TNKS encodes tankyrase-1/PARP5A, a multidomain NAD+-dependent ADP-ribosyltransferase that recognizes substrate proteins through ankyrin-repeat clusters and catalyzes protein poly- and auto-ADP-ribosylation. Its core functions include PARylation-dependent control of AXIN turnover and Wnt/beta-catenin signaling, telomere-associated TRF1 biology, and NuMA-dependent spindle organization, with activity distributed across cytoplasmic, nuclear/telomeric, and spindle-associated compartments.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: nucleus localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: cytoplasm localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0070198 protein localization to chromosome, telomeric region | IBA GO_REF:0000033 | ACCEPT | Summary: protein localization to chromosome, telomeric region is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: positive regulation of canonical Wnt signaling pathway is a canonical TNKS pathway output through AXIN PARylation. Reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing Wnt/beta-catenin pathway output. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md Multiple retrieved sources state that **tankyrase PARylates AXIN (AXIN1/2)**, which promotes **RNF146-mediated ubiquitination** and **proteasomal degradation** of AXIN. Loss of AXIN destabilizes the destruction complex, thereby **stabilizing β-catenin** and increasing pathway output. Conversely, **tankyrase inhibition stabilizes AXIN** and reduces cytosolic β-catenin and β-catenin–dependent transcription. file:human/TNKS/TNKS-deep-research-falcon.md **Primary pathway role:** TNKS1/2 control **Wnt/β-catenin signaling** by PARylating **AXIN1/2** to promote RNF146-dependent degradation; inhibition stabilizes AXIN and suppresses β-catenin output. file:human/TNKS/TNKS-deep-research-falcon.md The canonical E3 ligase is **RNF146**, described as a **PAR-directed E3** that binds PARylated substrates (via a PAR-binding WWE domain recognizing iso-ADP-ribose) and installs **K48-linked polyubiquitin chains**, driving proteasomal degradation. This underlies a major mechanism by which TNKS controls the abundance of multiple signaling proteins. |
| GO:1904355 positive regulation of telomere capping | IBA GO_REF:0000033 | ACCEPT | Summary: positive regulation of telomere capping is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Golgi membrane is a plausible reported localization but not the dominant site of TNKS core activity. Reason: TNKS has multi-compartment partner-mediated localization; the best-supported core locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0000209 protein polyubiquitination | IEA GO_REF:0000117 | MODIFY | Summary: Protein polyubiquitination captures a downstream consequence of TNKS PARylation but misstates the direct TNKS activity. Reason: TNKS does not function as the E3 ubiquitin ligase; it PARylates substrates that are then recognized by PAR-binding ubiquitin ligases such as RNF146. Proposed replacements: protein poly-ADP-ribosylation NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The canonical E3 ligase is **RNF146**, described as a **PAR-directed E3** that binds PARylated substrates (via a PAR-binding WWE domain recognizing iso-ADP-ribose) and installs **K48-linked polyubiquitin chains**, driving proteasomal degradation. This underlies a major mechanism by which TNKS controls the abundance of multiple signaling proteins. file:human/TNKS/TNKS-deep-research-falcon.md Multiple retrieved sources state that **tankyrase PARylates AXIN (AXIN1/2)**, which promotes **RNF146-mediated ubiquitination** and **proteasomal degradation** of AXIN. Loss of AXIN destabilizes the destruction complex, thereby **stabilizing β-catenin** and increasing pathway output. Conversely, **tankyrase inhibition stabilizes AXIN** and reduces cytosolic β-catenin and β-catenin–dependent transcription. |
| GO:0000242 pericentriolar material | IEA GO_REF:0000117 | ACCEPT | Summary: pericentriolar material localization is supported by TNKS spindle/centrosome-associated functions. Reason: TNKS is recruited to spindle poles via NuMA and is required for NuMA PARylation and spindle organization. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md TNKS also targets proteins involved in mitosis. A structural/functional analysis in the retrieved corpus reports that **TNKS PARylates NuMA**, and further states that **TNKS1 (but not TNKS2)** is specifically required for NuMA PARylation and correct mitotic spindle organization. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000120 | ACCEPT | Summary: Chromosome telomeric region localization is supported by TNKS recruitment through TRF1. Reason: Telomere recruitment is one of the hallmark TNKS localization contexts. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | ACCEPT | Summary: spindle pole localization is supported by TNKS spindle/centrosome-associated functions. Reason: TNKS is recruited to spindle poles via NuMA and is required for NuMA PARylation and spindle organization. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md TNKS also targets proteins involved in mitosis. A structural/functional analysis in the retrieved corpus reports that **TNKS PARylates NuMA**, and further states that **TNKS1 (but not TNKS2)** is specifically required for NuMA PARylation and correct mitotic spindle organization. