KAT7

The protein encoded by this gene is part of the multimeric HBO1 complex, which possesses histone H4-specific acetyltransferase activity. This activity is required for functional replication origins and is involved in transcriptional activation of some genes. In both cases, the acetylation of histone H4 helps unfold chromatin so that the DNA can be accessed and replicated or transcribed. [provided by RefSeq, Oct 2016]

Lysine Acetyltransferase 7

Catalytic subunit of histone acetyltransferase HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby regulating various processes, such as gene transcription, protein ubiquitination, immune regulation, stem cell pluripotent and self-renewal maintenance and embryonic development (PubMed:16387653, PubMed:21753189, PubMed:24065767, PubMed:26620551, PubMed:31767635, PubMed:31827282).
Some complexes also catalyze acetylation of histone H4 at 'Lys-5', 'Lys-8' and 'Lys-12' (H4K5ac, H4K8ac and H4K12ac, respectively), regulating DNA replication initiation, regulating DNA replication initiation (PubMed:10438470, PubMed:19187766, PubMed:20129055, PubMed:24065767).
Specificity of the HBO1 complexes is determined by the scaffold subunit: complexes containing BRPF scaffold (BRPF1, BRD1/BRPF2 or BRPF3) direct KAT7/HBO1 specificity towards H3K14ac, while complexes containing JADE (JADE1, JADE2 and JADE3) scaffold direct KAT7/HBO1 specificity towards histone H4 (PubMed:19187766, PubMed:20129055, PubMed:24065767, PubMed:26620551).
H3K14ac promotes transcriptional elongation by facilitating the processivity of RNA polymerase II (PubMed:31827282).
Acts as a key regulator of hematopoiesis by forming a complex with BRD1/BRPF2, directing KAT7/HBO1 specificity towards H3K14ac and promoting erythroid differentiation (PubMed:21753189).
H3K14ac is also required for T-cell development (By similarity).
KAT7/HBO1-mediated acetylation facilitates two consecutive steps, licensing and activation, in DNA replication initiation: H3K14ac facilitates the activation of replication origins, and histone H4 acetylation (H4K5ac, H4K8ac and H4K12ac) facilitates chromatin loading of MCM complexes, promoting DNA replication licensing (PubMed:10438470, PubMed:11278932, PubMed:18832067, PubMed:19187766, PubMed:20129055, PubMed:21856198, PubMed:24065767, PubMed:26620551).
Acts as a positive regulator of centromeric CENPA assembly: recruited to centromeres and mediates histone acetylation, thereby preventing centromere inactivation mediated by SUV39H1, possibly by increasing histone turnover/exchange (PubMed:27270040).
Involved in nucleotide excision repair: phosphorylation by ATR in response to ultraviolet irradiation promotes its localization to DNA damage sites, where it mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites (PubMed:28719581).
Acts as an inhibitor of NF-kappa-B independently of its histone acetyltransferase activity (PubMed:16997280).
Plays a central role in the maintenance of leukemia stem cells in acute myeloid leukemia (AML) (PubMed:31827282).
Acts by mediating acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby facilitating the processivity of RNA polymerase II to maintain the high expression of key genes, such as HOXA9 and HOXA10 that help to sustain the functional properties of leukemia stem cells (PubMed:31827282).

Chromatin organizationIEA:UniProtKB-KW
DNA repairIEA:UniProtKB-KW
DNA replicationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H3 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H3-K14 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H4 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H4-K12 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H4-K5 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H4-K8 acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone modificationManual Assertion Based On ExperimentIDA:ComplexPortal
Internal peptidyl-lysine acetylationManual Assertion Based On ExperimentIDA:UniProtKB
Natural killer cell differentiationISS:UniProtKB
Negative regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of DNA replicationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of DNA-templated transcription, elongationISS:UniProtKB
Positive regulation of erythrocyte differentiationIEA:Ensembl
Positive regulation of hematopoietic stem cell proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of histone H4 acetylationManual Assertion Based On ExperimentIMP:CAFA
Positive regulation of protein localization to nucleusManual Assertion Based On ExperimentIDA:GO_Central
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:CAFA
Regulation of cell cycleManual Assertion Based On ExperimentIDA:ComplexPortal
Regulation of cell growthManual Assertion Based On ExperimentIDA:ComplexPortal
Regulation of DNA biosynthetic processManual Assertion Based On ExperimentIDA:ComplexPortal
Regulation of DNA replicationManual Assertion Based On ExperimentIDA:ComplexPortal
Regulation of DNA-dependent DNA replication initiationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of nucleotide-excision repairManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:ComplexPortal
Response to actinomycin DManual Assertion Based On ExperimentIMP:CAFA
Response to anisomycinManual Assertion Based On ExperimentIMP:CAFA
Response to dithiothreitolManual Assertion Based On ExperimentIMP:CAFA
Response to hydroxyureaManual Assertion Based On ExperimentIMP:CAFA
Response to sorbitolManual Assertion Based On ExperimentIMP:CAFA
Stress-activated protein kinase signaling cascadeManual Assertion Based On ExperimentIDA:CAFA

Nucleus; Chromosome; Chromosome, centromere; Cytoplasm, cytosol. Associates with replication origins specifically during the G1 phase of the cell cycle (PubMed:18832067, PubMed:20129055).
Localizes to transcription start sites (PubMed:21753189, PubMed:24065767).
Localizes to ultraviolet-induced DNA damage sites following phosphorylation by ATR (PubMed:28719581).
Localizes to centromeres in G1 phase (PubMed:27270040).

Phosphorylated at Ser-50 and Ser-53 by ATR in response to DNA damage, promoting its ubiquitination by the CRL4(DDB2) complex and subsequent degradation (PubMed:26572825).
Phosphorylation at Ser-50 and Ser-53 by ATR in response to ultraviolet-induced DNA, promotes localization to DNA damage sites (PubMed:28719581).
Phosphorylation at Ser-57 by PLK1 during mitosis seems important for prereplicative complex formation and DNA replication licensing, and requires prior phosphorylation at Thr-85 and Thr-88 by CDK1 (PubMed:18250300).
Phosphorylated by MAP2K1, which accelerates its degradation (By similarity).
Ubiquitinated at Lys-338, leading to proteasomal degradation (PubMed:23319590).
Ubiquitinated by the CRL4(DDB2) complex following phosphorylation by ATR, leading to its subsequent degradation (PubMed:26572825).
Autoacetylation at Lys-432 is required for proper function.