UniProt functional annotation for Q7Z2E3



	UniProt functional annotation for Q7Z2E3

UniProt code: Q7Z2E3.

Organism: Homo sapiens (Human).

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

Function: DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair (PubMed:15380105, PubMed:15044383, PubMed:16964241, PubMed:17276982, PubMed:24362567). Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species (PubMed:16964241, PubMed:24362567). Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined (PubMed:16964241, PubMed:17276982, PubMed:24362567). Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity (PubMed:16547001). Likewise, catalyzes the release of 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA, but has higher specific activity with 5'-linked adenosine (AppDNA) (By similarity). {ECO:0000250|UniProtKB:O74859, ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:16547001, ECO:0000269|PubMed:16964241, ECO:0000269|PubMed:17276982, ECO:0000269|PubMed:24362567}.

Catalytic activity: Reaction=adenosine-5'-diphospho-5'-(DNA) + H2O = AMP + 2 H(+) + phospho-5'-(DNA); Xref=Rhea:RHEA:52128, Rhea:RHEA-COMP:13180, Rhea:RHEA-COMP:13181, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, ChEBI:CHEBI:136413, ChEBI:CHEBI:456215; EC=3.6.1.71; Evidence={ECO:0000269|PubMed:16964241, ECO:0000269|PubMed:17276982, ECO:0000269|PubMed:24362567, ECO:0000305|PubMed:16547001};

Catalytic activity: Reaction=adenosine-5'-diphospho-5'-(ribonucleotide)-(DNA) + H2O = 5'- phospho-(ribonucleotide)-(DNA) + AMP + 2 H(+); Xref=Rhea:RHEA:52132, Rhea:RHEA-COMP:13182, Rhea:RHEA-COMP:13183, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:136414, ChEBI:CHEBI:136415, ChEBI:CHEBI:456215; EC=3.6.1.71; Evidence={ECO:0000269|PubMed:16964241, ECO:0000269|PubMed:17276982, ECO:0000269|PubMed:24362567, ECO:0000305|PubMed:16547001};

Catalytic activity: Reaction=(DNA)-3'-diphospho-5'-guanosine + H2O = (DNA)-3'-phosphate + GMP + 2 H(+); Xref=Rhea:RHEA:52140, Rhea:RHEA-COMP:13186, Rhea:RHEA- COMP:13187, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58115, ChEBI:CHEBI:136419, ChEBI:CHEBI:136420; EC=3.6.1.72; Evidence={ECO:0000250|UniProtKB:O74859};

Biophysicochemical properties: Kinetic parameters: KM=18 uM for AppppA {ECO:0000269|PubMed:16547001}; KM=837.5 uM for AMP-NH(2) {ECO:0000269|PubMed:16547001};

Subunit: Interacts with single-strand break repair proteins XRCC1, XRCC4, ADPRT/PARP1 and p53/TP53 (PubMed:14755728, PubMed:15380105, PubMed:15044383, PubMed:16777843). Interacts with NCL (PubMed:15044383, PubMed:16777843). Interacts (via FHA-like domain) with MDC1 (phosphorylated) (PubMed:20008512). {ECO:0000269|PubMed:14755728, ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:16777843, ECO:0000269|PubMed:20008512}.

Subcellular location: Nucleus, nucleoplasm {ECO:0000269|PubMed:14755728, ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:15276230, ECO:0000269|PubMed:15380105}. Nucleus, nucleolus {ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:16777843}. Note=Upon genotoxic stress, colocalizes with XRCC1 at sites of DNA damage (PubMed:15380105). Colocalizes with MDC1 at sites of DNA double- strand breaks (PubMed:20008512). Interaction with NCL is required for nucleolar localization (PubMed:16777843). {ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:20008512}.

Subcellular location: [Isoform 12]: Cytoplasm {ECO:0000269|PubMed:15276230}.

Tissue specificity: Widely expressed; detected in liver, kidney and lymph node (at protein level) (PubMed:14755728). Isoform 1 is highly expressed in the cerebral cortex and cerebellum, compared to isoform 2 (at protein level) (PubMed:14755728). Widely expressed; detected throughout the brain, in liver, kidney, skeletal muscle, fibroblasts, lymphocytes and pancreas (PubMed:15276230, PubMed:11586299, PubMed:11586300). {ECO:0000269|PubMed:11586299, ECO:0000269|PubMed:11586300, ECO:0000269|PubMed:14755728, ECO:0000269|PubMed:15276230}.

