ANKS6

Summary: Isolated human ANKS6 and ANKS3 SAM domains bind directly.

Reason: PMID:24998259 directly characterizes binding of the human ANKS6 SAM domain to the human ANKS3 SAM domain by native gels and interface mutations, supporting the specific SAM domain binding term. The affinity and heterocomplex structure experiments use the ANKS3 I36E variant to suppress ANKS3 polymerization while retaining the heterointerface. These two-domain experiments do not by themselves establish a multiprotein scaffold; that activity has separate assembly evidence in PMID:23793029. The isolated ANKS6 SAM domain appears monomeric under the tested conditions, which does not determine the oligomeric state of full-length ANKS6 or imply binding to every SAM domain.

Proposed replacements: SAM domain binding

Summary: The named interaction partner NEK8 is a protein kinase.

Reason: PMID:26638075 is available here as an abstract describing a centrosome-cilium proximity-interaction survey; its ANKS6-NEK8 pair-level record was not inspected. The original IPI assertion and NEK8 partner are preserved. The kinase-partner refinement is supported independently by co-immunoprecipitation and domain mapping in PMID:23793029 and Figure 3C of PMID:26967905. It is not an assertion that this abstract demonstrates direct binding or NEK8 activation.

Proposed replacements: protein kinase binding

Summary: The named interaction partner NEK8 is a protein kinase.

Reason: Figure 3C of this source, PMID:26967905, assays GFP-NEK8 and Flag-ANKS6 co-immunoprecipitation in HEK293T cells and shows reduced association for NEK8 p.T87A. NEK8 is a protein kinase, making protein kinase binding more informative than generic binding. The Methods identify human NEK8 constructs; the ANKS6 construct species was not resolved from the retrieved Methods, and the human host does not settle that question. This interaction experiment is distinct from the source's patient-fibroblast localization and YAP phenotypes and does not itself demonstrate kinase activation.

Proposed replacements: protein kinase binding

Summary: DCAF7 association is curated, but the original pair-level evidence remains uninspected.

Reason: PMID:27173435 supplies the original IPI assertion for DCAF7 (UniProtKB:P61962). Its specific ANKS6-DCAF7 construct and assay record was not recovered in the accessed narrative or inspected in supplementary data. DCAF7 is a nonkinase partner, so kinase binding would be an incorrect partner-class refinement. No independently established functional replacement resolves this pair. The uncertainty is about the supporting experimental record, not a claim that the interaction is false.

Summary: The ANKS3 interaction in PMID:27173435 remains unresolved at the source-specific assay level.

Reason: The curated partner is ANKS3 (UniProtKB:Q6ZW76). The retrieved PMID:27173435 narrative does not expose the ANKS6-ANKS3 pair record and its construct-level evidence, and that supplementary record was not inspected. Independent human SAM-domain binding in PMID:24998259 supports the plausibility of the association, but it does not establish the specific experiment in this source or convert a pairwise interaction into scaffold activity. The scaffold refinement is therefore withdrawn from this row. The unresolved source evidence warrants UNDECIDED; neither the generic term nor the screening method establishes that the interaction is incorrect.

Summary: The named interaction partner NEK8 is a protein kinase.

Reason: PMID:27173435 supplies an IPI association with NEK8, a protein kinase; its specific supplementary pair record remains uninspected. Independent co-immunoprecipitation and domain mapping in PMID:23793029 and Figure 3C of PMID:26967905 support the same ANKS6-NEK8 association and the more informative partner class. Those experiments are supplemental support, not experiments attributed to this original screen. Activation is a separate function supported by PMID:25599650.

Proposed replacements: protein kinase binding

Summary: The named interaction partner NEK7 is a protein kinase; its activation by ANKS6 is not established.

Reason: PMID:27173435 supplies the original IPI association with NEK7; its supplementary pair record remains uninspected. The actual main Results of PMID:32707033 explicitly report ANKS6-NEK7 association in an affinity-purification mass-spectrometry network, independently supporting the protein-kinase partner class. This refinement preserves the original source assertion without claiming its pair table was read or that ANKS6 activates NEK7. Coassociation does not establish a purified binary interface.

