TNKS

id: O95271
gene_symbol: TNKS
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: '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.'
existing_annotations:
- term:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function.
    action: ACCEPT
    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.
    supported_by: &id004
    - &id012
      reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
    - &id013
      reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - &id014
      reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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.'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: nucleus localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: &id001
    - &id005
      reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'The retrieved evidence supports a “multi-compartment” view of TNKS localization
        via partner-mediated recruitment:'
    - &id006
      reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cytoplasm localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: *id001
- term:
    id: GO:0070198
    label: protein localization to chromosome, telomeric region
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: protein localization to chromosome, telomeric region is supported as a TNKS
      telomere-associated role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: &id002
    - &id011
      reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - &id015
      reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with
        roles in telomere biology).'
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of canonical Wnt signaling pathway is a canonical TNKS pathway
      output through AXIN PARylation.
    action: ACCEPT
    reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing
      Wnt/beta-catenin pathway output.
    supported_by: &id007
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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.'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
- term:
    id: GO:1904355
    label: positive regulation of telomere capping
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of telomere capping is supported as a TNKS telomere-associated
      role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Golgi membrane is a plausible reported localization but not the dominant site of TNKS
      core activity.
    action: KEEP_AS_NON_CORE
    reason: TNKS has multi-compartment partner-mediated localization; the best-supported core
      locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites.
    supported_by: *id001
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Protein polyubiquitination captures a downstream consequence of TNKS PARylation but
      misstates the direct TNKS activity.
    action: MODIFY
    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_replacement_terms: &id018
    - id: GO:0070212
      label: protein poly-ADP-ribosylation
    - id: GO:0003950
      label: NAD+ poly-ADP-ribosyltransferase activity
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
- term:
    id: GO:0000242
    label: pericentriolar material
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: pericentriolar material localization is supported by TNKS spindle/centrosome-associated
      functions.
    action: ACCEPT
    reason: TNKS is recruited to spindle poles via NuMA and is required for NuMA PARylation and
      spindle organization.
    supported_by: &id003
    - &id009
      reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - &id010
      reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
- term:
    id: GO:0000781
    label: chromosome, telomeric region
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Chromosome telomeric region localization is supported by TNKS recruitment through TRF1.
    action: ACCEPT
    reason: Telomere recruitment is one of the hallmark TNKS localization contexts.
    supported_by: *id002
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: spindle pole localization is supported by TNKS spindle/centrosome-associated functions.
    action: ACCEPT
    reason: TNKS is recruited to spindle poles via NuMA and is required for NuMA PARylation and
      spindle organization.
    supported_by: *id003
- term:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: nuclear envelope is a plausible reported localization but not the dominant site of TNKS
      core activity.
    action: KEEP_AS_NON_CORE
    reason: TNKS has multi-compartment partner-mediated localization; the best-supported core
      locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites.
    supported_by: *id001
- term:
    id: GO:0005643
    label: nuclear pore
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: nuclear pore is a plausible reported localization but not the dominant site of TNKS
      core activity.
    action: KEEP_AS_NON_CORE
    reason: TNKS has multi-compartment partner-mediated localization; the best-supported core
      locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites.
    supported_by: *id001
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: cytoplasm localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: *id001
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: centrosome localization is supported by TNKS spindle/centrosome-associated functions.
    action: ACCEPT
    reason: TNKS is recruited to spindle poles via NuMA and is required for NuMA PARylation and
      spindle organization.
    supported_by: *id003
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: protein transport is a context-specific transport-related role rather than the primary
      TNKS function.
    action: KEEP_AS_NON_CORE
    reason: Transport annotations are secondary to TNKS substrate PARylation and pathway regulation.
    supported_by:
    - *id005
    - *id006
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
- term:
    id: GO:0016055
    label: Wnt signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Wnt signaling pathway is a canonical TNKS pathway output through AXIN PARylation.
    action: ACCEPT
    reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing
      Wnt/beta-catenin pathway output.
    supported_by: *id007
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: transferase activity is too broad for TNKS catalytic activity.
    action: MODIFY
    reason: The supported activity is NAD+-dependent protein
      ADP-ribosyltransferase/poly-ADP-ribosyltransferase activity, not a generic transferase label.
