CSNK1G1

CSNK1G1

CSNK1G1: Human casein kinase gamma 1
PDB Code: 2CMW
Description
CK1 represents a unique group of serine/threonine protein kinases ubiquitously expressed in eukaryotic organisms. Seven mammalian CK1 isoforms (α, β, γ1, γ2, γ3, δ and ε) and various splice variants have been identified to date. CK1 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 to act as monomeric, constitutively active enzymes. In the CK1 family the Asp-Pro-Glu motif of domain VIII, which is common to most Ser/Thr kinases is replaced by Ser-Ile-Asn. CK1-γ1 is the most abundant serine/threonine kinase in eukaryotic cell extracts. Several splice variants exist from which two splice variants have been described in more detail: CK1-γ1S encoding 393 amino acids and CK1-γ1L encoding 422 amino acids. CK1-γ1L has a characteristic sequence of 50 amino acids at the C-terminal end and this motif was shown to be shared by the CK1-γ2 and γ3 from rat and human, suggesting that it is a signature sequence of the gamma-isoforms.
CK1-γ1 is widely expressed with high RNA levels detected in liver, skeletal muscle, heart and kidney. The short splice variant is mainly detected in testis.
Mutations and deregulation of CK1 expression and activity has been linked to various diseases including neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, sleeping disorders and proliferative diseases such as cancer.
We determined the structure of CK1-γ1 in complex with an inhibitor of the purine class, a potent, cell-permeable, and selective inhibitor of the cell cycle-regulating kinase, Cdc28p (IC50 = 7 µM), and the related Pho85p kinase (IC50 = 2 µM).

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