UniProt functional annotation for O75367



	UniProt functional annotation for O75367

UniProt code: O75367.

Organism: Homo sapiens (Human).

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

Function: Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription (PubMed:12718888, PubMed:15621527, PubMed:16428466). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Involved in stable X chromosome inactivation (PubMed:15897469). Inhibits the binding of transcription factors, including NF-kappa-B, and interferes with the activity of remodeling SWI/SNF complexes (PubMed:12718888, PubMed:16428466). Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin (PubMed:16428466, PubMed:16107708). {ECO:0000269|PubMed:12718888, ECO:0000269|PubMed:15621527, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:16107708, ECO:0000269|PubMed:16428466}.

Function: [Isoform 1]: Binds ADP-ribose and O-acetyl-ADP-ribose, and may be involved in ADP-ribose-mediated chromatin modulation (PubMed:15902274). Increases the expression of genes involved in redox metabolism, including SOD3 (PubMed:23022728). {ECO:0000269|PubMed:15902274, ECO:0000269|PubMed:23022728}.

Function: [Isoform 2]: Represses SOD3 gene expression. {ECO:0000269|PubMed:23022728}.

Subunit: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. Interacts with HDAC1 and HDAC2 (By similarity). Interacts with SPOP. Part of a complex consisting of MACROH2A1, CUL3 and SPOP. {ECO:0000250, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:16107708, ECO:0000269|PubMed:19818708}.

Subcellular location: Nucleus {ECO:0000269|PubMed:15621527, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:9634239}. Chromosome {ECO:0000269|PubMed:15621527, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:9634239}. Note=Enriched in inactive X chromosome chromatin and in senescence-associated heterochromatin. {ECO:0000269|PubMed:15621527, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:9634239}.

Tissue specificity: Widely expressed. {ECO:0000269|PubMed:9714746}.

Ptm: Monoubiquitinated at either Lys-116 or Lys-117. May also be polyubiquitinated. Ubiquitination is mediated by the CUL3/SPOP E3 complex and does not promote proteasomal degradation. Instead, it is required for enrichment in inactive X chromosome chromatin. {ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:16129414, ECO:0000269|PubMed:19818708}.

Miscellaneous: [Isoform 2]: The preferential expression of isoform 2 over that of isoform 1 requires the presence of DDX5/DDX17. {ECO:0000269|PubMed:23022728}.

Miscellaneous: [Isoform 1]: Specifically binds ADP-ribose and O-acetyl- ADP-ribose. Important residues for binding are Asp-203, Gly-224, Gly- 314 and Phe-348. Preferentially expressed over isoform 2 in the absence of DDX5/DDX17. {ECO:0000269|PubMed:15902274, ECO:0000269|PubMed:23022728}.

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:		Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription (PubMed:12718888, PubMed:15621527, PubMed:16428466). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Involved in stable X chromosome inactivation (PubMed:15897469). Inhibits the binding of transcription factors, including NF-kappa-B, and interferes with the activity of remodeling SWI/SNF complexes (PubMed:12718888, PubMed:16428466). Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin (PubMed:16428466, PubMed:16107708). {ECO:0000269\|PubMed:12718888, ECO:0000269\|PubMed:15621527, ECO:0000269\|PubMed:15897469, ECO:0000269\|PubMed:16107708, ECO:0000269\|PubMed:16428466}.



Function:		[Isoform 1]: Binds ADP-ribose and O-acetyl-ADP-ribose, and may be involved in ADP-ribose-mediated chromatin modulation (PubMed:15902274). Increases the expression of genes involved in redox metabolism, including SOD3 (PubMed:23022728). {ECO:0000269\|PubMed:15902274, ECO:0000269\|PubMed:23022728}.



Function:		[Isoform 2]: Represses SOD3 gene expression. {ECO:0000269\|PubMed:23022728}.


Subunit:		The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. Interacts with HDAC1 and HDAC2 (By similarity). Interacts with SPOP. Part of a complex consisting of MACROH2A1, CUL3 and SPOP. {ECO:0000250, ECO:0000269\|PubMed:15897469, ECO:0000269\|PubMed:16107708, ECO:0000269\|PubMed:19818708}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:15621527, ECO:0000269\|PubMed:15897469, ECO:0000269\|PubMed:9634239}. Chromosome {ECO:0000269\|PubMed:15621527, ECO:0000269\|PubMed:15897469, ECO:0000269\|PubMed:9634239}. Note=Enriched in inactive X chromosome chromatin and in senescence-associated heterochromatin. {ECO:0000269\|PubMed:15621527, ECO:0000269\|PubMed:15897469, ECO:0000269\|PubMed:9634239}.
Tissue specificity:		Widely expressed. {ECO:0000269\|PubMed:9714746}.
Ptm:		Monoubiquitinated at either Lys-116 or Lys-117. May also be polyubiquitinated. Ubiquitination is mediated by the CUL3/SPOP E3 complex and does not promote proteasomal degradation. Instead, it is required for enrichment in inactive X chromosome chromatin. {ECO:0000269\|PubMed:15897469, ECO:0000269\|PubMed:16129414, ECO:0000269\|PubMed:19818708}.
Miscellaneous:		[Isoform 2]: The preferential expression of isoform 2 over that of isoform 1 requires the presence of DDX5/DDX17. {ECO:0000269\|PubMed:23022728}.
Miscellaneous:		[Isoform 1]: Specifically binds ADP-ribose and O-acetyl- ADP-ribose. Important residues for binding are Asp-203, Gly-224, Gly- 314 and Phe-348. Preferentially expressed over isoform 2 in the absence of DDX5/DDX17. {ECO:0000269\|PubMed:15902274, ECO:0000269\|PubMed:23022728}.