    proposed_replacement_terms: &id008
    - id: GO:0003950
      label: NAD+ poly-ADP-ribosyltransferase activity
    - id: GO:0140806
      label: NAD+-protein-aspartate ADP-ribosyltransferase activity
    - id: GO:0140807
      label: NAD+-protein-glutamate ADP-ribosyltransferase activity
    supported_by: *id004
- term:
    id: GO:0016757
    label: glycosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: glycosyltransferase activity is too broad for TNKS catalytic activity.
    action: MODIFY
    reason: The supported activity is NAD+-dependent protein
      ADP-ribosyltransferase/poly-ADP-ribosyltransferase activity, not a generic transferase label.
    proposed_replacement_terms: *id008
    supported_by: *id004
- term:
    id: GO:0016779
    label: nucleotidyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: nucleotidyltransferase activity is too broad for TNKS catalytic activity.
    action: MODIFY
    reason: The supported activity is NAD+-dependent protein
      ADP-ribosyltransferase/poly-ADP-ribosyltransferase activity, not a generic transferase label.
    proposed_replacement_terms: *id008
    supported_by: *id004
- term:
    id: GO:0032212
    label: positive regulation of telomere maintenance via telomerase
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: positive regulation of telomere maintenance via telomerase is supported as a TNKS
      telomere-associated role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: metal ion binding is plausible as a structural/catalytic-site feature but is not the
      main function.
    action: KEEP_AS_NON_CORE
    reason: Recent structural synthesis supports a zinc-binding motif in the catalytic acceptor-site
      architecture, but the core molecular function is ADP-ribosyltransferase activity.
    supported_by: &id019
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
- term:
    id: GO:0051028
    label: mRNA transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: mRNA transport is a context-specific transport-related role rather than the primary
      TNKS function.
    action: KEEP_AS_NON_CORE
    reason: Transport annotations are secondary to TNKS substrate PARylation and pathway regulation.
    supported_by:
    - *id005
    - *id006
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
- term:
    id: GO:0051301
    label: cell division
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: cell division is supported as a mitotic or telomere-cohesion output of TNKS activity.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - *id009
    - *id010
    - *id011
- term:
    id: GO:0070198
    label: protein localization to chromosome, telomeric region
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: protein localization to chromosome, telomeric region is supported as a TNKS
      telomere-associated role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:0070212
    label: protein poly-ADP-ribosylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: protein poly-ADP-ribosylation is a direct TNKS catalytic process.
    action: ACCEPT
    reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners.
    supported_by: *id004
- term:
    id: GO:0070213
    label: protein auto-ADP-ribosylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: protein auto-ADP-ribosylation is a direct TNKS catalytic process.
    action: ACCEPT
    reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners.
    supported_by: *id004
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: positive regulation of canonical Wnt signaling pathway is a canonical TNKS pathway
      output through AXIN PARylation.
    action: ACCEPT
    reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing
      Wnt/beta-catenin pathway output.
    supported_by: *id007
- term:
    id: GO:0140806
    label: NAD+-protein-aspartate ADP-ribosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  review:
    summary: NAD+-protein-aspartate ADP-ribosyltransferase activity is a core TNKS catalytic
      molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0140807
    label: NAD+-protein-glutamate ADP-ribosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  review:
    summary: NAD+-protein-glutamate ADP-ribosyltransferase activity is a core TNKS catalytic
      molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:1904355
    label: positive regulation of telomere capping
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: positive regulation of telomere capping is supported as a TNKS telomere-associated
      role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:1904357
    label: negative regulation of telomere maintenance via telomere lengthening
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Negative regulation of telomere maintenance via telomere lengthening is not justified
      by the current TNKS synthesis.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms:
    - id: GO:1904358
      label: positive regulation of telomere maintenance via telomere lengthening
    - id: GO:0032212
      label: positive regulation of telomere maintenance via telomerase
    supported_by:
    - &id016
      reference_id: PMID:12782650
      supporting_text: ADP-ribosylation of TRF1 by tankyrase 1 released TRF1 from telomeres and
        promoted telomere elongation.
    - &id017
      reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with
        roles in telomere biology).'
