UniProt functional annotation for Q92793



	UniProt functional annotation for Q92793

UniProt code: Q92793.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Acetylates histones, giving a specific tag for transcriptional activation (PubMed:24616510). Also acetylates non- histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:9707565, PubMed:24207024, PubMed:28790157, PubMed:30540930). 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 (PubMed:14645221). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). Acetylates DDX21, thereby inhibiting DDX21 helicase activity (PubMed:28790157). Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (PubMed:30540930). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493). {ECO:0000269|PubMed:10490106, ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:12738767, ECO:0000269|PubMed:12929931, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:24616510, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:30540930, ECO:0000269|PubMed:9707565}.

Catalytic activity: Reaction=acetyl-CoA + L-lysyl-[histone] = CoA + H(+) + N(6)-acetyl-L- lysyl-[histone]; Xref=Rhea:RHEA:21992, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:11338, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48; Evidence={ECO:0000269|PubMed:24616510}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21993; Evidence={ECO:0000269|PubMed:24616510};

Catalytic activity: Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L- lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; Evidence={ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:12738767, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:30540930}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45949; Evidence={ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:12738767, ECO:0000269|PubMed:24207024, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:28790157, ECO:0000269|PubMed:30540930};

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 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 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 with IRF3 (when phosphorylated); forming the dsRNA- activated factor 1 (DRAF1), a complex which activates the transcription of the type I interferon genes (PubMed:27302953). 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 NPAS2, CLOCK and ARNTL/BMAL1. Interacts with ASF1A and ASF1B; this promotes histone acetylation. Interacts with acetylated TP53/p53 and with the acetylated histones H3 and H4. Interacts (via transactivation domain and C-terminus) with PCNA; the interaction occurs on chromatin in UV-irradiated damaged cells (PubMed:24939902). Interacts with DHX9 (via N-terminus); this interaction mediates association with RNA polymerase II holoenzyme and stimulates CREB- dependent transcriptional activation (PubMed:9323138). Interacts with SMAD4; negatively regulated by ZBTB7A (PubMed:25514493). Interacts with DUX4 (via C-terminus) (PubMed:26951377). Forms a complex with KMT2A and CREB1 (PubMed:23651431). Interacts with DDX3X; this interaction may facilitate HNF4A acetylation (PubMed:28128295). {ECO:0000250, ECO:0000269|PubMed:10077561, ECO:0000269|PubMed:10347196, ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:10866662, ECO:0000269|PubMed:11154691, ECO:0000269|PubMed:11349124, ECO:0000269|PubMed:11481323, ECO:0000269|PubMed:11514544, ECO:0000269|PubMed:11568182, ECO:0000269|PubMed:11744733, ECO:0000269|PubMed:11864910, ECO:0000269|PubMed:11959977, ECO:0000269|PubMed:11971985, ECO:0000269|PubMed:12730195, ECO:0000269|PubMed:12738767, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:14716005, ECO:0000269|PubMed:15075319, ECO:0000269|PubMed:15126506, ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:18316612, ECO:0000269|PubMed:23651431, ECO:0000269|PubMed:24616510, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:26951377, ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:28128295, ECO:0000269|PubMed:8684459, ECO:0000269|PubMed:8917528, ECO:0000269|PubMed:9323138, ECO:0000269|PubMed:9707565}.

Subunit: (Microbial infection) Interacts with HTLV-1 Tax, p30II and HBZ. {ECO:0000269|PubMed:11463834, ECO:0000269|PubMed:11559821, ECO:0000269|PubMed:9528808}.

Subunit: (Microbial infection) Interacts with human herpes virus 8/HHV- 8 protein vIRF-1; this interaction inhibits CREBBP binding to IRF3. {ECO:0000269|PubMed:11314014}.

Subunit: (Microbial infection) Interacts with HIV-1 Tat. {ECO:0000269|PubMed:14744133}.

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). {ECO:0000250|UniProtKB:P45481}.

Ptm: 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. {ECO:0000269|PubMed:17434128}.