Domain: The histidine triad, also called HIT motif, forms part of the binding loop for the alpha-phosphate of purine mononucleotide. {ECO:0000269|PubMed:24362567}.

Domain: The FHA-like domain mediates interaction with NCL; XRCC1 and XRCC4.

Domain: The HIT domain is required for enzymatic activity.

Domain: The C2H2-type zinc finger mediates DNA-binding.

Disease: Ataxia-oculomotor apraxia syndrome (AOA) [MIM:208920]: An autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy. {ECO:0000269|PubMed:11586299, ECO:0000269|PubMed:11586300, ECO:0000269|PubMed:12196655, ECO:0000269|PubMed:12629250, ECO:0000269|PubMed:14506070, ECO:0000269|PubMed:15699391, ECO:0000269|PubMed:15852392, ECO:0000269|PubMed:24362567}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 1]: Major form. {ECO:0000305|PubMed:14755728}.

Miscellaneous: [Isoform 2]: Minor form. {ECO:0000305|PubMed:14755728}.

Miscellaneous: [Isoform 3]: May be an aberrant isoform present in cancer cell lines. {ECO:0000305}.

Miscellaneous: [Isoform 4]: May be an aberrant isoform present in cancer cell lines. {ECO:0000305}.

Miscellaneous: [Isoform 5]: May be an aberrant isoform present in cancer cell lines. {ECO:0000305}.

Miscellaneous: [Isoform 6]: May be an aberrant isoform present in cancer cell lines. {ECO:0000305}.

Miscellaneous: [Isoform 8]: May be an aberrant isoform present in cancer cell lines. {ECO:0000305}.

Miscellaneous: [Isoform 10]: May be an aberrant isoform present in cancer cell lines. {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-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair (PubMed:15380105, PubMed:15044383, PubMed:16964241, PubMed:17276982, PubMed:24362567). Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species (PubMed:16964241, PubMed:24362567). Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined (PubMed:16964241, PubMed:17276982, PubMed:24362567). Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity (PubMed:16547001). Likewise, catalyzes the release of 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA, but has higher specific activity with 5'-linked adenosine (AppDNA) (By similarity). {ECO:0000250\|UniProtKB:O74859, ECO:0000269\|PubMed:15044383, ECO:0000269\|PubMed:15380105, ECO:0000269\|PubMed:16547001, ECO:0000269\|PubMed:16964241, ECO:0000269\|PubMed:17276982, ECO:0000269\|PubMed:24362567}.


