SUFU (Suppressor of fused homolog) is a 484-residue intracellular protein with no catalytic domain and no enzymatic activity, and the single human member of the Suppressor of fused family. It is the principal negative regulator of the vertebrate Hedgehog pathway acting downstream of Smoothened. SUFU binds full-length GLI1, GLI2 and GLI3 zinc-finger transcription factors through a conserved interface that closes around the SYGHL motif of GLI, and this single interaction accounts for its several documented effects: GLI is held in the cytoplasm and blocked from entering the nucleus, its transcriptional activity is repressed even where the two are bound together on DNA, and it is protected from proteasomal degradation. In the pathway-off state SUFU additionally acts as an adaptor that promotes proteolytic conversion of full-length GLI3 into the GLI3R repressor by recruiting GSK3B to GLI3; the SUFU-GLI3 complex is delivered to the primary cilium, and intraflagellar transport moves it between the ciliary base, where the processing kinases act, and the ciliary tip. Hedgehog signalling releases GLI from SUFU: the Fused-family kinases STK36 and ULK3, the ciliary kinase DYRK2, ERK/MAPK and S6K1 each weaken the SUFU-GLI interface by phosphorylating GLI, and SCF(FBXL17) ubiquitylates SUFU itself at Lys-257 to drive its turnover in the nucleus. SUFU is expressed ubiquitously in adult tissues and is found in the cytoplasm, the nucleoplasm and the cilium. Loss of SUFU raises Hedgehog output: knockout is embryonic-lethal in mouse, germline loss-of-function in humans predisposes to medulloblastoma and causes basal cell nevus syndrome, and hypomorphic recessive missense variants cause Joubert syndrome with cranio-facial and skeletal defects.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:10564661 Characterization of the human suppressor of fused, a negativ... | ACCEPT | Summary: Stone et al. showed that human SUFU represses the transcriptional activity of GLI in reporter assays while binding GLI1, GLI2 and GLI3 directly. Because SUFU acts on the transcription factor itself rather than on an upstream input, repression of GLI target genes is an immediate consequence of SUFU binding. Reason: Accepted as a core process. GLI1/2/3 are RNA polymerase II transcription factors, and SUFU's only established biochemical activity is to bind them and hold them inactive, so this term names something SUFU genuinely executes rather than a distant downstream phenotype. The same term carries an IBD at the PTHR10928 ancestral node PTN000859153 in the local PAINT slice, placing the repression function deep in Eumetazoa. (The human GOA snapshot does not yet carry a matching IBA row for GO:0000122; that is snapshot lag between the PAINT slice and the GOA release, not a disagreement, and it changes nothing here.) Supporting Evidence: PMID:10564661 HSu(fu) was found to repress activity of the zinc-finger transcription factor Gli, which mediates Hedgehog signaling in vertebrates, and to physically interact with Gli, Gli2 and Gli3 PMID:10564661 our data provide biochemical and functional evidence for the hypothesis that Su(fu) is a key negative regulator in the vertebrate Hedgehog signaling pathway |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000117 | ACCEPT | Summary: An ARBA machine-learning rule (ARBA00029133) assigns negative regulation of Pol II transcription to SUFU on the basis of its UniProt family and functional annotation. Reason: Accepted. The electronic assignment lands on exactly the term that the human IDA row and the PAINT node independently support, so the rule is correct for this protein rather than being a broad default. Where an ARBA rule is too generic for SUFU it has been modified instead (see GO:0007165), so this is not blanket acceptance of the ARBA source. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00029133 SUPPORTS TRANSFER Rule output coincides with the human IDA annotation and with the PTHR10928 IBD node, so the electronic call is independently corroborated. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling |
| GO:0000122 negative regulation of transcription by RNA polymerase II | TAS PMID:11001584 The sonic hedgehog-patched-gli pathway in human development ... | ACCEPT | Summary: A GOA row taken from the Villavicencio et al. review of the sonic hedgehog-patched-gli pathway in human development and disease, asserting that SUFU negatively regulates GLI-driven transcription. Reason: Accepted. The cached record for this review contains citation metadata only, with no abstract or full text, so the author statement behind the TAS cannot be quoted here and no supporting_text is offered. The assertion itself is not in doubt: it duplicates a claim that the IDA row from PMID:10564661 establishes experimentally in human cells and that the ancestral PAINT node supports phylogenetically. A TAS row that restates a well-evidenced term is redundant rather than wrong, and UNDECIDED would misrepresent the state of the evidence for this term. |
| GO:0003714 transcription corepressor activity | TAS PMID:10559945 Mammalian suppressor-of-fused modulates nuclear-cytoplasmic ... | KEEP AS NON CORE | Summary: Kogerman et al. showed that SUFU sequesters GLI1 in the cytoplasm but can also interact with GLI1 while it is on DNA, which is the observation behind reading SUFU as a transcriptional corepressor rather than purely a cytoplasmic anchor. Reason: Kept, but marked non-core. It is not wrong: SUFU is found with GLI1 on DNA, and UniProt records a DNA-bound corepressor complex containing SAP18, GLI1 and SIN3. But two things keep it off the core list. First, both GOA rows are TAS and the corepressor complex itself is annotated in UniProt only By similarity from mouse, so the human evidence is thinner than for sequestration. Second, and more decisively, the repression readout is already accounted for by the sequestering activity: Zhang et al. showed that mutating the single SUFU-GLI interface simultaneously abolishes transcriptional repression, cytoplasmic tethering and protection from proteasomal degradation, which means these are three readouts of one binding event rather than three activities. Promoting GO:0003714 to core would put a less-established mechanism on the same footing as the one that the PAINT node, the hedgehog_signaling module and all five curated GO-CAM models agree on. Supporting Evidence: PMID:10559945 the gene product interacts physically with the transcriptional effector GLI-1, can sequester GLI-1 in the cytoplasm, but can also interact with GLI-1 on DNA PMID:24217340 Mutations of critical interface residues disrupt the Sufu-Gli complex and prevent Sufu from repressing Gli-mediated transcription, tethering Gli in the cytoplasm and protecting Gli from the 26S proteasome-mediated degradation. file:human/SUFU/SUFU-uniprot.txt corepressor complex containing SAP18, GLI1 and SIN3 (By similarity). |
