The Function of SIK1
Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1 and CRTC2/TORC2. Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1.
Protein names
Recommended name:
Serine/threonine-protein kinase SIK1Short name:
SIK-1Alternative name(s):
Salt-inducible kinase 1Serine/threonine-protein kinase SNF1-like kinase 1
Serine/threonine-protein kinase SNF1LK
- RS229353 (SIK1) ??
- RS8003722 (SIK1) ??
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Top Gene-Substance Interactions
Substances That Increase SIK1
| Substances | Interaction | Organism | Category |
Substances That Decrease SIK1
| Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
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Conditions with Decreased Gene Activity
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Technical
The following transcription factors affect gene expression:
Enzyme Regulation:
Activated by phosphorylation on Thr-182. Also activated by phosphorylation on Thr-322 in response to increases in intracellular sodium in parallel with elevations in intracellular calcium through the reversible sodium/calcium exchanger.
Molecular Function:
- 14-3-3 Protein Binding
- Atp Binding
- Camp Response Element Binding Protein Binding
- Magnesium Ion Binding
- Protein Kinase Binding
- Protein Serine/Threonine Kinase Activity
Biological Processes:
- Cardiac Muscle Cell Differentiation
- Cell Cycle
- Cellular Response To Hormone Stimulus
- Entrainment Of Circadian Clock By Photoperiod
- Intracellular Signal Transduction
- Negative Regulation Of Creb Transcription Factor Activity
- Negative Regulation Of Gluconeogenesis
- Negative Regulation Of Triglyceride Biosynthetic Process
- Positive Regulation Of Anoikis
- Protein Autophosphorylation
- Protein Phosphorylation
- Regulation Of Cell Differentiation
- Regulation Of Mitotic Cell Cycle
- Regulation Of Myotube Differentiation
- Regulation Of Sodium Ion Transport
- Rhythmic Process