ID:CBP_HUMAN DESCRIPTION: RecName: Full=CREB-binding protein; EC=2.3.1.48; FUNCTION: Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300. CATALYTIC ACTIVITY: Acetyl-CoA + [histone] = CoA + acetyl- [histone]. SUBUNIT: Found in a complex containing NCOA2; NCOA3; IKKA; IKKB and IKBKG. Probably part of a complex with HIF1A and EP300. Interacts with GATA1; the interaction results in acetylation and enhancement of transcriptional activity of GATA1. Interacts with MAF AND ZCCHC12. Interacts with DAXX; the interaction is dependent on CBP sumoylation and results in suppression of the transcriptional activiy via recruitment of HDAC2 to DAAX (By similarity). Interacts with phosphorylated CREB1. Interacts with CITED4 (C-terminal region). Interacts (via the TAZ-type 1 domain) with HIF1A. Interacts with SRCAP, CARM1, ELF3, MLLT7/FOXO4, N4BP2, NCOA1, NCOA3, NCOA6, PCAF, DDX5, DDX17, PELP1, PML, SMAD1, SMAD2, SMAD3, SPIB and TRERF1. Interacts with HTLV-1 Tax and p30II. Interacts with HIV-1 Tat. Interacts with KLF1; the interaction results in acetylation of KLF1 and enhancement of its transcriptional activity. Interacts with MTDH. Interacts with NFATC4. Interacts with MAFG; the interaction acetylates MAFG in the basic region and stimulates NFE2 transcriptional activity through increasing its DNA-binding activity. Interacts with IRF2; the interaction acetylates IRF2 and regulates its activity on the H4 promoter. Interacts (via N-terminus) with SS18L1/CREST (via C- terminus). Interacts with MECOM. Interacts with CITED1 (via C- terminus). Interacts with FOXO1; the interaction acetylates FOXO1 and inhibits its transcriptional activity. INTERACTION: P10275:AR; NbExp=2; IntAct=EBI-81215, EBI-608057; Q9UER7:DAXX; NbExp=2; IntAct=EBI-81215, EBI-77321; Q12778:FOXO1; NbExp=2; IntAct=EBI-81215, EBI-1108782; P48551:IFNAR2; NbExp=4; IntAct=EBI-81215, EBI-958408; Q14653:IRF3; NbExp=3; IntAct=EBI-81215, EBI-2650369; Q92831:KAT2B; NbExp=3; IntAct=EBI-81215, EBI-477430; Q86UE4:MTDH; NbExp=2; IntAct=EBI-81215, EBI-1046588; P55209:NAP1L1; NbExp=3; IntAct=EBI-81215, EBI-356392; Q14686:NCOA6; NbExp=2; IntAct=EBI-81215, EBI-78670; Q04206:RELA; NbExp=3; IntAct=EBI-81215, EBI-73886; P04637:TP53; NbExp=6; IntAct=EBI-81215, EBI-366083; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Recruited to nuclear bodies by SS18L1/CREST. In the presence of ALX1 relocalizes from the cytoplasm to the nucleus. DOMAIN: The KIX domain mediates binding to HIV-1 Tat. PTM: Methylation of the KIX domain by CARM1 blocks association with CREB. This results in the blockade of CREB signaling, and in activation of apoptotic response (By similarity). PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylated by CHUK/IKKA at Ser-1382 and Ser-1386; these phosphorylations promote cell growth by switching the binding preference of CREBBP from TP53 to NF-kappa-B. PTM: Sumoylation negatively regulates transcriptional activity via the recruitment of DAAX (By similarity). DISEASE: Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. DISEASE: Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:180849]. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies. SIMILARITY: Contains 1 bromo domain. SIMILARITY: Contains 1 KIX domain. SIMILARITY: Contains 2 TAZ-type zinc fingers. SIMILARITY: Contains 1 ZZ-type zinc finger. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CBPID42.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CREBBP"; WEB RESOURCE: Name=Wikipedia; Note=P300/CBP entry; URL="http://en.wikipedia.org/wiki/P300/CBP";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q92793
