UniProt functional annotation for P0CF65



	UniProt functional annotation for P0CF65

UniProt code: P0CF65.

Organism: Gallus gallus (Chicken).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; Phasianinae; Gallus.

Function: Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2 (Probable). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8 (PubMed:20223979). Maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons. Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1 (By similarity). May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism (By similarity). {ECO:0000250|UniProtKB:Q8C7D2, ECO:0000250|UniProtKB:Q96SW2, ECO:0000269|PubMed:20223979, ECO:0000305}.

Pathway: Protein modification; protein ubiquitination. {ECO:0000250|UniProtKB:Q96SW2}.

Subunit: Component of a DCX (DDB1-CUL4-X-box) protein ligase complex. Interacts directly with DDB1 (PubMed:25043012). {ECO:0000269|PubMed:25043012, ECO:0000305}.

Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q96SW2}. Nucleus {ECO:0000250|UniProtKB:Q96SW2}.

Miscellaneous: Thalidomide is teratogenic in human, chicken and zebrafish, but not in mice. Binding of thalidomide and related drugs changes the substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein ligase complex, leading to decreased degradation of endogenous target proteins and increased degradation of other proteins that are not normal substrates. This is probably the underlying cause of the teratogenic activity of thalidomide, possibly due to abnormal regulation of the BMP and FGF8 signaling pathways (PubMed:20223979). {ECO:0000305|PubMed:20223979}.

Similarity: Belongs to the CRBN family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Gallus gallus (Chicken).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; Phasianinae; Gallus.



Function:		Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2 (Probable). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8 (PubMed:20223979). Maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons. Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1 (By similarity). May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism (By similarity). {ECO:0000250\|UniProtKB:Q8C7D2, ECO:0000250\|UniProtKB:Q96SW2, ECO:0000269\|PubMed:20223979, ECO:0000305}.


Pathway:		Protein modification; protein ubiquitination. {ECO:0000250\|UniProtKB:Q96SW2}.
Subunit:		Component of a DCX (DDB1-CUL4-X-box) protein ligase complex. Interacts directly with DDB1 (PubMed:25043012). {ECO:0000269\|PubMed:25043012, ECO:0000305}.
Subcellular location:		Cytoplasm {ECO:0000250\|UniProtKB:Q96SW2}. Nucleus {ECO:0000250\|UniProtKB:Q96SW2}.
Miscellaneous:		Thalidomide is teratogenic in human, chicken and zebrafish, but not in mice. Binding of thalidomide and related drugs changes the substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein ligase complex, leading to decreased degradation of endogenous target proteins and increased degradation of other proteins that are not normal substrates. This is probably the underlying cause of the teratogenic activity of thalidomide, possibly due to abnormal regulation of the BMP and FGF8 signaling pathways (PubMed:20223979). {ECO:0000305\|PubMed:20223979}.
Similarity:		Belongs to the CRBN family. {ECO:0000305}.