BioPAX pathway converted from "Crebbp acetylates replicative histone H2B, H3, H4" in the Reactome database.

2.3.1.48

Crebbp acetylates replicative histone H2B, H3, H4

CREBBP (CBP) is named after its interaction with the CRE-binding protein CREB, though it interacts with many other proteins. It is thought to act as an integrator of signals from various pathways (Goodman & Smolik 2000), which compete for a limited amount of nuclear CREBBP. CREBBP and EP300 (p300) are closely related and have overlapping functions but also unique properties, particularly in vivo (Kalkhoven 2004). Both proteins form a physical bridge between DNA-binding transcription factors and the RNA polymerase II complex. Histones are believed to be the main acetylation targets of CREBBP and EP300, but their ability to acetylate and thereby regulate transcription factors such as p53 (Gu & Roeder 1997) is considered significant additional function (Kasper et al. 2006). CREBBP has intrinsic histone acetyltransferase (HAT) activity on lysine-12 of H2B, lysine-14 of H3 and lysine-8 of H4 (Bannister & Kouzarides 1996, Rekowski & Giannis 2010, Barrett et al. 2011). Homozygous knockout of Crebbp results in embryonic lethality (Tanaka et al. 1997). Focal deletion of Crebbp demonstrates that it is critical for the in vivo acetylation of lysines on histones H2B, H3 and H4, and cannot be compensated for by the p300 (Barrett et al. 2011). Genomic aberrations in CREBBP are associated with Rubinstein-Taybi syndrome (Torress et al. 2013).

Authored: Jupe, S, 2013-03-12Reviewed: Karagiannis, Tom, 2013-11-18Edited: Jupe, S, 2013-11-18

Converted from EntitySet in Reactome

Reactome DB_ID: 4568937

nucleoplasmGO0005654

Histone H2B, H3, H4 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityHistone H2B type 1-P [nucleoplasm]Histone H2B subacrosomal variant [nucleoplasm]Histone H2B type 1-F/J/L [nucleoplasm]Hist1h3b [nucleoplasm]Histone H2B type 3-A [nucleoplasm]Histone H3.1 [nucleoplasm]Histone H2B type 1-C/E/G [nucleoplasm]Histone H2B type 1-B [nucleoplasm]Histone H2B type 1-M [nucleoplasm]Histone H3.3 [nucleoplasm]Histone H2B type 2-E [nucleoplasm]Histone H2B type 2-B [nucleoplasm]Histone H2B type 1-K [nucleoplasm]Histone H2B type 3-B [nucleoplasm]Histone H2B type 1-A [nucleoplasm]Histone H2B type 1-H [nucleoplasm]Histone H4 [nucleoplasm]

Reactomehttp://www.reactome.orgMus musculus

NCBI Taxonomy10090UniProtQ8CGP2UniProtQ9D9Z7UniProtP10853UniProtP84228UniProtQ9D2U9UniProtP68433UniProtQ6ZWY9UniProtQ64475UniProtP10854UniProtP84244UniProtQ64524UniProtQ64525UniProtQ8CGP1UniProtQ8CGP0UniProtP70696UniProtQ64478UniProtP62806Converted from EntitySet in Reactome

Reactome DB_ID: 4568948

AcK-histone H2B, H3, H4 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityAcK13-Histone H2B type 2-E [nucleoplasm]AcK13-Histone H2B type 3-A [nucleoplasm]AcK13-Histone H2B type 1-F/J/L [nucleoplasm]AcK13-Histone H2B type 1-K [nucleoplasm]AcK15-histone H3.2 [nucleoplasm]AcK13-Histone H2B type 1-M [nucleoplasm]AcK13-Histone H2B type 1-B [nucleoplasm]AcK13-Histone H2B type 1-P [nucleoplasm]AcK13-Histone H2B type 3-B [nucleoplasm]AcK9-histone H4 [nucleoplasm]AcK13-Histone H2B type 2-B [nucleoplasm]AcK15-histone H3.3 [nucleoplasm]AcK13-Histone H2B type 1-C/E/G [nucleoplasm]AcK15-histone H3.1 [nucleoplasm]AcK13-Histone H2B subacrosomal variant [nucleoplasm]AcK13-Histone H2B type 1-H [nucleoplasm]AcK13-Histone H2B type 1-A [nucleoplasm]

