UniProt functional annotation for Q04724



	UniProt functional annotation for Q04724

UniProt code: Q04724.

Organism: Homo sapiens (Human).

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

Function: Transcriptional corepressor that binds to a number of transcription factors. Inhibits NF-kappa-B-regulated gene expression. Inhibits the transcriptional activation mediated by FOXA2, and by CTNNB1 and TCF family members in Wnt signaling. Enhances FOXG1/BF- 1- and HES1-mediated transcriptional repression (By similarity). The effects of full-length TLE family members may be modulated by association with dominant-negative AES. Unusual function as coactivator for ESRRG. {ECO:0000250|UniProtKB:Q62440, ECO:0000269|PubMed:10660609}.

Subunit: Homooligomer and heterooligomer with other family members. Binds RUNX1, RUNX3, FOXA2, KDM6A, UTY, histone H3, HESX1, ESRRG and the NF-kappa-B subunit RELA. Interacts with HES1 (via WRPW motif). Binds TCF7, LEF1, TCF7L1 and TCF7L2 (By similarity). Interacts with SIX3. Interacts with EFNB1. Interacts with TLE4 (By similarity). Interacts with FOXG1/BF-1; the interaction is inhibited by TLE6/GRG6 (By similarity). {ECO:0000250|UniProtKB:Q62440, ECO:0000269|PubMed:10660609, ECO:0000269|PubMed:10748198, ECO:0000269|PubMed:11731482, ECO:0000269|PubMed:12441302, ECO:0000269|PubMed:14651967, ECO:0000269|PubMed:21429299, ECO:0000269|PubMed:8649374, ECO:0000269|PubMed:8687460, ECO:0000269|PubMed:9334241, ECO:0000269|PubMed:9751710, ECO:0000269|PubMed:9854018, ECO:0000269|PubMed:9874198}.

Subcellular location: Nucleus {ECO:0000269|PubMed:12397081}. Note=Nuclear and chromatin-associated, depending on isoforms and phosphorylation status. Hyperphosphorylation decreases the affinity for nuclear components.

Tissue specificity: In all tissues examined, mostly in brain, liver and muscle.

Domain: WD repeat Groucho/TLE family members are characterized by 5 regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a central CcN domain, containing a nuclear localization signal, and a serine/proline-rich SP domain. The most highly conserved are the N- terminal Q domain and the C-terminal WD-repeat domain. {ECO:0000305|PubMed:18254933}.

Ptm: Phosphorylated, probably by CDK1. The degree of phosphorylation varies throughout the cell cycle, and is highest at the G2/M transition. Becomes hyperphosphorylated in response to cell differentiation and interaction with HES1 or RUNX1.

Ptm: Ubiquitinated by XIAP/BIRC4. {ECO:0000269|PubMed:22304967}.

Similarity: Belongs to the WD repeat Groucho/TLE 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:		Transcriptional corepressor that binds to a number of transcription factors. Inhibits NF-kappa-B-regulated gene expression. Inhibits the transcriptional activation mediated by FOXA2, and by CTNNB1 and TCF family members in Wnt signaling. Enhances FOXG1/BF- 1- and HES1-mediated transcriptional repression (By similarity). The effects of full-length TLE family members may be modulated by association with dominant-negative AES. Unusual function as coactivator for ESRRG. {ECO:0000250\|UniProtKB:Q62440, ECO:0000269\|PubMed:10660609}.


Subunit:		Homooligomer and heterooligomer with other family members. Binds RUNX1, RUNX3, FOXA2, KDM6A, UTY, histone H3, HESX1, ESRRG and the NF-kappa-B subunit RELA. Interacts with HES1 (via WRPW motif). Binds TCF7, LEF1, TCF7L1 and TCF7L2 (By similarity). Interacts with SIX3. Interacts with EFNB1. Interacts with TLE4 (By similarity). Interacts with FOXG1/BF-1; the interaction is inhibited by TLE6/GRG6 (By similarity). {ECO:0000250\|UniProtKB:Q62440, ECO:0000269\|PubMed:10660609, ECO:0000269\|PubMed:10748198, ECO:0000269\|PubMed:11731482, ECO:0000269\|PubMed:12441302, ECO:0000269\|PubMed:14651967, ECO:0000269\|PubMed:21429299, ECO:0000269\|PubMed:8649374, ECO:0000269\|PubMed:8687460, ECO:0000269\|PubMed:9334241, ECO:0000269\|PubMed:9751710, ECO:0000269\|PubMed:9854018, ECO:0000269\|PubMed:9874198}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:12397081}. Note=Nuclear and chromatin-associated, depending on isoforms and phosphorylation status. Hyperphosphorylation decreases the affinity for nuclear components.
Tissue specificity:		In all tissues examined, mostly in brain, liver and muscle.
Domain:		WD repeat Groucho/TLE family members are characterized by 5 regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a central CcN domain, containing a nuclear localization signal, and a serine/proline-rich SP domain. The most highly conserved are the N- terminal Q domain and the C-terminal WD-repeat domain. {ECO:0000305\|PubMed:18254933}.
Ptm:		Phosphorylated, probably by CDK1. The degree of phosphorylation varies throughout the cell cycle, and is highest at the G2/M transition. Becomes hyperphosphorylated in response to cell differentiation and interaction with HES1 or RUNX1.
Ptm:		Ubiquitinated by XIAP/BIRC4. {ECO:0000269\|PubMed:22304967}.
Similarity:		Belongs to the WD repeat Groucho/TLE family. {ECO:0000305}.