HDAC8

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. May play a role in smooth muscle cell contractility

HDAC8 Related Areas

Signal Transduction>>Transcription Factor & Regulator>>HDAC8

HDAC8 Alternative Names

HDAC8, HD8, CDA07, HDACL1, RPD3 [Homo sapiens]

HDAC8, HD8, RP23-331B22.1, 2610007D20Rik [Mus musculus]

Summaries for HDAC8

Entrez Gene summary for HDAC8:

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 class I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors. Multiple transcript variants encoding different isoforms have been found for this gene.

OMIM - description for HDAC8:

By searching an EST database for sequences similar to HDAC1, HDAC2, and HDAC3, followed by 5-prime and 3-prime RACE, Hu et al. (2000) and Van den Wyngaert et al. (2000) obtained cDNAs encoding HDAC8. Sequence analysis predicted that the 377-amino acid HDAC8 protein contains the 9 conserved HDAC blocks that are presumably important for catalytic function (Hu et al., 2000). Van den Wyngaert et al. (2000) noted that the approximately 30 amino acids at the N and C termini of HDAC8 are quite distinct from those of other HDACs. HDAC8 shares 54% sequence similarity with HDAC1 and HDAC2 and 39% similarity with HDAC3, making it a class I HDAC. Northern blot analysis detected HDAC8 transcripts of approximately 2.0 and 2.4 kb in all normal tissues tested, with strongest expression in brain, unlike other class I HDACs, and in cancer cell lines. Immunofluorescence analysis indicated a nuclear localization with possible exclusion from the nucleolus. By Western blot analysis, Hu et al. (2000) confirmed the nuclear localization and showed that HDAC8 is expressed as a 49-kD protein.

Wikipedia summary for HDAC8:

Histone deacetylase 8 is an enzyme that in humans is encoded by the HDAC8 gene, and is biologically involved in skull morphogenesis and metabolic control of the ERR-alpha/PGC1-alpha transcriptional complex. 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 class I of the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter.

Human HDAC8 Protein General Information

 

• Protein names: Recommended name: Histone deacetylase 8 Short name=HD8
• Sequence length: 377 AA.
• Sequence similarities: Belongs to the histone deacetylase family. HD type 1 subfamily.
• Post-translational modification: Phosphorylated by PKA on serine 39. Phosphorylation reduces deacetylase activity observed preferentially on histones H3 and H4.
• Subunit structure: Interacts with PEPB2-MYH11, a fusion protein consisting of the 165 N-terminal residues of CBF-beta (PEPB2) with the tail region of MYH11 produced by the inversion Inv(16)(p13q22), a translocation associated with acute myeloid leukemia of M4EO subtype. The PEPB2-MYH1 fusion protein also interacts with RUNX1, a well known transcriptional regulator, suggesting that the interaction with HDAC8 may participate in the conversion of RUNX1 into a constitutive transcriptional repressor. Interacts with CBFA2T3. Interacts with phosphorylated SMG5/EST1B; this interaction protects SMG5 from ubiquitin-mediated degradation. Associates with alpha-SMA (smooth muscle alpha-actin)
• Subcellular location: Nucleus. Cytoplasm. Note: Excluded from the nucleoli. Found in the cytoplasm of cells showing smooth muscle differentiation.
• Tissue specificity: Weakly expressed in most tissues. Expressed at higher level in heart, brain, kidney and pancreas and also in liver, lung, placenta, prostate and kidney.

General information above from UniProt

Function for HDAC8 Protein

UniProtKB:

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. May play a role in smooth muscle cell contractility

Genatlas:

• regulator of cell proliferation, putative role in cancer development
• associates with the smooth muscle actin cytoskeleton and may regulate the contractile capacity of smooth muscle cells
• HDAC8 has inhibitory effect on forskolin-induced CREB activation
• HDAC8 may be activated by either or both of metals (Fe(2+) or Zn(2+))depending on cellular concentrations

Homology for human HDAC8

• homolog to yeast RpD3