- term:
    id: GO:1990404
    label: NAD+-protein mono-ADP-ribosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: NAD+-protein mono-ADP-ribosyltransferase activity is a core TNKS catalytic molecular
      function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12080061
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14596906
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17003112
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17043677
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19759537
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20696165
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21251231
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21799911
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22699936
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25327252
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26373281
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26972000
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31413325
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cytosol localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: *id001
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4641257
  review:
    summary: positive regulation of canonical Wnt signaling pathway is a canonical TNKS pathway
      output through AXIN PARylation.
    action: ACCEPT
    reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing
      Wnt/beta-catenin pathway output.
    supported_by: *id007
- term:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3640858
  review:
    summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8948800
  review:
    summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0010521
    label: telomerase inhibitor activity
  evidence_type: IMP
  original_reference_id: PMID:25939383
  review:
    summary: Telomerase inhibitor activity is not the best direct molecular-function description for
      TNKS.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id008
    supported_by:
    - *id012
    - *id013
    - *id014
    - *id011
    - *id015
- term:
    id: GO:0010521
    label: telomerase inhibitor activity
  evidence_type: IDA
  original_reference_id: PMID:9822378
  review:
    summary: Telomerase inhibitor activity is not the best direct molecular-function description for
      TNKS.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms: *id008
    supported_by:
    - *id012
    - *id013
    - *id014
    - *id011
    - *id015
- term:
    id: GO:0032210
    label: regulation of telomere maintenance via telomerase
  evidence_type: IDA
  original_reference_id: PMID:9822378
  review:
    summary: regulation of telomere maintenance via telomerase is supported as a TNKS
      telomere-associated role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:1904358
    label: positive regulation of telomere maintenance via telomere lengthening
  evidence_type: IDA
  original_reference_id: PMID:12782650
  review:
    summary: positive regulation of telomere maintenance via telomere lengthening is supported as a
      TNKS telomere-associated role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:1990404
    label: NAD+-protein mono-ADP-ribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:15133513
  review:
    summary: NAD+-protein mono-ADP-ribosyltransferase activity is a core TNKS catalytic molecular
      function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:1990404
    label: NAD+-protein mono-ADP-ribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:9822378
  review:
    summary: NAD+-protein mono-ADP-ribosyltransferase activity is a core TNKS catalytic molecular
      function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0070212
    label: protein poly-ADP-ribosylation
  evidence_type: IDA
  original_reference_id: PMID:25043379
  review:
    summary: protein poly-ADP-ribosylation is a direct TNKS catalytic process.
    action: ACCEPT
    reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners.
    supported_by: *id004
- term:
    id: GO:1990404
    label: NAD+-protein mono-ADP-ribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:25043379
  review:
    summary: NAD+-protein mono-ADP-ribosyltransferase activity is a core TNKS catalytic molecular
      function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:16076287
  review:
    summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16076287
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0070212
    label: protein poly-ADP-ribosylation
  evidence_type: IDA
  original_reference_id: PMID:16076287
  review:
    summary: protein poly-ADP-ribosylation is a direct TNKS catalytic process.
    action: ACCEPT
    reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners.
    supported_by: *id004
- term:
    id: GO:0097431
    label: mitotic spindle pole
  evidence_type: IDA
  original_reference_id: PMID:16076287
  review:
    summary: mitotic spindle pole localization is supported by TNKS spindle/centrosome-associated
      functions.
    action: ACCEPT
    reason: TNKS is recruited to spindle poles via NuMA and is required for NuMA PARylation and
      spindle organization.
    supported_by: *id003
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11854288
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:11854288
  review:
    summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:1904908
    label: negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric
  evidence_type: IMP
  original_reference_id: PMID:26373281
  review:
    summary: negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric is
      supported as a mitotic or telomere-cohesion output of TNKS activity.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - *id009
    - *id010
    - *id011
- term:
    id: GO:0000781
    label: chromosome, telomeric region
  evidence_type: IDA
  original_reference_id: PMID:9822378
  review:
    summary: Chromosome telomeric region localization is supported by TNKS recruitment through TRF1.
    action: ACCEPT
    reason: Telomere recruitment is one of the hallmark TNKS localization contexts.
