CRTC3
Function
Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR).
Post-translational modifications
Phosphorylation/dephosphorylation states of Ser-273 are required for regulating transduction of CREB activity (By similarity). CRTCs/TORCs are inactive when phosphorylated, and active when dephosphorylated at this site (By similarity). May be phosphorylated at Ser-391 by MAPK3/ERK1 and/or MAPK1/ERK2 or by some cyclin-dependent kinases such as CDK1,CDK2 or CDK5 (PubMed:30611118). Following adenylyl cyclase activation, dephosphorylated at Ser-162 and Ser-273 resulting in its dissociation from 14-3-3 proteins probably promoting CRTC3 translocation into the nucleus (PubMed:30611118).
Sequence Similarities
Belongs to the TORC family.
Tissue Specificity
Predominantly expressed in B and T lymphocytes. Highest levels in lung. Also expressed in brain, colon, heart, kidney, ovary, and prostate. Weak expression in liver, pancreas, muscle, small intestine, spleen and stomach.
Cellular localization
- Nucleus
- Cytoplasm
- Appears to be mainly nuclear (PubMed:15454081). Translocates to the nucleus following adenylyl cyclase or MAP kinase activation (PubMed:30611118).
Alternative names
TORC3, CRTC3, CREB-regulated transcription coactivator 3, Transducer of regulated cAMP response element-binding protein 3, TORC-3, Transducer of CREB protein 3