CSNK1G3 + CGP74514A

CSNK1G3 + CGP74514A

CSNK1G3 + CGP74514A: Human Casein Kinase I gamma 3
PDB Code: 2IZT
Casein kinase I (CKI) represents a unique group of serine/threonine protein kinases that is ubiquitously expressed in eukaryotic organisms. Seven mammalian CKI isoforms ( α, β, γ1, γ2, γ3, δ and ε ) and various splice variants have been identified to date. CKI family members contain a highly conserved N-terminal catalytic domain coupled to a variable C-terminal region that ranges in size from 40 to 180 amino acids. Casein kinases have been described as monomeric, constitutively active enzymes.
CSNK1G3 is widely expressed with high RNA levels detected in testis and levels found in brain, heart, liver, kidney and muscle . The characterization of the substrate specificity of CKI isoforms initially led to the identification of the canonical consensus sequence S/T(P)-X 1-2 -S/T, indicating that modification of serine or threonine residues by CKI requires the preceding phosphorylation of amino acid residues N-terminal of the target site. This requirement of a priming phosphorylation by another kinase restricted CKI to a function in the hierarchical phosphorylation of substrates. However, further studies revealed that a cluster of acidic amino acids N-terminal of the target serine/ threonine and an acidic amino acid in position n-3 could substitute for the phosphoamino acid efficiently. This non-canonical motif consisting of the sequence SLS has been shown to be recognized by CKI in combination with a cluster of acidic amino acid residues C-terminal of the phosphoacceptor site. The CKI substrates NF-AT and b -catenin exhibit such motifs, but phosphorylation of this non-canonical motif is 15-25 fold less efficient compar

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