Tchem SIK1 Serine/threonine-protein kinase SIK1

Protein Summary

Description

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. Inhibits CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signaling (PubMed:29211348). 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 (By similarity). This gene encodes a serine/threonine protein kinase that contains a ubiquitin-associated (UBA) domain. The encoded protein is a member of the adenosine monophosphate-activated kinase (AMPK) subfamily of kinases that play a role in conserved signal transduction pathways. A mutation in this gene is associated with early infantile epileptic encephalopathy 30. [provided by RefSeq, Nov 2016]

Uniprot Accession IDs

• P57059
• A6NC84
• Q5R2V5
• Q6ZNL8
• Q86YJ2

Gene Name

• SIK1

Ensembl ID

• ENST00000270162
• ENSP00000270162
• ENSG00000142178

Symbol

• SIK
• SNF1LK
• MSK
• SIK
• SIK-1
• SIK1B
• SNF1LK

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
small molecule perturbation	0.8
transcription factor perturbation	0.74
transcription factor binding site profile	0.73
small molecule	0.68
disease	0.66

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Serine/threonine-protein Kinase Sik1

DTO Classes

Protein / Kinase / Protein Kinase / Camk Group / Camkl Family / Qik Subfamily / Serine/threonine-protein Kinase Sik1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 287.38   (req: < 5)

Gene RIFs: 32   (req: <= 3)

Antibodies: 269   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 287.38   (req: >= 5)

Gene RIFs: 32   (req: > 3)

Antibodies: 269   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 23

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 11

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2