UniProt functional annotation for Q9NUW8



	UniProt functional annotation for Q9NUW8

UniProt code: Q9NUW8.

Organism: Homo sapiens (Human).

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

Function: DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead- end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can remove a single nucleoside from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3'phosphate. {ECO:0000269|PubMed:12023295, ECO:0000269|PubMed:15111055, ECO:0000269|PubMed:15811850, ECO:0000269|PubMed:16141202, ECO:0000269|PubMed:22822062}.

Biophysicochemical properties: Kinetic parameters: KM=0.08 uM for 14-mer single-stranded oligo with a 3'-phosphotyrosine {ECO:0000269|PubMed:22822062}; Note=kcat is 7 sec(-1) with single-stranded 5'-tyrosyl DNA as substrate.;

Subunit: Monomer. {ECO:0000269|PubMed:11839309}.

Subcellular location: Nucleus {ECO:0000269|PubMed:15647511}. Cytoplasm {ECO:0000269|PubMed:15647511}.

Tissue specificity: Ubiquitously expressed. Similar expression throughout the central nervous system (whole brain, amygdala, caudate nucleus, cerebellum, cerebral cortex, frontal lobe, hippocampus, medulla oblongata, occipital lobe, putamen, substantia nigra, temporal lobe, thalamus, nucleus accumbens and spinal cord) and increased expression in testis and thymus. {ECO:0000269|PubMed:12244316, ECO:0000269|PubMed:17948061}.

Ptm: Phosphorylated on serine and/or threonine residues, but not on tyrosine residues. {ECO:0000269|PubMed:15647511}.

Disease: Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 (SCAN1) [MIM:607250]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAN1 is an autosomal recessive cerebellar ataxia (ARCA) associated with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie- Tooth neuropathy. All affected individuals have normal intelligence. {ECO:0000269|PubMed:12244316, ECO:0000269|PubMed:15647511, ECO:0000269|PubMed:15920477, ECO:0000269|PubMed:16141202, ECO:0000269|PubMed:17948061}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the tyrosyl-DNA phosphodiesterase 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:		DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead- end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can remove a single nucleoside from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3'phosphate. {ECO:0000269\|PubMed:12023295, ECO:0000269\|PubMed:15111055, ECO:0000269\|PubMed:15811850, ECO:0000269\|PubMed:16141202, ECO:0000269\|PubMed:22822062}.


Biophysicochemical properties:		Kinetic parameters: KM=0.08 uM for 14-mer single-stranded oligo with a 3'-phosphotyrosine {ECO:0000269\|PubMed:22822062}; Note=kcat is 7 sec(-1) with single-stranded 5'-tyrosyl DNA as substrate.;
Subunit:		Monomer. {ECO:0000269\|PubMed:11839309}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:15647511}. Cytoplasm {ECO:0000269\|PubMed:15647511}.
Tissue specificity:		Ubiquitously expressed. Similar expression throughout the central nervous system (whole brain, amygdala, caudate nucleus, cerebellum, cerebral cortex, frontal lobe, hippocampus, medulla oblongata, occipital lobe, putamen, substantia nigra, temporal lobe, thalamus, nucleus accumbens and spinal cord) and increased expression in testis and thymus. {ECO:0000269\|PubMed:12244316, ECO:0000269\|PubMed:17948061}.
Ptm:		Phosphorylated on serine and/or threonine residues, but not on tyrosine residues. {ECO:0000269\|PubMed:15647511}.
Disease:		Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 (SCAN1) [MIM:607250]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAN1 is an autosomal recessive cerebellar ataxia (ARCA) associated with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie- Tooth neuropathy. All affected individuals have normal intelligence. {ECO:0000269\|PubMed:12244316, ECO:0000269\|PubMed:15647511, ECO:0000269\|PubMed:15920477, ECO:0000269\|PubMed:16141202, ECO:0000269\|PubMed:17948061}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the tyrosyl-DNA phosphodiesterase family. {ECO:0000305}.