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0005635 nuclear envelope | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: nuclear envelope is a plausible reported localization but not the dominant site of TNKS core activity. Reason: TNKS has multi-compartment partner-mediated localization; the best-supported core locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005643 nuclear pore | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: nuclear pore is a plausible reported localization but not the dominant site of TNKS core activity. Reason: TNKS has multi-compartment partner-mediated localization; the best-supported core locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: cytoplasm localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: centrosome localization is supported by TNKS spindle/centrosome-associated functions. Reason: TNKS is recruited to spindle poles via NuMA and is required for NuMA PARylation and spindle organization. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md TNKS also targets proteins involved in mitosis. A structural/functional analysis in the retrieved corpus reports that **TNKS PARylates NuMA**, and further states that **TNKS1 (but not TNKS2)** is specifically required for NuMA PARylation and correct mitotic spindle organization. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: protein transport is a context-specific transport-related role rather than the primary TNKS function. Reason: Transport annotations are secondary to TNKS substrate PARylation and pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0016055 Wnt signaling pathway | IEA GO_REF:0000043 | ACCEPT | Summary: Wnt signaling pathway is a canonical TNKS pathway output through AXIN PARylation. Reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing Wnt/beta-catenin pathway output. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md Multiple retrieved sources state that **tankyrase PARylates AXIN (AXIN1/2)**, which promotes **RNF146-mediated ubiquitination** and **proteasomal degradation** of AXIN. Loss of AXIN destabilizes the destruction complex, thereby **stabilizing β-catenin** and increasing pathway output. Conversely, **tankyrase inhibition stabilizes AXIN** and reduces cytosolic β-catenin and β-catenin–dependent transcription. file:human/TNKS/TNKS-deep-research-falcon.md **Primary pathway role:** TNKS1/2 control **Wnt/β-catenin signaling** by PARylating **AXIN1/2** to promote RNF146-dependent degradation; inhibition stabilizes AXIN and suppresses β-catenin output. file:human/TNKS/TNKS-deep-research-falcon.md The canonical E3 ligase is **RNF146**, described as a **PAR-directed E3** that binds PARylated substrates (via a PAR-binding WWE domain recognizing iso-ADP-ribose) and installs **K48-linked polyubiquitin chains**, driving proteasomal degradation. This underlies a major mechanism by which TNKS controls the abundance of multiple signaling proteins. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MODIFY | Summary: transferase activity is too broad for TNKS catalytic activity. Reason: The supported activity is NAD+-dependent protein ADP-ribosyltransferase/poly-ADP-ribosyltransferase activity, not a generic transferase label. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity NAD+-protein-aspartate ADP-ribosyltransferase activity NAD+-protein-glutamate ADP-ribosyltransferase activity Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0016757 glycosyltransferase activity | IEA GO_REF:0000043 | MODIFY | Summary: glycosyltransferase activity is too broad for TNKS catalytic activity. Reason: The supported activity is NAD+-dependent protein ADP-ribosyltransferase/poly-ADP-ribosyltransferase activity, not a generic transferase label. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity NAD+-protein-aspartate ADP-ribosyltransferase activity NAD+-protein-glutamate ADP-ribosyltransferase activity Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0016779 nucleotidyltransferase activity | IEA GO_REF:0000043 | MODIFY | Summary: nucleotidyltransferase activity is too broad for TNKS catalytic activity. Reason: The supported activity is NAD+-dependent protein ADP-ribosyltransferase/poly-ADP-ribosyltransferase activity, not a generic transferase label. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity NAD+-protein-aspartate ADP-ribosyltransferase activity NAD+-protein-glutamate ADP-ribosyltransferase activity Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0032212 positive regulation of telomere maintenance via telomerase | IEA GO_REF:0000117 | ACCEPT | Summary: positive regulation of telomere maintenance via telomerase is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: metal ion binding is plausible as a structural/catalytic-site feature but is not the main function. Reason: Recent structural synthesis supports a zinc-binding motif in the catalytic acceptor-site architecture, but the core molecular function is ADP-ribosyltransferase activity. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. |