Ptm: Sumoylation negatively regulates transcriptional activity via the recruitment of DAAX. {ECO:0000250|UniProtKB:P45481}.

Ptm: Autoacetylation is required for binding to protein substrates, such as acetylated histones and acetylated TP53/p53. {ECO:0000269|PubMed:24616510}.

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 KMT2A/MLL1; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription.

Disease: 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. {ECO:0000269|PubMed:11331617, ECO:0000269|PubMed:12114483, ECO:0000269|PubMed:12566391, ECO:0000269|PubMed:15706485, ECO:0000269|PubMed:20684013, ECO:0000269|PubMed:24616510, ECO:0000269|PubMed:25388907}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Menke-Hennekam syndrome 1 (MKHK1) [MIM:618332]: A form of Menke-Hennekam syndrome, a congenital autosomal dominant disease characterized by developmental delay, growth retardation, and craniofacial dysmorphism. Patients have intellectual disability of variable severity, speech delay, autistic behavior, short stature and microcephaly. Main facial characteristics include short palpebral fissures, telecanthi, depressed nasal ridge, short nose, anteverted nares, short columella and long philtrum. {ECO:0000269|PubMed:27311832, ECO:0000269|PubMed:29460469, ECO:0000269|PubMed:30737887}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=BAE06125.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Acetylates histones, giving a specific tag for transcriptional activation (PubMed:24616510). Also acetylates non- histone proteins, like DDX21, FBL, IRF2, MAFG, NCOA3, POLR1E/PAF53 and FOXO1 (PubMed:10490106, PubMed:11154691, PubMed:12738767, PubMed:12929931, PubMed:9707565, PubMed:24207024, PubMed:28790157, PubMed:30540930). 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 (PubMed:14645221). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates POLR1E/PAF53, leading to decreased association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). Acetylates DDX21, thereby inhibiting DDX21 helicase activity (PubMed:28790157). Acetylates FBL, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me) (PubMed:30540930). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493). {ECO:0000269\|PubMed:10490106, ECO:0000269\|PubMed:11154691, ECO:0000269\|PubMed:12738767, ECO:0000269\|PubMed:12929931, ECO:0000269\|PubMed:14645221, ECO:0000269\|PubMed:24207024, ECO:0000269\|PubMed:24616510, ECO:0000269\|PubMed:24939902, ECO:0000269\|PubMed:25514493, ECO:0000269\|PubMed:28790157, ECO:0000269\|PubMed:30540930, ECO:0000269\|PubMed:9707565}.