    supported_by: *id002
- term:
    id: GO:0042393
    label: histone binding
  evidence_type: IPI
  original_reference_id: PMID:26373281
  review:
    summary: Histone binding is supported in a telomere-cohesion context but is secondary to TNKS
      ADP-ribosyltransferase function.
    action: KEEP_AS_NON_CORE
    reason: This interaction fits a specialized telomere/chromatin context rather than the primary
      TNKS catalytic function.
    supported_by:
    - reference_id: PMID:26373281
      supporting_text: 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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15133513
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0032212
    label: positive regulation of telomere maintenance via telomerase
  evidence_type: IDA
  original_reference_id: PMID:12782650
  review:
    summary: positive regulation of telomere maintenance via telomerase is supported as a TNKS
      telomere-associated role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:0070198
    label: protein localization to chromosome, telomeric region
  evidence_type: IMP
  original_reference_id: PMID:15133513
  review:
    summary: protein localization to chromosome, telomeric region is supported as a TNKS
      telomere-associated role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:0070212
    label: protein poly-ADP-ribosylation
  evidence_type: IMP
  original_reference_id: PMID:25939383
  review:
    summary: protein poly-ADP-ribosylation is a direct TNKS catalytic process.
    action: ACCEPT
    reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners.
    supported_by: *id004
- term:
    id: GO:0070212
    label: protein poly-ADP-ribosylation
  evidence_type: IDA
  original_reference_id: PMID:9822378
  review:
    summary: protein poly-ADP-ribosylation is a direct TNKS catalytic process.
    action: ACCEPT
    reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners.
    supported_by: *id004
- term:
    id: GO:1904357
    label: negative regulation of telomere maintenance via telomere lengthening
  evidence_type: IMP
  original_reference_id: PMID:25939383
  review:
    summary: Negative regulation of telomere maintenance via telomere lengthening is not justified
      by the current TNKS synthesis.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms:
    - id: GO:1904358
      label: positive regulation of telomere maintenance via telomere lengthening
    - id: GO:0032212
      label: positive regulation of telomere maintenance via telomerase
    supported_by:
    - *id016
    - *id017
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:25939383
  review:
    summary: positive regulation of canonical Wnt signaling pathway is a canonical TNKS pathway
      output through AXIN PARylation.
    action: ACCEPT
    reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing
      Wnt/beta-catenin pathway output.
    supported_by: *id007
- term:
    id: GO:1904355
    label: positive regulation of telomere capping
  evidence_type: IMP
  original_reference_id: PMID:25939383
  review:
    summary: positive regulation of telomere capping is supported as a TNKS telomere-associated
      role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:21270334
  review:
    summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3640844
  review:
    summary: cytosol localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: *id001
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3640858
  review:
    summary: cytosol localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: *id001
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3640861
  review:
    summary: cytosol localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: *id001
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3640862
  review:
    summary: cytosol localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: *id001
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3640872
  review:
    summary: cytosol localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: *id001
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3640874
  review:
    summary: cytosol localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: *id001
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5262606
  review:
    summary: cytosol localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: *id001
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8948800
  review:
    summary: cytosol localization is consistent with TNKS multi-compartment activity.
    action: ACCEPT
    reason: TNKS acts in nuclear/telomeric and cytoplasmic signaling contexts, including Wnt pathway
      regulation.
    supported_by: *id001
- term:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:22864114
  review:
    summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22864114
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: PMID:22864114
  review:
    summary: Golgi apparatus is a plausible reported localization but not the dominant site of TNKS
      core activity.
    action: KEEP_AS_NON_CORE
    reason: TNKS has multi-compartment partner-mediated localization; the best-supported core
      locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites.
    supported_by: *id001
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:19245366
  review:
    summary: Positive regulation of transcription by RNA polymerase II is an indirect
      Wnt/beta-catenin or YAP pathway output.
    action: KEEP_AS_NON_CORE
    reason: TNKS regulates transcriptional outputs indirectly by PARylating pathway regulators such
      as AXIN rather than functioning as a transcription factor.
    supported_by: *id007
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IDA
  original_reference_id: PMID:19759537
  review:
    summary: Protein polyubiquitination captures a downstream consequence of TNKS PARylation but
      misstates the direct TNKS activity.