| GO:0051028 mRNA transport | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: mRNA transport is a context-specific transport-related role rather than the primary TNKS function. Reason: Transport annotations are secondary to TNKS substrate PARylation and pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0051301 cell division | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: cell division is supported as a mitotic or telomere-cohesion output of TNKS activity. Reason: These cell-cycle phenotypes are downstream of TNKS PARylation of substrates such as NuMA or telomere-associated factors, but the core activity is ADP-ribosyltransferase activity. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md TNKS also targets proteins involved in mitosis. A structural/functional analysis in the retrieved corpus reports that **TNKS PARylates NuMA**, and further states that **TNKS1 (but not TNKS2)** is specifically required for NuMA PARylation and correct mitotic spindle organization. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0070198 protein localization to chromosome, telomeric region | IEA GO_REF:0000117 | ACCEPT | Summary: protein localization to chromosome, telomeric region is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0070212 protein poly-ADP-ribosylation | IEA GO_REF:0000117 | ACCEPT | Summary: protein poly-ADP-ribosylation is a direct TNKS catalytic process. Reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0070213 protein auto-ADP-ribosylation | IEA GO_REF:0000117 | ACCEPT | Summary: protein auto-ADP-ribosylation is a direct TNKS catalytic process. Reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: positive regulation of canonical Wnt signaling pathway is a canonical TNKS pathway output through AXIN PARylation. Reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing Wnt/beta-catenin pathway output. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md Multiple retrieved sources state that **tankyrase PARylates AXIN (AXIN1/2)**, which promotes **RNF146-mediated ubiquitination** and **proteasomal degradation** of AXIN. Loss of AXIN destabilizes the destruction complex, thereby **stabilizing β-catenin** and increasing pathway output. Conversely, **tankyrase inhibition stabilizes AXIN** and reduces cytosolic β-catenin and β-catenin–dependent transcription. file:human/TNKS/TNKS-deep-research-falcon.md **Primary pathway role:** TNKS1/2 control **Wnt/β-catenin signaling** by PARylating **AXIN1/2** to promote RNF146-dependent degradation; inhibition stabilizes AXIN and suppresses β-catenin output. file:human/TNKS/TNKS-deep-research-falcon.md The canonical E3 ligase is **RNF146**, described as a **PAR-directed E3** that binds PARylated substrates (via a PAR-binding WWE domain recognizing iso-ADP-ribose) and installs **K48-linked polyubiquitin chains**, driving proteasomal degradation. This underlies a major mechanism by which TNKS controls the abundance of multiple signaling proteins. |
| GO:0140806 NAD+-protein-aspartate ADP-ribosyltransferase activity | IEA GO_REF:0000116 | ACCEPT | Summary: NAD+-protein-aspartate ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0140807 NAD+-protein-glutamate ADP-ribosyltransferase activity | IEA GO_REF:0000116 | ACCEPT | Summary: NAD+-protein-glutamate ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:1904355 positive regulation of telomere capping | IEA GO_REF:0000117 | ACCEPT | Summary: positive regulation of telomere capping is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:1904357 negative regulation of telomere maintenance via telomere lengthening | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Negative regulation of telomere maintenance via telomere lengthening is not justified by the current TNKS synthesis. Reason: Canonical TNKS/TRF1 evidence supports release of TRF1 from telomeres and promotion of telomere elongation; the negative-direction annotation should not be accepted without context-specific evidence. Proposed replacements: positive regulation of telomere maintenance via telomere lengthening positive regulation of telomere maintenance via telomerase Supporting Evidence: PMID:12782650 ADP-ribosylation of TRF1 by tankyrase 1 released TRF1 from telomeres and promoted telomere elongation. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IEA GO_REF:0000117 | ACCEPT | Summary: NAD+-protein mono-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0005515 protein binding | IPI PMID:12080061 Identification of a tankyrase-binding motif shared by IRAP, ... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:14596906 The formin-binding protein 17, FBP17, binds via a TNKS bindi... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:17003112 Posttranslational hydroxylation of ankyrin repeats in Ikappa... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:17043677 Disrupted in Schizophrenia 1 Interactome: evidence for the c... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:19759537 Tankyrase inhibition stabilizes axin and antagonizes Wnt sig... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:20696165 Tankyrase-1 assembly to large protein complexes blocks its t... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:21251231 Factor-inhibiting hypoxia-inducible factor (FIH) catalyses t... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:21799911 Ubiquitin ligase RNF146 regulates tankyrase and Axin to prom... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:22699936 Tankyrase 1 regulates centrosome function by controlling CPA... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:25327252 Allosteric activation of the RNF146 ubiquitin ligase by a po... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:26373281 Loss of ATRX Suppresses Resolution of Telomere Cohesion to C... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:26972000 Substrate-Trapped Interactors of PHD3 and FIH Cluster in Dis... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: cytosol localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | TAS Reactome:R-HSA-4641257 | ACCEPT | Summary: positive regulation of canonical Wnt signaling pathway is a canonical TNKS pathway output through AXIN PARylation. Reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing Wnt/beta-catenin pathway output. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md Multiple retrieved sources state that **tankyrase PARylates AXIN (AXIN1/2)**, which promotes **RNF146-mediated ubiquitination** and **proteasomal degradation** of AXIN. Loss of AXIN destabilizes the destruction complex, thereby **stabilizing β-catenin** and increasing pathway output. Conversely, **tankyrase inhibition stabilizes AXIN** and reduces cytosolic β-catenin and β-catenin–dependent transcription. file:human/TNKS/TNKS-deep-research-falcon.md **Primary pathway role:** TNKS1/2 control **Wnt/β-catenin signaling** by PARylating **AXIN1/2** to promote RNF146-dependent degradation; inhibition stabilizes AXIN and suppresses β-catenin output. file:human/TNKS/TNKS-deep-research-falcon.md The canonical E3 ligase is **RNF146**, described as a **PAR-directed E3** that binds PARylated substrates (via a PAR-binding WWE domain recognizing iso-ADP-ribose) and installs **K48-linked polyubiquitin chains**, driving proteasomal degradation. This underlies a major mechanism by which TNKS controls the abundance of multiple signaling proteins. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | TAS Reactome:R-HSA-3640858 | ACCEPT | Summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | TAS Reactome:R-HSA-8948800 | ACCEPT | Summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0010521 telomerase inhibitor activity | IMP PMID:25939383 Disruption of Wnt/β-Catenin Signaling and Telomeric Shorteni... | MARK AS OVER ANNOTATED | Summary: Telomerase inhibitor activity is not the best direct molecular-function description for TNKS. Reason: TNKS regulates telomere maintenance through PARylation of telomere-associated proteins such as TRF1; the direct activity should be represented as ADP-ribosyltransferase activity and telomere-maintenance processes. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity NAD+-protein-aspartate ADP-ribosyltransferase activity NAD+-protein-glutamate ADP-ribosyltransferase activity Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0010521 telomerase inhibitor activity | IDA PMID:9822378 Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. | MARK AS OVER ANNOTATED | Summary: Telomerase inhibitor activity is not the best direct molecular-function description for TNKS. Reason: TNKS regulates telomere maintenance through PARylation of telomere-associated proteins such as TRF1; the direct activity should be represented as ADP-ribosyltransferase activity and telomere-maintenance processes. Proposed replacements: NAD+ poly-ADP-ribosyltransferase activity NAD+-protein-aspartate ADP-ribosyltransferase activity NAD+-protein-glutamate ADP-ribosyltransferase activity Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0032210 regulation of telomere maintenance via telomerase | IDA PMID:9822378 Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. | ACCEPT | Summary: regulation of telomere maintenance via telomerase is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:1904358 positive regulation of telomere maintenance via telomere lengthening | IDA PMID:12782650 TRF1 is degraded by ubiquitin-mediated proteolysis after rel... | ACCEPT | Summary: positive regulation of telomere maintenance via telomere lengthening is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:15133513 TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere le... | ACCEPT | Summary: NAD+-protein mono-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:9822378 Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. | ACCEPT | Summary: NAD+-protein mono-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0070212 protein poly-ADP-ribosylation | IDA PMID:25043379 Family-wide analysis of poly(ADP-ribose) polymerase activity... | ACCEPT | Summary: protein poly-ADP-ribosylation is a direct TNKS catalytic process. Reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity | IDA PMID:25043379 Family-wide analysis of poly(ADP-ribose) polymerase activity... | ACCEPT | Summary: NAD+-protein mono-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:16076287 NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyr... | ACCEPT | Summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0005515 protein binding | IPI PMID:16076287 NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyr... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0070212 protein poly-ADP-ribosylation | IDA PMID:16076287 NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyr... | ACCEPT | Summary: protein poly-ADP-ribosylation is a direct TNKS catalytic process. Reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0097431 mitotic spindle pole | IDA PMID:16076287 NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyr... | ACCEPT | Summary: mitotic spindle pole localization is supported by TNKS spindle/centrosome-associated functions. Reason: TNKS is recruited to spindle poles via NuMA and is required for NuMA PARylation and spindle organization. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md TNKS also targets proteins involved in mitosis. A structural/functional analysis in the retrieved corpus reports that **TNKS PARylates NuMA**, and further states that **TNKS1 (but not TNKS2)** is specifically required for NuMA PARylation and correct mitotic spindle organization. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005515 protein binding | IPI PMID:11854288 The telomeric poly(ADP-ribose) polymerase, tankyrase 1, cont... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:11854288 The telomeric poly(ADP-ribose) polymerase, tankyrase 1, cont... | ACCEPT | Summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:1904908 negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric | IMP PMID:26373281 Loss of ATRX Suppresses Resolution of Telomere Cohesion to C... | KEEP AS NON CORE | Summary: negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric is supported as a mitotic or telomere-cohesion output of TNKS activity. Reason: These cell-cycle phenotypes are downstream of TNKS PARylation of substrates such as NuMA or telomere-associated factors, but the core activity is ADP-ribosyltransferase activity. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md TNKS also targets proteins involved in mitosis. A structural/functional analysis in the retrieved corpus reports that **TNKS PARylates NuMA**, and further states that **TNKS1 (but not TNKS2)** is specifically required for NuMA PARylation and correct mitotic spindle organization. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0000781 chromosome, telomeric region | IDA PMID:9822378 Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. | ACCEPT | Summary: Chromosome telomeric region localization is supported by TNKS recruitment through TRF1. Reason: Telomere recruitment is one of the hallmark TNKS localization contexts. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0042393 histone binding | IPI PMID:26373281 Loss of ATRX Suppresses Resolution of Telomere Cohesion to C... | KEEP AS NON CORE | Summary: Histone binding is supported in a telomere-cohesion context but is secondary to TNKS ADP-ribosyltransferase function. Reason: This interaction fits a specialized telomere/chromatin context rather than the primary TNKS catalytic function. Supporting Evidence: PMID:26373281 In the absence of ATRX, the histone variant macroH2A1.1 binds to the poly(ADP-ribose) polymerase tankyrase 1, preventing it from localizing to telomeres and resolving cohesion. |
| GO:0005515 protein binding | IPI PMID:15133513 TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere le... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0032212 positive regulation of telomere maintenance via telomerase | IDA PMID:12782650 TRF1 is degraded by ubiquitin-mediated proteolysis after rel... | ACCEPT | Summary: positive regulation of telomere maintenance via telomerase is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0070198 protein localization to chromosome, telomeric region | IMP PMID:15133513 TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere le... | ACCEPT | Summary: protein localization to chromosome, telomeric region is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0070212 protein poly-ADP-ribosylation | IMP PMID:25939383 Disruption of Wnt/β-Catenin Signaling and Telomeric Shorteni... | ACCEPT | Summary: protein poly-ADP-ribosylation is a direct TNKS catalytic process. Reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0070212 protein poly-ADP-ribosylation | IDA PMID:9822378 Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. | ACCEPT | Summary: protein poly-ADP-ribosylation is a direct TNKS catalytic process. Reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:1904357 negative regulation of telomere maintenance via telomere lengthening | IMP PMID:25939383 Disruption of Wnt/β-Catenin Signaling and Telomeric Shorteni... | MARK AS OVER ANNOTATED | Summary: Negative regulation of telomere maintenance via telomere lengthening is not justified by the current TNKS synthesis. Reason: Canonical TNKS/TRF1 evidence supports release of TRF1 from telomeres and promotion of telomere elongation; the negative-direction annotation should not be accepted without context-specific evidence. Proposed replacements: positive regulation of telomere maintenance via telomere lengthening positive regulation of telomere maintenance via telomerase Supporting Evidence: PMID:12782650 ADP-ribosylation of TRF1 by tankyrase 1 released TRF1 from telomeres and promoted telomere elongation. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IMP PMID:25939383 Disruption of Wnt/β-Catenin Signaling and Telomeric Shorteni... | ACCEPT | Summary: positive regulation of canonical Wnt signaling pathway is a canonical TNKS pathway output through AXIN PARylation. Reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing Wnt/beta-catenin pathway output. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md Multiple retrieved sources state that **tankyrase PARylates AXIN (AXIN1/2)**, which promotes **RNF146-mediated ubiquitination** and **proteasomal degradation** of AXIN. Loss of AXIN destabilizes the destruction complex, thereby **stabilizing β-catenin** and increasing pathway output. Conversely, **tankyrase inhibition stabilizes AXIN** and reduces cytosolic β-catenin and β-catenin–dependent transcription. file:human/TNKS/TNKS-deep-research-falcon.md **Primary pathway role:** TNKS1/2 control **Wnt/β-catenin signaling** by PARylating **AXIN1/2** to promote RNF146-dependent degradation; inhibition stabilizes AXIN and suppresses β-catenin output. file:human/TNKS/TNKS-deep-research-falcon.md The canonical E3 ligase is **RNF146**, described as a **PAR-directed E3** that binds PARylated substrates (via a PAR-binding WWE domain recognizing iso-ADP-ribose) and installs **K48-linked polyubiquitin chains**, driving proteasomal degradation. This underlies a major mechanism by which TNKS controls the abundance of multiple signaling proteins. |
