Mouse Anti-SIK1 Recombinant Antibody (CBXS-2857) (CBMAB-S5607-CQ)

salt-inducible kinase 1

MSK; SIK; SIK-1; SIK1B; SNF1LK

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).

Biological Process anoikisIEA:Ensembl
Biological Process cardiac muscle cell differentiationISS:UniProtKB
Biological Process cell cycleIEA:UniProtKB-KW
Biological Process cellular response to glucose starvationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process entrainment of circadian clock by photoperiodISS:UniProtKB
Biological Process intracellular signal transductionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of CREB transcription factor activityISS:UniProtKB
Biological Process negative regulation of gluconeogenesisISS:UniProtKB
Biological Process negative regulation of triglyceride biosynthetic processISS:UniProtKB
Biological Process positive regulation of anoikisManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process protein autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of cell differentiationISS:UniProtKB
Biological Process regulation of mitotic cell cycleISS:UniProtKB
Biological Process regulation of myotube differentiationISS:UniProtKB
Biological Process regulation of sodium ion transportISS:UniProtKB
Biological Process rhythmic processIEA:UniProtKB-KW

Cytoplasm
Nucleus
Locates to cytoplasm when inactive following cAMP-induced phosphorylation, probably by PKA (PubMed:29211348).

Developmental and epileptic encephalopathy 30 (DEE30):
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent.

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 in response to cAMP signaling promotes translocation to the cytoplasm (PubMed:29211348).
Phosphorylation at Thr-322 by CaMK1 following intracellular sodium concentration leads to activation.