Recombinant Human CREB-binding protein (CREBBP), partial

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Code CSB-EP838805HU1
Size $256
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Product Details

Purity
Greater than 85% as determined by SDS-PAGE.
Target Names
CREBBP
Uniprot No.
Research Area
Cancer
Alternative Names
Histone lysine acetyltransferase CREBBP;Protein-lysine acetyltransferase CREBBP
Species
Homo sapiens (Human)
Source
E.coli
Expression Region
1081-1197aa
Target Protein Sequence
RKKIFKPEELRQALMPTLEALYRQDPESLPFRQPVDPQLLGIPDYFDIVKNPMDLSTIKRKLDTGQYQEPWQYVDDVWLMFNNAWLYNRKTSRVYKFCSKLAEVFEQEIDPVMQSLG
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
40.7 kDa
Protein Length
Partial
Tag Info
N-terminal GST-tagged
Form
Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer
If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
3-7 business days
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA
Please contact us to get it.
Description

Amino acids 1081-1197 form the expressed segment for recombinant Human CREBBP. This CREBBP protein is theoretically predicted to have a molecular weight of 40.7 kDa. This CREBBP recombinant protein is manufactured in e.coli. The CREBBP gene fragment has been modified by fusing the N-terminal GST tag, providing convenience in detecting and purifying the recombinant CREBBP protein during the following stages.

The human CREB-binding protein (CREBBP) is a versatile transcriptional coactivator that plays a pivotal role in gene regulation. CREBBP is involved in modulating various cellular processes by interacting with a wide range of transcription factors and nuclear receptors. It serves as a histone acetyltransferase, facilitating chromatin remodeling and promoting transcriptional activation. CREBBP is essential for embryonic development and has implications for cell growth, differentiation, and apoptosis. Dysregulation or mutations in CREBBP are associated with several genetic disorders, including Rubinstein-Taybi syndrome. Ongoing research focuses on unraveling the molecular mechanisms of CREBBP function, its involvement in disease pathways, and potential therapeutic interventions targeting its activity.

