ID:SIK1_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase SIK1; EC=2.7.11.1; AltName: Full=Salt-inducible kinase 1; Short=SIK-1; AltName: Full=Serine/threonine-protein kinase SNF1-like kinase 1; Short=Serine/threonine-protein kinase SNF1LK; FUNCTION: 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, TORC1/CRTC1 and TORC2/CRTC2. 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 TORC1/CRTC1 and TORC2/CRTC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium (By similarity). 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. SUBUNIT: Interacts with ATP1A1 (By similarity). Interacts (when phosphorylated on Thr-182 and Ser-186) with YWHAZ. INTERACTION: P63104:YWHAZ; NbExp=4; IntAct=EBI-1181640, EBI-347088; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Following ACTH (adrenocorticotropic hormone) treatment and subsequent phosphorylation by PKA, translocates to the cytoplasm, where it binds to YWHAZ. DOMAIN: The RK-rich region determines the subcellular location (By similarity). PTM: Phosphorylated at Thr-182 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39, leading to its activation. Phosphorylation at Thr-182 promotes autophosphorylation at Ser-186, which is required for sustained activity. Autophosphorylation at Ser-186 is maintained by sequential phosphorylation at Thr-182 by GSK3-beta. GSK3-beta cannot initiate phosphorylation at Thr-182, it can only maintain it. Phosphorylation at Ser-575 by PKA promotes translocation to the cytoplasm. Phosphorylation at Thr-322 by CaMK1 following intracellular sodium concentration leads to activation. Phosphorylated upon DNA damage, probably by ATM or ATR. DISEASE: Note=Defects in SIK1 may be associated with some cancers, such as breast cancers. Loss of SIK1 correlates with poor patient outcome in breast cancers (PubMed:19622832). SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. AMPK subfamily. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 UBA domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P57059
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002028 regulation of sodium ion transport GO:0006468 protein phosphorylation GO:0007049 cell cycle GO:0007275 multicellular organism development GO:0007346 regulation of mitotic cell cycle GO:0010830 regulation of myotube differentiation GO:0010868 negative regulation of triglyceride biosynthetic process GO:0016310 phosphorylation GO:0030154 cell differentiation GO:0032792 negative regulation of CREB transcription factor activity GO:0032870 cellular response to hormone stimulus GO:0035556 intracellular signal transduction GO:0043153 entrainment of circadian clock by photoperiod GO:0045595 regulation of cell differentiation GO:0045721 negative regulation of gluconeogenesis GO:0046777 protein autophosphorylation GO:0048511 rhythmic process GO:0055007 cardiac muscle cell differentiation GO:2000210 positive regulation of anoikis
US Server