| GO:0003714 transcription corepressor activity | TAS PMID:10564661 Characterization of the human suppressor of fused, a negativ... | KEEP AS NON CORE | Summary: Stone et al. reported that SUFU represses GLI-mediated transactivation while bound to GLI, and that repression is potentiated by co-expression of Slimb, consistent with SUFU acting on the transcription factor at the promoter as well as in the cytoplasm. Reason: Kept, but marked non-core. It is not wrong: SUFU is found with GLI1 on DNA, and UniProt records a DNA-bound corepressor complex containing SAP18, GLI1 and SIN3. But two things keep it off the core list. First, both GOA rows are TAS and the corepressor complex itself is annotated in UniProt only By similarity from mouse, so the human evidence is thinner than for sequestration. Second, and more decisively, the repression readout is already accounted for by the sequestering activity: Zhang et al. showed that mutating the single SUFU-GLI interface simultaneously abolishes transcriptional repression, cytoplasmic tethering and protection from proteasomal degradation, which means these are three readouts of one binding event rather than three activities. Promoting GO:0003714 to core would put a less-established mechanism on the same footing as the one that the PAINT node, the hedgehog_signaling module and all five curated GO-CAM models agree on. Supporting Evidence: PMID:10564661 The data further suggest that Su(fu) can act by binding to Gli and inhibiting Gli-mediated transactivation as well as by serving as an adaptor protein, which links Gli to the Slimb-dependent proteasomal degradation pathway. PMID:10564661 Coexpression of Slimb with Su(fu) potentiated the Su(fu)-mediated repression of Gli. file:human/SUFU/SUFU-uniprot.txt corepressor complex containing SAP18, GLI1 and SIN3 (By similarity). |
| GO:0005515 protein binding | IPI PMID:10564661 Characterization of the human suppressor of fused, a negativ... | MODIFY | Summary: GOA records this physical-interaction row from the original characterisation of human SUFU, with GLI3 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:10806483 Gli regulation by the opposing activities of fused and suppr... | MODIFY | Summary: GOA records this physical-interaction row from the study of the opposing activities of Fused and Suppressor of fused with the Fused-family kinase STK36 as the partner. STK36 is the vertebrate orthologue of Drosophila Fused and acts on the SUFU-GLI complex to release GLI, so the interaction has a defined mechanistic role rather than being an isolated detection. Reason: Generic protein binding is uninformative, but here the partner class is itself the information: STK36 is a serine/threonine protein kinase and UniProt records the interaction together with its functional consequence. Protein kinase binding is the evidence-backed replacement, and SUFU already carries that term by IPI for the related kinase ULK3 (GO:0019901, PMID:20643644), so the replacement makes the record internally consistent rather than introducing a new claim. Proposed replacements: protein kinase binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt with STK36; promoting dissociation between SUFU and GLI |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: GOA records this physical-interaction row from a proteome-scale yeast two-hybrid map; the reported partner is PEX26. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. PEX26 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: GOA records this physical-interaction row from a proteome-scale yeast two-hybrid map; the reported partner is GLIS3. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. GLIS3 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: GOA records this physical-interaction row from a proteome-scale yeast two-hybrid map; the reported partner is RCN3. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. RCN3 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: GOA records this physical-interaction row from a proteome-scale yeast two-hybrid map; the reported partner is ZNF764. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF764 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: GOA records this physical-interaction row from a proteome-scale yeast two-hybrid map; the reported partner is MID1IP1. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. MID1IP1 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: GOA records this physical-interaction row from a proteome-scale yeast two-hybrid map; the reported partner is ZNF446. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF446 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:20211142 An atlas of combinatorial transcriptional regulation in mous... | MODIFY | Summary: GOA records this physical-interaction row from an atlas of combinatorial transcriptional regulation, with GLI1 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:20211142 An atlas of combinatorial transcriptional regulation in mous... | REMOVE | Summary: GOA records this physical-interaction row from an atlas of combinatorial transcriptional regulation; the reported partner is HDX. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. HDX is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:20211142 An atlas of combinatorial transcriptional regulation in mous... | REMOVE | Summary: GOA records this physical-interaction row from an atlas of combinatorial transcriptional regulation; the reported partner is GLIS3. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. GLIS3 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:20211142 An atlas of combinatorial transcriptional regulation in mous... | REMOVE | Summary: GOA records this physical-interaction row from an atlas of combinatorial transcriptional regulation; the reported partner is ZNF747. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF747 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:22439934 The crosstalk of mTOR/S6K1 and Hedgehog pathways. | MODIFY | Summary: GOA records this physical-interaction row from a study of mTOR/S6K1-Hedgehog crosstalk, with GLI1 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:24035498 Parallel SCF adaptor capture proteomics reveals a role for S... | REMOVE | Summary: GOA records this row from a parallel SCF-adaptor capture proteomics screen, with FBXL17 as the partner. That study is a systematic survey of F-box protein interactors whose validation went to BACH1 and the NRF2 axis; SUFU appears as one candidate among many. Reason: Removed as uninformative. The SUFU-FBXL17 relationship is real and is retained through the companion row anchored to PMID:27234298, which established it mechanistically and is modified here to ubiquitin protein ligase binding. This screening row would add a second bare protein-binding assertion for the same pair without adding functional content. |
| GO:0005515 protein binding | IPI PMID:24217340 Structural insight into the mutual recognition and regulatio... | MODIFY | Summary: GOA records this physical-interaction row from the SUFU-Gli/Ci co-structure study, with GLI1 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:24217340 Structural insight into the mutual recognition and regulatio... | MODIFY | Summary: GOA records this physical-interaction row from the SUFU-Gli/Ci co-structure study, with mouse Gli2 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:24311597 Structural basis of SUFU-GLI interaction in human Hedgehog s... | MODIFY | Summary: GOA records this physical-interaction row from the human SUFU-GLI co-structure study, with GLI1 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:24311597 Structural basis of SUFU-GLI interaction in human Hedgehog s... | MODIFY | Summary: GOA records this physical-interaction row from the human SUFU-GLI co-structure study, with GLI3 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: GOA records this physical-interaction row from an in situ proximity-ligation survey of endogenous interactions, with GLI1 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: GOA records this physical-interaction row from an in situ proximity-ligation survey of endogenous interactions with the Fused-family kinase STK36 as the partner. STK36 is the vertebrate orthologue of Drosophila Fused and acts on the SUFU-GLI complex to release GLI, so the interaction has a defined mechanistic role rather than being an isolated detection. Reason: Generic protein binding is uninformative, but here the partner class is itself the information: STK36 is a serine/threonine protein kinase and UniProt records the interaction together with its functional consequence. Protein kinase binding is the evidence-backed replacement, and SUFU already carries that term by IPI for the related kinase ULK3 (GO:0019901, PMID:20643644), so the replacement makes the record internally consistent rather than introducing a new claim. Proposed replacements: protein kinase binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt with STK36; promoting dissociation between SUFU and GLI |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: GOA records this physical-interaction row from a proteome-scale binary interactome map; the reported partner is ZNF747. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF747 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:25609649 Proteomic analyses reveal distinct chromatin-associated and ... | MODIFY | Summary: GOA records this physical-interaction row from a proteomic survey of chromatin-associated and soluble transcription factor complexes, with GLI1 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:27234298 SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signa... | MODIFY | Summary: This row is anchored to the mechanistic study of SCF(FBXL17), which shows that FBXL17 - the substrate-recognition F-box subunit of an SCF ubiquitin ligase - engages SUFU and targets it for proteolysis in the nucleus, thereby releasing GLI1. Reason: Generic protein binding is uninformative, and here a specific, evidence-backed term is available: SUFU is the substrate that engages an SCF E3 ubiquitin ligase complex, which GO expresses as ubiquitin protein ligase binding. UniProt localises the resulting modification to Lys-257, so the engagement is documented at residue level rather than inferred from co-purification. Note the direction of the claim - this term says SUFU binds the ligase, not that SUFU ubiquitylates anything. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:27234298 Here, we show that Fbxl17 (F-box and leucine-rich repeat protein 17) targets Sufu for proteolysis in the nucleus. PMID:27234298 The ubiquitylation of Sufu, mediated by Fbxl17, allows the release of Gli1 from Sufu for proper Hh signal transduction. file:human/SUFU/SUFU-uniprot.txt Polyubiquitinated at Lys-257 by the SCF(FBXL17) complex, leading |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: GOA records this physical-interaction row from a large-scale interactome survey of protein communities; the reported partner is OVOL1. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. OVOL1 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: GOA records this physical-interaction row from a large-scale interactome survey of protein communities; the reported partner is NFATC3. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. NFATC3 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: GOA records this physical-interaction row from a large-scale interactome survey of protein communities; the reported partner is BFSP2. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. BFSP2 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: GOA records this physical-interaction row from a large-scale interactome survey of protein communities; the reported partner is ZNF764. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF764 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: GOA records this physical-interaction row from a large-scale interactome survey of protein communities; the reported partner is ZNF747. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF747 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:28965847 Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedg... | MODIFY | Summary: GOA records this physical-interaction row from the SUFU Joubert-syndrome study, with GLI1 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:28965847 Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedg... | MODIFY | Summary: GOA records this physical-interaction row from the SUFU Joubert-syndrome study, with GLI3 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:31403225 The interactome of KRAB zinc finger proteins reveals the evo... | REMOVE | Summary: GOA records this physical-interaction row from a KRAB zinc-finger protein interactome survey; the reported partner is ZNF764. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF764 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: GOA records this physical-interaction row from a screen for interaction disruption by human genetic variants; the reported partner is ZNF747. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF747 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is NME4. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. NME4 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is CRX. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. CRX is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is KRT75. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. KRT75 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map, with GLI1 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is FXR1. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. FXR1 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is TLE5. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. TLE5 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is ZNF763. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF763 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is BFSP2. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. BFSP2 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is ZIC1. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZIC1 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is CRTC2. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. CRTC2 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is Q6FHY5. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. Q6FHY5 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is HDX. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. HDX is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is KRT27. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. KRT27 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is LCA5. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. LCA5 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is STX19. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. STX19 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is ZNF114. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF114 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is ZSCAN18. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZSCAN18 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is RCN3. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. RCN3 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is SLC41A3. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. SLC41A3 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is ZNF764. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF764 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is L3MBTL3. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. L3MBTL3 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is DISC1. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. DISC1 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is ZNF446. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF446 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is ABI3. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ABI3 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is MAGEL2. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. MAGEL2 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is LZTS1. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. LZTS1 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: GOA records this physical-interaction row from the HuRI reference binary interactome map; the reported partner is ZNF330. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF330 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: GOA records this physical-interaction row from a neurodegenerative-disease protein interaction map; the reported partner is ATN1. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ATN1 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: GOA records this physical-interaction row from a neurodegenerative-disease protein interaction map; the reported partner is KLK6. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. KLK6 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: GOA records this physical-interaction row from the cell-line-resolved dual proteome-scale interactome; the reported partner is OVOL1. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. OVOL1 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: GOA records this physical-interaction row from the cell-line-resolved dual proteome-scale interactome; the reported partner is NFATC3. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. NFATC3 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: GOA records this physical-interaction row from the cell-line-resolved dual proteome-scale interactome; the reported partner is BFSP2. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. BFSP2 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: GOA records this physical-interaction row from the cell-line-resolved dual proteome-scale interactome; the reported partner is ZSCAN18. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZSCAN18 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: GOA records this physical-interaction row from the cell-line-resolved dual proteome-scale interactome; the reported partner is ZNF764. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF764 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: GOA records this physical-interaction row from the cell-line-resolved dual proteome-scale interactome; the reported partner is ZNF747. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF747 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: GOA records this physical-interaction row from the cell-line-resolved dual proteome-scale interactome; the reported partner is MID1IP1. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. MID1IP1 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:35140242 Human transcription factor protein interaction networks. | MODIFY | Summary: GOA records this physical-interaction row from a human transcription-factor interaction network, with GLI3 as the reported partner. SUFU-GLI association is the most heavily replicated biochemical fact about this protein: UniProt cites eleven primary papers for the sequestering function, IntAct records 27 experiments for the GLI1 pair alone, and two independent co-structures define the interface. The bare term records none of that. Reason: Generic protein binding is uninformative and is not kept, but the row should be promoted rather than discarded, because the cited evidence supports a specific term. GLI1, GLI2 and GLI3 are sequence-specific zinc-finger DNA-binding transcription factors, so DNA-binding transcription factor binding is precisely what this IPI row demonstrates, and it is the binding event from which every downstream SUFU readout follows - cytoplasmic tethering, transcriptional repression and protection from proteasomal degradation are three consequences of one interaction, not three activities. GO has no GLI-specific child term, so GO:0140297 is the most specific defensible replacement. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Negative regulator in the hedgehog/smoothened signaling file:human/SUFU/SUFU-uniprot.txt transcription factors in the cytoplasm |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: GOA records this row from a screen for mutation-directed neo-interactions in cancer, with BRAF as the reported partner. That dataset is designed to surface interactions gained by mutant proteins rather than interactions of the wild-type pair. Reason: Removed as uninformative, and the experimental design additionally blocks promotion to a specific term. A neo-interaction involving a mutant kinase is not evidence that wild-type SUFU has protein kinase binding activity toward BRAF, so unlike the STK36 and ULK3 rows this one cannot be rescued by a more informative molecular function. No SUFU-BRAF relationship appears in the UniProt FUNCTION or SUBUNIT annotations. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: GOA records this physical-interaction row from a multimodal cell-map dataset; the reported partner is BFSP2. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. BFSP2 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: GOA records this physical-interaction row from a multimodal cell-map dataset; the reported partner is ZNF764. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF764 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: GOA records this physical-interaction row from a multimodal cell-map dataset; the reported partner is ZNF747. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. ZNF747 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: GOA records this physical-interaction row from a multimodal cell-map dataset; the reported partner is MID1IP1. The row asserts only that the two proteins were co-detected, and says nothing about what SUFU does. Reason: Removed because the generic term carries no functional information, not because the measurement is doubted. MID1IP1 is not a documented participant in any SUFU mechanism recorded in the UniProt FUNCTION or SUBUNIT annotations, nor in the Hedgehog literature reviewed here, so there is no evidence-backed molecular function to promote the row to; inventing one from a single large-scale detection is exactly what the curation guidelines forbid. The interaction itself remains available in IntAct and in the UniProt INTERACTION block, where it is a better fit than a GO molecular-function assertion. Supporting Evidence: file:human/SUFU/SUFU-notes.md a bare `protein binding` row |
| GO:0005634 nucleus | EXP PMID:10559945 Mammalian suppressor-of-fused modulates nuclear-cytoplasmic ... | ACCEPT | Summary: The original human SUFU paper localised the protein and showed that it modulates the nuclear-cytoplasmic distribution of GLI1. Reason: Accepted as a functionally relevant location rather than as incidental presence. The nuclear pool does work: SUFU engages GLI1 on DNA (PMID:10559945), and SCF(FBXL17) degrades SUFU specifically in the nucleus to release GLI1 (PMID:27234298), so nuclear SUFU is both an actor and a regulated target there. The shuttling behaviour is the mechanism by which SUFU controls where GLI is allowed to accumulate. Supporting Evidence: PMID:10559945 may affect nuclear-cytoplasmic shuttling of GLI-1 or the activity of GLI-1 in the nucleus PMID:10559945 the gene product interacts physically with the transcriptional effector GLI-1, can sequester GLI-1 in the cytoplasm, but can also interact with GLI-1 on DNA |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference from PTHR10928 node PTN000859153, which carries an IBD for nucleus seeded by Drosophila Su(fu), mouse Sufu and human SUFU. Reason: Accepted. This is a node assertion, not a similarity transfer: the PAINT curator judged that nuclear localisation is ancestral within the Suppressor of fused family and human SUFU descends from that node. Human SUFU appears in the WITH/FROM because its own experimental localisation is one of the descendant evidences used to place the IBD - that is the expected pattern for a gene with direct evidence, and the IBA then adds the further claim that the localisation is inherited rather than vertebrate-specific. Independent human experimental rows (EXP, IDA, IMP) agree. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000859153 · PTN000859153 SUPPORTS TRANSFER PTHR10928 node PTN000859153, placed at taxon:6072 with IBD support seeded by Drosophila Su(fu) (FB:FBgn0005355), mouse Sufu (MGI:MGI:1345643) and human SUFU. Human SUFU appearing among the seeds is expected, not circular: its own experimental annotations are part of the descendant evidence the PAINT curator used to place the node. Supporting Evidence: file:human/SUFU/SUFU-notes.md those experimental rows file:human/SUFU/SUFU-notes.md then says something *additional* |
