Creb1 phospho S133
Function
Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters (By similarity). Transcription activation is enhanced by the TORC coactivators which act independently of Ser-119 phosphorylation (By similarity). Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells (By similarity). Regulates the expression of apoptotic and inflammatory response factors in cardiomyocytes in response to ERFE-mediated activation of AKT signaling (PubMed:30566056).
Post-translational modifications
Phosphorylation of Ser-119 allows CREBBP binding. Stimulated by phosphorylation. Phosphorylation of both Ser-128 and Ser-119 in the SCN regulates the activity of CREB and participate in circadian rhythm generation (By similarity). Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-119. CaMK4 is much more potent than CaMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-128. Phosphorylation of Ser-128 blocks CREB-mediated transcription even when Ser-119 is phosphorylated. Phosphorylated by CaMK1. Phosphorylation of Ser-257 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP. Phosphorylated at Ser-119 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli (By similarity). CREBL2 positively regulates phosphorylation at Ser-119 thereby stimulating CREB1 transcriptional activity. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion (By similarity). Phosphorylated by TSSK4 on Ser-119 (By similarity).
Sumoylated with SUMO1. Sumoylation on Lys-290, but not on Lys-271, is required for nuclear localization of this protein. Sumoylation is enhanced under hypoxia, promoting nuclear localization and stabilization (By similarity).
Sequence Similarities
Belongs to the bZIP family.
Cellular localization
- Nucleus
Alternative names
Creb-1, Creb1, Cyclic AMP-responsive element-binding protein 1, CREB-1, cAMP-responsive element-binding protein 1
Database links
Other research areas
- Epigenetics
- Immuno-oncology
- Immunology & Infectious Disease
- Oncology