UniProt functional annotation for Q92995



	UniProt functional annotation for Q92995

UniProt code: Q92995.

Organism: Homo sapiens (Human).

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

Function: Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy and endoplasmic reticulum-associated degradation (ERAD). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34- containing complexes. Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Has a weak deubiquitinase activity in vitro and preferentially cleaves 'Lys-63'-linked polyubiquitin chains. In contrast to USP5, it is not able to mediate unanchored polyubiquitin disassembly. Able to cleave ISG15 in vitro; however, additional experiments are required to confirm such data. {ECO:0000269|PubMed:17653289, ECO:0000269|PubMed:21571647, ECO:0000269|PubMed:21659512, ECO:0000269|PubMed:21811243, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:22216260, ECO:0000269|PubMed:24424410}.

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;

Activity regulation: Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP13 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34- containing complexes. The weak deubiquitinase activity in vitro suggests the existence of some mechanism that activates the enzyme. {ECO:0000269|PubMed:21962518}.

Subunit: Interacts with UFD1. Interacts (via UBA domains) with SIAH2 (when ubiquitinated). Interacts with BAG6; the interaction is direct and may mediate UBL4A deubiquitination (PubMed:24424410). Interacts (via UBA 2 domain) with AMFR; the interaction is direct (PubMed:24424410). Interacts with UBL4A; may be indirect via BAG6 (PubMed:24424410). {ECO:0000269|PubMed:21571647, ECO:0000269|PubMed:21659512, ECO:0000269|PubMed:24424410}.

Tissue specificity: Highly expressed in ovary and testes.

Domain: The UBP-type zinc finger has lost its ability to bind ubiquitin and USP13 is not activated by unanchored ubiquitin. Swapping with the UBP-type zinc finger from USP5 restores ability to bind unanchored ubiquitin and subsequent activation of the protein (PubMed:22216260). {ECO:0000269|PubMed:22216260}.

Domain: The UBA domains mediate binding to ubiquitin. {ECO:0000269|PubMed:22216260}.

Similarity: Belongs to the peptidase C19 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:		Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy and endoplasmic reticulum-associated degradation (ERAD). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34- containing complexes. Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Has a weak deubiquitinase activity in vitro and preferentially cleaves 'Lys-63'-linked polyubiquitin chains. In contrast to USP5, it is not able to mediate unanchored polyubiquitin disassembly. Able to cleave ISG15 in vitro; however, additional experiments are required to confirm such data. {ECO:0000269\|PubMed:17653289, ECO:0000269\|PubMed:21571647, ECO:0000269\|PubMed:21659512, ECO:0000269\|PubMed:21811243, ECO:0000269\|PubMed:21962518, ECO:0000269\|PubMed:22216260, ECO:0000269\|PubMed:24424410}.


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;
Activity regulation:		Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP13 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34- containing complexes. The weak deubiquitinase activity in vitro suggests the existence of some mechanism that activates the enzyme. {ECO:0000269\|PubMed:21962518}.
Subunit:		Interacts with UFD1. Interacts (via UBA domains) with SIAH2 (when ubiquitinated). Interacts with BAG6; the interaction is direct and may mediate UBL4A deubiquitination (PubMed:24424410). Interacts (via UBA 2 domain) with AMFR; the interaction is direct (PubMed:24424410). Interacts with UBL4A; may be indirect via BAG6 (PubMed:24424410). {ECO:0000269\|PubMed:21571647, ECO:0000269\|PubMed:21659512, ECO:0000269\|PubMed:24424410}.
Tissue specificity:		Highly expressed in ovary and testes.
Domain:		The UBP-type zinc finger has lost its ability to bind ubiquitin and USP13 is not activated by unanchored ubiquitin. Swapping with the UBP-type zinc finger from USP5 restores ability to bind unanchored ubiquitin and subsequent activation of the protein (PubMed:22216260). {ECO:0000269\|PubMed:22216260}.
Domain:		The UBA domains mediate binding to ubiquitin. {ECO:0000269\|PubMed:22216260}.
Similarity:		Belongs to the peptidase C19 family. {ECO:0000305}.