HDAC5

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the class II histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. It coimmunoprecipitates only with HDAC3 family member and might form multicomplex proteins. It also interacts with myocyte enhancer factor-2 (MEF2) proteins, resulting in repression of MEF2-dependent genes. This gene is thought to be associated with colon cancer. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Full Name

Histone Deacetylase 5

Function

Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Serves as a corepressor of RARA and causes its deacetylation (PubMed:28167758).

In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758).

Biological Process

B cell activation Source: UniProtKB
B cell differentiation Source: UniProtKB
Cellular response to insulin stimulus Source: BHF-UCL
Chromatin organization Source: UniProtKB
Chromatin remodeling Source: ProtInc
Heterochromatin assembly Source: ProtInc
Histone deacetylation Source: BHF-UCL
Inflammatory response Source: UniProtKB
Negative regulation of cell migration involved in sprouting angiogenesis Source: BHF-UCL
Negative regulation of myotube differentiation Source: BHF-UCL
Negative regulation of transcription, DNA-templated Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: MGI
Positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Protein deacetylation Source: UniProtKB
Regulation of gene expression, epigenetic Source: UniProtKB
Regulation of myotube differentiation Source: UniProtKB
Regulation of protein binding Source: BHF-UCL

Cellular Location

Nucleus; Cytoplasm. Shuttles between the nucleus and the cytoplasm. In muscle cells, it shuttles into the cytoplasm during myocyte differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-259 and Ser-498 by AMPK, CaMK1 and SIK1.

PTM

Phosphorylated by AMPK, CaMK1, SIK1 and PRKD1 at Ser-259 and Ser-498. The phosphorylation is required for the export to the cytoplasm and inhibition. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import. Phosphorylated by GRK5, leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription (By similarity).
Ubiquitinated. Polyubiquitination however does not lead to its degradation.