Catalytic activity:		Reaction=acetyl-CoA + L-lysyl-[histone] = CoA + H(+) + N(6)-acetyl-L- lysyl-[histone]; Xref=Rhea:RHEA:21992, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:11338, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48; Evidence={ECO:0000269\|PubMed:24616510}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21993; Evidence={ECO:0000269\|PubMed:24616510};
Catalytic activity:		Reaction=acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L- lysyl-[protein]; Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; Evidence={ECO:0000269\|PubMed:11154691, ECO:0000269\|PubMed:12738767, ECO:0000269\|PubMed:24207024, ECO:0000269\|PubMed:24939902, ECO:0000269\|PubMed:30540930}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45949; Evidence={ECO:0000269\|PubMed:11154691, ECO:0000269\|PubMed:12738767, ECO:0000269\|PubMed:24207024, ECO:0000269\|PubMed:24939902, ECO:0000269\|PubMed:28790157, ECO:0000269\|PubMed:30540930};
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 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 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 with IRF3 (when phosphorylated); forming the dsRNA- activated factor 1 (DRAF1), a complex which activates the transcription of the type I interferon genes (PubMed:27302953). 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 NPAS2, CLOCK and ARNTL/BMAL1. Interacts with ASF1A and ASF1B; this promotes histone acetylation. Interacts with acetylated TP53/p53 and with the acetylated histones H3 and H4. Interacts (via transactivation domain and C-terminus) with PCNA; the interaction occurs on chromatin in UV-irradiated damaged cells (PubMed:24939902). Interacts with DHX9 (via N-terminus); this interaction mediates association with RNA polymerase II holoenzyme and stimulates CREB- dependent transcriptional activation (PubMed:9323138). Interacts with SMAD4; negatively regulated by ZBTB7A (PubMed:25514493). Interacts with DUX4 (via C-terminus) (PubMed:26951377). Forms a complex with KMT2A and CREB1 (PubMed:23651431). Interacts with DDX3X; this interaction may facilitate HNF4A acetylation (PubMed:28128295). {ECO:0000250, ECO:0000269\|PubMed:10077561, ECO:0000269\|PubMed:10347196, ECO:0000269\|PubMed:10722728, ECO:0000269\|PubMed:10866662, ECO:0000269\|PubMed:11154691, ECO:0000269\|PubMed:11349124, ECO:0000269\|PubMed:11481323, ECO:0000269\|PubMed:11514544, ECO:0000269\|PubMed:11568182, ECO:0000269\|PubMed:11744733, ECO:0000269\|PubMed:11864910, ECO:0000269\|PubMed:11959977, ECO:0000269\|PubMed:11971985, ECO:0000269\|PubMed:12730195, ECO:0000269\|PubMed:12738767, ECO:0000269\|PubMed:14645221, ECO:0000269\|PubMed:14716005, ECO:0000269\|PubMed:15075319, ECO:0000269\|PubMed:15126506, ECO:0000269\|PubMed:15220471, ECO:0000269\|PubMed:18316612, ECO:0000269\|PubMed:23651431, ECO:0000269\|PubMed:24616510, ECO:0000269\|PubMed:24939902, ECO:0000269\|PubMed:25514493, ECO:0000269\|PubMed:26951377, ECO:0000269\|PubMed:27302953, ECO:0000269\|PubMed:28128295, ECO:0000269\|PubMed:8684459, ECO:0000269\|PubMed:8917528, ECO:0000269\|PubMed:9323138, ECO:0000269\|PubMed:9707565}.
Subunit:		(Microbial infection) Interacts with HTLV-1 Tax, p30II and HBZ. {ECO:0000269\|PubMed:11463834, ECO:0000269\|PubMed:11559821, ECO:0000269\|PubMed:9528808}.
Subunit:		(Microbial infection) Interacts with human herpes virus 8/HHV- 8 protein vIRF-1; this interaction inhibits CREBBP binding to IRF3. {ECO:0000269\|PubMed:11314014}.
Subunit:		(Microbial infection) Interacts with HIV-1 Tat. {ECO:0000269\|PubMed:14744133}.
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). {ECO:0000250\|UniProtKB:P45481}.
Ptm:		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. {ECO:0000269\|PubMed:17434128}.
Ptm:		Sumoylation negatively regulates transcriptional activity via the recruitment of DAAX. {ECO:0000250\|UniProtKB:P45481}.
Ptm:		Autoacetylation is required for binding to protein substrates, such as acetylated histones and acetylated TP53/p53. {ECO:0000269\|PubMed:24616510}.
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 KMT2A/MLL1; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription.
Disease:		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. {ECO:0000269\|PubMed:11331617, ECO:0000269\|PubMed:12114483, ECO:0000269\|PubMed:12566391, ECO:0000269\|PubMed:15706485, ECO:0000269\|PubMed:20684013, ECO:0000269\|PubMed:24616510, ECO:0000269\|PubMed:25388907}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Menke-Hennekam syndrome 1 (MKHK1) [MIM:618332]: A form of Menke-Hennekam syndrome, a congenital autosomal dominant disease characterized by developmental delay, growth retardation, and craniofacial dysmorphism. Patients have intellectual disability of variable severity, speech delay, autistic behavior, short stature and microcephaly. Main facial characteristics include short palpebral fissures, telecanthi, depressed nasal ridge, short nose, anteverted nares, short columella and long philtrum. {ECO:0000269\|PubMed:27311832, ECO:0000269\|PubMed:29460469, ECO:0000269\|PubMed:30737887}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=BAE06125.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};