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. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.

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 (By similarity). Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity (By similarity). Interacts (phosphorylated form) with TOX3. Interacts with ARRB1. Binds to HIPK2. Interacts with SGK1.

Nucleus.

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). CREBL2 positively regulates phosphorylation at Ser-133 thereby stimulating CREB1 transcriptional activity (By similarity). Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-133. CaMK4 is much more potent than CaMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-142. Phosphorylation of Ser-142 blocks CREB-mediated transcription even when Ser-133 is phosphorylated. Phosphorylated by CaMK1 (By similarity). Phosphorylation of Ser-271 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP. Phosphorylated at Ser-133 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli.
Sumoylated with SUMO1. Sumoylation on Lys-304, but not on Lys-285, is required for nuclear localization of this protein. Sumoylation is enhanced under hypoxia, promoting nuclear localization and stabilization.

Defects in CREB1 may be a cause of angiomatoid fibrous histiocytoma (AFH) [MIM:612160]. A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. Note=A chromosomal aberration involving CREB1 is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type.
Note=A CREB1 mutation has been found in a patient with multiple congenital anomalies consisting of agenesis of the corpus callosum, cerebellar hypoplasia, severe neonatal respiratory distress refractory to surfactant, thymus hypoplasia, and thyroid follicular hypoplasia (PubMed:22267179).

Belongs to the bZIP family.
Contains 1 bZIP domain.
Contains 1 KID (kinase-inducible) domain.

Entrez Gene: 281713 Cow

Entrez Gene: 1385 Human

Entrez Gene: 12912 Mouse

Entrez Gene: 81646 Rat

Omim: 123810 Human

SwissProt: P27925 Cow

SwissProt: P16220 Human

SwissProt: Q01147 Mouse

SwissProt: P15337 Rat

Unigene: 516646 Human

Unigene: 453295 Mouse

Unigene: 90061 Rat

The ATF/CREB family consists of transcription factors that function through binding to the cAMP responsive element (CRE) palindromic octanucleotide, TGACCTCA. The best characterized members of this gene family include CREB-1, CREB-2, ATF-1,ATF-2,ATF-3and ATF-4. these transcription factors share highly-related COOH terminal leucine zipper demerization and basic DNA bindings but are highly divergent in their amino terminal domains. Although each of the ATF/CREB proteins bind CREs in their homodimeric form, in cerain instances they also bind as heterodimers, both within the ATF/CREB family and with members of the AP-1 transcription factor family. It has recentlybeen shown that protein kinase A-mediated CREB phosphorylation results in its binding to a 265kDa nuclear protein designated CBP (CREB-binding protein), which may reprecent a CREB co-activator.