SIK 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. 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. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. AMPK subfamily. Note: This description may include information from UniProtKB.
Protein type: CAMK group; CAMKL family; EC; Kinase, protein; Motility/polarity/chemotaxis; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor); QIK subfamily; Tumor suppressor
Chromosomal Location of mouse Ortholog: 17 B1|17 17.25 cM
Cellular Component:  cytoplasm; cytosol; nucleus
Molecular Function:  14-3-3 protein binding; ATP binding; cAMP response element binding protein binding; histone deacetylase binding; kinase activity; magnesium ion binding; metal ion binding; nucleotide binding; protein binding; protein kinase activity; protein kinase binding; protein serine/threonine kinase activity; transferase activity
Biological Process:  anoikis; cardiac muscle cell differentiation; cell cycle; cell differentiation; cellular response to glucose starvation; entrainment of circadian clock by photoperiod; intracellular signal transduction; multicellular organism development; negative regulation of CREB transcription factor activity; negative regulation of gluconeogenesis; negative regulation of transcription by RNA polymerase II; negative regulation of triglyceride biosynthetic process; phosphorylation; 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
Reference #:  Q60670 (UniProtKB)
Alt. Names/Synonyms: HRT-20; Msk; Myocardial SNF1-like kinase; Probable serine/threonine protein kinase SNF1LK (HRT-20) (Myocardial SNF1-like kinase); salt inducible kinase 1; Salt-inducible kinase 1; Salt-inducible protein kinase 1; Serine/threonine-protein kinase SIK1; Serine/threonine-protein kinase SNF1-like kinase 1; Serine/threonine-protein kinase SNF1LK; Sik; SIK-1; Sik1; Snf; SNF1-like kinase; Snf1lk
Gene Symbols: Sik1
Molecular weight: 85,115 Da
Basal Isoelectric point: 6.41  Predict pI for various phosphorylation states
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  BioGPS  |  KinBase  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein