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) . ,polymorphism:Variant Cys-379 , under a dominant model , linked to a recessive mutation in LKB1 , may be asssociated with susceptibility to type II or non-insulin-dependent diabetes mellitus (NIDDM) . ,PTM:Phosphorylation/dephosphorylation states of Ser-171 are required for regulating transduction of CREB activity. 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 by LKB1. Both insulin and AMPK increase this phosphorylation , of TORC2 while glucagon suppresses it. ,similarity:Belongs to the TORC family. ,subcellular location:Translocated from the nucleus to the cytoplasm on interaction of the phosphorylated form with 14-3-3 protein. In response to cAMP levels and glucagon , relocated to the nucleus. ,subunit: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 (By similarity) . Interacts with PPP3CA/calcineurin alpha , SNF1LK2 and 14-3-3 proteins , YWHAB and YWHAG. Interaction with the human T-cell leukemia virus type 1 (HTLV-1) Tax protein is essential for optimal transcription activation by Tax. Interaction with RFWD2/COP1 mediates nuclear export and degradation of TORC2. ,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. ,
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