Target Information
| Target General Information | Top | |||||
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| Target ID |
T39698
(Former ID: TTDI03403)
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| Target Name |
NIMA-related kinase 7 (NEK7)
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| Synonyms |
Serine/threonine-protein kinase Nek7; NimA-related protein kinase 7; Never in mitosis A-related kinase 7
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| Gene Name |
NEK7
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Protein kinase which plays an important role in mitotic cell cycle progression. Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis. Phosphorylates RPS6KB1.
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
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| Sequence |
MDEQSQGMQGPPVPQFQPQKALRPDMGYNTLANFRIEKKIGRGQFSEVYRAACLLDGVPV
ALKKVQIFDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLELADAGDLS RMIKHFKKQKRLIPERTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKLGDL GLGRFFSSKTTAAHSLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYGDK MNLYSLCKKIEQCDYPPLPSDHYSEELRQLVNMCINPDPEKRPDVTYVYDVAKRMHACTA SS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| 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 ADP-bound human Nek7 | PDB:2WQN | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [2] |
| PDB Sequence |
ALRPDMGYNT
30 LANFRIEKKI40 GRGQFSEVYR50 AACLLDGVPV60 ALKKVQIFDL70 MDAKARADCI 80 KEIDLLKQLN90 HPNVIKYYAS100 FIEDNELNIV110 LELADAGDLS120 RMIKHFKKQK 130 RLIPERTVWK140 YFVQLCSALE150 HMHSRRVMHR160 DIKPANVFIT170 ATGVVKLGDL 180 TPYYMSPERI208 HENGYNFKSD218 IWSLGCLLYE228 MAALQSPFYM241 NLYSLCKKIE 251 QCDYPPLPSD261 HYSEELRQLV271 NMCINPDPEK281 RPDVTYVYDV291 AKRMHACTA |
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| Ligand Name: 3-[[6-(cyclohexylmethoxy)-7~{H}-purin-2-yl]amino]-~{N}-[3-(dimethylamino)propyl]benzenesulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of Nek7 bound to compound 51 | PDB:6S75 | ||||
| Method | X-ray diffraction | Resolution | 3.30 Å | Mutation | No | [3] |
| PDB Sequence |
QKALRPDMGY
28 NTLANFRIEK38 KIGRGQFSEV48 YRAACLLDGV58 PVALKKVQIF68 DLMDAKARAD 78 CIKEIDLLKQ88 LNHPNVIKYY98 ASFIEDNELN108 IVLELADAGD118 LSRMIKHFKK 128 QKRLIPERTV138 WKYFVQLCSA148 LEHMHSRRVM158 HRDIKPANVF168 ITATGVVKLG 178 DLGLGTPYYM203 SPERIHENGY213 NFKSDIWSLG223 CLLYEMAALQ233 SPFYGDKMNL 243 YSLCKKIEQC253 DYPPLPSDHY263 SEELRQLVNM273 CINPDPEKRP283 DVTYVYDVAK 293 RMHACTA
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ILE40
3.398
GLY41
2.284
ARG42
2.272
GLY43
4.298
SER46
4.528
VAL48
2.233
ARG50
4.258
ALA61
3.582
ILE95
2.914
LEU111
3.282
GLU112
3.050
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| 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).
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 Tissue Distribution
Human Pathway Affiliation
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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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| NOD-like receptor signaling pathway | hsa04621 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 3 | Degree centrality | 3.22E-04 | Betweenness centrality | 4.05E-04 |
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| Closeness centrality | 1.88E-01 | Radiality | 1.32E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 7.00E+00 | 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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| References | Top | |||||
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| REF 1 | Substituted 2H-isoquinolin-1-one as potent Rho-Kinase inhibitors. Part 1: Hit-to-lead account. Bioorg Med Chem Lett. 2010 Jun 1;20(11):3235-9. | |||||
| REF 2 | An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase is released through binding of Nek9. Mol Cell. 2009 Nov 25;36(4):560-70. | |||||
| REF 3 | Nek7 conformational flexibility and inhibitor binding probed through protein engineering of the R-spine. Biochem J. 2020 Apr 30;477(8):1525-1539. | |||||
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