UniProt functional annotation for Q9JJX7



	UniProt functional annotation for Q9JJX7

UniProt code: Q9JJX7.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead- end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DNA double-strand breaks/DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'- phosphate termini that are ready for ligation (PubMed:23104055, PubMed:24808172, PubMed:27099339, PubMed:27060144). Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2 (PubMed:22740648). Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DSBs due to DNA damage by radiation and free radicals. Has preference for single- stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Has also 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Constitutes the major if not only 5'-tyrosyl-DNA phosphodiesterase in cells. Also acts as an adapter by participating in the specific activation of MAP3K7/TAK1 in response to TGF-beta: associates with components of the TGF-beta receptor-TRAF6- TAK1 signaling module and promotes their ubiquitination dependent complex formation. Involved in non-canonical TGF-beta induced signaling routes. May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B activation. Acts as a regulator of ribosome biogenesis following stress (By similarity). {ECO:0000250|UniProtKB:O95551, ECO:0000269|PubMed:22740648, ECO:0000269|PubMed:23104055, ECO:0000269|PubMed:24808172, ECO:0000269|PubMed:27060144, ECO:0000269|PubMed:27099339}.

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:23104055, ECO:0000269|PubMed:24808172, ECO:0000269|PubMed:27060144, ECO:0000269|PubMed:27099339}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:23104055, ECO:0000269|PubMed:27060144}; Note=Binds 1 magnesium or manganese ion per subunit. {ECO:0000269|PubMed:23104055, ECO:0000269|PubMed:24808172, ECO:0000269|PubMed:27060144, ECO:0000269|PubMed:27099339};

Subunit: Interacts with TRAF2, TRAF3, TRAF5, TRAF6, TNFRSF8/CD30, TNFRSF5/CD40, TNFRSF1B/TNF-R75, ETS1, ETS2, FLI1, SMAD3 and ACVR1B/ALK4. {ECO:0000250|UniProtKB:O95551}.

Subcellular location: Nucleus {ECO:0000250|UniProtKB:O95551}. Nucleus, PML body {ECO:0000250|UniProtKB:O95551}. Nucleus, nucleolus {ECO:0000250|UniProtKB:O95551}. Cytoplasm {ECO:0000250|UniProtKB:O95551}. Note=Localizes to nucleolar cavities following stress; localization to nucleolus is dependent on PML protein. {ECO:0000250|UniProtKB:O95551}.

Tissue specificity: Widely expressed (PubMed:10764746). Expressed in whole brain, cerebellum, quiescent cortical astrocytes and cerebellar granule neurons (PubMed:24658003). {ECO:0000269|PubMed:10764746, ECO:0000269|PubMed:24658003}.

Ptm: Ubiquitinated by TRAF6. {ECO:0000250|UniProtKB:O95551}.

Miscellaneous: Can partially complement the absence of Tdp1 due to its weak 3'-tyrosyl DNA phosphodiesterase activity. {ECO:0000305|PubMed:22740648}.

Similarity: Belongs to the CCR4/nocturin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead- end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DNA double-strand breaks/DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'- phosphate termini that are ready for ligation (PubMed:23104055, PubMed:24808172, PubMed:27099339, PubMed:27060144). Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2 (PubMed:22740648). Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DSBs due to DNA damage by radiation and free radicals. Has preference for single- stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Has also 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Constitutes the major if not only 5'-tyrosyl-DNA phosphodiesterase in cells. Also acts as an adapter by participating in the specific activation of MAP3K7/TAK1 in response to TGF-beta: associates with components of the TGF-beta receptor-TRAF6- TAK1 signaling module and promotes their ubiquitination dependent complex formation. Involved in non-canonical TGF-beta induced signaling routes. May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B activation. Acts as a regulator of ribosome biogenesis following stress (By similarity). {ECO:0000250\|UniProtKB:O95551, ECO:0000269\|PubMed:22740648, ECO:0000269\|PubMed:23104055, ECO:0000269\|PubMed:24808172, ECO:0000269\|PubMed:27060144, ECO:0000269\|PubMed:27099339}.


Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:23104055, ECO:0000269\|PubMed:24808172, ECO:0000269\|PubMed:27060144, ECO:0000269\|PubMed:27099339}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269\|PubMed:23104055, ECO:0000269\|PubMed:27060144}; Note=Binds 1 magnesium or manganese ion per subunit. {ECO:0000269\|PubMed:23104055, ECO:0000269\|PubMed:24808172, ECO:0000269\|PubMed:27060144, ECO:0000269\|PubMed:27099339};
Subunit:		Interacts with TRAF2, TRAF3, TRAF5, TRAF6, TNFRSF8/CD30, TNFRSF5/CD40, TNFRSF1B/TNF-R75, ETS1, ETS2, FLI1, SMAD3 and ACVR1B/ALK4. {ECO:0000250\|UniProtKB:O95551}.
Subcellular location:		Nucleus {ECO:0000250\|UniProtKB:O95551}. Nucleus, PML body {ECO:0000250\|UniProtKB:O95551}. Nucleus, nucleolus {ECO:0000250\|UniProtKB:O95551}. Cytoplasm {ECO:0000250\|UniProtKB:O95551}. Note=Localizes to nucleolar cavities following stress; localization to nucleolus is dependent on PML protein. {ECO:0000250\|UniProtKB:O95551}.
Tissue specificity:		Widely expressed (PubMed:10764746). Expressed in whole brain, cerebellum, quiescent cortical astrocytes and cerebellar granule neurons (PubMed:24658003). {ECO:0000269\|PubMed:10764746, ECO:0000269\|PubMed:24658003}.
Ptm:		Ubiquitinated by TRAF6. {ECO:0000250\|UniProtKB:O95551}.
Miscellaneous:		Can partially complement the absence of Tdp1 due to its weak 3'-tyrosyl DNA phosphodiesterase activity. {ECO:0000305\|PubMed:22740648}.
Similarity:		Belongs to the CCR4/nocturin family. {ECO:0000305}.