Names & Taxonomy

Uniprot ID:
P57059
Entry Name:
SIK1_HUMAN
Status:
reviewed
Protein Names:
Serine/threonine-protein kinase SIK1 (EC 2.7.11.1) (Salt-inducible kinase 1) (SIK-1) (Serine/threonine-protein kinase SNF1-like kinase 1) (Serine/threonine-protein kinase SNF1LK)
Gene Names:
SIK1 SIK SNF1LK
Gene Names Primary:
SIK1
Organism:
Homo sapiens (Human)

Structure

Length:
783
Sequence:
MVIMSEFSADPAGQGQGQQKPLRVGFYDIERTLGKGNFAVVKLARHRVTKTQVAIKIIDKTRLDSSNLEKIYREVQLMKLLNHPHIIKLYQVMETKDMLYIVTEFAKNGEMFDYLTSNGHLSENEARKKFWQILSAVEYCHDHHIVHRDLKTENLLLDGNMDIKLADFGFGNFYKSGEPLSTWCGSPPYAAPEVFEGKEYEGPQLDIWSLGVVLYVLVCGSLPFDGPNLPTLRQRVLEGRFRIPFFMSQDCESLIRRMLVVDPARRITIAQIRQHRWMRAEPCLPGPACPAFSAHSYTSNLGDYDEQALGIMQTLGVDRQRTVESLQNSSYNHFAAIYYLLLERLKEYRNAQCARPGPARQPRPRSSDLSGLEVPQEGLSTDPFRPALLCPQPQTLVQSVLQAEMDCELQSSLQWPLFFPVDASCSGVFRPRPVSPSSLLDTAISEEARQGPGLEEEQDTQESLPSSTGRRHTLAEVSTRLSPLTAPCIVVSPSTTASPAEGTSSDSCLTFSASKSPAGLSGTPATQGLLGACSPVRLASPFLGSQSATPVLQAQGGLGGAVLLPVSFQEGRRASDTSLTQGLKAFRQQLRKTTRTKGFLGLNKIKGLARQVCQAPASRASRGGLSPFHAPAQSPGLHGGAAGSREGWSLLEEVLEQQRLLQLQHHPAAAPGCSQAPQPAPAPFVIAPCDGPGAAPLPSTLLTSGLPLLPPPLLQTGASPVASAAQLLDTHLHIGTGPTALPAVPPPRLARLAPGCEPLGLLQGDCEMEDLMPCSLGTFVLVQ
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm

Function

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 (By similarity).
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Cofactor:
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation:
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.
Active Site:
ACT_SITE 149 149 Proton acceptor.
Cross Reference Drug Bank:
DB08912
Gene Ontology Go:
cytoplasm
nucleus
14-3-3 protein binding
ATP binding
cAMP response element binding protein binding
magnesium ion binding
protein kinase binding
protein serine/threonine kinase activity
cardiac muscle cell differentiation
cell cycle
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
Gene Ontology Biological Process:
cardiac muscle cell differentiation
cell cycle
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
Gene Ontology 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
Gene Ontology Cellular Component:
cytoplasm
nucleus
Keywords:
ATP-binding
Biological rhythms
Cell cycle
Complete proteome
Cytoplasm
Developmental protein
Differentiation
Disease mutation
Epilepsy
Kinase
Magnesium
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase
Tumor suppressor
Interacts With:
P63104

Publication

PubMed ID:
14976552 10830953 15489334 14702039 16306228 18348280 19622832 25839329 17344846