Protein: Serine/threonine-protein kinase SIK1 (EC 2.7.11.1) (HRT-20) (Myocardial SNF1-like kinase) (Salt-inducible kinase 1) (SIK-1) (Serine/threonine-protein kinase SNF1-like kinase 1) (Serine/threonine-protein kinase SNF1LK) (Q60670)
Organism: Mus musculus (Mouse)
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, 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.
Subcellular location: Cytoplasm. Nucleus. Note=Following ACTH (adrenocorticotropic hormone) treatment and subsequent phosphorylation by PKA, translocates to the cytoplasm, where it binds to YWHAZ.
Sequence: MVIMSEFSAVPSGTGQGQQKPLRVGFYDVERTLGKGNFAVVKLARHRVTKTQVAIKIIDKTRLDSSNLEKIYREVQLMKLLNHPNIIKLYQVMETKDMLYIVTEFAKNGEMFDYLTSNGHLSENEARQKFWQILSAVEYCHNHHIVHRDLKTENLLLDSNMDIKLADFGFGNFYKPGEPLSTWCGSPPYAAPEVFEGKEYEGPQLDVWSLGVVLYVLVCGSLPFDGPNLPTLRQRVLEGRFRIPFFMSQDCETLIRRMLVVDPAKRITIAQIRQHRWMQADPTLLQQDDPAFDMQGYTSNLGDYNEQVLGIMQALGIDRQRTIESLQNSSYNHFAAIYYLLLERLKEHRSAQPSSRPTPAPTRQPQLRSSDLSSLEVPQEILPCDPFRPSLLCPQPQALAQSVLQAEIDCDLHSSLQPLLFPLDTNCSGVFRHRSISPSSLLDTAISEEARQGPSLEEEQEVQEPLPGSTGRRHTLAEVSTHFSPLNPPCIIVSSSATASPSEGTSSDSCLPFSASEGPAGLGSGLATPGLLGTSSPVRLASPFLGSQSATPVLQTQAGLGTAVLPPVSFQEGRRASDTSLTQGLKAFRQQLRKNARTKGFLGLNKIKGLARQVCQSSVRTPRGGMSTFHTPAPSSGLQGCTTSNREGRSLLEEVLHQQRLLQLQHHSSTAAASSGCQQGPQLSPVPYVLAPCDSLLVSGIPLLPTPLLQAGMSPVASAAHLLDTHLHISAGPVALPTGPLPQCLTRLSPGCDPAGLPQGDCEMEDLTSGQRGTFVLVQ
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [24-279]
- IPR015940: Ubiquitin-associated domain (domain) [303-343]
- IPR008271: Serine/threonine-protein kinase, active site (active_site) [145-157]
- IPR017090: Serine/threonine-protein kinase, SIK1/2 (family) [1-779]
- IPR017441: Protein kinase, ATP binding site (binding_site) [33-56]
- IPR034672: Salt-Inducible kinase, catalytic domain (domain) [26-278]
- IPR000719: Protein kinase domain (domain) [27-278]
- IPR057380: Protein kinase SIK1/2/3, UBA domain (domain) [306-344]
Interaction partners: - CREB-regulated transcription coactivator 2
- CREB-regulated transcription coactivator 3
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0004672 (protein kinase activity), GO:0019899 (enzyme binding), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0019900 (kinase binding), GO:0004674 (protein serine/threonine kinase activity), GO:0016301 (kinase activity), GO:0019901 (protein kinase binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009892 (negative regulation of metabolic process), GO:0044237 (cellular metabolic process), GO:0019222 (regulation of metabolic process), GO:0032879 (regulation of localization), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0071704 (organic substance metabolic process), GO:0048523 (negative regulation of cellular process), GO:0044238 (primary metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0051049 (regulation of transport), GO:1901564 (organonitrogen compound metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0019538 (protein metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0080090 (regulation of primary metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0006793 (phosphorus metabolic process), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0006796 (phosphate-containing compound metabolic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0043269 (regulation of monoatomic ion transport), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010468 (regulation of gene expression), GO:2001141 (regulation of RNA biosynthetic process), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0006468 (protein phosphorylation), GO:0006355 (regulation of DNA-templated transcription), GO:0010959 (regulation of metal ion transport), GO:0016310 (phosphorylation), GO:0006357 (regulation of transcription by RNA polymerase II), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:0002028 (regulation of sodium ion transport), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0045892 (negative regulation of DNA-templated transcription), GO:0000122 (negative regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)