UniProt functional annotation for Q92831



	UniProt functional annotation for Q92831

UniProt code: Q92831.

Organism: Homo sapiens (Human).

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

Function: Functions as a histone acetyltransferase (HAT) to promote transcriptional activation (PubMed:8945521). Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles (PubMed:8945521). Also acetylates non- histone proteins, such as ACLY, PLK4, RRP9/U3-55K and TBX5 (PubMed:9707565, PubMed:10675335, PubMed:27796307, PubMed:23932781, PubMed:26867678, PubMed:29174768). Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A (PubMed:8684459). 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). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Acetylates RRP9/U3-55K, a core subunit of the U3 snoRNP complex, impairing pre-rRNA processing (PubMed:26867678). Also acetylates spermidine (PubMed:27389534). {ECO:0000269|PubMed:10675335, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:26867678, ECO:0000269|PubMed:27389534, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29174768, ECO:0000269|PubMed:8684459, ECO:0000269|PubMed:8945521, ECO:0000269|PubMed:9707565}.

Function: (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. {ECO:0000269|PubMed:12486002}.

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; EC=2.3.1.48; Evidence={ECO:0000269|PubMed:27389534, ECO:0000269|PubMed:8945521}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45949; Evidence={ECO:0000305|PubMed:27389534};

Catalytic activity: Reaction=acetyl-CoA + spermidine = CoA + H(+) + N(8)-acetylspermidine; Xref=Rhea:RHEA:28270, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57834, ChEBI:CHEBI:58535; EC=2.3.1.57; Evidence={ECO:0000269|PubMed:27389534}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28271; Evidence={ECO:0000305|PubMed:27389534};

Activity regulation: Activated in vitro by very low concentrations of spermidine, but inhibited at spermidine concentrations higher than 4 uM. The activating effect of low spermidine concentrations may be mediated by N(8)-acetylspermidine produced by KAT2B/P/CAF itself acting as a positive feedback loop. {ECO:0000269|PubMed:27389534}.

Biophysicochemical properties: Kinetic parameters: KM=1.74 uM for acetyl-CoA {ECO:0000269|PubMed:27389534}; KM=2.29 uM for spermidine {ECO:0000269|PubMed:27389534};

Subunit: Interacts with SIRT1. Interacts (unsumoylated form) with NR2C1; the interaction promotes transactivation activity (By similarity). Interacts with EP300, CREBBP and DDX17. Interacts with NCOA1 and NCOA3. Component of a large chromatin remodeling complex, at least composed of MYSM1, KAT2B/PCAF, RBM10 and KIF11/TRIP5. Interacts with NR2C2 (hypophosphorylated and unsumoylated form); the interaction promotes the transactivation activity of NR2C2. Interacts with KLF1; the interaction does not acetylate KLF1 and there is no enhancement of its transactivational activity. Interacts with NFE4. Interacts with MECOM. Interacts with E2F1; the interaction acetylates E2F1 augmenting its DNA-binding and transcriptional activity. Interacts with NPAS2, ARNTL/BMAL1 and CLOCK. Interacts with BCAS3. Interacts with CEBPB (PubMed:17301242). Interacts with NR4A3 (By similarity). Interacts with NFATC2 (By similarity). Interacts with TBX5 (PubMed:29174768). Interacts with PLK4 (PubMed:27796307). Interacts with RB1; this interaction leads to RB1 acetylation (By similarity). {ECO:0000250|UniProtKB:Q9JHD1, ECO:0000269|PubMed:10675335, ECO:0000269|PubMed:11568182, ECO:0000269|PubMed:11931765, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:14767476, ECO:0000269|PubMed:15273251, ECO:0000269|PubMed:16887930, ECO:0000269|PubMed:17226766, ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:17505058, ECO:0000269|PubMed:17707232, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29174768, ECO:0000269|PubMed:8684459, ECO:0000269|PubMed:9296499, ECO:0000269|PubMed:9346901, ECO:0000269|PubMed:9707565}.

