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TORC2

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 gluconeogenesis as a component of the LKB1/AMPK/TORC2 signaling pathway. Regulates the expression of specific 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-171 are required for regulating transduction of CREB activity (PubMed:15589160, PubMed:17210223). CRTCs/TORCs are inactive when phosphorylated, and active when dephosphorylated at this site (PubMed:17210223). This primary site of phosphorylation, is regulated by cAMP and calcium levels and is dependent on the phosphorylation of SIKs (SIK1 and SIK2) by LKB1 (PubMed:15454081, PubMed:16817901). Following adenylyl cyclase activation, dephosphorylated at Ser-171 by PPP3CA/calcineurin A resulting in CRTC2 dissociation from 14-3-3 proteins and PPP3CA (By similarity). Both insulin and AMPK increase this phosphorylation of CRTC2 while glucagon suppresses it (PubMed:15454081). Phosphorylation at Ser-274 by MARK2 is induced under low glucose conditions and dephosphorylated in response to glucose influx (PubMed:18626018). Phosphorylation at Ser-274 promotes interaction with 14-3-3 proteins and translocation to the cytoplasm (PubMed:18626018).

Asymmetric dimethylation of arginine resisues by PRMT6 enhances the association of CRTC2 with CREB on the promoters of gluconeogenic genes.

Sequence similarities

Belongs to the TORC family.

Tissue specificity

Most abundantly expressed in the thymus. Present in both B and T-lymphocytes. Highly expressed in HEK293T cells and in insulinomas. High levels also in spleen, ovary, muscle and lung, with highest levels in muscle. Lower levels found in brain, colon, heart, kidney, prostate, small intestine and stomach. Weak expression in liver and pancreas.

Cellular localization

  • Cytoplasm
  • Nucleus
  • Translocated from the nucleus to the cytoplasm on interaction of the phosphorylated form with 14-3-3 protein (PubMed:15454081). In response to cAMP levels and glucagon, relocated to the nucleus (PubMed:15454081).

Alternative names

  • CREB-regulated transcription coactivator 2
  • Transducer of regulated cAMP response element-binding protein 2
  • TORC-2
  • Transducer of CREB protein 2
  • TORC2
  • CRTC2

Target type

Proteins

Molecular weight

73302Da