Target Information
| Target General Information | Top | |||||
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| Target ID |
T38134
(Former ID: TTDI03070)
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| Target Name |
CaM-kinase IV kinase (CAMKK1)
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| Synonyms |
Calcium/calmodulin-dependent protein kinase kinase alpha; Calcium/calmodulin-dependent protein kinase kinase 1; CaMKK alpha; CaMKK 1; CaM-kinase kinase alpha; CaM-kinase kinase 1; CaM-KK alpha; CaM-KK 1; CAMKKA
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| Gene Name |
CAMKK1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.17
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| Sequence |
MEGGPAVCCQDPRAELVERVAAIDVTHLEEADGGPEPTRNGVDPPPRARAASVIPGSTSR
LLPARPSLSARKLSLQERPAGSYLEAQAGPYATGPASHISPRAWRRPTIESHHVAISDAE DCVQLNQYKLQSEIGKGAYGVVRLAYNESEDRHYAMKVLSKKKLLKQYGFPRRPPPRGSQ AAQGGPAKQLLPLERVYQEIAILKKLDHVNVVKLIEVLDDPAEDNLYLVFDLLRKGPVME VPCDKPFSEEQARLYLRDVILGLEYLHCQKIVHRDIKPSNLLLGDDGHVKIADFGVSNQF EGNDAQLSSTAGTPAFMAPEAISDSGQSFSGKALDVWATGVTLYCFVYGKCPFIDDFILA LHRKIKNEPVVFPEEPEISEELKDLILKMLDKNPETRIGVPDIKLHPWVTKNGEEPLPSE EEHCSVVEVTEEEVKNSVRLIPSWTTVILVKSMLRKRSFGNPFEPQARREERSMSAPGNL LVKEGFGEGGKSPELPGVQEDEAAS 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: GSK-650394 | Ligand Info | |||||
| Structure Description | Crystal Structure of the Human CAMKK1A in complex with GSK650394 | PDB:6CD6 | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [2] |
| PDB Sequence |
LNQYKLQSEI
134 GKGAYGVVRL144 AYNESEDRHY154 AMKVLSKKKL164 LKQQLLPLER195 VYQEIAILKK 205 LDHVNVVKLI215 EVLDDPAEDN225 LYLVFDLLRK235 GPVMEVPCDK245 PFSEEQARLY 255 LRDVILGLEY265 LHCQKIVHRD275 IKPSNLLLGD285 DGHVKIADFG295 VSNQFEGNDA 305 QLSSTAGTPA315 FMAPEAISGQ327 SFSGKALDVW337 ATGVTLYCFV347 YGKCPFIDDF 357 ILALHRKIKN367 EPVVFPEEPE377 ISEELKDLIL387 KMLDKNPETR397 IGVPDIKLHP 407 WVTK
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ILE134
3.211
GLY135
3.919
LYS136
3.894
GLY137
3.568
ALA138
4.426
TYR139
3.934
VAL142
3.513
ALA155
3.274
LYS157
2.831
GLU199
4.184
VAL212
4.248
PHE230
3.447
ASP231
2.948
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| Ligand Name: N-[2-OXO-3-((E)-PHENYL{[4-(PIPERIDIN-1-YLMETHYL)PHENYL]IMINO}METHYL)-2,6-DIHYDRO-1H-INDOL-5-YL]ETHANESULFONAMIDE | Ligand Info | |||||
| Structure Description | Crystal Structure of the Human CAMKK1A in complex with Hesperadin | PDB:6CCF | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [3] |
| PDB Sequence |
MQLNQYKLQS
132 EIGKGAYGVV142 RLAYNESEDR152 HYAMKVLSKK162 KLERVYQEIA201 ILKKLDHVNV 211 VKLIEVLDDP221 AEDNLYLVFD231 LLRKGPVMEV241 PCDKPFSEEQ251 ARLYLRDVIL 261 GLEYLHCQKI271 VHRDIKPSNL281 LLGDDGHVKI291 ADFGVSNQFE301 GNDAQLSSTA 311 GTPAFMAPEA321 ISDSGQSFSG331 KALDVWATGV341 TLYCFVYGKC351 PFIDDFILAL 361 HRKIKNEPVV371 FPEEPEISEE381 LKDLILKMLD391 KNPETRIGVP401 DIKLHPWVTK 411
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ILE134
3.459
GLY135
3.820
TYR139
3.714
VAL142
3.467
ALA155
3.402
LYS157
2.820
VAL212
3.649
PHE230
3.416
ASP231
2.953
LEU232
3.473
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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).
Human Similarity Proteins
Human Tissue Distribution
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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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| 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 | STO-609, a specific inhibitor of the Ca(2+)/calmodulin-dependent protein kinase kinase. J Biol Chem. 2002 May 3;277(18):15813-8. | |||||
| REF 2 | Crystal Structure of the Human CAMKK1A in complex with GSK650394 | |||||
| REF 3 | Crystal Structure of the Human CAMKK1A in complex with Hesperadin | |||||
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