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000987 core promoter proximal region sequence-specific DNA binding GO:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001085 RNA polymerase II transcription factor binding GO:0001102 RNA polymerase II activating transcription factor binding GO:0001105 RNA polymerase II transcription coactivator activity GO:0001191 transcriptional repressor activity, RNA polymerase II transcription factor binding GO:0002039 p53 binding GO:0003682 chromatin binding GO:0003684 damaged DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0003712 transcription cofactor activity GO:0003713 transcription coactivator activity GO:0004402 histone acetyltransferase activity GO:0004871 signal transducer activity GO:0005515 protein binding GO:0008134 transcription factor binding GO:0008270 zinc ion binding GO:0016407 acetyltransferase activity GO:0016740 transferase activity GO:0016746 transferase activity, transferring acyl groups GO:0034212 peptide N-acetyltransferase activity GO:0043426 MRF binding GO:0046872 metal ion binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001666 response to hypoxia GO:0002223 stimulatory C-type lectin receptor signaling pathway GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006367 transcription initiation from RNA polymerase II promoter GO:0006473 protein acetylation GO:0007165 signal transduction GO:0007219 Notch signaling pathway GO:0007221 positive regulation of transcription of Notch receptor target GO:0008589 regulation of smoothened signaling pathway GO:0016032 viral process GO:0016573 histone acetylation GO:0018076 N-terminal peptidyl-lysine acetylation GO:0019216 regulation of lipid metabolic process GO:0031648 protein destabilization GO:0032481 positive regulation of type I interferon production GO:0034644 cellular response to UV GO:0042592 homeostatic process GO:0042733 embryonic digit morphogenesis GO:0042981 regulation of apoptotic process GO:0045637 regulation of myeloid cell differentiation GO:0045747 positive regulation of Notch signaling pathway GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048511 rhythmic process GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0065003 macromolecular complex assembly GO:1900034 regulation of cellular response to heat GO:1904837 beta-catenin-TCF complex assembly
U47741 - Human CREB-binding protein (CBP) mRNA, complete cds. AB210043 - Homo sapiens mRNA for CREBBP variant protein, clone: pf01047. U85962 - Homo sapiens CREB-binding protein mRNA, complete cds. AB527452 - Synthetic construct DNA, clone: pF1KB0067, Homo sapiens CREBBP gene for CREB binding protein, without stop codon, in Flexi system. AK304771 - Homo sapiens cDNA FLJ57039 partial cds, highly similar to CREB-binding protein (EC 2.3.1.48). BC036486 - Homo sapiens CREB binding protein, mRNA (cDNA clone IMAGE:5261283), partial cds. JD303805 - Sequence 284829 from Patent EP1572962. U89355 - Homo sapiens clone cRT16 CREB-binding protein mRNA, partial cds. JD095595 - Sequence 76619 from Patent EP1572962. JD298801 - Sequence 279825 from Patent EP1572962. JD436000 - Sequence 417024 from Patent EP1572962. JD314452 - Sequence 295476 from Patent EP1572962. JD469673 - Sequence 450697 from Patent EP1572962. JD562580 - Sequence 543604 from Patent EP1572962. JD183741 - Sequence 164765 from Patent EP1572962. U89354 - Homo sapiens clone cRT0 CREB-binding protein mRNA, partial cds. JD137934 - Sequence 118958 from