SIK3

SIK3 is activated by phosphorylation on Thr 163 by STK11 in complex with STE20 related adapter alpha (STRAD alpha) pseudo kinase and CAB39. SIK3 binds to and is activated by YWHAZ.

Full Name

SIK family kinase 3

Function

Positive regulator of mTOR signaling that functions by triggering the degradation of DEPTOR, an mTOR inhibitor. Involved in the dynamic regulation of mTOR signaling in chondrocyte differentiation during skeletogenesis (PubMed:30232230).
Negatively regulates cAMP signaling pathway possibly by acting on CRTC2/TORC2 and CRTC3/TORC3 (Probable). Prevents HDAC4 translocation to the nucleus (By similarity).

Biological Process

Biological Process intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Biological Process microtubule cytoskeleton organizationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process positive regulation of TORC1 signalingManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of TORC2 signalingManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Cytoplasm
Locates to punctate structures within the cytoplasm on binding to YWHAZ.

Involvement in disease

Spondyloepimetaphyseal dysplasia, Krakow type (SEMDK):
An autosomal recessive skeletal disorder characterized by severe spondyloepimetaphyseal dysplasia, rhizomelia, mesomelia with significant anterior bowing of all limbs, severe immunodeficiency, and developmental delay.

PTM

Phosphorylated at Thr-221 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39 (PubMed:14976552).
Phosphorylation at Thr-221 is inhibited in response to PTHLH/PTHrP (PubMed:30232230).
Phosphorylated at Thr-469 and Ser-551 in response to cAMP signaling (Probable).