| GO:0005634 nucleus | IDA PMID:10806483 Gli regulation by the opposing activities of fused and suppr... | ACCEPT | Summary: Murone et al. localised SUFU and GLI in the context of the opposing activities of Fused and Suppressor of fused. Reason: Accepted as a functionally relevant location rather than as incidental presence. The nuclear pool does work: SUFU engages GLI1 on DNA (PMID:10559945), and SCF(FBXL17) degrades SUFU specifically in the nucleus to release GLI1 (PMID:27234298), so nuclear SUFU is both an actor and a regulated target there. The shuttling behaviour is the mechanism by which SUFU controls where GLI is allowed to accumulate. The cached record for this paper is title and citation only, so no supporting_text can be quoted; the localisation it supports is nonetheless recorded in UniProt with an experimental evidence code and is duplicated by four other GOA rows. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation (GO_REF:0000120) assigning nucleus, drawing on an ARBA rule, the mouse orthologue Sufu (Q9Z0P7) and the UniProt subcellular-location vocabulary. Reason: Accepted. The electronic call agrees with four independent human rows including EXP and IMP evidence, and with the PTHR10928 IBD node, so nothing here rests on the automated inference alone. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z0P7 · Sufu SUPPORTS TRANSFER Mouse Sufu carries the same localisation; SUFU is single-copy in both species so there is no paralog ambiguity in the transfer. ARBA:ARBA00026330 SUPPORTS TRANSFER Rule output coincides with direct human experimental evidence. |
| GO:0005634 nucleus | IMP PMID:28965847 Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedg... | ACCEPT | Summary: De Mori et al. examined SUFU localisation in patient fibroblasts and cellular models carrying hypomorphic SUFU missense variants. Reason: Accepted as a functionally relevant location rather than as incidental presence. The nuclear pool does work: SUFU engages GLI1 on DNA (PMID:10559945), and SCF(FBXL17) degrades SUFU specifically in the nucleus to release GLI1 (PMID:27234298), so nuclear SUFU is both an actor and a regulated target there. The shuttling behaviour is the mechanism by which SUFU controls where GLI is allowed to accumulate. This row rests on a human loss-of-function study; the cached record is abstract-only, so the localisation experiment itself is not visible here and no supporting_text is offered, but the conclusion matches every other row for this term. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: An immunofluorescence-based localisation (GO_REF:0000052, the Human Protein Atlas curation stream) placing SUFU in the nucleoplasm. Reason: Accepted. Nucleoplasm is the specific sub-compartment of the nuclear pool that the other five nucleus rows report more coarsely, and it is where a soluble, non-chromatin-bound regulator of a transcription factor would be expected. It adds granularity without asserting anything the nucleus rows do not. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference from PTHR10928 node PTN000859153, which carries an IBD for cytoplasm seeded by Drosophila Su(fu), mouse Sufu and human SUFU. Reason: Accepted as the primary site of the core activity. Sequestration is definitionally a statement about location: SUFU holds GLI1/2/3 in the cytoplasm and thereby blocks their nuclear translocation, so the cytoplasmic pool is where the molecular function is executed. All five curated GO-CAM models that contain SUFU place its protein sequestering activity in the cytoplasm, and the PTHR10928 node carries an IBD for this term. The IBA is a node assertion rather than a pairwise transfer, and the appearance of human SUFU in its own WITH/FROM reflects that its experimental localisation helped place the node. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000859153 · PTN000859153 SUPPORTS TRANSFER PTHR10928 node PTN000859153, placed at taxon:6072 with IBD support seeded by Drosophila Su(fu) (FB:FBgn0005355), mouse Sufu (MGI:MGI:1345643) and human SUFU. Human SUFU appearing among the seeds is expected, not circular: its own experimental annotations are part of the descendant evidence the PAINT curator used to place the node. Supporting Evidence: file:human/SUFU/SUFU-notes.md those experimental rows file:human/SUFU/SUFU-notes.md Independent curator judgment therefore converges on the same |
| GO:0005737 cytoplasm | IDA PMID:10559945 Mammalian suppressor-of-fused modulates nuclear-cytoplasmic ... | ACCEPT | Summary: Kogerman et al. showed that SUFU can sequester GLI1 in the cytoplasm. Reason: Accepted as the primary site of the core activity. Sequestration is definitionally a statement about location: SUFU holds GLI1/2/3 in the cytoplasm and thereby blocks their nuclear translocation, so the cytoplasmic pool is where the molecular function is executed. All five curated GO-CAM models that contain SUFU place its protein sequestering activity in the cytoplasm, and the PTHR10928 node carries an IBD for this term. Supporting Evidence: PMID:10559945 the gene product interacts physically with the transcriptional effector GLI-1, can sequester GLI-1 in the cytoplasm, but can also interact with GLI-1 on DNA |
| GO:0005737 cytoplasm | IDA PMID:10564661 Characterization of the human suppressor of fused, a negativ... | ACCEPT | Summary: Stone et al. described Su(fu) as a cytoplasmic protein and showed that human SUFU binds and represses GLI. Reason: Accepted as the primary site of the core activity. Sequestration is definitionally a statement about location: SUFU holds GLI1/2/3 in the cytoplasm and thereby blocks their nuclear translocation, so the cytoplasmic pool is where the molecular function is executed. All five curated GO-CAM models that contain SUFU place its protein sequestering activity in the cytoplasm, and the PTHR10928 node carries an IBD for this term. Supporting Evidence: PMID:10564661 Drosophila Suppressor of fused (Su(fu)) encodes a novel 468-amino-acid cytoplasmic protein which, by genetic analysis, functions as a negative regulator of the Hedgehog segment polarity pathway. |
