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FLASH GENE
Symbol CREB1 contributors: mct/shn - updated : 08-06-2016
HGNC name cAMP responsive element binding protein 1
HGNC id 2345
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a NH2-terminal acidic region containing a potential transcriptional activation domain
  • basic leucine zipper (bZIP) protein
  • a COOH-terminal basic region
  • conjugated PhosphoP
    mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to Creb1, Mus musculus
    ortholog to Creb1, rattus norvegicus
    ortholog to CREB1, Pan troglodytes
    ortholog to creb1, Danio rerio
    Homologene
    FAMILY
  • BZIP family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,nucleus,nucleoplasm
    text present in the mitochondrial matrix of neurons
    basic FUNCTION
  • important regulator of cardiac myocyte function
  • role in hippocampus-dependent learning
  • crucial for the consolidation of long-term conditioned fear memories, but not for encoding, storage or retrieval of these memories
  • acting as a transcription regulator, with a role in survival of neurons (inhibition of neuronal suicide)
  • involved in spermatogenesis
  • playing a role in neuronal protection
  • decreasing the protein level of RCAN1
  • role of CREB1 and CREM in stimulus-dependent transcription and neuronal homeostasis
  • has a context-dependent role in activity-regulated transcription and maintains neuronal cholesterol homeostasis
  • acts as a negative regulator of CCN1/CYR61 transcription
  • acting as a positive regulator of MMP2 expression and melanoma cell invasion (these effects can be explained, in part, by the CREB1-mediated inhibition of CCN1/CYR61 expression)
  • photoreceptors degeneration leads to phosphorylation and increase expression of CREB1/ATF1 complex which is associated with a neuroprotective outcome in photoreceptors
  • central intracellular regulator in several signaling pathways and influences a variety of neural processes
  • required for acquisition of ischemic tolerance, an endogenous neuroprotective mechanism whereby prior exposure to brief ischemia produces resilience to subsequent normally injurious ischemia
  • functions in concert with a family of latent cytoplasmic co-activators called cAMP-regulated transcriptional co-activators (CRTCs), which are activated through dephosphorylation
  • CREB1 and CRTCs mediate the effects of fasting and feeding signals on the expression of metabolic programmes in insulin-sensitive tissues
  • is a novel protein target of PTEN phosphatase, which contributes to better understanding of PTEN function in the nucleus
  • integrates potentially neurotrophic and metabolic signals in the orchestration of complex neuroprotective responses that oppose brain aging
  • effector of neurotrophins involved in several age-associated neurodegenerative diseases, mediates at least some brain responses to dietary restriction
  • nuclear transcription factor that is critical for normal and neoplastic hematopoiesis
  • SOX4 and CREB1 cooperate and contribute to increased proliferation of hematopoietic progenitor cells
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    CREB1-CRTC1 pathway mediates the central effects of hormones and nutrients on energy balance and fertility
    a component
  • component of an heterodimer with ATF
  • important component of the CREB1 regulatory circuit acting by placing a constraint on calcineurin activity
  • INTERACTION
    DNA binds directly to cyclic AMP response elements (CREs) found within the mitochondrial genome
    RNA
    small molecule
    protein
  • activating transcription factor-1, ATF1
  • YY1 transcription factor, YY1
  • Abelson murine leukemia virus, v-Abl
  • serum response factor, SRF
  • homeoprotein LFB3
  • GLI family zinc finger 2, GLI2
  • Tat interactive protein 60 kDa, TIP60
  • Histone binding protein RbAp48
  • CCAAT/enhancer binding protein (C/EBP) beta, CEBPB
  • MECT1-MAML2 complex
  • PSEN1
  • bound CRTC1 (to regulate CARTPT and KISS1 gene expression through a direct mechanism)
  • is a critical regulator of human GRPR expression in gastrointestinal cancer and might be activated through different upstream intracellular pathways
  • binding to HDAC8 (inactivating CREB1 activation and decreasing CREB1 mediated gene transcription)
  • SRY (sex determining region Y)-box 9, SOX9
  • binding partner for LYL1 but not for TAL1
  • interaction with CCDC6 reduces CREB1 binding to AREG promoter
  • CREB1, SP1, and TFAP4 play roles in modulating PPP2R2B expression
  • interacting with TOX3
  • SIK2 plays critical roles in neuronal survival, is modulated by CaMKI/IV, and regulates CREB1 via CRTC1
  • protein target of PTEN phosphatase and PTEN deficiency leads to CREB1 phosphorylation independent of the PI3K/AKT pathway
  • CREB1 gene silencing decreased IL13-induced transcription of eotaxin-3 (CCL26)
