HAT1

The protein encoded by this gene is a type B histone acetyltransferase (HAT) that is involved in the rapid acetylation of newly synthesized cytoplasmic histones, which are in turn imported into the nucleus for de novo deposition onto nascent DNA chains. Histone acetylation, particularly of histone H4, plays an important role in replication-dependent chromatin assembly. Specifically, this HAT can acetylate soluble but not nucleosomal histone H4 at lysines 5 and 12, and to a lesser degree, histone H2A at lysine 5. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jun 2009]

Full Name

Histone Acetyltransferase 1

Function

Histone acetyltransferase that plays a role in different biological processes including cell cycle progression, glucose metabolism, histone production or DNA damage repair (PubMed:31278053, PubMed:20953179, PubMed:23653357, PubMed:32081014).

Coordinates histone production and acetylation via H4 promoter binding (PubMed:31278053).

Acetylates histone H4 at 'Lys-5' (H4K5ac) and 'Lys-12' (H4K12ac) and, to a lesser extent, histone H2A at 'Lys-5' (H2AK5ac) (PubMed:22615379, PubMed:11585814).

Drives H4 production by chromatin binding to support chromatin replication and acetylation. Since transcription of H4 genes is tightly coupled to S-phase, plays an important role in S-phase entry and progression (PubMed:31278053).

Promotes homologous recombination in DNA repair by facilitating histone turnover and incorporation of acetylated H3.3 at sites of double-strand breaks (PubMed:23653357).

In addition, acetylates other substrates such as chromatin-related proteins (PubMed:32081014).

Acetylates also RSAD2 which mediates the interaction of ubiquitin ligase UBE4A with RSAD2 leading to RSAD2 ubiquitination and subsequent degradation (PubMed:31812350).

(Microbial infection) Contributes to hepatitis B virus (HBV) replication by acetylating histone H4 at the sites of 'Lys-5' and 'Lys-12' on the covalently closed circular DNA (cccDNA) minichromosome leading to its accumulation within the host cell.

Biological Process

DNA packaging Source: ProtInc
DNA replication-dependent chromatin assembly Source: UniProtKB
DNA replication-independent chromatin assembly Source: UniProtKB
Histone H4 acetylation Source: UniProtKB
Internal protein amino acid acetylation Source: ProtInc

Cellular Location

Isoform A: Nucleus matrix; Mitochondrion
Isoform B: Nucleus; Nucleus matrix; Nucleoplasm; Cytoplasm. Localization is predominantly nuclear in normal cells. Treatment with hydrogen peroxide or ionizing radiation enhances nuclear localization through redistribution of existing protein.

PTM

Phosphorylated by AMPK at Ser-190; phosphorylation increases HAT1 activity.