| GO:0005737 cytoplasm | IDA PMID:10806483 Gli regulation by the opposing activities of fused and suppr... | ACCEPT | Summary: Murone et al. localised SUFU in the context of Fused/Suppressor-of-fused antagonism. Reason: Accepted as the primary site of the core activity. Sequestration is definitionally a statement about location: SUFU holds GLI1/2/3 in the cytoplasm and thereby blocks their nuclear translocation, so the cytoplasmic pool is where the molecular function is executed. All five curated GO-CAM models that contain SUFU place its protein sequestering activity in the cytoplasm, and the PTHR10928 node carries an IBD for this term. The cached record for this paper is title and citation only, so no supporting_text is quoted; the compartment is independently recorded in UniProt with an experimental evidence code. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation (GO_REF:0000120) assigning cytoplasm from the mouse orthologue Sufu (Q9Z0P7) and the UniProt subcellular-location vocabulary. Reason: Accepted. The electronic call reproduces a location with direct human IDA and IMP support and with an ancestral IBD, so the transfer adds no risk. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z0P7 · Sufu SUPPORTS TRANSFER Mouse Sufu is the single-copy orthologue and carries the same cytoplasmic localisation; no paralog or compartment ambiguity arises. |
| GO:0005737 cytoplasm | IMP PMID:28965847 Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedg... | ACCEPT | Summary: De Mori et al. assessed SUFU distribution in cells carrying hypomorphic SUFU variants. Reason: Accepted as the primary site of the core activity. Sequestration is definitionally a statement about location: SUFU holds GLI1/2/3 in the cytoplasm and thereby blocks their nuclear translocation, so the cytoplasmic pool is where the molecular function is executed. All five curated GO-CAM models that contain SUFU place its protein sequestering activity in the cytoplasm, and the PTHR10928 node carries an IBD for this term. The cached record is abstract-only, so the imaging is not visible here; the conclusion agrees with six other rows for this term. |
| GO:0005737 cytoplasm | NAS PMID:10564661 Characterization of the human suppressor of fused, a negativ... | ACCEPT | Summary: A non-traceable author statement in Stone et al. placing SUFU in the cytoplasm. Reason: Accepted. NAS is the weakest evidence code in this set, but the statement it records is corroborated by three IDA rows, an IMP row, an IEA row and an ancestral IBD for the same term, so there is nothing for the weak code to carry on its own. |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: An ARBA machine-learning rule (ARBA00029243) assigning cytosol to SUFU. Reason: Accepted. Cytosol is the specific compartment of the cytoplasmic pool in which the GLI:SUFU complex is held, and Reactome's reaction-level curation of the Hedgehog pathway assigns SUFU to it consistently across the off-state reactions. This refines rather than duplicates the cytoplasm rows. The electronic call agrees with seven independent Reactome reaction-level assignments. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00029243 SUPPORTS TRANSFER Rule output coincides with Reactome's curated compartment assignment for the same protein in the same reactions. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5610723 | ACCEPT | Summary: Reactome assigns SUFU to the cytosol as a participant in the curated reaction "GLI proteins bind SUFU". Reason: Accepted. Cytosol is the specific compartment of the cytoplasmic pool in which the GLI:SUFU complex is held, and Reactome's reaction-level curation of the Hedgehog pathway assigns SUFU to it consistently across the off-state reactions. This refines rather than duplicates the cytoplasm rows. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5610754 | ACCEPT | Summary: Reactome assigns SUFU to the cytosol as a participant in the curated reaction "GLI3 is partially degraded by the proteasome to yield the GLI3 repressor". Reason: Accepted. Cytosol is the specific compartment of the cytoplasmic pool in which the GLI:SUFU complex is held, and Reactome's reaction-level curation of the Hedgehog pathway assigns SUFU to it consistently across the off-state reactions. This refines rather than duplicates the cytoplasm rows. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5610758 | ACCEPT | Summary: Reactome assigns SUFU to the cytosol as a participant in the curated reaction "GLI1 is degraded by the proteasome after ubiquitination by beta-TrCP". Reason: Accepted. Cytosol is the specific compartment of the cytoplasmic pool in which the GLI:SUFU complex is held, and Reactome's reaction-level curation of the Hedgehog pathway assigns SUFU to it consistently across the off-state reactions. This refines rather than duplicates the cytoplasm rows. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5610760 | ACCEPT | Summary: Reactome assigns SUFU to the cytosol as a participant in the curated reaction "GLI1 is degraded by the proteasome after ubiquitination by ITCH". Reason: Accepted. Cytosol is the specific compartment of the cytoplasmic pool in which the GLI:SUFU complex is held, and Reactome's reaction-level curation of the Hedgehog pathway assigns SUFU to it consistently across the off-state reactions. This refines rather than duplicates the cytoplasm rows. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5610767 | ACCEPT | Summary: Reactome assigns SUFU to the cytosol as a participant in the curated reaction "The intraflagellar transport B (IFT-B) complex is required for the transit of GLI:SUFU complexes to the ciliary tip". Reason: Accepted. Cytosol is the specific compartment of the cytoplasmic pool in which the GLI:SUFU complex is held, and Reactome's reaction-level curation of the Hedgehog pathway assigns SUFU to it consistently across the off-state reactions. This refines rather than duplicates the cytoplasm rows. Note that this reaction is about departure from the cytosol toward the cilium, so the cytosolic assignment refers to the starting pool, which is the same pool the other rows describe. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5635860 | ACCEPT | Summary: Reactome assigns SUFU to the cytosol as a participant in the curated reaction "GLI:SUFU translocates to the ciliary tip in response to Hh signaling". Reason: Accepted. Cytosol is the specific compartment of the cytoplasmic pool in which the GLI:SUFU complex is held, and Reactome's reaction-level curation of the Hedgehog pathway assigns SUFU to it consistently across the off-state reactions. This refines rather than duplicates the cytoplasm rows. |
| GO:0005829 cytosol | TAS Reactome:R-NUL-5610751 | ACCEPT | Summary: Reactome assigns SUFU to the cytosol as a participant in the curated reaction "Gli2is degraded by the proteasome". Reason: Accepted. Cytosol is the specific compartment of the cytoplasmic pool in which the GLI:SUFU complex is held, and Reactome's reaction-level curation of the Hedgehog pathway assigns SUFU to it consistently across the off-state reactions. This refines rather than duplicates the cytoplasm rows. This row is anchored to an R-NUL- reaction, a Reactome inference not assigned to a named species; it is retained because the compartment it asserts is identical to the seven human-curated rows and nothing turns on it. |
