Phospho-TORC2 (Ser275) Antibody - #AF3579

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).

Phosphorylation/dephosphorylation states of Ser-171 are required for regulating transduction of CREB activity. CRTCs/TORCs are inactive when phosphorylated, and active when dephosphorylated at this site. 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. 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. Phosphorylation at Ser-274 by MARK2 is induced under low glucose conditions and dephosphorylated in response to glucose influx. Phosphorylation at Ser-274 promotes interaction with 14-3-3 proteins and translocation to the cytoplasm.

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

Cytoplasm. Nucleus.
Note: 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).

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.

Binds, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1. 'Arg-314' in the bZIP domain of CREB1 is essential for this interaction. Interaction, via its C-terminal, with TAF4, enhances recruitment of TAF4 to CREB1. Interacts with SIK2. Interacts with 14-3-3 proteins, YWHAB and YWHAG. Interacts (probably when phosphorylated at Ser-171) with YWHAE. Interacts with calmodulin-dependent catalytic subunit PPP3CA/calcineurin A. Interaction with COP1 mediates nuclear export and degradation of CRTC2 (By similarity).

(Microbial infection) Interaction with the human T-cell leukemia virus type 1 (HTLV-1) Tax protein is essential for optimal transcription activation by Tax.

Belongs to the TORC family.