CREB1
CREB1 (CAMP Responsive Element Binding Protein 1) is a Protein Coding gene. Diseases associated with CREB1 include Histiocytoma, Angiomatoid Fibrous and Melanoma Of Soft Tissue. Among its related pathways are Apoptotic Pathways in Synovial Fibroblasts and DAG and IP3 signaling. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and enzyme binding. An important paralog of this gene is CREM.
Full Name
CAMP Responsive Element Binding Protein 1
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-119 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.
Biological Process
Aging Source: Ensembl
Axonogenesis Source: Ensembl
Cellular response to fatty acid Source: Ensembl
Cellular response to hepatocyte growth factor stimulus Source: Ensembl
Cellular response to insulin-like growth factor stimulus Source: Ensembl
Cellular response to leukemia inhibitory factor Source: Ensembl
Cellular response to nerve growth factor stimulus Source: Ensembl
Cellular response to platelet-derived growth factor stimulus Source: Ensembl
Cellular response to retinoic acid Source: ARUK-UCL
Cellular response to zinc ion Source: Ensembl
Chemotaxis to arachidonic acid Source: Ensembl
Circadian rhythm Source: UniProtKB
Lactation Source: Ensembl
Lung saccule development Source: Ensembl
Memory Source: Ensembl
Negative regulation of gene expression Source: Ensembl
Negative regulation of inflammatory response to antigenic stimulus Source: Reactome
Negative regulation of neuron death Source: Ensembl
Negative regulation of transcription by competitive promoter binding Source: BHF-UCL
Pituitary gland development Source: Ensembl
Positive regulation of apoptotic process Source: Ensembl
Positive regulation of cardiac muscle tissue development Source: Ensembl
Positive regulation of fat cell differentiation Source: UniProtKB
Positive regulation of hormone secretion Source: Ensembl
Positive regulation of lipid biosynthetic process Source: UniProtKB
Positive regulation of long-term synaptic potentiation Source: Ensembl
Positive regulation of multicellular organism growth Source: Ensembl
Positive regulation of osteoclast differentiation Source: Ensembl
Positive regulation of RNA polymerase II transcription preinitiation complex assembly Source: Ensembl
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: NTNU_SB
Positive regulation of transforming growth factor beta3 production Source: Ensembl
Protein phosphorylation Source: MGI
Protein stabilization Source: UniProtKB
Regulation of cell size Source: Ensembl
Regulation of circadian rhythm Source: Ensembl
Regulation of fibroblast proliferation Source: Ensembl
Regulation of glial cell proliferation Source: Ensembl
Regulation of transcription by RNA polymerase II Source: GO_Central
Response to activity Source: Ensembl
Response to drug Source: Ensembl
Response to glucagon Source: UniProtKB
Response to hypoxia Source: Ensembl
Response to L-glutamate Source: Ensembl
Response to nicotine Source: Ensembl
Response to organic substance Source: MGI
Secretory granule organization Source: Ensembl
Signal transduction Source: ProtInc
Transcription by RNA polymerase II Source: Ensembl
Transforming growth factor beta receptor signaling pathway Source: Ensembl
Type I pneumocyte differentiation Source: Ensembl
Viral process Source: UniProtKB-KW
Visual learning Source: Ensembl
Cellular Location
Nucleus
Involvement in disease
Angiomatoid fibrous histiocytoma (AFH):
The gene represented in this entry may be involved in disease pathogenesis. 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. 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.
PTM
timulated by phosphorylation. Phosphorylation of both Ser-119 and Ser-128 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylation of Ser-119 allows CREBBP binding. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion (By similarity). CREBL2 positively regulates phosphorylation at Ser-119 thereby stimulating CREB1 transcriptional activity (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 (By similarity). 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. Phosphorylated by TSSK4 on Ser-119 (PubMed:15964553).
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.
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