UniProt functional annotation for Q86YT6



	UniProt functional annotation for Q86YT6

UniProt code: Q86YT6.

Organism: Homo sapiens (Human).

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

Function: E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. Probably mediates ubiquitination and subsequent proteasomal degradation of DAPK1, thereby antagonizing anti-apoptotic effects of DAPK1 to promote TNF-induced apoptosis (By similarity). Involved in ubiquitination of centriolar satellite CEP131, CEP290 and PCM1 proteins and hence inhibits primary cilium formation in proliferating cells. Mediates 'Lys-63'-linked polyubiquitination of TBK1, which probably participates in kinase activation. {ECO:0000250, ECO:0000269|PubMed:24121310}.

Catalytic activity: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;

Pathway: Protein modification; protein ubiquitination.

Subunit: Interacts with CEP131 and PCM1. {ECO:0000269|PubMed:24121310}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:24121310}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriolar satellite {ECO:0000269|PubMed:24121310}. Cell membrane {ECO:0000250}. Note=Localizes to the plasma membrane (By similarity). According to PubMed:15048887, it is mitochondrial, however such localization remains unclear. Displaced from centriolar satellites in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock. {ECO:0000250}.

Tissue specificity: Widely expressed at low level. Expressed at higher level in spinal cord, ovary, whole brain, and all specific brain regions examined. {ECO:0000269|PubMed:10718198}.

Ptm: Ubiquitinated; possibly via autoubiquitination (By similarity). Ubiquitinated; this modification is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock. {ECO:0000250, ECO:0000269|PubMed:21903422, ECO:0000269|PubMed:24121310}.

Disease: Left ventricular non-compaction 7 (LVNC7) [MIM:615092]: A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC7 is an autosomal dominant condition. {ECO:0000269|PubMed:23314057}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: In epilepsy brain tissue, levels of expression are increased in the cytoplasm and microsomal fractions (endoplasmic reticulum).

Sequence caution: Sequence=AAH22403.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAN18023.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAC11439.1; Type=Erroneous initiation; 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:		E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. Probably mediates ubiquitination and subsequent proteasomal degradation of DAPK1, thereby antagonizing anti-apoptotic effects of DAPK1 to promote TNF-induced apoptosis (By similarity). Involved in ubiquitination of centriolar satellite CEP131, CEP290 and PCM1 proteins and hence inhibits primary cilium formation in proliferating cells. Mediates 'Lys-63'-linked polyubiquitination of TBK1, which probably participates in kinase activation. {ECO:0000250, ECO:0000269\|PubMed:24121310}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;
Pathway:		Protein modification; protein ubiquitination.
Subunit:		Interacts with CEP131 and PCM1. {ECO:0000269\|PubMed:24121310}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:24121310}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriolar satellite {ECO:0000269\|PubMed:24121310}. Cell membrane {ECO:0000250}. Note=Localizes to the plasma membrane (By similarity). According to PubMed:15048887, it is mitochondrial, however such localization remains unclear. Displaced from centriolar satellites in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock. {ECO:0000250}.
Tissue specificity:		Widely expressed at low level. Expressed at higher level in spinal cord, ovary, whole brain, and all specific brain regions examined. {ECO:0000269\|PubMed:10718198}.
Ptm:		Ubiquitinated; possibly via autoubiquitination (By similarity). Ubiquitinated; this modification is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock. {ECO:0000250, ECO:0000269\|PubMed:21903422, ECO:0000269\|PubMed:24121310}.
Disease:		Left ventricular non-compaction 7 (LVNC7) [MIM:615092]: A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC7 is an autosomal dominant condition. {ECO:0000269\|PubMed:23314057}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		In epilepsy brain tissue, levels of expression are increased in the cytoplasm and microsomal fractions (endoplasmic reticulum).
Sequence caution:		Sequence=AAH22403.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=AAN18023.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAC11439.1; Type=Erroneous initiation; Evidence={ECO:0000305};