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CREB-binding protein; CBP transcriptional coactivator (CREBBP, CBP)

Function: - binds to cAMP protein kinase phosphorylated form of CREB & interacts with at least one CREB family member as a specific DNA-bound complex - intrinsic histone acetyltransferase (HAT) activity [3] - acetylates histones, giving a specific tag for transcriptional activation [3] - also acetylates non-histone proteins, including NCOA3 coactivator - binds specifically to phosphorylated CREB & enhances its transcriptional activity toward cAMP-responsive genes - binds to cAMP protein kinase phosphorylated form of CREB & interacts with at least one CREB family member as a specific DNA-bound complex - methylation of the KIX domain by CARM1 blocks association with CREB; this results in the blockade of CREB signaling, & in activation of apoptotic response (putative) - phosphorylated upon DNA damage, probably by ATM or ATR - sumoylation negatively regulates transcriptional activity via recruitment of DAAX (putative) - found in a complex containing NCOA2; NCOA3; IKKA; IKKB & IKBKG - probably part of a complex with HIF1A & EP300 - interacts with phosphorylated CREB1 - interacts with the C-terminal region of CITED4 - the TAZ-type 1 domain interacts with HIF1A - interacts with MAF, SRCAP, CARM1, ELF3, MLLT7/FOXO4, N4BP2, NCOA1, NCOA3, NCOA6, PCAF, PELP1, PML, SMAD1, SMAD2, SMAD3, SPIB & TRERF1 - interacts with KLF1; the interaction results in acetylation of KLF1 & enhancement of its transcriptional activity - interacts with ZCCHC12 (putative) - interacts with DAXX; the interaction is dependent on CBP sumoylation & results in suppression of the transcriptional activiy via recruitment of HDAC2 to DAAX - interacts with MTDH - interacts with NFATC4 - interacts with MAFG; the interaction acetylates MAFG in the basic region & stimulates NFE2 transcriptional activity through increasing its DNA-binding activity - interacts with IRF2; the interaction acetylates IRF2 & regulates its activity on the H4 promoter - interacts with TFIIB Structure: - the KIX domain mediates binding to HIV-1 Tat - contains 1 bromo domain - contains 1 KIX domain - contains 2 TAZ-type Zn+2 fingers - contains 1 ZZ-type Zn+2 finger Compartment: nucleus Pathology: - binding of adenovirus E1a oncoprotein inhibits activity (does not disrupt histone acetyltransferase activity) - loss of heterozygosity described in 80% of glioblastomas [4] - loss of heterozygocity around CBP gene locus seen in hepatocellular carcinoma - chromosomal translocations in acute leukemia - t(8;16)(p11;p13) involving CBP & MOZ - t(11;16)(q23;p13.3) involving CBP & MLL - t(10;16)(q22;p13) involving CBP & MYST4 (AML) - mutations associated with Rubinstein-Taybi syndrome - interacts with HTLV-1 Tax & p30II - interacts with HIV-1 Tat

Interactions

molecular events

Related

CREBBP (CBP) gene histone acetyltransferase p300; p300 HAT; E1A-associated protein p300 (EP300, P300) IkB kinase complex

General

histone acetyltransferase phosphoprotein transcriptional adaptor protein; transcriptional coactivator zinc finger protein

Properties

SIZE: entity length = 2442 aa MW = 265 kD COMPARTMENT: cell nucleus MOTIF: breakpoint {29-30} Ser phosphorylation site {S121} Ser phosphorylation site {S124} SRCAP interaction {227-410} MOTIF: breakpoint {266-267} Zinc finger NAME: Zinc finger SITE: 347-433 EFFECTOR-BOUND: Zn+2 KIX {587-666} Thr phosphorylation site {T1001} Ser phosphorylation site {S1030} glutamate-rich region {1061-1064} MOTIF: glutamate residue (SEVERAL) Ser phosphorylation site {S1072} bromodomain {1103-1175} histidine-rich region {1199-1487} MOTIF: histidine residue (SEVERAL) TRERF1 interaction {1460-1891} MOTIF: glutamate-rich region {1555-1562} MOTIF: glutamate residue (SEVERAL) Zn finger ZZ-type NAME: Zn finger ZZ-type SITE: 1701-1744 EFFECTOR-BOUND: Zn+2 Ser phosphorylation site {S1755} Zinc finger NAME: Zinc finger SITE: 1765-1846 EFFECTOR-BOUND: Zn+2 proline-rich region SITE: 1943-1948 MOTIF: proline residue (SEVERAL) glutamine-rich region {1967-1970} MOTIF: glutamine residue (SEVERAL) Ser phosphorylation site {S2063} Ser phosphorylation site {S2076} Ser phosphorylation site {S2079} glutamine-rich region {2081-2085} MOTIF: glutamine residue (SEVERAL) glutamine-rich region {2199-2216} MOTIF: glutamine residue (SEVERAL) glutamine-rich region {2245-2248} MOTIF: glutamine residue (SEVERAL) glutamine-rich region {2297-2300} MOTIF: glutamine residue (SEVERAL)

References

  1. Arany Z et al A family of transcriptional adaptor proteins targeted by the E1A oncoprotein. Nature 374:81 1995 PMID: 7870178
  2. Lundblad JR et al Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature 374:85 1995 PMID: 7870179
  3. Bannister AJ & Kouzarides T The CBP co-activator is a histone acetyltransferase. Nature 384:641-3 1996 PMID: 8967953
  4. Marks P et al Histone deacetylases and cancer: causes and therapies. Nature Reviews Cancer 1:194-202, 2001 PMID: 11902574
  5. UniProt :accession Q92793
  6. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/CBPID42.html
  7. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=CREBBP
  8. Wikipedia; Note: P300/CBP entry http://en.wikipedia.org/wiki/P300/CBP

Component-of

molecular complex

Databases & Figures

OMIM correlations MORBIDMAP 600140 UniProt Q92793 PFAM correlations Entrez Gene 1387 KEGG correlations ENZYME 2.3.1.48 Figures/diagrams/slides/tables related to CREB-binding protein