  • new role for TIRAP as a key upstream regulator of CREB1 and as a contributor to the expression of both pro- and anti-inflammatory genes
  • RCAN1 acting as an important regulatory component in the control of CREB1 signaling
  • BDNF uses CREB1 and EGR3 to regulate NMDA receptor levels in cortical neurons
  • complex interplay between CREB1 and SIRT1: CREB1 directly regulates the transcription of the sirtuin in neuronal cells by binding to SIRT1 chromatin and, in turn, is recruited by CREB1 to DNA
  • NR4A2 is a downstream target of CREB1 and it is responsible for the NMDA-mediated increase in BDNF, which is necessary for the NMDA-mediated prosurvival effect on neurons
  • SOX4 transcription factor is a gene that cooperates with CREB1 in myeloid leukemogenesis
  • CREB1 has been postulated to regulate TRH expression
  • overactivation of CAPN1 caused by calcium overload proteolyses CREB1, resulting in a reduction of SLC2A3 expression and consequently impairing glucose uptake and metabolism in AD brain
  • CREB1 mediates the PRKAA-stimulated degradation of GRIP1 through protein-protein interaction and stimulation of proteasomal degradation of ubiquitinated GRIP1
  • is necessary for the specific maintenance of the GRIA1 subunit and for its trafficking within the post-synaptic densities (PSD) during the occurrence of learning
  • CREB1 regulates TIGAR expression via a CRE-binding site at the TIGAR promoter
  • IGF1 regulates MSTN expression via CREB1 transcription factor during muscle cell differentiation
  • negative regulation of CREB1 activity by endogenous CAMK2D-dependent CREB1-Ser(142) phosphorylation, suggesting a potential mechanism for CAMK2D/CREB1 signaling in modulating proliferation and migration in vascular smooth muscle cells
  • KDELR1, KDELR2 activates CREB1 and other transcription factors that upregulate transport-related genes
  • is positioned to interact with the MEF2C pathway known to be important in developmental epilepsies and the CREB1 pathway implicated in epilepsy pathogenesis
  • CREB1 is a negative regulator of the TNFAIP1 gene
  • depletion of CREB1 decreased the expression of ERN1 and EIF2AK3, two critical UPR signaling molecules, and CREB1 binds to the promoter region of these genes and regulates their expression
  • GSK3A is regulated by CREB1 in lung cancer and is required for the cell viability
  • cell & other
    REGULATION
    activated by MAPK14 (role for MAPK14 in activating CREB1 metabolic pathway in the events leading to erythroid differentiation)
    intracellular HIV-1 Tat protein
    Calmodulin-dependent protein kinase II
    fear memory expression
    inhibited by thyroid hormone receptor
    repressed by CCDC6 (represses its transcriptional activity by recruiting histone deacetylase 1 and protein phosphatase 1 proteins at the CRE site of the CREB1 target genes)
    Other phosphorylated by ataxia telangiectasia mutated in response to genotoxic stress
    transactivated by epidermal growth factor (EGF)
    phosphorylated by MSK1 and MSK2 in response to to both mitogenic and stress stimuli (Wiggin 2002)
    can be phosphorylated by erum/glucocorticoid-inducible kinase
    phosphorylated by testis-specific serine/threonine kinase 5
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    decreased mitochondrial CREB activity contributes to the mitochondrial dysfunction and neuronal loss associated with neurodegenerative disorders
    constitutional germinal mutation      
    a p.D116G mutation in CREB1 leads to novel multiple malformation syndrome
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    mental retardationtrisomy 
    identification of direct endogenous CREB1 target genes may have important insight into the causes and treatments of Down syndrome pathogenesis
    cancerlung 
    CREB1-GSK3A axis is a novel therapeutic target for lung cancer treatment
    ANIMAL & CELL MODELS
  • transgenic mice expressing a dominant-negative form of the CREB1 develop dilated cardiomyopathy associated with hepatic congestion and peripheral edema, intracardiac thrombi, and premature mortality
  • CREB null mice are smaller, display a strong reduction in the corpus callosum and the anterior commissures in brain and die immediately after birth from respiratory distress
  • mice with a disruption of CREB1exhibit fasting hypoglycaemia and reduced expression of gluconeogenic enzymes
  • disrupted Creb1 and Crem in brain of developing and adult mice using the Cre/loxP system leads to progressive neurodegeneration in the hippocampus and in the dorsolateral striatum
  • mice harboring a null mutation in the Creb gene, sensory neurons exhibit excess apoptosis and degeneration, and display impaired axonal growth and projections
  • mice deficient in CREB activity have a fatty liver phenotype and display elevated expression of the nuclear hormone receptor PPAR-gamma (ID: 14614508)
  • mice expressing a dominant-negative CREB transgene exhibit a dystrophic phenotype along with reduced MEF2 activity