Patent EP1572962. JD297294 - Sequence 278318 from Patent EP1572962. JD100174 - Sequence 81198 from Patent EP1572962. JD110986 - Sequence 92010 from Patent EP1572962. AK124320 - Homo sapiens cDNA FLJ42329 fis, clone TRACH3000558, highly similar to CREB-BINDING PROTEIN. AJ251844 - Homo sapiens partial mRNA for MOZ/CBP chimeric transcript type II. AJ251843 - Homo sapiens partial mRNA for MOZ/CBP chimeric transcript type I. AJ251845 - Homo sapiens partial mRNA for CBP/MOZ chimeric transcript. JD488562 - Sequence 469586 from Patent EP1572962. JD408431 - Sequence 389455 from Patent EP1572962. JD140499 - Sequence 121523 from Patent EP1572962. JD164327 - Sequence 145351 from Patent EP1572962. MK172839 - Homo sapiens CREBBP/SRGAP2B fusion, partial sequence.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_pelp1Pathway - Pelp1 Modulation of Estrogen Receptor Activity h_pitx2Pathway - Multi-step Regulation of Transcription by Pitx2 h_wntPathway - WNT Signaling Pathway h_tgfbPathway - TGF beta signaling pathway h_pcafpathway - The information-processing pathway at the IFN-beta enhancer h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) h_il7Pathway - IL-7 Signal Transduction h_HuntingtonPathway - Inhibition of Huntington's disease neurodegeneration by histone deacetylase inhibitors h_pmlPathway - Regulation of transcriptional activity by PML h_RELAPathway - Acetylation and Deacetylation of RelA in The Nucleus h_nthiPathway - NFkB activation by Nontypeable Hemophilus influenzae h_ppargPathway - Role of PPAR-gamma Coactivators in Obesity and Thermogenesis h_CSKPathway - Activation of Csk by cAMP-dependent Protein Kinase Inhibits Signaling through the T Cell Receptor h_carm-erPathway - CARM1 and Regulation of the Estrogen Receptor h_carm1Pathway - Transcription Regulation by Methyltransferase of CARM1 h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart) h_setPathway - Granzyme A mediated Apoptosis Pathway h_vdrPathway - Control of Gene Expression by Vitamin D Receptor
Reactome (by CSHL, EBI, and GO)
Protein Q92793 (Reactome details) participates in the following event(s):
R-HSA-212356 Formation of CSL-NICD coactivator complex R-HSA-381309 PPARG:RXRA heterodimer binds to fatty acid-like ligands R-HSA-1912394 NICD1 in complex with RBPJ (CSL) recruits MAML R-HSA-2220964 NICD1 PEST domain mutants in complex with RBPJ (CSL) bind MAML R-HSA-6797993 TP53 and CREBBP bind BNIP3L gene R-HSA-8864307 TFAP2 homo- and heterodimers bind CITED and EP300/CREBBP R-HSA-8938231 RUNX1:CBFB binds CREBBP R-HSA-9038052 GREB1 binds ESR1:ESTG and co-activators R-HSA-1912391 NICD1 is phosphorylated by CDK8 R-HSA-2220971 CDK8 phosphorylates NICD1 PEST domain mutants R-HSA-1912393 MAML in complex with NICD1 recruits CDK8 R-HSA-4396347 NOTCH1 Coactivator Complex binds HES1 promoter R-HSA-4396371 NOTCH1 Coactivator Complex binds MYC promoter R-HSA-4396379 NOTCH1 Coactivator Complex binds HES5 promoter R-HSA-4396382 NOTCH1 Coactivator Complex binds promoters of HEY genes R-HSA-8878220 RUNX3 binds the NOTCH1 coactivator complex R-HSA-9017835 NOTCH1 coactivator complex binds NOTCH3 gene R-HSA-2220957 NOTCH1 PEST domain mutants coactivator complex binds CDK8:CCNC R-HSA-4396392 NOTCH1 PEST domain mutants bind HES1 promoter R-HSA-4396393 NOTCH1 PEST domain mutants bind MYC promoter R-HSA-4396401 NOTCH1 PEST domain mutants bind HES5 promoter R-HSA-4396402 NOTCH1 PEST domain mutants bind promoters of HEY genes R-HSA-4395227 CCND1:CREBBP binds NOTCH1 promoter R-HSA-8938228 RUNX1:CBFB:CREBBP binds