UniProt functional annotation for O60907



	UniProt functional annotation for O60907

UniProt code: O60907.

Organism: Homo sapiens (Human).

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

Function: F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units (PubMed:14980219). Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of corepressor complexes that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of transcription repressor complexes, thereby allowing cofactor exchange (PubMed:21240272). {ECO:0000269|PubMed:14980219, ECO:0000269|PubMed:21240272}.

Subunit: Homotetramer; dimer of dimers (PubMed:21240272). Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (PubMed:10809664, PubMed:21240272). Interacts with GPS2 (when sumoylated); leading to protect GPS2 against degradation by the proteasome (PubMed:24943844). Component of a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X (PubMed:11389839). Probably part of other corepressor complexes, that do not contain NCOR1 and NCOR2. Interacts with histones H2B, H3a and H4. Interacts with MECP2; recruits TBL1X to the heterochromatin foci (By similarity). {ECO:0000250|UniProtKB:Q9QXE7, ECO:0000269|PubMed:10809664, ECO:0000269|PubMed:11389839, ECO:0000269|PubMed:21240272, ECO:0000269|PubMed:24943844}.

Subcellular location: Nucleus {ECO:0000250}. Note=Colocalized with MECP2 to the heterochromatin foci. {ECO:0000250|UniProtKB:Q9QXE7}.

Tissue specificity: Ubiquitous. {ECO:0000269|PubMed:10330347}.

Domain: The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes. {ECO:0000250}.

Disease: Hypothyroidism, congenital, non-goitrous, 8 (CHNG8) [MIM:301033]: A form of central hypothyroidism, a disorder characterized by sub-optimal thyroid hormone secretion, due to insufficient stimulation by the thyroid stimulating hormone of an otherwise normal thyroid gland. It may be caused by congenital or acquired disorders of the pituitary gland or hypothalamus. CHNG8 is a congenital, X-linked, relatively mild form which may be accompanied by hearing loss in some patients. {ECO:0000269|PubMed:27603907, ECO:0000269|PubMed:30591955}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the WD repeat EBI family. {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:		F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units (PubMed:14980219). Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of corepressor complexes that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of transcription repressor complexes, thereby allowing cofactor exchange (PubMed:21240272). {ECO:0000269\|PubMed:14980219, ECO:0000269\|PubMed:21240272}.


Subunit:		Homotetramer; dimer of dimers (PubMed:21240272). Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (PubMed:10809664, PubMed:21240272). Interacts with GPS2 (when sumoylated); leading to protect GPS2 against degradation by the proteasome (PubMed:24943844). Component of a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X (PubMed:11389839). Probably part of other corepressor complexes, that do not contain NCOR1 and NCOR2. Interacts with histones H2B, H3a and H4. Interacts with MECP2; recruits TBL1X to the heterochromatin foci (By similarity). {ECO:0000250\|UniProtKB:Q9QXE7, ECO:0000269\|PubMed:10809664, ECO:0000269\|PubMed:11389839, ECO:0000269\|PubMed:21240272, ECO:0000269\|PubMed:24943844}.
Subcellular location:		Nucleus {ECO:0000250}. Note=Colocalized with MECP2 to the heterochromatin foci. {ECO:0000250\|UniProtKB:Q9QXE7}.
Tissue specificity:		Ubiquitous. {ECO:0000269\|PubMed:10330347}.
Domain:		The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes. {ECO:0000250}.
Disease:		Hypothyroidism, congenital, non-goitrous, 8 (CHNG8) [MIM:301033]: A form of central hypothyroidism, a disorder characterized by sub-optimal thyroid hormone secretion, due to insufficient stimulation by the thyroid stimulating hormone of an otherwise normal thyroid gland. It may be caused by congenital or acquired disorders of the pituitary gland or hypothalamus. CHNG8 is a congenital, X-linked, relatively mild form which may be accompanied by hearing loss in some patients. {ECO:0000269\|PubMed:27603907, ECO:0000269\|PubMed:30591955}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the WD repeat EBI family. {ECO:0000305}.