    action: MODIFY
    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_replacement_terms: *id018
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
- term:
    id: GO:0000209
    label: protein polyubiquitination
  evidence_type: IDA
  original_reference_id: PMID:21478859
  review:
    summary: Protein polyubiquitination captures a downstream consequence of TNKS PARylation but
      misstates the direct TNKS activity.
    action: MODIFY
    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_replacement_terms: *id018
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
- term:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:19759537
  review:
    summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:21478859
  review:
    summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21478859
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0070213
    label: protein auto-ADP-ribosylation
  evidence_type: IDA
  original_reference_id: PMID:21478859
  review:
    summary: protein auto-ADP-ribosylation is a direct TNKS catalytic process.
    action: ACCEPT
    reason: TNKS catalyzes protein PARylation and auto-PARylation of itself and binding partners.
    supported_by: *id004
- term:
    id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:19759537
  review:
    summary: positive regulation of canonical Wnt signaling pathway is a canonical TNKS pathway
      output through AXIN PARylation.
    action: ACCEPT
    reason: TNKS PARylates AXIN1/2 to promote RNF146-dependent AXIN degradation, thereby increasing
      Wnt/beta-catenin pathway output.
    supported_by: *id007
- term:
    id: GO:0070198
    label: protein localization to chromosome, telomeric region
  evidence_type: IMP
  original_reference_id: PMID:18221737
  review:
    summary: protein localization to chromosome, telomeric region is supported as a TNKS
      telomere-associated role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:0000242
    label: pericentriolar material
  evidence_type: TAS
  original_reference_id: PMID:11454873
  review:
    summary: pericentriolar material localization is supported by TNKS spindle/centrosome-associated
      functions.
    action: ACCEPT
    reason: TNKS is recruited to spindle poles via NuMA and is required for NuMA PARylation and
      spindle organization.
    supported_by: *id003
- term:
    id: GO:0000781
    label: chromosome, telomeric region
  evidence_type: IDA
  original_reference_id: PMID:11739745
  review:
    summary: Chromosome telomeric region localization is supported by TNKS recruitment through TRF1.
    action: ACCEPT
    reason: Telomere recruitment is one of the hallmark TNKS localization contexts.
    supported_by: *id002
- term:
    id: GO:0005643
    label: nuclear pore
  evidence_type: TAS
  original_reference_id: PMID:11454873
  review:
    summary: nuclear pore is a plausible reported localization but not the dominant site of TNKS
      core activity.
    action: KEEP_AS_NON_CORE
    reason: TNKS has multi-compartment partner-mediated localization; the best-supported core
      locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites.
    supported_by: *id001
- term:
    id: GO:0007052
    label: mitotic spindle organization
  evidence_type: TAS
  original_reference_id: PMID:17026964
  review:
    summary: mitotic spindle organization is supported as a mitotic or telomere-cohesion output of
      TNKS activity.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - *id009
    - *id010
    - *id011
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IDA
  original_reference_id: PMID:18436240
  review:
    summary: zinc ion binding is plausible as a structural/catalytic-site feature but is not the
      main function.
    action: KEEP_AS_NON_CORE
    reason: Recent structural synthesis supports a zinc-binding motif in the catalytic acceptor-site
      architecture, but the core molecular function is ADP-ribosyltransferase activity.
    supported_by: *id019
- term:
    id: GO:0031965
    label: nuclear membrane
  evidence_type: TAS
  original_reference_id: PMID:11454873
  review:
    summary: nuclear membrane is a plausible reported localization but not the dominant site of TNKS
      core activity.
    action: KEEP_AS_NON_CORE
    reason: TNKS has multi-compartment partner-mediated localization; the best-supported core
      locations are cytosol/cytoplasm, nucleus/telomeres, and spindle-associated sites.
    supported_by: *id001
- term:
    id: GO:0032212
    label: positive regulation of telomere maintenance via telomerase
  evidence_type: IMP
  original_reference_id: PMID:11739745
  review:
    summary: positive regulation of telomere maintenance via telomerase is supported as a TNKS
      telomere-associated role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:0032212
    label: positive regulation of telomere maintenance via telomerase
  evidence_type: IDA
  original_reference_id: PMID:18221737
  review:
    summary: positive regulation of telomere maintenance via telomerase is supported as a TNKS
      telomere-associated role.
