UniProt functional annotation for Q9BY41



	UniProt functional annotation for Q9BY41

UniProt code: Q9BY41.

Organism: Homo sapiens (Human).

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

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. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility. {ECO:0000269|PubMed:10748112, ECO:0000269|PubMed:10922473, ECO:0000269|PubMed:10926844, ECO:0000269|PubMed:14701748, ECO:0000269|PubMed:22885700}.

Catalytic activity: Reaction=H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl- [histone]; Xref=Rhea:RHEA:58196, Rhea:RHEA-COMP:9845, Rhea:RHEA- COMP:11338, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089, ChEBI:CHEBI:61930; EC=3.5.1.98;

Cofactor: Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Note=Binds 1 divalent metal cation per subunit.;

Activity regulation: Its activity is inhibited by trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), 3-(1-methyl-4-phenylacetyl-1H- 2-pyrrolyl)-N-hydroxy-2-propenamide (APHA), 4-dimethylamino-N-(6- hydroxycarbamoyethyl)benzamide-N-hydroxy-7-(4- dimethylaminobenzoyl)aminoheptanamide (MS-344), 5-(4-methyl- benzoylamino)-biphenyl-3,4'-dicarboxylic acid 3-dimethylamide 4'- hydroxyamide (CRA-A) and butyrate. {ECO:0000269|PubMed:15242608}.

Subunit: 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). {ECO:0000269|PubMed:11533236, ECO:0000269|PubMed:12509458, ECO:0000269|PubMed:16809764, ECO:0000269|PubMed:17721440}.

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. {ECO:0000269|PubMed:10926844, ECO:0000269|PubMed:14701748, ECO:0000269|PubMed:15772115, ECO:0000269|PubMed:16538051}.

Ptm: Phosphorylated by PKA on serine 39. Phosphorylation reduces deacetylase activity observed preferentially on histones H3 and H4. {ECO:0000269|PubMed:14701748, ECO:0000269|PubMed:15242608}.

Disease: Cornelia de Lange syndrome 5 (CDLS5) [MIM:300882]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269|PubMed:22885700}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Wilson-Turner X-linked mental retardation syndrome (WTS) [MIM:309585]: A neurologic disorder characterized by severe intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Affected females have a milder phenotype than affected males. {ECO:0000269|PubMed:22889856}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the histone deacetylase family. HD type 1 subfamily. {ECO:0000305}.

Sequence caution: Sequence=AAK14930.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={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:		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. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility. {ECO:0000269\|PubMed:10748112, ECO:0000269\|PubMed:10922473, ECO:0000269\|PubMed:10926844, ECO:0000269\|PubMed:14701748, ECO:0000269\|PubMed:22885700}.


Catalytic activity:		Reaction=H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl- [histone]; Xref=Rhea:RHEA:58196, Rhea:RHEA-COMP:9845, Rhea:RHEA- COMP:11338, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089, ChEBI:CHEBI:61930; EC=3.5.1.98;
Cofactor:		Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Note=Binds 1 divalent metal cation per subunit.;
Activity regulation:		Its activity is inhibited by trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), 3-(1-methyl-4-phenylacetyl-1H- 2-pyrrolyl)-N-hydroxy-2-propenamide (APHA), 4-dimethylamino-N-(6- hydroxycarbamoyethyl)benzamide-N-hydroxy-7-(4- dimethylaminobenzoyl)aminoheptanamide (MS-344), 5-(4-methyl- benzoylamino)-biphenyl-3,4'-dicarboxylic acid 3-dimethylamide 4'- hydroxyamide (CRA-A) and butyrate. {ECO:0000269\|PubMed:15242608}.
Subunit:		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). {ECO:0000269\|PubMed:11533236, ECO:0000269\|PubMed:12509458, ECO:0000269\|PubMed:16809764, ECO:0000269\|PubMed:17721440}.
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. {ECO:0000269\|PubMed:10926844, ECO:0000269\|PubMed:14701748, ECO:0000269\|PubMed:15772115, ECO:0000269\|PubMed:16538051}.
Ptm:		Phosphorylated by PKA on serine 39. Phosphorylation reduces deacetylase activity observed preferentially on histones H3 and H4. {ECO:0000269\|PubMed:14701748, ECO:0000269\|PubMed:15242608}.
Disease:		Cornelia de Lange syndrome 5 (CDLS5) [MIM:300882]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269\|PubMed:22885700}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Wilson-Turner X-linked mental retardation syndrome (WTS) [MIM:309585]: A neurologic disorder characterized by severe intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Affected females have a milder phenotype than affected males. {ECO:0000269\|PubMed:22889856}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the histone deacetylase family. HD type 1 subfamily. {ECO:0000305}.
Sequence caution:		Sequence=AAK14930.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};