UniProt functional annotation for Q5VVQ6



	UniProt functional annotation for Q5VVQ6

UniProt code: Q5VVQ6.

Organism: Homo sapiens (Human).

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

Function: Hydrolase that can remove conjugated ubiquitin from proteins and participates in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by triming the ubiquitin chain on the associated substrate to facilitate their threading through the VCP/p97 pore. Ubiquitin moieties on substrates may present a steric impediment to the threading process when the substrate is transferred to the VCP pore and threaded through VCP's axial channel. Mediates deubiquitination of 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains. Also able to hydrolyze 'Lys-11'-linked ubiquitin chains. Cleaves both polyubiquitin and di-ubiquitin. May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes. May recruit PLAA, UBXN6 and VCP to damaged lysosome membranes decorated with K48-linked ubiquitin chains and remove these chains allowing autophagosome formation (PubMed:27753622). {ECO:0000269|PubMed:19818707, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:27753622}.

Catalytic activity: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:19818707, ECO:0000269|PubMed:23827681};

Subunit: Interacts with VCP; the interaction is direct. Interacts with FAF2/UBXD8. Interacts with DERL1; however interaction is dependent on the UBAX-like region, suggesting that it may be indirect. Interacts with PLAA, UBXN6 and VCP; may form a complex involved in macroautophagy (PubMed:27753622). {ECO:0000269|PubMed:19818707, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:27753622}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:27753622}. Note=Recruited to damaged lysosomes decorated with K48-linked ubiquitin chains. {ECO:0000269|PubMed:27753622}.

Domain: The UBAX-like region mediates the interaction with VCP. According to PubMed:19818707, it corresponds to a UBX domain, which is a hallmark for VCP-associated proteins. However, no canonical UBX is detected by prediction tools such as Pfam or PROSITE.

Domain: The C2H2-type zinc finger mediates specificity for 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains but not for 'Lys- 11'-linked ubiquitin chains. Selectivity for 'Lys-11'-linked ubiquitin chains is provided by recognition of the sequence surrounding 'Lys-11' in ubiquitin. The S2 site region provides specificity for longer 'Lys- 11'-linked ubiquitin chains (PubMed:23827681). {ECO:0000269|PubMed:23827681}.

Sequence caution: Sequence=AAF71033.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305}; Sequence=EAW93510.1; Type=Erroneous gene model prediction; 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:		Hydrolase that can remove conjugated ubiquitin from proteins and participates in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by triming the ubiquitin chain on the associated substrate to facilitate their threading through the VCP/p97 pore. Ubiquitin moieties on substrates may present a steric impediment to the threading process when the substrate is transferred to the VCP pore and threaded through VCP's axial channel. Mediates deubiquitination of 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains. Also able to hydrolyze 'Lys-11'-linked ubiquitin chains. Cleaves both polyubiquitin and di-ubiquitin. May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes. May recruit PLAA, UBXN6 and VCP to damaged lysosome membranes decorated with K48-linked ubiquitin chains and remove these chains allowing autophagosome formation (PubMed:27753622). {ECO:0000269\|PubMed:19818707, ECO:0000269\|PubMed:23827681, ECO:0000269\|PubMed:27753622}.


Catalytic activity:		Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269\|PubMed:19818707, ECO:0000269\|PubMed:23827681};
Subunit:		Interacts with VCP; the interaction is direct. Interacts with FAF2/UBXD8. Interacts with DERL1; however interaction is dependent on the UBAX-like region, suggesting that it may be indirect. Interacts with PLAA, UBXN6 and VCP; may form a complex involved in macroautophagy (PubMed:27753622). {ECO:0000269\|PubMed:19818707, ECO:0000269\|PubMed:23827681, ECO:0000269\|PubMed:27753622}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:27753622}. Note=Recruited to damaged lysosomes decorated with K48-linked ubiquitin chains. {ECO:0000269\|PubMed:27753622}.
Domain:		The UBAX-like region mediates the interaction with VCP. According to PubMed:19818707, it corresponds to a UBX domain, which is a hallmark for VCP-associated proteins. However, no canonical UBX is detected by prediction tools such as Pfam or PROSITE.
Domain:		The C2H2-type zinc finger mediates specificity for 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains but not for 'Lys- 11'-linked ubiquitin chains. Selectivity for 'Lys-11'-linked ubiquitin chains is provided by recognition of the sequence surrounding 'Lys-11' in ubiquitin. The S2 site region provides specificity for longer 'Lys- 11'-linked ubiquitin chains (PubMed:23827681). {ECO:0000269\|PubMed:23827681}.
Sequence caution:		Sequence=AAF71033.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305}; Sequence=EAW93510.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};