    action: ACCEPT
    reason: TNKS is recruited to telomeres through TRF1 and regulates telomere-associated protein
      localization and telomere maintenance/capping outputs.
    supported_by: *id002
- term:
    id: GO:0051225
    label: spindle assembly
  evidence_type: TAS
  original_reference_id: PMID:17026964
  review:
    summary: spindle assembly is supported as a mitotic or telomere-cohesion output of TNKS
      activity.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - *id009
    - *id010
    - *id011
- term:
    id: GO:0018105
    label: peptidyl-serine phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:17026964
  review:
    summary: peptidyl-serine phosphorylation is not supported as a TNKS catalytic activity.
    action: REMOVE
    reason: TNKS is an ADP-ribosyltransferase, not a protein kinase catalyzing serine or threonine
      phosphorylation.
    supported_by: *id004
- term:
    id: GO:0018107
    label: peptidyl-threonine phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:17026964
  review:
    summary: peptidyl-threonine phosphorylation is not supported as a TNKS catalytic activity.
    action: REMOVE
    reason: TNKS is an ADP-ribosyltransferase, not a protein kinase catalyzing serine or threonine
      phosphorylation.
    supported_by: *id004
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12768206
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
- term:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:9822378
  review:
    summary: NAD+ poly-ADP-ribosyltransferase activity is a core TNKS catalytic molecular function.
    action: ACCEPT
    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.
    supported_by: *id004
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9822378
  review:
    summary: Protein binding is supported but too generic for TNKS substrate recognition.
    action: MARK_AS_OVER_ANNOTATED
    reason: TNKS recognizes substrate proteins through ankyrin-repeat clusters and then catalyzes
      ADP-ribosylation; generic protein binding hides the enzymatic mechanism.
    supported_by:
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 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.
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: 'Tankyrase-1 is a **multidomain “scaffold-enzyme”**:'
    - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
      supporting_text: '**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).'
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary
    mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using
    Ensembl Compara
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11454873
  title: TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell
    death upon overexpression.
  findings: []
- id: PMID:11739745
  title: >-
    Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human
    telomeres.
  findings: []
- id: PMID:11854288
  title: The telomeric poly(ADP-ribose) polymerase, tankyrase 1, contains multiple binding sites for
    telomeric repeat binding factor 1 (TRF1) and a novel acceptor, 182-kDa tankyrase-binding protein
    (TAB182).
  findings: []
- id: PMID:12080061
  title: Identification of a tankyrase-binding motif shared by IRAP, TAB182, and human TRF1 but not
    mouse TRF1. NuMA contains this RXXPDG motif and is a novel tankyrase partner.
  findings: []
- id: PMID:12768206
  title: POT1 as a terminal transducer of TRF1 telomere length control.
  findings: []
- id: PMID:12782650
  title: TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres.
  findings: []
- id: PMID:14596906
  title: The formin-binding protein 17, FBP17, binds via a TNKS binding motif to tankyrase, a
    protein involved in telomere maintenance.
  findings: []
- id: PMID:15133513
  title: TIN2 is a tankyrase 1 PARP modulator in the TRF1 telomere length control complex.
  findings: []
- id: PMID:16076287
  title: NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyrase 1 in mitosis.
  findings: []
- id: PMID:17003112
  title: Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the
    hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH).
  findings: []
- id: PMID:17026964
  title: Mitotic phosphorylation of tankyrase, a PARP that promotes spindle assembly, by GSK3.
  findings: []
- id: PMID:17043677
  title: 'Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes
    and a potential synaptic basis for schizophrenia.'
  findings: []
- id: PMID:18221737
  title: Telomere elongation by a mutant tankyrase 1 without TRF1 poly(ADP-ribosyl)ation.
  findings: []
- id: PMID:18436240
  title: Zinc binding catalytic domain of human tankyrase 1.
  findings: []
- id: PMID:19245366
  title: MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the
    asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH).
  findings: []
- id: PMID:19759537
  title: Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling.
