UniProt functional annotation for Q13107



	UniProt functional annotation for Q13107

UniProt code: Q13107.

Organism: Homo sapiens (Human).

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

Function: Deubiquitinating enzyme that removes conjugated ubiquitin from target proteins (PubMed:16316627, PubMed:16472766, PubMed:16339847, PubMed:20595234, PubMed:22347420, PubMed:25404403). Deubiquitinates PDPK1 (PubMed:22347420). Deubiquitinates TRIM21 (PubMed:16316627). Deubiquitinates receptor ADORA2A which increases the amount of functional receptor at the cell surface (PubMed:16339847). May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3 (PubMed:20595234). This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP (PubMed:20595234). May also play a role in the regulation of quality control in the ER (PubMed:16339847). {ECO:0000269|PubMed:16316627, ECO:0000269|PubMed:16339847, ECO:0000269|PubMed:16472766, ECO:0000269|PubMed:20595234, ECO:0000269|PubMed:22347420, ECO:0000269|PubMed:25404403}.

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:16316627, ECO:0000269|PubMed:16339847, ECO:0000269|PubMed:16472766, ECO:0000269|PubMed:20595234, ECO:0000269|PubMed:22347420, ECO:0000269|PubMed:25404403};

Activity regulation: The completion of the deubiquitinase reaction is mediated by the DUSP and ubiquitin-like 1 domains which promotes the release of ubiquitin from the catalytic site enabling subsequent reactions to occur. {ECO:0000269|PubMed:25404403}.

Biophysicochemical properties: Kinetic parameters: KM=0.15 uM for ubiquitin-rhodamine {ECO:0000269|PubMed:25404403};

Subunit: Interacts with RB1 (both dephosphorylated and hypophosphorylated forms) (PubMed:11571652). Interacts with RBL1 and RBL2 (By similarity). Interacts with ADORA2A (via cytoplasmic C- terminus); the interaction is direct (PubMed:16339847). Interacts with SART3; recruits USP4 to its substrate PRPF3 (PubMed:20595234). {ECO:0000250|UniProtKB:P35123, ECO:0000269|PubMed:11571652, ECO:0000269|PubMed:16339847, ECO:0000269|PubMed:20595234}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:16316627, ECO:0000269|PubMed:20595234}. Nucleus {ECO:0000269|PubMed:16316627, ECO:0000269|PubMed:20595234}. Note=Shuttles between the nucleus and cytoplasm. Exported to the cytoplasm in a CRM1-dependent manner and recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor. The relative amounts found in the nucleus and cytoplasm vary according to the cell type. {ECO:0000269|PubMed:16316627, ECO:0000269|PubMed:20595234}.

Tissue specificity: Overexpressed in small cell tumors and adenocarcinomas of the lung compared to wild-type lung (at protein level). Expressed in the hippocampal neurons. {ECO:0000269|PubMed:16339847, ECO:0000269|PubMed:7784062}.

Domain: The DUSP and ubiquitin-like 1 domains promote ubiquitin release and thus enhance USB4 catalytic activity. However, these domains do not bind ubiquitin. {ECO:0000269|PubMed:25404403}.

Ptm: Monoubiquitinated by TRIM21. Ubiquitination does not lead to its proteasomal degradation. Autodeubiquitinated. {ECO:0000269|PubMed:16472766, ECO:0000269|PubMed:22347420}.

Similarity: Belongs to the peptidase C19 family. USP4 subfamily. {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:		Deubiquitinating enzyme that removes conjugated ubiquitin from target proteins (PubMed:16316627, PubMed:16472766, PubMed:16339847, PubMed:20595234, PubMed:22347420, PubMed:25404403). Deubiquitinates PDPK1 (PubMed:22347420). Deubiquitinates TRIM21 (PubMed:16316627). Deubiquitinates receptor ADORA2A which increases the amount of functional receptor at the cell surface (PubMed:16339847). May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3 (PubMed:20595234). This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP (PubMed:20595234). May also play a role in the regulation of quality control in the ER (PubMed:16339847). {ECO:0000269\|PubMed:16316627, ECO:0000269\|PubMed:16339847, ECO:0000269\|PubMed:16472766, ECO:0000269\|PubMed:20595234, ECO:0000269\|PubMed:22347420, ECO:0000269\|PubMed:25404403}.


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:16316627, ECO:0000269\|PubMed:16339847, ECO:0000269\|PubMed:16472766, ECO:0000269\|PubMed:20595234, ECO:0000269\|PubMed:22347420, ECO:0000269\|PubMed:25404403};
Activity regulation:		The completion of the deubiquitinase reaction is mediated by the DUSP and ubiquitin-like 1 domains which promotes the release of ubiquitin from the catalytic site enabling subsequent reactions to occur. {ECO:0000269\|PubMed:25404403}.
Biophysicochemical properties:		Kinetic parameters: KM=0.15 uM for ubiquitin-rhodamine {ECO:0000269\|PubMed:25404403};
Subunit:		Interacts with RB1 (both dephosphorylated and hypophosphorylated forms) (PubMed:11571652). Interacts with RBL1 and RBL2 (By similarity). Interacts with ADORA2A (via cytoplasmic C- terminus); the interaction is direct (PubMed:16339847). Interacts with SART3; recruits USP4 to its substrate PRPF3 (PubMed:20595234). {ECO:0000250\|UniProtKB:P35123, ECO:0000269\|PubMed:11571652, ECO:0000269\|PubMed:16339847, ECO:0000269\|PubMed:20595234}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:16316627, ECO:0000269\|PubMed:20595234}. Nucleus {ECO:0000269\|PubMed:16316627, ECO:0000269\|PubMed:20595234}. Note=Shuttles between the nucleus and cytoplasm. Exported to the cytoplasm in a CRM1-dependent manner and recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor. The relative amounts found in the nucleus and cytoplasm vary according to the cell type. {ECO:0000269\|PubMed:16316627, ECO:0000269\|PubMed:20595234}.
Tissue specificity:		Overexpressed in small cell tumors and adenocarcinomas of the lung compared to wild-type lung (at protein level). Expressed in the hippocampal neurons. {ECO:0000269\|PubMed:16339847, ECO:0000269\|PubMed:7784062}.
Domain:		The DUSP and ubiquitin-like 1 domains promote ubiquitin release and thus enhance USB4 catalytic activity. However, these domains do not bind ubiquitin. {ECO:0000269\|PubMed:25404403}.
Ptm:		Monoubiquitinated by TRIM21. Ubiquitination does not lead to its proteasomal degradation. Autodeubiquitinated. {ECO:0000269\|PubMed:16472766, ECO:0000269\|PubMed:22347420}.
Similarity:		Belongs to the peptidase C19 family. USP4 subfamily. {ECO:0000305}.