Disease:A chromosomal aberration involving CREB1 is associated with angiomatoid fibrous histiocytoma (AFH) [MIM:612160]. Translocation t (2;22) (q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type. ,Function:This protein binds the cAMP response element (CRE) , a sequence present in many viral and cellular promoters. CREB stimulates transcription on binding to the CRE. Transciption activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Implicated in synchronization of circadian rhythmicity. ,PTM:Stimulated by phosphorylation. Phosphorylation of both Ser-133 and Ser-142 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylation of Ser-133 allows CREBBP binding (By similarity) . Phosphorylated upon DNA damage , probably by ATM or ATR. ,similarity:Belongs to the bZIP family. ,similarity:Contains 1 bZIP domain. ,similarity:Contains 1 KID (kinase-inducible) domain. ,subunit:Interacts with PPRC1. Binds DNA as a dimer. This dimer is stabilized by magnesium ions. Interacts , through the bZIP domain , with the coactivators TORC1/CRTC1 , TORC2/CRTC2 and TORC3/CRTC3. When phosphorylated on Ser-133 , binds CREBBP. ,
展开内容