Disease:A chromosomal aberration involving CRTC1 is found in mucoepidermoid carcinomas , benign Warthin tumors and clear cell hidradenomas. Translocation t (11;19) (q21;p13) with MAML2. The fusion protein consists of the N-terminus of CRTC1 joined to the C-terminus of MAML2. The reciprocal fusion protein consisting of the N-terminus of MAML2 joined to the C-terminus of CRTC1 has been detected in a small number of mucoepidermoid carcinomas. ,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 PGC1alpha 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) . In the hippocampus , involved in late-phase long-term potentiation (L-LTP) maintenance at the Schaffer collateral-CA1 synapses. ,PTM:Phosphorylation/dephosphorylation states of Ser-151 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 (By similarity) . Phosphorylated upon DNA damage , probably by ATM or ATR. ,similarity:Belongs to the TORC family. ,subcellular location:Cytoplasmic when phosphorylated by SIK or AMPK and when sequestered by 14-3-3 proteins (By similarity) . Translocated to the nucleus on Ser-151 dephosphorylation , instigated by a number of factors including calcium ion and cAMP levels. ,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. Binds HTLV1 Tax. ,tissue specificity:Highly expressed in adult and fetal brain. Located to specific regions such as the prefrontal cortex and cerebellum. Very low expression in other tissues such as heart , spleen , lung , skeletal muscle , salivary gland , ovary and kidney. ,
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