UniProt functional annotation for O95271



	UniProt functional annotation for O95271

UniProt code: O95271.

Organism: Homo sapiens (Human).

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

Function: Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking (PubMed:10988299, PubMed:11739745, PubMed:16076287, PubMed:19759537, PubMed:21478859, PubMed:22864114, PubMed:23622245, PubMed:25043379). Acts as an activator of the Wnt signaling pathway by mediating poly- ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation (PubMed:19759537, PubMed:21478859). Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination (PubMed:21478859). Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length (PubMed:11739745). Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI (PubMed:22864114). May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles (PubMed:10988299). May be involved in spindle pole assembly through PARsylation of NUMA1 (PubMed:16076287). Stimulates 26S proteasome activity (PubMed:23622245). {ECO:0000269|PubMed:10988299, ECO:0000269|PubMed:11739745, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:19759537, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:22864114, ECO:0000269|PubMed:23622245, ECO:0000269|PubMed:25043379}.

Catalytic activity: Reaction=NAD(+) + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D- ribosyl)(n+1)-acceptor.; EC=2.4.2.30; Evidence={ECO:0000269|PubMed:19759537};

Catalytic activity: Reaction=L-aspartyl-[protein] + NAD(+) = 4-O-(ADP-D-ribosyl)-L- aspartyl-[protein] + nicotinamide; Xref=Rhea:RHEA:54424, Rhea:RHEA- COMP:9867, Rhea:RHEA-COMP:13832, ChEBI:CHEBI:17154, ChEBI:CHEBI:29961, ChEBI:CHEBI:57540, ChEBI:CHEBI:138102; Evidence={ECO:0000305}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54425; Evidence={ECO:0000305};

Catalytic activity: Reaction=L-glutamyl-[protein] + NAD(+) = 5-O-(ADP-D-ribosyl)-L- glutamyl-[protein] + nicotinamide; Xref=Rhea:RHEA:58224, Rhea:RHEA- COMP:10208, Rhea:RHEA-COMP:15089, ChEBI:CHEBI:17154, ChEBI:CHEBI:29973, ChEBI:CHEBI:57540, ChEBI:CHEBI:142540; Evidence={ECO:0000305}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58225; Evidence={ECO:0000305};

Activity regulation: Specifically inhibited by XAV939, a small molecule, leading to inhibit the Wnt signaling pathway by stabilizing AXIN1 and AXIN2. {ECO:0000269|PubMed:19759537}.

Subunit: Oligomerizes and associates with TNKS2. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles. Binds to the N-terminus of telomeric TERF1 via the ANK repeats. Found in a complex with POT1; TERF1 and TINF2 (PubMed:12768206). Interacts with AXIN1 (PubMed:19759537, PubMed:21478859, PubMed:21799911). Interacts with AXIN2 (PubMed:19759537, PubMed:21478859). Interacts with BLZF1 and CASC3 (PubMed:21478859). Interacts with NUMA1 (PubMed:12080061). {ECO:0000269|PubMed:12080061, ECO:0000269|PubMed:12768206, ECO:0000269|PubMed:19759537, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:21799911}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:10523501, ECO:0000269|PubMed:21799911, ECO:0000269|PubMed:22864114}. Golgi apparatus membrane {ECO:0000269|PubMed:22864114}; Peripheral membrane protein {ECO:0000269|PubMed:22864114}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:10523501, ECO:0000269|PubMed:21799911}. Nucleus, nuclear pore complex {ECO:0000269|PubMed:10523501}. Chromosome, telomere {ECO:0000305|PubMed:9822378}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:16076287}. Note=Associated with the Golgi and with juxtanuclear SLC2A4/GLUT4-vesicles (PubMed:22864114). A minor proportion is also found at nuclear pore complexes and around the pericentriolar matrix of mitotic centromeres (PubMed:10523501). During interphase, a small fraction of TNKS is found in the nucleus, associated with TERF1 (PubMed:12768206). Localizes to spindle poles at mitosis onset via interaction with NUMA1 (PubMed:12080061). {ECO:0000269|PubMed:10523501, ECO:0000269|PubMed:12080061, ECO:0000269|PubMed:12768206, ECO:0000269|PubMed:22864114}.

Tissue specificity: Ubiquitous; highest levels in testis.

Ptm: Phosphorylated on serine residues by MAPK kinases upon insulin stimulation. Phosphorylated during mitosis. {ECO:0000269|PubMed:10988299}.

Ptm: Ubiquitinated by RNF146 when auto-poly-ADP-ribosylated, leading to its degradation. {ECO:0000269|PubMed:21478859}.

Ptm: ADP-ribosylated (-auto). Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination. {ECO:0000269|PubMed:21478859}.