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 556795

UniProt:P45481 Crebbp

Crebbp

CrebbpCbpFUNCTION Acetylates histones, giving a specific tag for transcriptional activation (By similarity). Also acetylates non-histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10207073, PubMed:11701890, PubMed:16287980, PubMed:15220471). Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes (By similarity). Acts as a coactivator of ALX1 (By similarity). Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers (By similarity). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24737000). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (By similarity). Acetylates DDX21, thereby inhibiting DDX21 helicase activity (By similarity). Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (By similarity). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (By similarity).SUBUNIT Interacts with DHX9 (via N-terminus); this interaction mediates association with RNA polymerase II holoenzyme and stimulates CREB-dependent transcriptional activation (By similarity). Interacts (via transactivation domain and C-terminus) with PCNA; the interaction occurs on chromatin in UV-irradiated damaged cells (By similarity). Found in a complex containing NCOA2; NCOA3; IKKA; IKKB and IKBKG. Probably part of a complex with HIF1A and EP300. The TAZ-type 1 domain interacts with HIF1A. Interacts with SRCAP, ELF3, MLLT7/FOXO4, N4BP2, NCOA6, PCAF, PELP1, PML, SMAD1, SMAD2, SMAD3, SPIB and TRERF1. Interacts with KLF1; the interaction results in acetylation and enhancement of transcriptional activity of KLF1. 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 with IRF3 (when phosphorylated); forming the dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I interferon genes (By similarity). Interacts (via N-terminus) with SS18L1/CREST (via C-terminus). Interacts with FOXO1; the interaction acetylates FOXO1 and inhibits its transcriptional activity. Interacts with MECOM and MTDH. Interacts with ASF1A and ASF1B; this promotes histone acetylation. Interacts with acetylated TP53/p53 and with the acetylated histones H3 and H4 (By similarity). Interacts with CITED1 (via C-terminus). Interacts with GATA1; the interaction results in acetylation and enhancement of transcriptional activity of GATA1. Interacts with MAF, CARM1. NCOA3, ZCCHC12, DDX17, DDX5 AND CITED4 (C-terminal region). Interacts with phosphorylated CREB1. Interacts with DAXX; the interaction is dependent on CBP sumoylation and results in suppression of the transcriptional activity via recruitment of HDAC2 to DAXX. Interacts with NPAS2, CLOCK and ARNTL/BMAL1. Interacts with SMAD4; negatively regulated by ZBTB7A (By similarity). Forms a complex with KMT2A and CREB1 (By similarity). Interacts with DDX3X; this interaction may facilitate HNF4A acetylation (By similarity).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.PTM Phosphorylated by CHUK/IKKA at Ser-1383 and Ser-1387; 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.PTM Autoacetylation is required for binding to protein substrates, such as acetylated histones and acetylated TP53/p53.

UniProtP45481

Chain Coordinates

EQUAL

2441

EQUAL

GO0004402

GO molecular function

Reactome Database ID Release 754568770Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4568770Reactome Database ID Release 754568768Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=4568768ReactomeR-MMU-4568768

Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-4568768.19294190Pubmed1997Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein-Taybi syndromeTanaka, YNaruse, IMaekawa, TMasuya, HShiroishi, TIshii, SProc. Natl. Acad. Sci. U.S.A. 94:10215-2020493978Pubmed2010Histone acetylation modulation by small molecules: a chemical approachRekowski, Margarete von WantochGiannis, AthanassiosBiochim. Biophys. Acta 1799:760-716428436Pubmed2006Conditional knockout mice reveal distinct functions for the global transcriptional coactivators CBP and p300 in T-cell developmentKasper, Lawryn HFukuyama, TomofusaBiesen, Michelle ABoussouar, FayçalTong, Cailide Pauw, AntoineMurray, Peter Jvan Deursen, Jan M ABrindle, Paul KMol. Cell. Biol. 26:789-8098967953Pubmed1996The CBP co-activator is a histone acetyltransferaseBannister, A JKouzarides, TNature 384:641-321508930Pubmed2011Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memoryBarrett, Ruth MMalvaez, MelissaKramar, EnikoMatheos, Dina PArrizon, AbrahamCabrera, Sara MLynch, GaryGreene, Robert WWood, Marcelo ANeuropsychopharmacology 36:1545-5623643710Pubmed2013Disruption of the CREBBP gene and decreased expression of CREB, NF?B p65, c-JUN, c-FOS, BCL2 and c-MYC suggest immune dysregulationTorres, Leuridan CavalcanteKulikowski, Leslie DomeniciRamos, Patrícia LocosqueSugayama, Sofia Mizuko MiuraMoreira-Filho, Carlos AlbertoCarneiro-Sampaio, MagdaHum. Immunol.9288740Pubmed1997Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domainGu, WRoeder, RGCell 90:595-60610887150Pubmed2000CBP/p300 in cell growth, transformation, and developmentGoodman, R HSmolik, SGenes Dev. 14:1553-7715313412Pubmed2004CBP and p300: HATs for different occasionsKalkhoven, EricBiochem. Pharmacol. 68:1145-55