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FLASH GENE
Symbol CREBBP contributors: mct/npt/pgu - updated : 21-02-2017
HGNC name CREB binding protein
HGNC id 2348
Corresponding disease
AMLT3 acute myeloid leukemia M4/M5 displaying monocytic differentiation erythrophagocytosis by the leukemic cells,poor response to chemotherapy,with translocation t(8;16)(p11;p13) and inversion inv(8) (p11;q13) and acute monocytic leukemia with t(8;22) (p11;q13)
RSTS Rubinstein-Taybi syndrome
Location 16p13.3      Physical location : 3.775.057 - 3.930.121
Synonym name CAAT/enhancer -binding protein
Synonym symbol(s) CREB3, CREBP, CBP, RTS, KAT3A
EC.number 2.3.1.48
DNA
TYPE functioning gene
STRUCTURE 155.07 kb     31 Exon(s)
10 Kb 5' upstream gene genomic sequence study
motif repetitive sequence   ALU
text structure percentage of interspersed repetitive elements (mainly Alu and LINEs in the CREBBP exon 2 region) is significantly higher suggesting that this characteristic may be involved in the region is vulnerability to breaking and nonhomologous pairing
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
30 - 10083 - 2404 - 1995 7606928
31 - 10197 265 2442 - 1995 7606928
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivemouthtongue  highly
Hearing/Equilibriumearinnercochlea highly
Lymphoid/Immunelymph node   highly
 thymus    
Reproductivemale systemtestis   
Respiratoryrespiratory tractlarynx  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text cochlea, pancreas
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • three cysteine-histidine rich (C4-H-C3) PHD type zinc finger motifs
  • a bromodomain (histone acetyltransferase domain, HAT)
  • a nuclear receptor interaction motif (LXXLL), the KIX domain for interaction with MYB
  • a highly conserved cysteine/histidine-rich region (CH2) domain that with the preceding bromodomain interact and mutually stabilize each other, implying a cooperative function
  • a TAZ1 domain, consisting of four alpha-helices (alpha(1)-alpha(4) stabilized by three zinc atoms (for binding to CITED2)
  • C-terminal domain, SID (SRC1 interacting domain) responsible for interaction with SRC1 (NCOA1), and other transcriptional regulators such as E1A, ETS2, IRF3, and p53
  • HOMOLOGY
    interspecies homolog to murine Crebbp
    homolog to EP300
    Homologene
    FAMILY
    CATEGORY transcription factor , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nucleus,chromatin/chromosome,heterochromosome
    text colocalizing with PML in special (PML/SP100) nuclear bodies (NB/POD)
    basic FUNCTION
  • playing an important role as a general co-integrator of multiple signaling pathways
  • potent histone acetyltransferase
  • transcriptional coactivator with EP300 of various nuclear receptors and hypoxia inducible factor 1A (HIF1A)
  • associating to PML which increases its localization in POD (promyelocytic oncoprotein domain)
  • acting as a potent nuclear receptor coactivator
  • playing a pivotal role in embryonic development
  • involved in a variety of transcriptional pathways through chromatin remodeling (acetylation of histone protein H3)
  • participating in basic cellular functions and acting rarely as classical suppressor of tumor
  • regulator with PCAF of involucrin expression in stratified squamous epithelial cells
  • promoting nucleosome acetylation at NOTCH enhancers and activating transcription via its binding to MAML1
  • dosage-dependent regulator of NFKB1 suppression by the estrogen receptor
  • CREBBP and EP300 function as transcriptional coactivators for a large number of DNA-binding transcription factors involved in multiple signalling and developmental pathways, by modifying lysine residues on both histone and non-histone nuclear proteins
  • histone acetyltransferase involved in mental retardation, in the genesis and maintenance of long-lasting systemic and behavioural adaptations to environmental enrichment (EE)(
  • important role for CREBBP in cognitive dysfunction in Huntington disease
  • CREBBP-dependent transcriptional neuroadaptation is an important mediator of EE-induced benefits, a finding with important implications for mental retardation therapeutics
  • CREBBP and KAT5 coordinate histone acetylation at both local and global levels to facilitate RAS-induced transformation