| GO:0005929 cilium | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation (GO_REF:0000120) assigning cilium, transferred from the mouse orthologue Sufu (Q9Z0P7) together with the UniProt subcellular-location vocabulary. Reason: Accepted. UniProt records the ciliary location for human SUFU only By similarity, but the compartment is mechanistically load-bearing rather than incidental in the vertebrate implementation of this pathway: the SUFU-GLI3 complex is recruited to cilia in the pathway-off state, which is where efficient GLI3 processing occurs, and Reactome curates the intraflagellar transport of GLI:SUFU between ciliary base and tip as explicit reactions. Independent work on DYRK2 reports abnormal SUFU localisation in Dyrk2-null cells while SMO localisation is unaffected, which is hard to explain unless SUFU is normally a ciliary resident. Accepting a By-similarity compartment is defensible here because three independent curation streams - UniProt, Reactome and the GO-CAM models - place SUFU there. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9Z0P7 · Sufu SUPPORTS TRANSFER Mouse Sufu ciliary localisation is the donor; the same compartment is curated independently by Reactome for the human protein, so the transfer is corroborated rather than standing alone. ARBA:ARBA00028353 SUPPORTS TRANSFER Rule output agrees with the orthologue-based transfer. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Cell projection, cilium file:human/SUFU/SUFU-uniprot.txt smoothened signaling, the SUFU-GLI3 complex is recruited to cilia, file:human/SUFU/SUFU-uniprot.txt Recruited to cilia in response to |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:24311597 Structural basis of SUFU-GLI interaction in human Hedgehog s... | MODIFY | Summary: Cherry et al. measured GLI1-driven reporter transcription in HEK 293 cells transfected with wild-type and interface-mutant SUFU constructs, showing that SUFU represses GLI activity and that specific interface residues are required for it. Reason: The essence is right but the term is the uninformative parent. SUFU regulates transcription in one direction only - it represses - and only at RNA polymerase II promoters driven by GLI transcription factors. There is no evidence anywhere in this record for SUFU raising transcription of anything, so the neutral parent term understates what is known. The child term proposed here is already carried by SUFU with IDA, IEA and TAS evidence and is supported by an IBD at the PTHR10928 ancestral node, so this is a demotion of a redundant parent rather than a new claim. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:24311597 we examined the transcriptional activity of GLI1 in HEK 293 cells transiently transfected with mutated SUFU constructs PMID:24311597 The mutation of Asp159 and Tyr147 had a significant effect on the ability of SUFU to repress GLI, whereas the mutation of Glu376 and His164 had a smaller effect. |
| GO:0006355 regulation of DNA-templated transcription | TAS PMID:10564661 Characterization of the human suppressor of fused, a negativ... | MODIFY | Summary: An author statement in Stone et al. that human SUFU regulates Gli-mediated transcription. Reason: The essence is right but the term is the uninformative parent. SUFU regulates transcription in one direction only - it represses - and only at RNA polymerase II promoters driven by GLI transcription factors. There is no evidence anywhere in this record for SUFU raising transcription of anything, so the neutral parent term understates what is known. The child term proposed here is already carried by SUFU with IDA, IEA and TAS evidence and is supported by an IBD at the PTHR10928 ancestral node, so this is a demotion of a redundant parent rather than a new claim. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:10564661 HSu(fu) was found to repress activity of the zinc-finger transcription factor Gli, which mediates Hedgehog signaling in vertebrates, and to physically interact with Gli, Gli2 and Gli3 |
| GO:0007165 signal transduction | IEA GO_REF:0000117 | MODIFY | Summary: An ARBA machine-learning rule (ARBA00029050) assigning the top-level signal transduction term to SUFU. Reason: The essence is right but the term is so general that it conveys nothing about this protein. SUFU is not a generic signal transducer: its entire documented role is one specific negative step in one specific pathway, and GOA already carries that precise term eight times with IBA, IDA, IEA, IMP and TAS evidence. The guideline that an IEA may legitimately be broader than the experimental picture does not stretch to a term this far up the hierarchy, because 'signal transduction' would be equally true of several thousand human proteins with no shared biology. Modifying rather than removing preserves the intent of the original assignment. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00029050 SOURCE WEAK OR INFERRED The rule identifies the right biology but fires at a level of the ontology that carries no information about SUFU specifically. Proposed replacements: negative regulation of smoothened signaling pathway |
| GO:0007165 signal transduction | TAS PMID:10559945 Mammalian suppressor-of-fused modulates nuclear-cytoplasmic ... | MODIFY | Summary: An author statement in Kogerman et al. that SUFU acts within the Sonic hedgehog signalling pathway. Reason: The essence is right but the term is so general that it conveys nothing about this protein. SUFU is not a generic signal transducer: its entire documented role is one specific negative step in one specific pathway, and GOA already carries that precise term eight times with IBA, IDA, IEA, IMP and TAS evidence. The guideline that an IEA may legitimately be broader than the experimental picture does not stretch to a term this far up the hierarchy, because 'signal transduction' would be equally true of several thousand human proteins with no shared biology. Modifying rather than removing preserves the intent of the original assignment. Proposed replacements: negative regulation of smoothened signaling pathway Supporting Evidence: PMID:10559945 These results show that SUFUH is a conserved negative regulator of GLI-1 signalling that may affect nuclear-cytoplasmic shuttling of GLI-1 or the activity of GLI-1 in the nucleus and thereby modulate cellular responses. |
| GO:0007286 spermatid development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: An Ensembl Compara projection (GO_REF:0000107) of spermatid development onto human SUFU from the rat orthologue Sufu (UniProtKB:A0A8I6A606). Reason: Not absurd, but over-annotated. Tracing the donor shows that the rat annotation is an IEP - inferred from expression pattern - made from PMID:21893610, 'Hedgehog signalling promotes germ cell survival in the rat testis'. Hedgehog signalling genuinely operates in the testis, so a SUFU role there is plausible, which is why this is flagged rather than removed. But an expression correlation in rat establishes only that the gene is present during spermatogenesis; it does not show that SUFU executes a step of spermatid development, and the inference then travels a second time, electronically, into human. Two stacked weak inferences should not produce a tissue-specific developmental process annotation on a human gene. No human or mouse experimental evidence for this term appears anywhere in the record. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:A0A8I6A606 · Sufu SOURCE WEAK OR INFERRED Rat donor annotation is IEP from PMID:21893610, an expression study of Hedgehog signalling in rat testis; expression during a process is not participation in it. Supporting Evidence: file:human/SUFU/SUFU-notes.md Tracing the donor annotations in QuickGO shows both rest on **IEP** |
| GO:0008013 beta-catenin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: An Ensembl Compara projection (GO_REF:0000107) of beta-catenin binding onto human SUFU from the mouse orthologue Sufu (Q9Z0P7). UniProt records the corresponding claims for human SUFU By similarity: part of a complex containing CTNNB1, and possible negative regulation of beta-catenin signalling. Reason: Kept as a non-core molecular function. Unlike generic protein binding this term is informative - it names a specific partner class - and it has a real mouse basis that UniProt propagates to the human entry. But it sits entirely outside the Hedgehog axis that defines SUFU, the human evidence is By similarity rather than direct, and no human experimental row, no PAINT node term and no GO-CAM model in this repository involves SUFU in Wnt signalling. That combination is the definition of a defensible but peripheral annotation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9Z0P7 · Sufu SUPPORTS TRANSFER Mouse Sufu is the donor for both the CTNNB1 complex and the beta-catenin regulatory role; the transfer is orthologue-to-orthologue in a single-copy family, but the claim has no independent human support. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Part of a complex containing CTNNB1 (By similarity). file:human/SUFU/SUFU-uniprot.txt May also act as a negative regulator of beta-catenin |