  findings: []
- id: PMID:20696165
  title: Tankyrase-1 assembly to large protein complexes blocks its telomeric function.
  findings: []
- id: PMID:21251231
  title: Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational
    hydroxylation of histidinyl residues within ankyrin repeat domains.
  findings: []
- id: PMID:21270334
  title: Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and
    mitotic progression.
  findings: []
- id: PMID:21478859
  title: RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt
    signalling.
  findings: []
- id: PMID:21799911
  title: Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling.
  findings: []
- id: PMID:22699936
  title: Tankyrase 1 regulates centrosome function by controlling CPAP stability.
  findings: []
- id: PMID:22864114
  title: Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation.
  findings: []
- id: PMID:25043379
  title: Family-wide analysis of poly(ADP-ribose) polymerase activity.
  findings: []
- id: PMID:25327252
  title: Allosteric activation of the RNF146 ubiquitin ligase by a poly(ADP-ribosyl)ation signal.
  findings: []
- id: PMID:25939383
  title: Disruption of Wnt/β-Catenin Signaling and Telomeric Shortening Are Inextricable
    Consequences of Tankyrase Inhibition in Human Cells.
  findings: []
- id: PMID:26373281
  title: Loss of ATRX Suppresses Resolution of Telomere Cohesion to Control Recombination in ALT
    Cancer Cells.
  findings: []
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries and
    abundances.
  findings: []
- id: PMID:26972000
  title: Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings: []
- id: PMID:31413325
  title: HENA, heterogeneous network-based data set for Alzheimer's disease.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:9822378
  title: Tankyrase, a poly(ADP-ribose) polymerase at human telomeres.
  findings: []
- id: Reactome:R-HSA-3640844
  title: RNF146 binds RibC-AXIN:TNKS complex
  findings: []
- id: Reactome:R-HSA-3640858
  title: Tankyrase ADP-ribosylates AXIN
  findings: []
- id: Reactome:R-HSA-3640861
  title: RNF146 ubiquitinates ADP-ribosylated AXIN
  findings: []
- id: Reactome:R-HSA-3640862
  title: Tankyrase binds AXIN
  findings: []
- id: Reactome:R-HSA-3640872
  title: USP34 deubiquitinates AXIN1,AXIN2
  findings: []
- id: Reactome:R-HSA-3640874
  title: Ub-RibC-AXIN is degraded by the proteasome
  findings: []
- id: Reactome:R-HSA-4641257
  title: Degradation of AXIN
  findings: []
- id: Reactome:R-HSA-5262606
  title: XAV939 binds tankyrase to stabilize axin and inhibit WNT signaling
  findings: []
- id: Reactome:R-HSA-8948800
  title: TNKS and TNKS2 PARylate PTEN
  findings: []
- id: file:human/TNKS/TNKS-deep-research-falcon.md
  title: Falcon deep research synthesis for TNKS
  findings: []
core_functions:
- description: NAD+-dependent protein poly-ADP-ribosyltransferase activity that PARylates TNKS
    itself and substrate proteins such as AXIN, enabling PAR-dependent ubiquitination and pathway
    regulation.
  molecular_function:
    id: GO:0003950
    label: NAD+ poly-ADP-ribosyltransferase activity
  directly_involved_in:
  - id: GO:0070212
    label: protein poly-ADP-ribosylation
  - id: GO:0070213
    label: protein auto-ADP-ribosylation
  - id: GO:0090263
    label: positive regulation of canonical Wnt signaling pathway
  - id: GO:0070198
    label: protein localization to chromosome, telomeric region
  - id: GO:1904355
    label: positive regulation of telomere capping
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005634
    label: nucleus
  - id: GO:0000781
    label: chromosome, telomeric region
  - id: GO:0097431
    label: mitotic spindle pole
  supported_by:
  - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
    supporting_text: '**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).'
  - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
    supporting_text: 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.
  - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
    supporting_text: 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.
  - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
    supporting_text: '**Telomeres**: recruitment via the telomeric factor **TRF1** (consistent with roles
      in telomere biology).'
  - reference_id: file:human/TNKS/TNKS-deep-research-falcon.md
    supporting_text: 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.
proposed_new_terms: []
suggested_questions: []
suggested_experiments: []