UniProt functional annotation for Q6GQQ9



	UniProt functional annotation for Q6GQQ9

UniProt code: Q6GQQ9.

Organism: Homo sapiens (Human).

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

Function: Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses. In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF- kappa-B. Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR (PubMed:22179831). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains (PubMed:27732584). Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure (PubMed:27732584). Hydrolyzes both linear and branched forms of polyubiquitin. {ECO:0000250|UniProtKB:B2RUR8, ECO:0000269|PubMed:11463333, ECO:0000269|PubMed:12682062, ECO:0000269|PubMed:18178551, ECO:0000269|PubMed:20622874, ECO:0000269|PubMed:22179831, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:27732584}.

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:12682062, ECO:0000269|PubMed:14748687, ECO:0000269|PubMed:22179831, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:27732584};

Activity regulation: Deubiquitinase activity is inhibited following interaction with PARK7. {ECO:0000269|PubMed:21097510}.

Subunit: Interacts with ZAP70 in activated T cells, but not in resting T cells (PubMed:26903241). Interacts with TRAF3 (By similarity). Interacts with TRAF6 (PubMed:11463333). Interacts with PARK7, leading to inhibit deubiquitinase activity (PubMed:21097510). Interacts with EGFR, ITCH and NEDD4 (PubMed:22179831). {ECO:0000250|UniProtKB:B2RUR8, ECO:0000269|PubMed:11463333, ECO:0000269|PubMed:21097510, ECO:0000269|PubMed:22179831, ECO:0000269|PubMed:26903241}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:11463333, ECO:0000269|PubMed:21888622}. Nucleus {ECO:0000269|PubMed:21888622}. Note=Shuttles be cytoplasm and the nucleus in a XPO1/CRM1-dependent manner. {ECO:0000269|PubMed:21888622}.

Tissue specificity: Widely expressed. Abundant in kidney, heart and fetal liver. Expressed differentially among B-cells at distinct developmental stages. Higher expression seen in primary immature B- cells as compared to the mature cells. {ECO:0000269|PubMed:11463333, ECO:0000269|PubMed:12682062}.

Induction: By TNF-alpha. {ECO:0000269|PubMed:18178551}.

Domain: The protein undergoes a significant conformation change upon binding to ubiquitinated substrates. The loop that precedes the active site is in an autoinhibitory conformation in the apoprotein. Ubiquitin binding leads to a conformation change; the loop is stabilized in a catalytically competent conformation with the result that the active site Cys can form the reaction state intermediate. {ECO:0000269|PubMed:27732584}.

Ptm: Phosphorylated by EGFR. {ECO:0000269|PubMed:22179831}.

Similarity: Belongs to the peptidase C64 family. {ECO:0000305}.

Sequence caution: Sequence=CAB97494.1; Type=Erroneous initiation; Note=Extended 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:		Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses. In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF- kappa-B. Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR (PubMed:22179831). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains (PubMed:27732584). Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure (PubMed:27732584). Hydrolyzes both linear and branched forms of polyubiquitin. {ECO:0000250\|UniProtKB:B2RUR8, ECO:0000269\|PubMed:11463333, ECO:0000269\|PubMed:12682062, ECO:0000269\|PubMed:18178551, ECO:0000269\|PubMed:20622874, ECO:0000269\|PubMed:22179831, ECO:0000269\|PubMed:23827681, ECO:0000269\|PubMed:27732584}.


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:12682062, ECO:0000269\|PubMed:14748687, ECO:0000269\|PubMed:22179831, ECO:0000269\|PubMed:23827681, ECO:0000269\|PubMed:26903241, ECO:0000269\|PubMed:27732584};
Activity regulation:		Deubiquitinase activity is inhibited following interaction with PARK7. {ECO:0000269\|PubMed:21097510}.
Subunit:		Interacts with ZAP70 in activated T cells, but not in resting T cells (PubMed:26903241). Interacts with TRAF3 (By similarity). Interacts with TRAF6 (PubMed:11463333). Interacts with PARK7, leading to inhibit deubiquitinase activity (PubMed:21097510). Interacts with EGFR, ITCH and NEDD4 (PubMed:22179831). {ECO:0000250\|UniProtKB:B2RUR8, ECO:0000269\|PubMed:11463333, ECO:0000269\|PubMed:21097510, ECO:0000269\|PubMed:22179831, ECO:0000269\|PubMed:26903241}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:11463333, ECO:0000269\|PubMed:21888622}. Nucleus {ECO:0000269\|PubMed:21888622}. Note=Shuttles be cytoplasm and the nucleus in a XPO1/CRM1-dependent manner. {ECO:0000269\|PubMed:21888622}.
Tissue specificity:		Widely expressed. Abundant in kidney, heart and fetal liver. Expressed differentially among B-cells at distinct developmental stages. Higher expression seen in primary immature B- cells as compared to the mature cells. {ECO:0000269\|PubMed:11463333, ECO:0000269\|PubMed:12682062}.
Induction:		By TNF-alpha. {ECO:0000269\|PubMed:18178551}.
Domain:		The protein undergoes a significant conformation change upon binding to ubiquitinated substrates. The loop that precedes the active site is in an autoinhibitory conformation in the apoprotein. Ubiquitin binding leads to a conformation change; the loop is stabilized in a catalytically competent conformation with the result that the active site Cys can form the reaction state intermediate. {ECO:0000269\|PubMed:27732584}.
Ptm:		Phosphorylated by EGFR. {ECO:0000269\|PubMed:22179831}.
Similarity:		Belongs to the peptidase C64 family. {ECO:0000305}.
Sequence caution:		Sequence=CAB97494.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};