UniProt functional annotation for P18887



	UniProt functional annotation for P18887

UniProt code: P18887.

Organism: Homo sapiens (Human).

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

Function: Involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes. Probably during DNA repair, negatively regulates ADP-ribose levels by modulating ADP- ribosyltransferase PARP1 activity. {ECO:0000269|PubMed:28002403}.

Subunit: Homodimer. Interacts with polynucleotide kinase (PNK), DNA polymerase-beta (POLB) and DNA ligase III (LIG3). Interacts with APTX and APLF. Interacts with APEX1; the interaction is induced by SIRT1 and increases with the acetylated form of APEX1. {ECO:0000269|PubMed:11163244, ECO:0000269|PubMed:14755728, ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:17353262, ECO:0000269|PubMed:17507382, ECO:0000269|PubMed:19155274, ECO:0000269|PubMed:19934257}.

Subcellular location: Nucleus {ECO:0000269|PubMed:17353262, ECO:0000269|PubMed:28002403}. Note=Moves from the nucleoli to the global nuclear chromatin upon DNA damage. {ECO:0000269|PubMed:28002403}.

Tissue specificity: Expressed in fibroblasts, retinal pigmented epithelial cells and lymphoblastoid cells (at protein level). {ECO:0000269|PubMed:28002403}.

Ptm: Phosphorylation of Ser-371 causes dimer dissociation. Phosphorylation by CK2 promotes interaction with APTX and APLF. {ECO:0000269|PubMed:15066279, ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:17353262, ECO:0000269|PubMed:19155274}.

Ptm: Sumoylated. {ECO:0000269|PubMed:15561718}.

Polymorphism: Carriers of the polymorphic Gln-399 allele may be at greater risk for tobacco- and age-related DNA damage.

Disease: Spinocerebellar ataxia, autosomal recessive, 26 (SCAR26) [MIM:617633]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR26 is a progressive disease characterized by gait and limb ataxia, loss of independent ambulation, oculomotor apraxia, and peripheral neuropathy with distal muscle weakness and areflexia. {ECO:0000269|PubMed:28002403}. Note=The disease is caused by variants affecting the gene represented in this entry.

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:		Involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes. Probably during DNA repair, negatively regulates ADP-ribose levels by modulating ADP- ribosyltransferase PARP1 activity. {ECO:0000269\|PubMed:28002403}.


Subunit:		Homodimer. Interacts with polynucleotide kinase (PNK), DNA polymerase-beta (POLB) and DNA ligase III (LIG3). Interacts with APTX and APLF. Interacts with APEX1; the interaction is induced by SIRT1 and increases with the acetylated form of APEX1. {ECO:0000269\|PubMed:11163244, ECO:0000269\|PubMed:14755728, ECO:0000269\|PubMed:15044383, ECO:0000269\|PubMed:15380105, ECO:0000269\|PubMed:16397295, ECO:0000269\|PubMed:17353262, ECO:0000269\|PubMed:17507382, ECO:0000269\|PubMed:19155274, ECO:0000269\|PubMed:19934257}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:17353262, ECO:0000269\|PubMed:28002403}. Note=Moves from the nucleoli to the global nuclear chromatin upon DNA damage. {ECO:0000269\|PubMed:28002403}.
Tissue specificity:		Expressed in fibroblasts, retinal pigmented epithelial cells and lymphoblastoid cells (at protein level). {ECO:0000269\|PubMed:28002403}.
Ptm:		Phosphorylation of Ser-371 causes dimer dissociation. Phosphorylation by CK2 promotes interaction with APTX and APLF. {ECO:0000269\|PubMed:15066279, ECO:0000269\|PubMed:15380105, ECO:0000269\|PubMed:16397295, ECO:0000269\|PubMed:17353262, ECO:0000269\|PubMed:19155274}.
Ptm:		Sumoylated. {ECO:0000269\|PubMed:15561718}.
Polymorphism:		Carriers of the polymorphic Gln-399 allele may be at greater risk for tobacco- and age-related DNA damage.
Disease:		Spinocerebellar ataxia, autosomal recessive, 26 (SCAR26) [MIM:617633]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR26 is a progressive disease characterized by gait and limb ataxia, loss of independent ambulation, oculomotor apraxia, and peripheral neuropathy with distal muscle weakness and areflexia. {ECO:0000269\|PubMed:28002403}. Note=The disease is caused by variants affecting the gene represented in this entry.