Subunit: (Microbial infection) Interacts with and acetylates HIV-1 Tat. {ECO:0000269|PubMed:12486002}.

Subunit: (Microbial infection) Interacts with HTLV-1 Tax. {ECO:0000269|PubMed:10766811}.

Subcellular location: Nucleus {ECO:0000269|PubMed:20940255, ECO:0000269|PubMed:29174768}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:29174768}. Cytoplasm {ECO:0000269|PubMed:20940255}. Note=Mainly localizes to the nucleus. Also localizes to centrosomes in late G1 and around the G1/S transition, coinciding with the onset of centriole formation. Subcellular location may vary depending upon cell differentiation state. Cytoplasmic at the very stages of keratinocyte differentiation, becomes nuclear at later differentiation stages. Cytoplasmic in basal epithelial cells (undifferentiated cells) and nuclear in parabasal cells (differentiated cells) (PubMed:20940255). {ECO:0000269|PubMed:20940255, ECO:0000269|PubMed:29174768}.

Tissue specificity: Ubiquitously expressed but most abundant in heart and skeletal muscle. Also expressed in the skin, in keratinocytes (at protein level) (PubMed:20940255). {ECO:0000269|PubMed:20940255, ECO:0000269|PubMed:8684459}.

Developmental stage: Up-regulated during keratinocyte differentiation (at protein level). {ECO:0000269|PubMed:20940255}.

Domain: (Microbial infection) The bromodomain mediates binding to HIV-1 Tat. {ECO:0000269|PubMed:11931765}.

Disease: Note=Defects in KAT2B has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269|PubMed:28493397}.

Similarity: Belongs to the acetyltransferase family. GCN5 subfamily. {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:		Functions as a histone acetyltransferase (HAT) to promote transcriptional activation (PubMed:8945521). Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles (PubMed:8945521). Also acetylates non- histone proteins, such as ACLY, PLK4, RRP9/U3-55K and TBX5 (PubMed:9707565, PubMed:10675335, PubMed:27796307, PubMed:23932781, PubMed:26867678, PubMed:29174768). Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A (PubMed:8684459). 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). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Acetylates RRP9/U3-55K, a core subunit of the U3 snoRNP complex, impairing pre-rRNA processing (PubMed:26867678). Also acetylates spermidine (PubMed:27389534). {ECO:0000269\|PubMed:10675335, ECO:0000269\|PubMed:14645221, ECO:0000269\|PubMed:23932781, ECO:0000269\|PubMed:26867678, ECO:0000269\|PubMed:27389534, ECO:0000269\|PubMed:27796307, ECO:0000269\|PubMed:29174768, ECO:0000269\|PubMed:8684459, ECO:0000269\|PubMed:8945521, ECO:0000269\|PubMed:9707565}.



Function:		(Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. {ECO:0000269\|PubMed:12486002}.


