Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T41702
(Former ID: TTDI03082)
|
|||||
| Target Name |
Casein kinase I gamma-1 (CSNK1G1)
|
|||||
| Synonyms |
Casein kinase I isoform gamma-1; CKI-gamma 1
Click to Show/Hide
|
|||||
| Gene Name |
CSNK1G1
|
|||||
| Target Type |
Literature-reported target
|
[1] | ||||
| Function |
Serine/threonine-protein kinase. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Regulates fast synaptic transmission mediated by glutamate (By similarity). Phosphorylates CLSPN.
Click to Show/Hide
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
|
|||||
| Sequence |
MDHPSREKDERQRTTKPMAQRSAHCSRPSGSSSSSGVLMVGPNFRVGKKIGCGNFGELRL
GKNLYTNEYVAIKLEPIKSRAPQLHLEYRFYKQLGSAGEGLPQVYYFGPCGKYNAMVLEL LGPSLEDLFDLCDRTFTLKTVLMIAIQLLSRMEYVHSKNLIYRDVKPENFLIGRQGNKKE HVIHIIDFGLAKEYIDPETKKHIPYREHKSLTGTARYMSINTHLGKEQSRRDDLEALGHM FMYFLRGSLPWQGLKADTLKERYQKIGDTKRNTPIEALCENFPEEMATYLRYVRRLDFFE KPDYEYLRTLFTDLFEKKGYTFDYAYDWVGRPIPTPVGSVHVDSGASAITRESHTHRDRP SQQQPLRNQVVSSTNGELNVDDPTGAHSNAPITAHAEVEVVEEAKCCCFFKRKRKKTAQR HK Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: 2-(2-Hydroxyethylamino)-6-(3-chloroanilino)-9-isopropylpurine | Ligand Info | |||||
| Structure Description | Structure of Human Casein kinase 1 gamma-1 in complex with 2-(2- Hydroxyethylamino)-6-(3-chloroanilino)-9-isopropylpurine | PDB:2CMW | ||||
| Method | X-ray diffraction | Resolution | 1.75 Å | Mutation | No | [2] |
| PDB Sequence |
MRVGKKIGCG
53 NFGELRLGKN63 LYTNEYVAIK73 LEPIKSRAPQ83 LHLEYRFYKQ93 LGSAGEGLPQ 103 VYYFGPGKYN114 AMVLELLGPS124 LEDLFDLCDR134 TFTLKTVLMI144 AIQLLSRMEY 154 VHSKNLIYRD164 VKPENFLIGR174 QGNKKEHVIH184 IIDFGLAKEY194 IDPETKKHIP 204 YREHKSLGTA215 RYMSINTHLG225 KEQSRRDDLE235 ALGHMFMYFL245 RGSLPWQGLK 255 ADTLKERYQK265 IGDTKRNTPI275 EALCENFPEE285 MATYLRYVRR295 LDFFEKPDYE 305 YLRTLFTDLF315 EKKGYTFDYA325 YDWVGRPIPT335 PVGS
|
|||||
|
|
VAL46
3.978
GLY47
3.623
ILE50
2.735
GLY51
3.399
CYS52
4.708
LEU58
3.444
LEU60
3.993
GLY61
3.346
LYS62
3.020
ASN63
3.326
LEU64
3.040
TYR65
3.521
VAL70
3.939
ALA71
3.802
ILE72
3.455
LYS73
4.524
TYR91
3.995
|
|||||
| Ligand Name: 3-(Ethyldisulfanyl)-l-alanine | Ligand Info | |||||
| Structure Description | Structure of Human Casein kinase 1 gamma-1 in complex with 2-(2- Hydroxyethylamino)-6-(3-chloroanilino)-9-isopropylpurine | PDB:2CMW | ||||
| Method | X-ray diffraction | Resolution | 1.75 Å | Mutation | No | [2] |
| PDB Sequence |
MRVGKKIGCG
53 NFGELRLGKN63 LYTNEYVAIK73 LEPIKSRAPQ83 LHLEYRFYKQ93 LGSAGEGLPQ 103 VYYFGPGKYN114 AMVLELLGPS124 LEDLFDLCDR134 TFTLKTVLMI144 AIQLLSRMEY 154 VHSKNLIYRD164 VKPENFLIGR174 QGNKKEHVIH184 IIDFGLAKEY194 IDPETKKHIP 204 YREHKSLGTA215 RYMSINTHLG225 KEQSRRDDLE235 ALGHMFMYFL245 RGSLPWQGLK 255 ADTLKERYQK265 IGDTKRNTPI275 EALCENFPEE285 MATYLRYVRR295 LDFFEKPDYE 305 YLRTLFTDLF315 EKKGYTFDYA325 YDWVGRPIPT335 PVGS
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
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
|
|
|
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.
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Hedgehog signaling pathway | hsa04340 | Affiliated Target |
|
| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 0.00E+00 |
|---|---|---|---|---|---|
| Closeness centrality | 2.02E-01 | Radiality | 1.35E+01 | Clustering coefficient | 1.00E+00 |
| Neighborhood connectivity | 4.35E+01 | Topological coefficient | 5.88E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg Med Chem. 2009 May 1;17(9):3342-51. | |||||
| REF 2 | Structure of Human Casein Kinase 1 Gamma-1 in Complex with 2-(2-Hydroxyethylamino)-6-(3-Chloroanilino)-9-Isopropylpurine (Casp Target) | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.