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Target Background

Function
Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers. Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region. Acetylates DDX21, thereby inhibiting DDX21 helicase activity. Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway.
Gene References into Functions
  1. Co-immunoprecipitation analysis and siRNA-mediated suppression of CREB expression indicated that phospho-CREB has a positive effect on pro-inflammatory gene expression in the crosstalk between BAFF- and TLR4-mediated signaling by forming trimeric complexes containing NF-kappaB, CBP, and CREB PMID: 28374824
  2. CREBBP and p300 may contribute to genome stability by fine-tuning the functions of DNA damage signaling and DNA repair factors, thereby expanding their role as tumor suppressors. (Review) PMID: 29170789
  3. This review is focused on the different targets and functions of p300/CBP in physiological and pathological processes, including lipogenesis, lipid export, gluconeogenesis, and liver fibrosis, also provided some nutrients as the regulator of p300/CBP for nutritional therapeutic approaches to treat liver diseases. PMID: 29862292
  4. provide evidence that both CREBBP and EP300 are bona fide tumor suppressors that control MHCII expression and promote tumor immune control; mutational inactivation of CREBBP, but not of EP300, has additional cell-intrinsic engraftment and growth-promoting effects PMID: 28831000
  5. BRD, PHD, and ZZ domains interact with SUMO-1 and Ubc9, and function as an intramolecular E3 ligase for SUMOylation of the cell cycle regulatory domain 1; the BRD is essential for histone H3 acetylation PMID: 28630323
  6. CREBBP Mutation is associated with Rubinstein-Taybi Syndrome and Medulloblastoma. PMID: 29551561
  7. The recruitment of COASY inhibits CBP-mediated TPX2 acetylation, promoting TPX2 degradation for mitotic exit. PMID: 29531224
  8. GATA3 interacts with and is acetylated by the acetyltransferase CBP. The major acetylated site of GATA3 in lung adenocarcinoma cells is lysine 119. PMID: 29453984
  9. Our study demonstrated the association of low CREBBP expression with adverse clinical and biological features, poor prednisone response, high MRD levels and inferior outcomes in paediatric Chinese patients with ALL who were treated with the BCH- 2003 and CCLG- 2008 pro- tocols. PMID: 28452416
  10. Knockdown of CREB suppressed the expression of matrix metallopeptidase (MMP)2/9. PMID: 28487942
  11. mutation unlikely to be an early event in squamous cell carcinogenesis PMID: 27094574
  12. Ectopic expression of EP300-ZNF384 and CREBBP-ZNF384 fusion altered differentiation of mouse hematopoietic stem and progenitor cells and also potentiated oncogenic transformation in vitro.our results indicate that gene fusion is a common class of genomic abnormalities in childhood ALL and that recurrent translocations involving EP300 and CREBBP may cause epigenetic deregulation with potential for therapeutic targeting. PMID: 27903646
  13. The CREBBP acetyltransferase is a haploinsufficient tumor suppressor in B-cell lymphoma. PMID: 28069569
  14. Understanding the effects of disrupting the acetyltransferase activity of CBP/p300 could pave the way for new therapeutic approaches to treat patients with these diseases PMID: 27380996
  15. How cancer cells use p300/CBP in their favor varies depending on the cellular context and is evident by the growing list of loss- and gain-of-function genetic alterations in p300 and CBP in solid tumors and hematological malignancies.[review] PMID: 27881443
  16. Mutations of CREBBP and SOCS1 are independent prognostic factors in diffuse large B cell lymphoma; CREBBP and EP300 mutations remained significant to predict worse OS, PFS, and EFS. PMID: 28302137
  17. We conclude that patients with missense mutations in this specific CREBBP region show a phenotype that differs substantially from that in patients with Rubinstein-Taybi syndrome, and may prove to constitute one (or more) separate entities. PMID: 27311832
  18. Pre-eclampsia occurs in 12/52 mothers of EP300 mutated individuals versus in 2/59 mothers of CREBBP mutated individuals, making pregnancy with an EP300 mutated fetus the strongest known predictor for pre-eclampsia PMID: 27648933
  19. Earlier loss of Crebbp is advantageous for lymphoid transformation and inform the cellular origins and subsequent evolution of lymphoid malignancies. PMID: 28825697
  20. Data show that specifically inhibiting the interaction between CBP and catenin with ICG-001 results in the differentiation of quiescent drug-resistant chronic myelogenous leukemia-initiating cells (CML LICs). PMID: 26657156
  21. 5-FU promotes global histone de-acetylation by enhancing the degradation of p300/CBP in colorectal neoplasms. PMID: 28465257
  22. CREBBP mutations were associated with inferior progression-free survival (PFS), whereas mutations in previously unreported HVCN1, a voltage-gated proton channel-encoding gene and B-cell receptor signaling modulator, were associated with improved PFS. PMID: 28064239