Similarity: Belongs to the ARTD/PARP 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:		Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking (PubMed:10988299, PubMed:11739745, PubMed:16076287, PubMed:19759537, PubMed:21478859, PubMed:22864114, PubMed:23622245, PubMed:25043379). Acts as an activator of the Wnt signaling pathway by mediating poly- ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation (PubMed:19759537, PubMed:21478859). Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination (PubMed:21478859). Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length (PubMed:11739745). Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI (PubMed:22864114). May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles (PubMed:10988299). May be involved in spindle pole assembly through PARsylation of NUMA1 (PubMed:16076287). Stimulates 26S proteasome activity (PubMed:23622245). {ECO:0000269\|PubMed:10988299, ECO:0000269\|PubMed:11739745, ECO:0000269\|PubMed:16076287, ECO:0000269\|PubMed:19759537, ECO:0000269\|PubMed:21478859, ECO:0000269\|PubMed:22864114, ECO:0000269\|PubMed:23622245, ECO:0000269\|PubMed:25043379}.


Catalytic activity:		Reaction=NAD(+) + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D- ribosyl)(n+1)-acceptor.; EC=2.4.2.30; Evidence={ECO:0000269\|PubMed:19759537};
Catalytic activity:		Reaction=L-aspartyl-[protein] + NAD(+) = 4-O-(ADP-D-ribosyl)-L- aspartyl-[protein] + nicotinamide; Xref=Rhea:RHEA:54424, Rhea:RHEA- COMP:9867, Rhea:RHEA-COMP:13832, ChEBI:CHEBI:17154, ChEBI:CHEBI:29961, ChEBI:CHEBI:57540, ChEBI:CHEBI:138102; Evidence={ECO:0000305}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54425; Evidence={ECO:0000305};
Catalytic activity:		Reaction=L-glutamyl-[protein] + NAD(+) = 5-O-(ADP-D-ribosyl)-L- glutamyl-[protein] + nicotinamide; Xref=Rhea:RHEA:58224, Rhea:RHEA- COMP:10208, Rhea:RHEA-COMP:15089, ChEBI:CHEBI:17154, ChEBI:CHEBI:29973, ChEBI:CHEBI:57540, ChEBI:CHEBI:142540; Evidence={ECO:0000305}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58225; Evidence={ECO:0000305};
Activity regulation:		Specifically inhibited by XAV939, a small molecule, leading to inhibit the Wnt signaling pathway by stabilizing AXIN1 and AXIN2. {ECO:0000269\|PubMed:19759537}.
Subunit:		Oligomerizes and associates with TNKS2. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles. Binds to the N-terminus of telomeric TERF1 via the ANK repeats. Found in a complex with POT1; TERF1 and TINF2 (PubMed:12768206). Interacts with AXIN1 (PubMed:19759537, PubMed:21478859, PubMed:21799911). Interacts with AXIN2 (PubMed:19759537, PubMed:21478859). Interacts with BLZF1 and CASC3 (PubMed:21478859). Interacts with NUMA1 (PubMed:12080061). {ECO:0000269\|PubMed:12080061, ECO:0000269\|PubMed:12768206, ECO:0000269\|PubMed:19759537, ECO:0000269\|PubMed:21478859, ECO:0000269\|PubMed:21799911}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:10523501, ECO:0000269\|PubMed:21799911, ECO:0000269\|PubMed:22864114}. Golgi apparatus membrane {ECO:0000269\|PubMed:22864114}; Peripheral membrane protein {ECO:0000269\|PubMed:22864114}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:10523501, ECO:0000269\|PubMed:21799911}. Nucleus, nuclear pore complex {ECO:0000269\|PubMed:10523501}. Chromosome, telomere {ECO:0000305\|PubMed:9822378}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269\|PubMed:16076287}. Note=Associated with the Golgi and with juxtanuclear SLC2A4/GLUT4-vesicles (PubMed:22864114). A minor proportion is also found at nuclear pore complexes and around the pericentriolar matrix of mitotic centromeres (PubMed:10523501). During interphase, a small fraction of TNKS is found in the nucleus, associated with TERF1 (PubMed:12768206). Localizes to spindle poles at mitosis onset via interaction with NUMA1 (PubMed:12080061). {ECO:0000269\|PubMed:10523501, ECO:0000269\|PubMed:12080061, ECO:0000269\|PubMed:12768206, ECO:0000269\|PubMed:22864114}.
Tissue specificity:		Ubiquitous; highest levels in testis.
Ptm:		Phosphorylated on serine residues by MAPK kinases upon insulin stimulation. Phosphorylated during mitosis. {ECO:0000269\|PubMed:10988299}.
Ptm:		Ubiquitinated by RNF146 when auto-poly-ADP-ribosylated, leading to its degradation. {ECO:0000269\|PubMed:21478859}.
Ptm:		ADP-ribosylated (-auto). Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination. {ECO:0000269\|PubMed:21478859}.
Similarity:		Belongs to the ARTD/PARP family. {ECO:0000305}.