| GO:1904355 positive regulation of telomere capping | IMP PMID:25939383 Disruption of Wnt/β-Catenin Signaling and Telomeric Shorteni... | ACCEPT | Summary: positive regulation of telomere capping is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:21270334 Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellula... | ACCEPT | Summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640844 | ACCEPT | Summary: cytosol localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640858 | ACCEPT | Summary: cytosol localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640861 | ACCEPT | Summary: cytosol localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640862 | ACCEPT | Summary: cytosol localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640872 | ACCEPT | Summary: cytosol localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3640874 | ACCEPT | Summary: cytosol localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5262606 | ACCEPT | Summary: cytosol localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8948800 | ACCEPT | Summary: cytosol localization is consistent with TNKS multi-compartment activity. Reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway regulation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:22864114 Poly-ADP ribosylation of Miki by tankyrase-1 promotes centro... | ACCEPT | Summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0005515 protein binding | IPI PMID:22864114 Poly-ADP ribosylation of Miki by tankyrase-1 promotes centro... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0005794 Golgi apparatus | IDA PMID:22864114 Poly-ADP ribosylation of Miki by tankyrase-1 promotes centro... | KEEP AS NON CORE | Summary: Golgi apparatus is a plausible reported localization but not the dominant site of TNKS core activity. Reason: TNKS has multi-compartment partner-mediated localization; the best-supported core locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:19245366 MYPT1, the targeting subunit of smooth-muscle myosin phospha... | KEEP AS NON CORE | Summary: Positive regulation of transcription by RNA polymerase II is an indirect Wnt/beta-catenin or YAP pathway output. Reason: TNKS regulates transcriptional outputs indirectly by PARylating pathway regulators such as AXIN rather than functioning as a transcription factor. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md Multiple retrieved sources state that **tankyrase PARylates AXIN (AXIN1/2)**, which promotes **RNF146-mediated ubiquitination** and **proteasomal degradation** of AXIN. Loss of AXIN destabilizes the destruction complex, thereby **stabilizing β-catenin** and increasing pathway output. Conversely, **tankyrase inhibition stabilizes AXIN** and reduces cytosolic β-catenin and β-catenin–dependent transcription. file:human/TNKS/TNKS-deep-research-falcon.md **Primary pathway role:** TNKS1/2 control **Wnt/β-catenin signaling** by PARylating **AXIN1/2** to promote RNF146-dependent degradation; inhibition stabilizes AXIN and suppresses β-catenin output. file:human/TNKS/TNKS-deep-research-falcon.md The canonical E3 ligase is **RNF146**, described as a **PAR-directed E3** that binds PARylated substrates (via a PAR-binding WWE domain recognizing iso-ADP-ribose) and installs **K48-linked polyubiquitin chains**, driving proteasomal degradation. This underlies a major mechanism by which TNKS controls the abundance of multiple signaling proteins. |
| GO:0000209 protein polyubiquitination | IDA PMID:19759537 Tankyrase inhibition stabilizes axin and antagonizes Wnt sig... | MODIFY | Summary: Protein polyubiquitination captures a downstream consequence of TNKS PARylation but misstates the direct TNKS activity. Reason: TNKS does not function as the E3 ubiquitin ligase; it PARylates substrates that are then recognized by PAR-binding ubiquitin ligases such as RNF146. Proposed replacements: protein poly-ADP-ribosylation NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The canonical E3 ligase is **RNF146**, described as a **PAR-directed E3** that binds PARylated substrates (via a PAR-binding WWE domain recognizing iso-ADP-ribose) and installs **K48-linked polyubiquitin chains**, driving proteasomal degradation. This underlies a major mechanism by which TNKS controls the abundance of multiple signaling proteins. file:human/TNKS/TNKS-deep-research-falcon.md Multiple retrieved sources state that **tankyrase PARylates AXIN (AXIN1/2)**, which promotes **RNF146-mediated ubiquitination** and **proteasomal degradation** of AXIN. Loss of AXIN destabilizes the destruction complex, thereby **stabilizing β-catenin** and increasing pathway output. Conversely, **tankyrase inhibition stabilizes AXIN** and reduces cytosolic β-catenin and β-catenin–dependent transcription. |
| GO:0000209 protein polyubiquitination | IDA PMID:21478859 RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulat... | MODIFY | Summary: Protein polyubiquitination captures a downstream consequence of TNKS PARylation but misstates the direct TNKS activity. Reason: TNKS does not function as the E3 ubiquitin ligase; it PARylates substrates that are then recognized by PAR-binding ubiquitin ligases such as RNF146. Proposed replacements: protein poly-ADP-ribosylation NAD+ poly-ADP-ribosyltransferase activity Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The canonical E3 ligase is **RNF146**, described as a **PAR-directed E3** that binds PARylated substrates (via a PAR-binding WWE domain recognizing iso-ADP-ribose) and installs **K48-linked polyubiquitin chains**, driving proteasomal degradation. This underlies a major mechanism by which TNKS controls the abundance of multiple signaling proteins. file:human/TNKS/TNKS-deep-research-falcon.md Multiple retrieved sources state that **tankyrase PARylates AXIN (AXIN1/2)**, which promotes **RNF146-mediated ubiquitination** and **proteasomal degradation** of AXIN. Loss of AXIN destabilizes the destruction complex, thereby **stabilizing β-catenin** and increasing pathway output. Conversely, **tankyrase inhibition stabilizes AXIN** and reduces cytosolic β-catenin and β-catenin–dependent transcription. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:19759537 Tankyrase inhibition stabilizes axin and antagonizes Wnt sig... | ACCEPT | Summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:21478859 RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulat... | ACCEPT | Summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0005515 protein binding | IPI PMID:21478859 RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulat... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0070213 protein auto-ADP-ribosylation | IDA PMID:21478859 RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulat... | ACCEPT | Summary: protein auto-ADP-ribosylation is a direct TNKS catalytic process. Reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IMP PMID:19759537 Tankyrase inhibition stabilizes axin and antagonizes Wnt sig... | ACCEPT | Summary: positive regulation of canonical Wnt signaling pathway is a canonical TNKS pathway output through AXIN PARylation. Reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing Wnt/beta-catenin pathway output. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md Multiple retrieved sources state that **tankyrase PARylates AXIN (AXIN1/2)**, which promotes **RNF146-mediated ubiquitination** and **proteasomal degradation** of AXIN. Loss of AXIN destabilizes the destruction complex, thereby **stabilizing β-catenin** and increasing pathway output. Conversely, **tankyrase inhibition stabilizes AXIN** and reduces cytosolic β-catenin and β-catenin–dependent transcription. file:human/TNKS/TNKS-deep-research-falcon.md **Primary pathway role:** TNKS1/2 control **Wnt/β-catenin signaling** by PARylating **AXIN1/2** to promote RNF146-dependent degradation; inhibition stabilizes AXIN and suppresses β-catenin output. file:human/TNKS/TNKS-deep-research-falcon.md The canonical E3 ligase is **RNF146**, described as a **PAR-directed E3** that binds PARylated substrates (via a PAR-binding WWE domain recognizing iso-ADP-ribose) and installs **K48-linked polyubiquitin chains**, driving proteasomal degradation. This underlies a major mechanism by which TNKS controls the abundance of multiple signaling proteins. |
| GO:0070198 protein localization to chromosome, telomeric region | IMP PMID:18221737 Telomere elongation by a mutant tankyrase 1 without TRF1 pol... | ACCEPT | Summary: protein localization to chromosome, telomeric region is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0000242 pericentriolar material | TAS PMID:11454873 TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, ca... | ACCEPT | Summary: pericentriolar material localization is supported by TNKS spindle/centrosome-associated functions. Reason: TNKS is recruited to spindle poles via NuMA and is required for NuMA PARylation and spindle organization. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md TNKS also targets proteins involved in mitosis. A structural/functional analysis in the retrieved corpus reports that **TNKS PARylates NuMA**, and further states that **TNKS1 (but not TNKS2)** is specifically required for NuMA PARylation and correct mitotic spindle organization. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0000781 chromosome, telomeric region | IDA PMID:11739745 Role for the related poly(ADP-Ribose) polymerases tankyrase ... | ACCEPT | Summary: Chromosome telomeric region localization is supported by TNKS recruitment through TRF1. Reason: Telomere recruitment is one of the hallmark TNKS localization contexts. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0005643 nuclear pore | TAS PMID:11454873 TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, ca... | KEEP AS NON CORE | Summary: nuclear pore is a plausible reported localization but not the dominant site of TNKS core activity. Reason: TNKS has multi-compartment partner-mediated localization; the best-supported core locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0007052 mitotic spindle organization | TAS PMID:17026964 Mitotic phosphorylation of tankyrase, a PARP that promotes s... | KEEP AS NON CORE | Summary: mitotic spindle organization is supported as a mitotic or telomere-cohesion output of TNKS activity. Reason: These cell-cycle phenotypes are downstream of TNKS PARylation of substrates such as NuMA or telomere-associated factors, but the core activity is ADP-ribosyltransferase activity. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md TNKS also targets proteins involved in mitosis. A structural/functional analysis in the retrieved corpus reports that **TNKS PARylates NuMA**, and further states that **TNKS1 (but not TNKS2)** is specifically required for NuMA PARylation and correct mitotic spindle organization. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0008270 zinc ion binding | IDA PMID:18436240 Zinc binding catalytic domain of human tankyrase 1. | KEEP AS NON CORE | Summary: zinc ion binding is plausible as a structural/catalytic-site feature but is not the main function. Reason: Recent structural synthesis supports a zinc-binding motif in the catalytic acceptor-site architecture, but the core molecular function is ADP-ribosyltransferase activity. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. |