Proposed replacements: protein kinase binding

Summary: The HuRI association with TMEM120B remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for TMEM120B (UniProtKB:A0PK00). The specific ANKS6-TMEM120B pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with SMIM1 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for SMIM1 (UniProtKB:B2RUZ4). The specific ANKS6-SMIM1 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with BET1 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for BET1 (UniProtKB:O15155). The specific ANKS6-BET1 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with STX7 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for STX7 (UniProtKB:O15400). The specific ANKS6-STX7 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with VAMP4 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for VAMP4 (UniProtKB:O75379). The specific ANKS6-VAMP4 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with C5 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for C5 (UniProtKB:P01031). The specific ANKS6-C5 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with STRIT1 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for STRIT1 (UniProtKB:P0DN84). The specific ANKS6-STRIT1 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with IGFBP5 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for IGFBP5 (UniProtKB:P24593). The specific ANKS6-IGFBP5 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with EMD remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for EMD (UniProtKB:P50402). The specific ANKS6-EMD pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with EMP1 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for EMP1 (UniProtKB:P54849). The specific ANKS6-EMP1 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with RTP2 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for RTP2 (UniProtKB:Q5QGT7). The specific ANKS6-RTP2 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with AGTRAP remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for AGTRAP (UniProtKB:Q6RW13-2). The specific ANKS6-AGTRAP pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with BCL2L2 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for BCL2L2 (UniProtKB:Q92843). The specific ANKS6-BCL2L2 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with TMEM60 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for TMEM60 (UniProtKB:Q9H2L4). The specific ANKS6-TMEM60 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with MARCHF5 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for MARCHF5 (UniProtKB:Q9NX47). The specific ANKS6-MARCHF5 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The HuRI association with PITPNC1 remains unresolved at the source-specific assay level.

Reason: PMID:32296183 supplies the original binary-interaction assertion for PITPNC1 (UniProtKB:Q9UKF7-2). The specific ANKS6-PITPNC1 pair entry, tested constructs and validation record were not inspected; availability of the article narrative does not establish those details. No independently supported functional replacement has been established for this pair. Its generic annotation is uninformative, but that alone does not establish an incorrect experimental assertion. UNDECIDED preserves this evidence boundary without rejecting the interaction from the partner's usual compartment or assuming that the screening assay is invalid.

Summary: The named interaction partner NEK8 is a protein kinase.

Reason: The PMID:32707033 Results place ANKS6 in the nephronophthisis module around NEK8 in the kinase interaction network. The curated IPI pair is independently supported by ANKS6-NEK8 co-immunoprecipitation and domain mapping in PMID:23793029 and Figure 3C of PMID:26967905. These sources support the protein-kinase partner class; the complete PMID:32707033 supplementary pair table was not read, and neither this network nor kinase binding alone establishes activation.

Proposed replacements: protein kinase binding

Summary: The named interaction partner NEK7 is a protein kinase; its activation by ANKS6 is not established.

Reason: The actual main Results of this source, PMID:32707033, explicitly report that ANKS6 interacted with NEK7 in the affinity-purification mass-spectrometry network. NEK7 is a protein kinase, so this directly supports the more informative partner class at the coassociation level. The text cites the earlier PMID:23793029 network as corroboration. No purified binary binding or NEK7 activation is inferred.

Proposed replacements: protein kinase binding

Summary: The ANKS3 interaction in PMID:33961781 remains unresolved at the source-specific assay level.

Reason: The curated partner is ANKS3 (UniProtKB:Q6ZW76). The retrieved PMID:33961781 narrative does not expose the ANKS6-ANKS3 pair record and its construct-level evidence, and that supplementary record was not inspected. Independent human SAM-domain binding in PMID:24998259 supports the plausibility of the association, but it does not establish the specific experiment in this source or convert a pairwise interaction into scaffold activity. The scaffold refinement is therefore withdrawn from this row. The unresolved source evidence warrants UNDECIDED; neither the generic term nor the screening method establishes that the interaction is incorrect.

