CSNK1D
Description
The CSNK1D (casein kinase 1 delta) is a protein-coding gene located on chromosome 17.
Casein kinase I isoform delta, also known as CKI-delta or CK1δ, is an enzyme that in humans is encoded by the gene CSNK1D, located on chromosome 17 (17q25.3). It is a member of the CK1 (formerly named casein kinase 1) family of serine/threonine specific eukaryotic protein kinases encompassing seven distinct isoforms (CK1α, γ1-3, δ, ε) as well as various post-transcriptionally processed splice variants (transcription variants, TVs) in mammalians. Meanwhile, CK1δ homologous proteins have been isolated from organisms like yeast, basidiomycetes, plants, algae, and protozoa.
== Genetic coding == In 1993, the gene sequence of CK1δ was initially described by Graves et al. who isolated the cDNA from testicles of rats. After sequencing and characterization of the gene, the construct was described as a 1284 nucleotide sequence resulting in a protein consisting of 428 amino acids after transcription. The molecular weight of the according protein was published as 49 kDa. Three years later, the same gene was identified in humans. The human CSNK1D contains 1245 nucleotides and is transcribed into a protein consisting of 415 amino acids. Ever since, CK1δ was investigated and described in various animals, plants, as well as parasites (Caenorhabditis elegans, 1998; Drosophila melanogaster, 1998; Mus musculus, 2002; Xenopus laevis, 2002.)
=== Transcriptional variants === So far, three different transcription variants (TVs) have been described for CK1δ in humans (Homo sapiens), mice (Mus musculus), and rats (Rattus norvegicus), which are highly homologous.
CSNK1D is a serine/threonine protein kinase crucial for regulating various cellular functions, including growth, survival, Wnt signaling, DNA repair, and circadian rhythms. It phosphorylates numerous proteins, including connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1, and PER2. CSNK1D is a central component of the circadian clock, working in balance with PP1 to control the rhythmicity and speed of PER1 and PER2 phosphorylation, determining the length of the circadian period. It regulates the nuclear transport and degradation of PER1 and PER2. CSNK1D phosphorylation of YAP1 promotes its degradation through SCF(beta-TRCP) E3 ubiquitin ligase. Phosphorylation of DNMT1 reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 enhances their activity and coactivation. Phosphorylation of DVL2 and DVL3 influences the WNT3A signaling pathway, controlling neurite outgrowth. CSNK1D phosphorylates NEDD9/HEF1, promoting EIF6 nuclear export. It triggers down-regulation of dopamine receptors in the forebrain. In vitro, it activates DCK through phosphorylation. TOP2A phosphorylation favors the formation of DNA cleavable complexes. CSNK1D may regulate mitotic spindle apparatus formation in extravillous trophoblasts. It modulates connexin-43/GJA1 gap junction assembly via phosphorylation. CSNK1D is likely involved in lymphocyte physiology and regulates fast synaptic transmission mediated by glutamate.
CSNK1D is also known as ASPS, CKI-delta, CKId, CKIdelta, FASPS2, HCKID.