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; EC=2.3.1.48; Evidence={ECO:0000269\|PubMed:27389534, ECO:0000269\|PubMed:8945521}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45949; Evidence={ECO:0000305\|PubMed:27389534};
Catalytic activity:		Reaction=acetyl-CoA + spermidine = CoA + H(+) + N(8)-acetylspermidine; Xref=Rhea:RHEA:28270, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57834, ChEBI:CHEBI:58535; EC=2.3.1.57; Evidence={ECO:0000269\|PubMed:27389534}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28271; Evidence={ECO:0000305\|PubMed:27389534};
Activity regulation:		Activated in vitro by very low concentrations of spermidine, but inhibited at spermidine concentrations higher than 4 uM. The activating effect of low spermidine concentrations may be mediated by N(8)-acetylspermidine produced by KAT2B/P/CAF itself acting as a positive feedback loop. {ECO:0000269\|PubMed:27389534}.
Biophysicochemical properties:		Kinetic parameters: KM=1.74 uM for acetyl-CoA {ECO:0000269\|PubMed:27389534}; KM=2.29 uM for spermidine {ECO:0000269\|PubMed:27389534};
Subunit:		Interacts with SIRT1. Interacts (unsumoylated form) with NR2C1; the interaction promotes transactivation activity (By similarity). Interacts with EP300, CREBBP and DDX17. Interacts with NCOA1 and NCOA3. Component of a large chromatin remodeling complex, at least composed of MYSM1, KAT2B/PCAF, RBM10 and KIF11/TRIP5. Interacts with NR2C2 (hypophosphorylated and unsumoylated form); the interaction promotes the transactivation activity of NR2C2. Interacts with KLF1; the interaction does not acetylate KLF1 and there is no enhancement of its transactivational activity. Interacts with NFE4. Interacts with MECOM. Interacts with E2F1; the interaction acetylates E2F1 augmenting its DNA-binding and transcriptional activity. Interacts with NPAS2, ARNTL/BMAL1 and CLOCK. Interacts with BCAS3. Interacts with CEBPB (PubMed:17301242). Interacts with NR4A3 (By similarity). Interacts with NFATC2 (By similarity). Interacts with TBX5 (PubMed:29174768). Interacts with PLK4 (PubMed:27796307). Interacts with RB1; this interaction leads to RB1 acetylation (By similarity). {ECO:0000250\|UniProtKB:Q9JHD1, ECO:0000269\|PubMed:10675335, ECO:0000269\|PubMed:11568182, ECO:0000269\|PubMed:11931765, ECO:0000269\|PubMed:14645221, ECO:0000269\|PubMed:14767476, ECO:0000269\|PubMed:15273251, ECO:0000269\|PubMed:16887930, ECO:0000269\|PubMed:17226766, ECO:0000269\|PubMed:17301242, ECO:0000269\|PubMed:17505058, ECO:0000269\|PubMed:17707232, ECO:0000269\|PubMed:27796307, ECO:0000269\|PubMed:29174768, ECO:0000269\|PubMed:8684459, ECO:0000269\|PubMed:9296499, ECO:0000269\|PubMed:9346901, ECO:0000269\|PubMed:9707565}.
Subunit:		(Microbial infection) Interacts with and acetylates HIV-1 Tat. {ECO:0000269\|PubMed:12486002}.
Subunit:		(Microbial infection) Interacts with HTLV-1 Tax. {ECO:0000269\|PubMed:10766811}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:20940255, ECO:0000269\|PubMed:29174768}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:29174768}. Cytoplasm {ECO:0000269\|PubMed:20940255}. Note=Mainly localizes to the nucleus. Also localizes to centrosomes in late G1 and around the G1/S transition, coinciding with the onset of centriole formation. Subcellular location may vary depending upon cell differentiation state. Cytoplasmic at the very stages of keratinocyte differentiation, becomes nuclear at later differentiation stages. Cytoplasmic in basal epithelial cells (undifferentiated cells) and nuclear in parabasal cells (differentiated cells) (PubMed:20940255). {ECO:0000269\|PubMed:20940255, ECO:0000269\|PubMed:29174768}.
Tissue specificity:		Ubiquitously expressed but most abundant in heart and skeletal muscle. Also expressed in the skin, in keratinocytes (at protein level) (PubMed:20940255). {ECO:0000269\|PubMed:20940255, ECO:0000269\|PubMed:8684459}.
Developmental stage:		Up-regulated during keratinocyte differentiation (at protein level). {ECO:0000269\|PubMed:20940255}.
Domain:		(Microbial infection) The bromodomain mediates binding to HIV-1 Tat. {ECO:0000269\|PubMed:11931765}.
Disease:		Note=Defects in KAT2B has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269\|PubMed:28493397}.
Similarity:		Belongs to the acetyltransferase family. GCN5 subfamily. {ECO:0000305}.