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Rabbit Anti-phospho-CREB-1(Ser129)/FITC Conjugated antibody
background:
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.
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. 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.
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 (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.
Subcellular Location:
Nucleus.
Post-translational modifications:
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.
DISEASE:
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).
Similarity:
Belongs to the bZIP family.
Contains 1 bZIP domain.
Contains 1 KID (kinase-inducible) domain.
Database links:
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
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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