  • KMT2C/KMT2D and H3K27 acetyltransferases CREBBP/EP300 are major enhancer epigenomic writers
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    text
  • MADH4 dependent TGFB transcriptional responses in endothelial cells
  • PATHWAY
    metabolism
    signaling signal transduction
    HH signaling transduction pathway
    a component
  • complexing with CITED2 (CBP/p300-interacting transactivator with ED-rich tail), inhibiting the activity of the hypoxia inducible factor (HIF-1alpha)
  • INTERACTION
    DNA binding to cAMP response element
    RNA
    small molecule
    protein
  • MADH4
  • TGFB
  • N4BP2
  • binding to GLI activators
  • SNIP1
  • MAML1
  • interacts with a large number of transcription factors and co-factors, through its numerous protein-binding domains
  • interacting with TRIP10, ZBTB17, SH3GL1, GAK, EIF2B1 in embryonic orofacial tissue
  • interacting with GATA2(CREBPP could increase GATA2 transcriptional activity in the dose-dependent manner)
  • MAP3K4 controls the activity of the histone acetyltransferase CREBBP, and acetylation of histones H2A and H2B by CREBBP is required to maintain the epithelial phenotype
  • displayed histone H3K9-me1/2 demethylase activity and induced leukemogenic oncogene LMO2 expression via a synergistic interaction with CREBBP
  • KIX domains of CREBBP, and especially EP300, are principal mediators of MYB-dependent gene activation and repression that is required for definitive hematopoiesis
  • TDG, as a new coactivator, promotes CTNNB1/TCFs transactivation and functionally cooperates with CREBBP in canonical WNT signaling
  • CREBBP and EP300 cooperate with several key Treg transcription factors that act on the FOXP3 promoter to promote FOXP3 production
  • destabilization of CREBBP by downregulation of PPP1R13L
  • expression levels appears to represent a molecular mechanism that contributes to chemoresistance in melanoma cells
  • AJUBA recruits CREBBP via its LIM domain and facilitates CREBBP binding to PPARG
  • complex regulation of CREBBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis
  • TLX3 directly interacts with the epigenetic co-activator cyclic adenosine monophosphate CREBBP and its homeodomain is essential for this interaction
  • CREBBP regulates lung cancer growth by targeting MAPK and CPSF4 signaling pathways 8)
  • interplay between the remodeling activity of SMARCAD1 and histone acetylation by CREBBP sheds light on the function of chromatin and the genome-integrity network
  • CREBBP and EP300, activate transcription of TP53-regulated stress response genes and stabilize TP53 against ubiquitin-mediated degradation
  • cell & other
    REGULATION
    activated by CREB and CREM after phosphorylation of respectively Ser133 and Ser 117
    ASSOCIATED DISORDERS
    corresponding disease(s) RSTS , AMLT3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with MYST3 in acute myeloid leukemia with translocation t(8;16)(p11;p13), see AML3, and with MLL (HRX) in therapy related acute leukemia with translocation t(11;16)(q23;p13), with MYST4 in AML with t(10;16) (q22;p13)
    tumoral fusion      
    fusion genes MYST3-CREBBP in acute myeloid leukemia (AML) by chromosomal translocation
    tumoral somatic mutation     loss of function
    in B-cell non-Hodgkin lymphoma
    tumoral somatic mutation      
    in relapsed acute lymphoblastic leukaemia, mutations impaired histone acetylation and transcriptional regulation of CREBBP targets, including glucocorticoid responsive genes, and may confer resistance to therapy (
    tumoral somatic mutation      
    in hypothalamic hamartoma with gelastic epilepsy
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    use of histone deacetylase inhibitors has a potential therapy in B-cell non-Hodgkin lymphoma
    cancerhemopathy 
    promising therapeutic targets across multiple subtypes in acute myeloid leukemia
    ANIMAL & CELL MODELS
  • mice with a deletion mutation in the CBP CH1 (TAZ1) domain have an Rubinstein-Taybi Syndrome (RTS)-like phenotype that includes ASD-relevant repetitive behaviors, hyperactivity, social interaction deficits, motor dysfunction, impaired recognition memory, and abnormal synaptic plasticity