UniProt functional annotation for Q9Y263



	UniProt functional annotation for Q9Y263

UniProt code: Q9Y263.

Organism: Homo sapiens (Human).

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

Function: Plays a role in protein ubiquitination, sorting and degradation through its association with VCP (PubMed:27753622). Involved in ubiquitin-mediated membrane proteins trafficking to late endosomes in an ESCRT-dependent manner, and hence plays a role in synaptic vesicle recycling (By similarity). May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes (PubMed:27753622). Plays a role in cerebellar Purkinje cell development (By similarity). Positively regulates cytosolic and calcium-independent phospholipase A2 activities in a tumor necrosis factor alpha (TNF-alpha)- or lipopolysaccharide (LPS)-dependent manner, and hence prostaglandin E2 biosynthesis (PubMed:18291623, PubMed:28007986). {ECO:0000250|UniProtKB:P27612, ECO:0000269|PubMed:18291623, ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:28007986}.

Subunit: Interacts with ubiquitin (PubMed:19423704). Interacts with UBXN6, VCP and YOD1; may form a complex involved in macroautophagy (PubMed:27753622, PubMed:19887378). {ECO:0000269|PubMed:19423704, ECO:0000269|PubMed:19887378, ECO:0000269|PubMed:27753622}.

Subcellular location: Nucleus {ECO:0000269|PubMed:28007986}. Cytoplasm {ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:28007986}. Cell junction, synapse {ECO:0000250|UniProtKB:P27612}. Note=Recruited to damaged lysosomes decorated with K48-linked ubiquitin chains. {ECO:0000269|PubMed:27753622}.

Induction: Up-regulated by tumor necrosis factor alpha (TNF-alpha) (at protein level) (PubMed:18291623). {ECO:0000269|PubMed:18291623}.

Domain: The PUL domain is composed of 6 armadillo-like repeats and mediates the interaction with VCP C-terminus. {ECO:0000269|PubMed:19887378}.

Domain: The PFU domain mediates interaction with ubiquitin. {ECO:0000269|PubMed:19887378}.

Disease: Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (NDMSBA) [MIM:617527]: An autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, spastic quadriparesis, global developmental delay, profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy. {ECO:0000269|PubMed:28007986, ECO:0000269|PubMed:28413018}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the WD repeat PLAP family. {ECO:0000305}.

Sequence caution: Sequence=AAD03030.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAD42075.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAD42075.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAA92105.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAD97264.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=CAB42881.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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:		Plays a role in protein ubiquitination, sorting and degradation through its association with VCP (PubMed:27753622). Involved in ubiquitin-mediated membrane proteins trafficking to late endosomes in an ESCRT-dependent manner, and hence plays a role in synaptic vesicle recycling (By similarity). May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes (PubMed:27753622). Plays a role in cerebellar Purkinje cell development (By similarity). Positively regulates cytosolic and calcium-independent phospholipase A2 activities in a tumor necrosis factor alpha (TNF-alpha)- or lipopolysaccharide (LPS)-dependent manner, and hence prostaglandin E2 biosynthesis (PubMed:18291623, PubMed:28007986). {ECO:0000250\|UniProtKB:P27612, ECO:0000269\|PubMed:18291623, ECO:0000269\|PubMed:27753622, ECO:0000269\|PubMed:28007986}.


Subunit:		Interacts with ubiquitin (PubMed:19423704). Interacts with UBXN6, VCP and YOD1; may form a complex involved in macroautophagy (PubMed:27753622, PubMed:19887378). {ECO:0000269\|PubMed:19423704, ECO:0000269\|PubMed:19887378, ECO:0000269\|PubMed:27753622}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:28007986}. Cytoplasm {ECO:0000269\|PubMed:27753622, ECO:0000269\|PubMed:28007986}. Cell junction, synapse {ECO:0000250\|UniProtKB:P27612}. Note=Recruited to damaged lysosomes decorated with K48-linked ubiquitin chains. {ECO:0000269\|PubMed:27753622}.
Induction:		Up-regulated by tumor necrosis factor alpha (TNF-alpha) (at protein level) (PubMed:18291623). {ECO:0000269\|PubMed:18291623}.
Domain:		The PUL domain is composed of 6 armadillo-like repeats and mediates the interaction with VCP C-terminus. {ECO:0000269\|PubMed:19887378}.
Domain:		The PFU domain mediates interaction with ubiquitin. {ECO:0000269\|PubMed:19887378}.
Disease:		Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (NDMSBA) [MIM:617527]: An autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, spastic quadriparesis, global developmental delay, profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy. {ECO:0000269\|PubMed:28007986, ECO:0000269\|PubMed:28413018}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the WD repeat PLAP family. {ECO:0000305}.
Sequence caution:		Sequence=AAD03030.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAD42075.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAD42075.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAA92105.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; Sequence=BAD97264.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=CAB42881.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};