  23. the rate-limiting transition state for binding between the TAZ1 domain of CREB binding protein and the intrinsically disordered transactivation domain of STAT2 (TAD-STAT2) by site-directed mutagenesis and kinetic experiments (Phi-value analysis) and found that the native protein-protein binding interface is not formed at the transition state for binding. PMID: 28707474
  24. In targeted sequencing, a disruptive mutation of TNFAIP3 was the most common alteration (54%), followed by mutations of TBL1XR1 (18%) and cAMP response element binding proteins (CREBBP) (17%). PMID: 28152507
  25. A mosaic variant in CREBBP identified as pathogenic in a patient with overlapping clinical features of Rubinstein-Taybi and Filippi syndromes tested negative for CKAP2L. PMID: 26956253
  26. CREBBP-BCORL1 fusion is associated with ossifying fibromyxoid tumors. PMID: 27537276
  27. Mapping the interactions of adenoviral E1A proteins with the p160 nuclear receptor coactivator binding domain of CBP PMID: 27699893
  28. CREBBP mutations might assist in enhancing oncogenic RAS signaling in acute lymphoblastic leukemia but do not alter response to MEK inhibitors. PMID: 27979926
  29. Mutations identified in patients with and without classical Rubinstein-Taybi syndrome lead to skipping of exon20 of CREBBP. PMID: 27165009
  30. Letter/Case Report: duplication mutation, c.5837dupC (p.P1947TfsX19), in CREBBP in patient with Rubinstein-Taybi syndrome with multiple pilomatricomas. PMID: 27342041
  31. C646 treatment attenuated ETV1 protein expression and inactivated KIT-dependent pathways. Taken together, the present study suggests that CBP/p300 may serve as novel antineoplastic targets and that use of the selective HAT inhibitor C646 is a promising antitumor strategy for Gastrointestinal stromal tumors. PMID: 27633918
  32. The CREBBP gene is believed to be the dosage-sensitive critical gene responsible for the reciprocal duplication and deletion syndrome PMID: 26873618
  33. Results show that CREBBP was the most frequent target of epigenetic modification in juvenile myelomonocytic leukemia. PMID: 27158276
  34. Data show that mutation of key residues in the binding site abolishes binding and that small ubiquitin-like modifier 1 (SUMO1) can simultaneously and non-cooperatively bind both the ZZ domain and a canonical SIM motif of CREB-binding protein (CBP/p300). PMID: 27129204
  35. Cyclic AMP Response Element Binding Protein Mediates Pathological Retinal Neovascularization via Modulating DLL4-NOTCH1 Signaling PMID: 26870802
  36. high expression of both CREB-binding protein and cleavage and polyadenylation specific factor 4 predicted a poor prognosis in the patients with lung adenocarcinomas. PMID: 26628108
  37. RFPL3 and CBP have roles in upregulating hTERT activity and promoting lung cancer growth PMID: 26318425
  38. Disruption of beta-catenin/CBP signaling inhibits human airway epithelial-mesenchymal transition and repair. PMID: 26315281
  39. Intrinsic protein disorder plays a prominent role in the function and interactions of the transcriptional co-activators CBP and p300. (Review) PMID: 26851278
  40. 42 new CREBBP mutations were reported in 46 Rubinstein-Taybi syndrome patients. PMID: 25388907
  41. Computational simulations were used to understand how phosphorylation affects the structure of the p53 terminal transactivation domain in complex with the CBP TAZ2 domain. PMID: 26742101
  42. these data suggest that CBP/p300 are promising therapeutic targets across multiple subtypes in acute myeloid leukemia. PMID: 25893291
  43. Conclude that the CBP/beta-catenin complex is a core component of the MDR1 transcriptional "enhancesome" in neoplasms. PMID: 25968898
  44. WNT/beta-catenin signaling does not affect nuclear translocation of the RelA subunit of NF-kappaB or its association with CBP (also known as CREBBP) PMID: 26021349
  45. Kaposi's sarcoma-associated herpesvirus vIRF4 targets the beta-catenin/CBP cofactor and blocks its occupancy on the cyclin D1 promoter, suppressing the G1-S cell cycle progression and enhancing virus replication. PMID: 26491150
  46. Case Report: novel nonsense mutation of CREBBP in a patient with Rubinstein-Taybi syndrome. PMID: 26603346
  47. destabilization of p300/CBP by downregulation of iASPP expression levels appears to represent a molecular mechanism that contributes to chemoresistance in melanoma cells. PMID: 25675294
  48. these findings suggest that sumoylation plays a critical role in the spatiotemporal co-activation of CLOCK-BMAL1 by CBP for immediate-early Per induction and the resetting of the circadian clock. PMID: 26164627
  49. First study of Korean Rubinstein-Taybi syndrome patients indicating distinct geographic distribution of CREBBP mutations PMID: 25108505
  50. CREBBP mutations are associated with recurrence in hyperdiploid acute lymphoblastic leukemia. PMID: 25917266

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Involvement in disease
Rubinstein-Taybi syndrome 1 (RSTS1)
Subcellular Location
Cytoplasm. Nucleus. Note=Recruited to nuclear bodies by SS18L1/CREST. In the presence of ALX1 relocalizes from the cytoplasm to the nucleus.
Database Links

HGNC: 2348

OMIM: 180849

KEGG: hsa:1387

STRING: 9606.ENSP00000262367

UniGene: Hs.459759

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