the CSF2 (GM-CSF) gene promoter R-HSA-400143 Fatty acid ligands activate PPARA R-HSA-933536 p-IRF7 dimer interacts with coactivator CBP/p300 R-HSA-1028817 CREBBP, EP300 binds p-T,4S-IRF3:p-T,4S-IRF3 R-HSA-1028820 Formation of VAF (virus-activated factor) complex R-HSA-3134883 Beta-catenin enhances association of IRF3 with CBP/p300 R-HSA-3322427 Beta-catenin recruits CBP/p300 R-HSA-5660666 CBP and p300 binds NF-kB complex R-HSA-3697008 CREBBP acetylates histone H2B, H3, H4 R-HSA-8878237 RUNX3:NOTCH1 coactivator complex binds the HES1 gene promoter R-HSA-9021451 NOTCH1,NOTCH3 coactivator complex binds PLXND1 gene promoter R-HSA-1028815 p-T,4S-IRF3:p-T,4S-IRF3:CREBBP, EP300 binds promoters of Interferon-beta R-HSA-5660660 p300 acetylates RELA subunit R-HSA-3371554 HSF1 acetylation at Lys80 R-HSA-1028819 VAF/pIRF7:CBP/p300 binds the promoters of type-I IFN genes R-HSA-157052 NICD traffics to nucleus R-HSA-350054 Notch-HLH transcription pathway R-HSA-381340 Transcriptional regulation of white adipocyte differentiation R-HSA-1234158 Regulation of gene expression by Hypoxia-inducible Factor R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis R-HSA-6803204 TP53 Regulates Transcription of Genes Involved in Cytochrome C Release R-HSA-8866907 Activation of the TFAP2 (AP-2) family of transcription factors R-HSA-8939246 RUNX1 regulates transcription of genes involved in differentiation of myeloid cells R-HSA-9018519 Estrogen-dependent gene expression R-HSA-8941856 RUNX3 regulates NOTCH signaling R-HSA-1912408 Pre-NOTCH Transcription and Translation R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) R-HSA-933541 TRAF6 mediated IRF7 activation R-HSA-918233 TRAF3-dependent IRF activation pathway R-HSA-3134973 LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex R-HSA-5621575 CD209 (DC-SIGN) signaling R-HSA-212436 Generic Transcription Pathway R-HSA-1266738 Developmental Biology R-HSA-1234174 Regulation of Hypoxia-inducible Factor (HIF) by oxygen R-HSA-1980143 Signaling by NOTCH1 R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer R-HSA-5619507 Activation of HOX genes during differentiation R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors R-HSA-8878171 Transcriptional regulation by RUNX1 R-HSA-8939211 ESR-mediated signaling R-HSA-3214847 HATs acetylate histones R-HSA-9013508 NOTCH3 Intracellular Domain Regulates Transcription R-HSA-8878159 Transcriptional regulation by RUNX3 R-HSA-1912422 Pre-NOTCH Expression and Processing R-HSA-556833 Metabolism of lipids R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA R-HSA-201681 TCF dependent signaling in response to WNT R-HSA-5621481 C-type lectin receptors (CLRs) R-HSA-3371568 Attenuation phase R-HSA-73857 RNA Polymerase II Transcription R-HSA-2262749 Cellular response to hypoxia R-HSA-157118 Signaling by NOTCH R-HSA-2644603 Signaling by NOTCH1 in Cancer R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-9006931 Signaling by Nuclear Receptors R-HSA-3247509 Chromatin modifying enzymes R-HSA-9012852 Signaling by NOTCH3 R-HSA-1430728 Metabolism R-HSA-168249 Innate Immune System R-HSA-195721 Signaling by WNT R-HSA-3371571 HSF1-dependent transactivation R-HSA-74160 Gene expression (Transcription) R-HSA-2262752 Cellular responses to stress R-HSA-162582 Signal Transduction R-HSA-5663202 Diseases of signal transduction R-HSA-4839726 Chromatin organization R-HSA-168256 Immune System R-HSA-3371556 Cellular response to heat stress R-HSA-8953897 Cellular responses to external stimuli R-HSA-1643685 Disease