UniProt functional annotation for Q9H2K2



	UniProt functional annotation for Q9H2K2

UniProt code: Q9H2K2.

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:11739745, PubMed:11802774, PubMed:19759537, PubMed:21478859, PubMed:23622245, PubMed:25043379). Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation 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 poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination (PubMed:21478859). Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length (PubMed:11739745). Stimulates 26S proteasome activity (PubMed:23622245). {ECO:0000269|PubMed:11739745, ECO:0000269|PubMed:11802774, ECO:0000269|PubMed:19759537, ECO:0000269|PubMed:21478859, 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, ECO:0000269|PubMed:21478859};

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 TNKS. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles (PubMed:11802774). Binds to the N-terminus of Grb14 and TRF1 with its ankyrin repeat region (PubMed:11802774). Interacts with HIF1AN (PubMed:18936059, PubMed:21251231). Interacts with RNF146; this interaction leads to ubiquitination and proteasomal degradation (PubMed:21799911). Interacts with NUMA1 (PubMed:12080061). {ECO:0000269|PubMed:11802774, ECO:0000269|PubMed:12080061, ECO:0000269|PubMed:18936059, ECO:0000269|PubMed:19759537, ECO:0000269|PubMed:21251231, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:21799911}.

Subcellular location: Cytoplasm. Golgi apparatus membrane; Peripheral membrane protein. Nucleus. Chromosome, telomere {ECO:0000305}. Note=Associated with the Golgi and with juxtanuclear SLC2A4/GLUT4- vesicles. Also found around the pericentriolar matrix of mitotic centromeres. During interphase, a small fraction of TNKS2 is found in the nucleus, associated with TRF1.

Tissue specificity: Highly expressed in placenta, skeletal muscle, liver, brain, kidney, heart, thymus, spinal cord, lung, peripheral blood leukocytes, pancreas, lymph nodes, spleen, prostate, testis, ovary, small intestine, colon, mammary gland, breast and breast carcinoma, and in common-type meningioma. Highly expressed in fetal liver, heart and brain.

Ptm: Ubiquitinated at 'Lys-48' and 'Lys-63' by RNF146 when auto-poly- ADP-ribosylated; this leads to degradation. {ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:21799911}.

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

Ptm: The crystallographic evidence suggests that the 3-hydroxyhistidine may be the (3S) stereoisomer. {ECO:0000269|PubMed:21251231}.

Similarity: Belongs to the ARTD/PARP family. {ECO:0000305}.

Sequence caution: Sequence=AAG25674.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB14665.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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:11739745, PubMed:11802774, PubMed:19759537, PubMed:21478859, PubMed:23622245, PubMed:25043379). Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation 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 poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination (PubMed:21478859). Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length (PubMed:11739745). Stimulates 26S proteasome activity (PubMed:23622245). {ECO:0000269\|PubMed:11739745, ECO:0000269\|PubMed:11802774, ECO:0000269\|PubMed:19759537, ECO:0000269\|PubMed:21478859, 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, ECO:0000269\|PubMed:21478859};
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 TNKS. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles (PubMed:11802774). Binds to the N-terminus of Grb14 and TRF1 with its ankyrin repeat region (PubMed:11802774). Interacts with HIF1AN (PubMed:18936059, PubMed:21251231). Interacts with RNF146; this interaction leads to ubiquitination and proteasomal degradation (PubMed:21799911). Interacts with NUMA1 (PubMed:12080061). {ECO:0000269\|PubMed:11802774, ECO:0000269\|PubMed:12080061, ECO:0000269\|PubMed:18936059, ECO:0000269\|PubMed:19759537, ECO:0000269\|PubMed:21251231, ECO:0000269\|PubMed:21478859, ECO:0000269\|PubMed:21799911}.
Subcellular location:		Cytoplasm. Golgi apparatus membrane; Peripheral membrane protein. Nucleus. Chromosome, telomere {ECO:0000305}. Note=Associated with the Golgi and with juxtanuclear SLC2A4/GLUT4- vesicles. Also found around the pericentriolar matrix of mitotic centromeres. During interphase, a small fraction of TNKS2 is found in the nucleus, associated with TRF1.
Tissue specificity:		Highly expressed in placenta, skeletal muscle, liver, brain, kidney, heart, thymus, spinal cord, lung, peripheral blood leukocytes, pancreas, lymph nodes, spleen, prostate, testis, ovary, small intestine, colon, mammary gland, breast and breast carcinoma, and in common-type meningioma. Highly expressed in fetal liver, heart and brain.
Ptm:		Ubiquitinated at 'Lys-48' and 'Lys-63' by RNF146 when auto-poly- ADP-ribosylated; this leads to degradation. {ECO:0000269\|PubMed:21478859, ECO:0000269\|PubMed:21799911}.
Ptm:		ADP-ribosylated (-auto). Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination. {ECO:0000269\|PubMed:21478859}.
Ptm:		The crystallographic evidence suggests that the 3-hydroxyhistidine may be the (3S) stereoisomer. {ECO:0000269\|PubMed:21251231}.
Similarity:		Belongs to the ARTD/PARP family. {ECO:0000305}.
Sequence caution:		Sequence=AAG25674.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB14665.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};