| GO:0031965 nuclear membrane | TAS PMID:11454873 TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, ca... | KEEP AS NON CORE | Summary: nuclear membrane is a plausible reported localization but not the dominant site of TNKS core activity. Reason: TNKS has multi-compartment partner-mediated localization; the best-supported core locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The retrieved evidence supports a “multi-compartment” view of TNKS localization via partner-mediated recruitment: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0032212 positive regulation of telomere maintenance via telomerase | IMP PMID:11739745 Role for the related poly(ADP-Ribose) polymerases tankyrase ... | ACCEPT | Summary: positive regulation of telomere maintenance via telomerase is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0032212 positive regulation of telomere maintenance via telomerase | IDA PMID:18221737 Telomere elongation by a mutant tankyrase 1 without TRF1 pol... | ACCEPT | Summary: positive regulation of telomere maintenance via telomerase is supported as a TNKS telomere-associated role. Reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein localization and telomere maintenance/capping outputs. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md **Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles in telomere biology). |
| GO:0051225 spindle assembly | TAS PMID:17026964 Mitotic phosphorylation of tankyrase, a PARP that promotes s... | KEEP AS NON CORE | Summary: spindle assembly is supported as a mitotic or telomere-cohesion output of TNKS activity. Reason: These cell-cycle phenotypes are downstream of TNKS PARylation of substrates such as NuMA or telomere-associated factors, but the core activity is ADP-ribosyltransferase activity. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md TNKS also targets proteins involved in mitosis. A structural/functional analysis in the retrieved corpus reports that **TNKS PARylates NuMA**, and further states that **TNKS1 (but not TNKS2)** is specifically required for NuMA PARylation and correct mitotic spindle organization. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:17026964 Mitotic phosphorylation of tankyrase, a PARP that promotes s... | REMOVE | Summary: peptidyl-serine phosphorylation is not supported as a TNKS catalytic activity. Reason: TNKS is an ADP-ribosyltransferase, not a protein kinase catalyzing serine or threonine phosphorylation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0018107 peptidyl-threonine phosphorylation | IDA PMID:17026964 Mitotic phosphorylation of tankyrase, a PARP that promotes s... | REMOVE | Summary: peptidyl-threonine phosphorylation is not supported as a TNKS catalytic activity. Reason: TNKS is an ADP-ribosyltransferase, not a protein kinase catalyzing serine or threonine phosphorylation. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0005515 protein binding | IPI PMID:12768206 POT1 as a terminal transducer of TRF1 telomere length contro... | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
| GO:0003950 NAD+ poly-ADP-ribosyltransferase activity | IDA PMID:9822378 Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. | ACCEPT | Summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function. Reason: TNKS is an NAD+-dependent PARP/ARTD enzyme that transfers ADP-ribose to itself and protein substrates, with acidic acceptor-residue specificity supported by recent structural synthesis. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). file:human/TNKS/TNKS-deep-research-falcon.md Mechanistically, TNKS cleaves NAD+ and transfers ADP-ribose to substrate acceptor sites; a structural/functional synthesis in the retrieved literature notes **preference for acidic acceptor residues (Glu/Asp)** and describes canonical catalytic features including an **HYE catalytic triad** and a catalytic acceptor-site architecture containing a **CHCC-type zinc-binding motif** important for structural integrity of the acceptor site. file:human/TNKS/TNKS-deep-research-falcon.md **Primary molecular function:** TNKS1 is an **NAD+-dependent PARP-family enzyme** that PARylates itself and protein partners, frequently acting as a switch to trigger PAR-dependent ubiquitination and turnover. |
| GO:0005515 protein binding | IPI PMID:9822378 Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. | MARK AS OVER ANNOTATED | Summary: Protein binding is supported but too generic for TNKS substrate recognition. Reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes ADP-ribosylation; generic protein binding hides the enzymatic mechanism. Supporting Evidence: file:human/TNKS/TNKS-deep-research-falcon.md The UniProt accession **O95271** corresponds to **human tankyrase-1**, encoded by **TNKS** (synonyms **PARP5A, ARTD5**). Recent literature explicitly distinguishes **tankyrase-1 (TNKS1/PARP5A/ARTD5)** from **tankyrase-2 (TNKS2/PARP5B/ARTD6)** and describes the expected multidomain architecture (HPS–ankyrin repeats/ARCs–SAM–PARP catalytic domain) and hallmark biology (Wnt/β-catenin via AXIN, telomere association via TRF1, spindle via NuMA, GLUT4 vesicles via IRAP), matching the UniProt-provided domain/family context. file:human/TNKS/TNKS-deep-research-falcon.md Tankyrase-1 is a **multidomain “scaffold-enzyme”**: file:human/TNKS/TNKS-deep-research-falcon.md **Tankyrase-1 (TNKS1)** is an **ADP-ribosyltransferase** of the PARP/ARTD family that **uses NAD+ as the substrate** to catalyze covalent transfer of ADP-ribose onto itself and protein binding partners, generating **poly(ADP-ribose) (PAR)** chains (i.e., PARylation). |
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