Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T82773
(Former ID: TTDI03083)
|
|||||
| Target Name |
Casein kinase I gamma-2 (CSNK1G2)
|
|||||
| Synonyms |
Casein kinase I isoform gamma-2; CKI-gamma 2; CK1G2
Click to Show/Hide
|
|||||
| Gene Name |
CSNK1G2
|
|||||
| Target Type |
Literature-reported target
|
[1] | ||||
| Function |
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. Phosphorylates COL4A3BP/CERT, MTA1 and SMAD3. Involved in brain development and vesicular trafficking and neurotransmitter releasing from small synaptic vesicles. Regulates fast synaptic transmission mediated by glutamate. SMAD3 phosphorylation promotes its ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses. Hyperphosphorylation of the serine-repeat motif of COL4A3BP/CERT leads to its inactivation by dissociation from the Golgi complex, thus down-regulating ER-to-Golgi transport of ceramide and sphingomyelin synthesis. Triggers PER1 proteasomal degradation probably through phosphorylation. Serine/threonine-protein kinase.
Click to Show/Hide
|
|||||
| BioChemical Class |
Kinase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
|
|||||
| Sequence |
MDFDKKGGKGETEEGRRMSKAGGGRSSHGIRSSGTSSGVLMVGPNFRVGKKIGCGNFGEL
RLGKNLYTNEYVAIKLEPIKSRAPQLHLEYRFYKQLSATEGVPQVYYFGPCGKYNAMVLE LLGPSLEDLFDLCDRTFTLKTVLMIAIQLITRMEYVHTKSLIYRDVKPENFLVGRPGTKR QHAIHIIDFGLAKEYIDPETKKHIPYREHKSLTGTARYMSINTHLGKEQSRRDDLEALGH MFMYFLRGSLPWQGLKADTLKERYQKIGDTKRATPIEVLCENFPEEMATYLRYVRRLDFF EKPDYDYLRKLFTDLFDRSGFVFDYEYDWAGKPLPTPIGTVHTDLPSQPQLRDKTQPHSK NQALNSTNGELNADDPTAGHSNAPITAPAEVEVADETKCCCFFKRRKRKSLQRHK 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: 3-Sulfinoalanine | Ligand Info | |||||
| Structure Description | Structure of casein kinase 1 gamma 2 | PDB:2C47 | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [2] |
| PDB Sequence |
PNFRVGKKIE
59 LRLGKNLYTN69 EYVAIKLEPI79 KSRAPQLHLE89 YRFYKQLSAT99 EGVPQVYYFG 109 PGKYNAMVLE120 LLGPSLEDLF130 DLCDRTFTLK140 TVLMIAIQLI150 TRMEYVHTKS 160 LIYRDVKPEN170 FLVGRPGTKR180 QHAIHIIDFG190 LAKEYIDPET200 KKHIPYREHK 210 SLTGTARYMS220 INTHLGKEQS230 RRDDLEALGH240 MFMYFLRGSL250 PWQGLKADTL 260 KERYQKIGDT270 KRATPIEVLC280 ENFPEEMATY290 LRYVRRLDFF300 EKPDYDYLRK 310 LFTDLFDRSG320 FVFDYEYDWA330 GKPLPTPI
|
|||||
|
|
||||||
| Ligand Name: 5'-iodotubercidin | Ligand Info | |||||
| Structure Description | Structure of casein kinase 1 gamma 2 | PDB:2C47 | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [2] |
| PDB Sequence |
PNFRVGKKIE
59 LRLGKNLYTN69 EYVAIKLEPI79 KSRAPQLHLE89 YRFYKQLSAT99 EGVPQVYYFG 109 PGKYNAMVLE120 LLGPSLEDLF130 DLCDRTFTLK140 TVLMIAIQLI150 TRMEYVHTKS 160 LIYRDVKPEN170 FLVGRPGTKR180 QHAIHIIDFG190 LAKEYIDPET200 KKHIPYREHK 210 SLTGTARYMS220 INTHLGKEQS230 RRDDLEALGH240 MFMYFLRGSL250 PWQGLKADTL 260 KERYQKIGDT270 KRATPIEVLC280 ENFPEEMATY290 LRYVRRLDFF300 EKPDYDYLRK 310 LFTDLFDRSG320 FVFDYEYDWA330 GKPLPTPI
|
|||||
|
|
||||||
| 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 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 Pathway Affiliation
Biological Network Descriptors
|
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Hedgehog signaling pathway | hsa04340 | Affiliated Target |
|
| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
|---|---|---|---|---|---|
| Closeness centrality | 1.26E-01 | Radiality | 1.09E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 2.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 15 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-interacting Proteins | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Structure-Based Design of Potent and Selective CK1gamma Inhibitors. ACS Med Chem Lett. 2012 Oct 18;3(12):1059-64. | |||||
| REF 2 | The Structure of Casein Kinase 1 Gamma 2 | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.