIVKLFEVIE TEKTLYLVMEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKFIVHRDLKAEN LLLDADMNIKIADFGFSNEFTFGNKLDTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVIL YTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKKFLILNPSKRGTLEQIMK DRWMNVGHEDDELKPYVEPLPDYKDPRRTELMVSMGYTREEIQDSLVGQRYNEVMATYLL LGYKSSELEGDTITLKPRPSADLTNSSAPSPSHKVQRSVSANPKQRRFSDQAAGPAIPTS NSYSKKTQSNNAENKRPEEDRESGRKASSTAKVPASPLPGLERKKTTPTPSTNSVLSTST NRSRNSPLLERASLGQASIQNGKDSLTMPGSRASTASASAAVSAARPRQHQKSMSASVHP NKASGLPPTESNCEVPRPSTAPQRVPVASPSAHNISSSGGAPDRTNFPRGVSSRSTFHAG QLRQVRDQQNLPYGVTPASPSGHSQGRRGASGSIFSKFTSKFVRRNLSFRFARRNLNEPE SKDRVETLRPHVVGSGGNDKEKEEFREAKPRSLRFTWSMKTTSSMEPNEMMREIRKVLDA NSCQSELHEKYMLLCMHGTPGHEDFVQWEMEVCKLPRLSLNGVRFKRISGTSMAFKNIAS KIANELKL 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: 7-[(1~{s})-1-(4-Fluorophenyl)ethyl]-5,5-Dimethyl-2-(Pyridin-3-Ylamino)pyrrolo[2,3-D]pyrimidin-6-One | Ligand Info | |||||
| Structure Description | Mark2 complex with 7-[(1S)-1-(4-fluorophenyl)ethyl]-5,5-dimethyl-2-(3-pyridylamino)pyrrolo[2,3-d]pyrimidin-6-one | PDB:5KZ7 | ||||
| Method | X-ray diffraction | Resolution | 3.20 Å | Mutation | No | [2] |
| PDB Sequence |
PHIGNYRLLK
57 TIGKGNFAKV67 KLARHILTGK77 EVAVKIIDKT87 QLNSSSLQKL97 FREVRIMKVL 107 NHPNIVKLFE117 VIETEKTLYL127 VMEYASGGEV137 FDYLVAHGRM147 KEKEARAKFR 157 QIVSAVQYCH167 QKFIVHRDLK177 AENLLLDADM187 NIKIADFGSP213 PYAAPELFQG 223 KDGPEVDVWS235 LGVILYTLVS245 GSLPFDNLKE257 LRERVLRGKY267 RIPFYMSTDC 277 ENLLKKFLIL287 NPSKRGTLEQ297 IMKDRWMNVG307 HEDDELKPYV317 EPLPDYKDPR 327 RTELMVSMGY337 TREEIQDSLV347 GQRYNEVMAT357 YLLLGY
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| Ligand Name: 2-anilino-7-[(1S)-4-hydroxy-1H-inden-1-yl]-5,5-dimethylpyrrolo[2,3-d]pyrimidin-6-one | Ligand Info | |||||
| Structure Description | Mark2 complex with 7-[(1S)-1-(4-fluorophenyl)ethyl]-5,5-dimethyl-2-(3-pyridylamino)pyrrolo[2,3-d]pyrimidin-6-one | PDB:5KZ8 | ||||
| Method | X-ray diffraction | Resolution | 3.21 Å | Mutation | No | [2] |
| PDB Sequence |
PHIGNYRLLK
57 TIGKGNFAKV67 KLARHILTGK77 EVAVKIIDKT87 QLNSSSLQKL97 FREVRIMKVL 107 NHPNIVKLFE117 VIETEKTLYL127 VMEYASGGEV137 FDYLVAHGRM147 KEKEARAKFR 157 QIVSAVQYCH167 QKFIVHRDLK177 AENLLLDADM187 NIKIADFGCG211 SPPYAAPELF 221 QGKKYDGPEV231 DVWSLGVILY241 TLVSGSLPFD251 GQNLKELRER261 VLRGKYRIPF 271 YMSTDCENLL281 KKFLILNPSK291 RGTLEQIMKD301 RWMNVGHEDD311 ELKPYVEPLP 321 DYKDPRRTEL331 MVSMGYTREE341 IQDSLVGQRY351 NEVMATYLLL361 GY |
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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 | 3 | Degree centrality | 3.22E-04 | Betweenness centrality | 5.64E-06 |
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| Closeness centrality | 2.10E-01 | Radiality | 1.37E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.93E+01 | Topological coefficient | 3.33E-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 | A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug Repurposing. Nature. 2020 Apr 30. doi: 10.1038/s41586-020-2286-9. | |||||
| REF 2 | Structure guided design of a series of selective pyrrolopyrimidinone MARK inhibitors. Bioorg Med Chem Lett. 2017 Jan 1;27(1):114-120. | |||||
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