Summary: The named interaction partner NEK7 is a protein kinase; its activation by ANKS6 is not established.

Reason: PMID:33961781 supplies the original BioPlex IPI association with NEK7; its ANKS6-NEK7 supplementary pair record remains uninspected. Independent main-text evidence in PMID:32707033 explicitly reports the same association and supports the protein-kinase partner class. The refinement does not attribute that later-read assay evidence to BioPlex or claim that a network association proves NEK7 activation or a purified binary interface.

Proposed replacements: protein kinase binding

Summary: The annotated cytoplasm localization is consistent with the primary localization evidence.

Reason: Cytoplasmic/ciliary localization is supported by primary ANKS6 evidence. Preserve the inference source and do not treat donor count or a coexisting more specific location as disproof. PAINT node/PTN and worm donor are preserved; no tree/MSA reconstruction or independent node-placement claim is made.

Summary: The annotated cytoplasm localization is consistent with the primary localization evidence.

Reason: Cytoplasmic/ciliary localization is supported by primary ANKS6 evidence. Preserve the inference source and do not treat donor count or a coexisting more specific location as disproof.

Summary: The annotated cilium localization is consistent with the primary localization evidence.

Reason: Cytoplasmic/ciliary localization is supported by primary ANKS6 evidence. Preserve the inference source and do not treat donor count or a coexisting more specific location as disproof.

Summary: The annotated ciliary inversin compartment localization is consistent with the primary localization evidence.

Reason: The specific proximal ciliary inversin compartment is supported by independent localization studies 23793029/25599650 and human control/patient fibroblasts 26967905. Preserve mouse/Ensembl transfer identifiers; this consultation did not reconstruct its entire donor chain.

Summary: A conserved NEK8-activating function is inferred from experimental rat Anks6 evidence.

Reason: The original study coexpressed rat Anks6 and mouse Nek8 in human 293T cells. ANKS6-dependent autophosphorylation and phosphorylation of the added alpha-casein substrate, with inactive-kinase and domain controls, support activation. A purified assay could not be performed because the bacterial recombinant constructs were insoluble. The human assertion is therefore an ortholog-based ISS inference, with rat Anks6 P0C0T2 as the supporting entity, rather than a direct human IDA result. The conserved ANK-repeat interaction architecture and human ciliopathy context support this interpretation; no intrinsic kinase activity is assigned to ANKS6.

Summary: Human ANKS6 binds RNA in a UV-crosslinking assay.

Reason: The targeted FLASH comparison explicitly used hANKS6 in inducible Flp-In T-REx 293 cells, with a C-terminal 3xFLAG-HBH tag. UV-C crosslinking, successive affinity purifications and high-salt washes identified ANKS6-associated RNAs across at least eight experiments, with ARL13B and BBS3 controls. This directly supports RNA binding; it does not establish a specific RNA-processing reaction or physiological target set. The Results and Discussion differ in their qualitative description of AGO2-mRNA binding, so no affinity claim is made. This activity is not promoted to a core function because its physiological contribution remains unresolved.

Summary: A conserved protein-complex scaffold activity is inferred from rat Anks6 assembly experiments.

Reason: In PMID:23793029, Anks6 associates with NEK8, INVS and NPHP3, increases recovery of INVS with NEK8, and enables NPHP3 to co-precipitate with NEK8. This is an assembly role that holds components together, beyond detection of an isolated binding pair. The published Figure 3b legend and adjoining Results identify rat Anks6 in this construct series; the human-host experiments are therefore represented as an ISS inference to human ANKS6, with rat P0C0T2 as the supporting entity. Human SAM-domain binding and later ANKS3-containing complex studies corroborate conserved interaction architecture but do not establish a direct ANKS6-BICC1 interface. The external published legend is documented in the notes without changing the cached author manuscript. No biological-process annotation is added.