Catalytic activity:		Reaction=adenosine-5'-diphospho-5'-(DNA) + H2O = AMP + 2 H(+) + phospho-5'-(DNA); Xref=Rhea:RHEA:52128, Rhea:RHEA-COMP:13180, Rhea:RHEA-COMP:13181, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, ChEBI:CHEBI:136413, ChEBI:CHEBI:456215; EC=3.6.1.71; Evidence={ECO:0000269\|PubMed:16964241, ECO:0000269\|PubMed:17276982, ECO:0000269\|PubMed:24362567, ECO:0000305\|PubMed:16547001};
Catalytic activity:		Reaction=adenosine-5'-diphospho-5'-(ribonucleotide)-(DNA) + H2O = 5'- phospho-(ribonucleotide)-(DNA) + AMP + 2 H(+); Xref=Rhea:RHEA:52132, Rhea:RHEA-COMP:13182, Rhea:RHEA-COMP:13183, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:136414, ChEBI:CHEBI:136415, ChEBI:CHEBI:456215; EC=3.6.1.71; Evidence={ECO:0000269\|PubMed:16964241, ECO:0000269\|PubMed:17276982, ECO:0000269\|PubMed:24362567, ECO:0000305\|PubMed:16547001};
Catalytic activity:		Reaction=(DNA)-3'-diphospho-5'-guanosine + H2O = (DNA)-3'-phosphate + GMP + 2 H(+); Xref=Rhea:RHEA:52140, Rhea:RHEA-COMP:13186, Rhea:RHEA- COMP:13187, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58115, ChEBI:CHEBI:136419, ChEBI:CHEBI:136420; EC=3.6.1.72; Evidence={ECO:0000250\|UniProtKB:O74859};
Biophysicochemical properties:		Kinetic parameters: KM=18 uM for AppppA {ECO:0000269\|PubMed:16547001}; KM=837.5 uM for AMP-NH(2) {ECO:0000269\|PubMed:16547001};
Subunit:		Interacts with single-strand break repair proteins XRCC1, XRCC4, ADPRT/PARP1 and p53/TP53 (PubMed:14755728, PubMed:15380105, PubMed:15044383, PubMed:16777843). Interacts with NCL (PubMed:15044383, PubMed:16777843). Interacts (via FHA-like domain) with MDC1 (phosphorylated) (PubMed:20008512). {ECO:0000269\|PubMed:14755728, ECO:0000269\|PubMed:15044383, ECO:0000269\|PubMed:15380105, ECO:0000269\|PubMed:16777843, ECO:0000269\|PubMed:20008512}.
Subcellular location:		Nucleus, nucleoplasm {ECO:0000269\|PubMed:14755728, ECO:0000269\|PubMed:15044383, ECO:0000269\|PubMed:15276230, ECO:0000269\|PubMed:15380105}. Nucleus, nucleolus {ECO:0000269\|PubMed:15044383, ECO:0000269\|PubMed:16777843}. Note=Upon genotoxic stress, colocalizes with XRCC1 at sites of DNA damage (PubMed:15380105). Colocalizes with MDC1 at sites of DNA double- strand breaks (PubMed:20008512). Interaction with NCL is required for nucleolar localization (PubMed:16777843). {ECO:0000269\|PubMed:15044383, ECO:0000269\|PubMed:15380105, ECO:0000269\|PubMed:20008512}.
Subcellular location:		[Isoform 12]: Cytoplasm {ECO:0000269\|PubMed:15276230}.
Tissue specificity:		Widely expressed; detected in liver, kidney and lymph node (at protein level) (PubMed:14755728). Isoform 1 is highly expressed in the cerebral cortex and cerebellum, compared to isoform 2 (at protein level) (PubMed:14755728). Widely expressed; detected throughout the brain, in liver, kidney, skeletal muscle, fibroblasts, lymphocytes and pancreas (PubMed:15276230, PubMed:11586299, PubMed:11586300). {ECO:0000269\|PubMed:11586299, ECO:0000269\|PubMed:11586300, ECO:0000269\|PubMed:14755728, ECO:0000269\|PubMed:15276230}.
Domain:		The histidine triad, also called HIT motif, forms part of the binding loop for the alpha-phosphate of purine mononucleotide. {ECO:0000269\|PubMed:24362567}.
Domain:		The FHA-like domain mediates interaction with NCL; XRCC1 and XRCC4.
Domain:		The HIT domain is required for enzymatic activity.
Domain:		The C2H2-type zinc finger mediates DNA-binding.
Disease:		Ataxia-oculomotor apraxia syndrome (AOA) [MIM:208920]: An autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy. {ECO:0000269\|PubMed:11586299, ECO:0000269\|PubMed:11586300, ECO:0000269\|PubMed:12196655, ECO:0000269\|PubMed:12629250, ECO:0000269\|PubMed:14506070, ECO:0000269\|PubMed:15699391, ECO:0000269\|PubMed:15852392, ECO:0000269\|PubMed:24362567}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 1]: Major form. {ECO:0000305\|PubMed:14755728}.
Miscellaneous:		[Isoform 2]: Minor form. {ECO:0000305\|PubMed:14755728}.
Miscellaneous:		[Isoform 3]: May be an aberrant isoform present in cancer cell lines. {ECO:0000305}.
Miscellaneous:		[Isoform 4]: May be an aberrant isoform present in cancer cell lines. {ECO:0000305}.
Miscellaneous:		[Isoform 5]: May be an aberrant isoform present in cancer cell lines. {ECO:0000305}.
Miscellaneous:		[Isoform 6]: May be an aberrant isoform present in cancer cell lines. {ECO:0000305}.
Miscellaneous:		[Isoform 8]: May be an aberrant isoform present in cancer cell lines. {ECO:0000305}.
Miscellaneous:		[Isoform 10]: May be an aberrant isoform present in cancer cell lines. {ECO:0000305}.