Scientific Background: CBP or CREB-binding protein is a nuclear transcriptional coactivator protein that binds specifically to the PKA-phosphorylated form of the CREB protein. Microinjection of an anti-CBP antiserum into fibroblasts leads to inhibition of transcription from a cAMP promoter (1). CBP can also cooperates with upstream activators, such as JUN. When JUN is phosphorylated at the transcriptionally stimulatory sites ser73 and ser63, it binds CBP with comparable affinity to CREB. Insulin signaling may directly regulate many cAMP signaling pathways at the transcriptional level by controlling CBP recruitment (2). Mutant CBP can be aberrantly recruited to CREB protein, resulting in inappropriate activation of gluconeogenesis and glucose intolerance.
2. Zhong, H. et al: The phosphorylation status of nuclear NF-kappa-B determines its association with CBP/p300 or HDAC-1. Molec. Cell 9: 625-636, 2002.
NCBI and Uniprot Product Information
NCBI Description
This gene is ubiquitously expressed and is involved in the transcriptional coactivation of many different transcription factors. First isolated as a nuclear protein that binds to cAMP-response element binding protein (CREB), this gene is now known to play critical roles in embryonic development, growth control, and homeostasis by coupling chromatin remodeling to transcription factor recognition. The protein encoded by this gene has intrinsic histone acetyltransferase activity and also acts as a scaffold to stabilize additional protein interactions with the transcription complex. This protein acetylates both histone and non-histone proteins. This protein shares regions of very high sequence similarity with protein p300 in its bromodomain, cysteine-histidine-rich regions, and histone acetyltransferase domain. Mutations in this gene cause Rubinstein-Taybi syndrome (RTS). Chromosomal translocations involving this gene have been associated with acute myeloid leukemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2009]
Uniprot Description
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. Ref.11 Ref.17 Ref.28 Ref.30
Catalytic activity: Acetyl-CoA + [histone] = CoA + acetyl-[histone].
Subunit structure: 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 activity via recruitment of HDAC2 to DAXX
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. Interacts with human herpes virus 8/HHV-8 protein vIRF-1; this interaction inhibits CREBBP binding to IRF3. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.31 Ref.32 Ref.34 Ref.35 Ref.38
Subcellular location: Cytoplasm. Nucleus. Note: Recruited to nuclear bodies by SS18L1/CREST. In the presence of ALX1 relocalizes from the cytoplasm to the nucleus. Ref.30 Ref.33
Domain: The KIX domain mediates binding to HIV-1 Tat.
Post-translational modification: 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.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. Ref.36Sumoylation negatively regulates transcriptional activity via the recruitment of DAAX
By similarity.
Involvement in disease: 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 KMT2A/MLL1; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription.Rubinstein-Taybi syndrome 1 (RSTS1) [MIM:180849]: A disorder characterized by craniofacial abnormalities, postnatal growth deficiency, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.49 Ref.50 Ref.51 Ref.52
Sequence similarities: Contains 1 bromo domain.Contains 1 KIX domain.Contains 2 TAZ-type zinc fingers.Contains 1 ZZ-type zinc finger.
Sequence caution: The sequence BAE06125.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
Research Articles on CBP
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Product Notes
The CBP crebbp (Catalog #AAA515298) is a Recombinant Protein produced from E Coli and is intended for research purposes only. The product is available for immediate purchase. The immunogen sequence is 1319-1710 with tag GST tag!!Expression System||E.coli!!Source Note||Recombinant human CBP (1319-1710) was expressed in E. coli cells. AAA Biotech's CBP can be used in a range of immunoassay formats including, but not limited to, Western Blot (WB). Researchers should empirically determine the suitability of the CBP crebbp for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "CBP, Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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