| GO:0010954 positive regulation of protein processing | IEA GO_REF:0000107 | ACCEPT | Summary: An Ensembl Compara projection (GO_REF:0000107) from mouse Sufu of a role in promoting protein processing. The referent is GLI3: in the pathway-off state the SUFU-GLI3 complex is recruited to cilia and SUFU promotes the recruitment of GSK3B to GLI3, driving efficient proteolytic conversion of full-length GLI3 into the repressor form GLI3R. Reason: Accepted as core, and it passes the participation test explicitly. SUFU is not merely required for GLI3 processing and is not the substrate of it - GLI3 is. SUFU does part of the work: it holds GLI3 and recruits the kinase that marks it, which is the scaffolding contribution that GO counts as participation. The human evidence is direct rather than purely orthologous: De Mori et al. showed that hypomorphic human SUFU variants reduce the capacity to bind GLI3 and promote its cleavage into GLI3R, which is a loss-of-function test of exactly this claim in human cells. This is also the one SUFU activity that is genuinely separable from sequestration, which is why it is given its own core function below. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z0P7 · Sufu SUPPORTS TRANSFER Mouse Sufu is the donor, but the transferred claim is independently established in human cells by PMID:28965847, so the row does not rest on the projection. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 file:human/SUFU/SUFU-uniprot.txt leading to the efficient processing of full-length GLI3 into PMID:28965847 Functional studies on cellular models and fibroblasts showed that both variants significantly reduced SUFU stability and its capacity to bind GLI3 and promote its cleavage into the repressor form GLI3R. |
| GO:0019901 protein kinase binding | IPI PMID:20643644 Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic he... | ACCEPT | Summary: Maloverjan et al. showed that ULK3 interacts with SUFU through its kinase domain, and that SUFU in turn blocks ULK3 autophosphorylation and its ability to phosphorylate and activate GLI proteins. UniProt records the interaction with that consequence. Reason: Accepted. This is an informative binding term with a named kinase partner and a documented functional consequence, which is precisely the standard that bare protein binding fails. Note the direction: SUFU inhibits the kinase rather than being its substrate, and the SUFU-ULK3 complex promotes formation of the GLI2 repressor, so the interaction serves the same negative-regulatory role as the rest of SUFU's biology. It is the anchor for the two STK36 protein-binding rows modified to this same term. Supporting Evidence: PMID:20643644 We demonstrate that Ulk3 through its kinase domain interacts with Suppressor of Fused (Sufu), a protein required for negative regulation of Gli proteins. PMID:20643644 Sufu blocks Ulk3 autophosphorylation and abolishes its ability to phosphorylate and positively regulate Gli proteins. PMID:20643644 We demonstrate that the Sufu-Ulk3 complex, when co-expressed with Gli2, promotes generation of the Gli2 repressor form file:human/SUFU/SUFU-uniprot.txt Interacts with ULK3; inactivating the protein kinase |
| GO:0030674 protein-macromolecule adaptor activity | IEA GO_REF:0000107 | ACCEPT | Summary: An Ensembl Compara projection (GO_REF:0000107) from mouse Sufu of adaptor activity. The underlying biology is that SUFU physically bridges GLI to the enzymes that act on it - GSK3B for GLI3 processing, and the Slimb/BTRC-dependent degradation machinery. Reason: Accepted as core. This is the term the curation guidelines point to as the informative alternative to generic protein binding, and it is the one molecular function that captures what SUFU does beyond holding GLI still. The claim is not only orthologous: Stone et al. proposed the adaptor reading from human data in the original characterisation, describing SUFU as linking Gli to the Slimb-dependent proteasomal degradation pathway, and UniProt records the GSK3B-recruitment mechanism for GLI3 processing. Together with GO:0010954 this forms the second of the two core functions. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z0P7 · Sufu SUPPORTS TRANSFER Mouse Sufu is the donor, but the adaptor reading originates in human work (PMID:10564661) and the GSK3B-recruitment mechanism is recorded for human SUFU in UniProt, so the transfer restates rather than introduces the claim. Supporting Evidence: PMID:10564661 The data further suggest that Su(fu) can act by binding to Gli and inhibiting Gli-mediated transactivation as well as by serving as an adaptor protein, which links Gli to the Slimb-dependent proteasomal degradation pathway. file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 |
| GO:0042308 negative regulation of protein import into nucleus | TAS PMID:11001584 The sonic hedgehog-patched-gli pathway in human development ... | ACCEPT | Summary: A GOA row from the Villavicencio et al. review, asserting that SUFU negatively regulates nuclear import. The referent is GLI: SUFU holds GLI1/2/3 in the cytoplasm and thereby blocks their translocation into the nucleus. Reason: Accepted. This is the process-level statement of the sequestering activity, and it is directly evidenced rather than inferred: Yoshida et al. state plainly that SUFU inhibits Hedgehog signalling by retaining GLI2 and GLI3 in the cytoplasm and blocking their nuclear translocation, and the same paper shows that relieving the interaction by phosphorylation permits translocation. A negative-regulation term is the correct construction here: nuclear import is performed by the import machinery, and SUFU regulates whether GLI is available to it. The cached record for the cited review is citation metadata only, so the supporting text is taken from the primary literature and attributed to it. Supporting Evidence: PMID:38968120 Another negative regulator, SUFU, inhibits Hh signaling by retaining GLI2 and GLI3 in the cytoplasm and blocking their nuclear translocation. PMID:38968120 This phosphorylation induces the dissociation of GLI2/GLI3 from suppressor, SUFU, and their translocation into the nucleus. PMID:10559945 may affect nuclear-cytoplasmic shuttling of GLI-1 or the activity of GLI-1 in the nucleus |
| GO:0045668 negative regulation of osteoblast differentiation | TAS PMID:11001584 The sonic hedgehog-patched-gli pathway in human development ... | KEEP AS NON CORE | Summary: A GOA row from the Villavicencio et al. review. The underlying experimental observation is in Kogerman et al., who showed that SUFU inhibits osteogenic differentiation in response to Sonic hedgehog signalling; UniProt additionally notes SUFU expression in osteoblasts of the perichondrium in the developing limb. Reason: Kept, but non-core. The observation is real and is human, so removal would be wrong. It is nevertheless a downstream tissue-level consequence of SUFU restraining GLI activity in a particular cell type, not a distinct thing SUFU does: the molecular event is the same GLI-sequestering step already annotated, read out through an osteogenic differentiation assay. SUFU has no osteoblast-specific mechanism and no bone-restricted partner in the record. This is the standard treatment for the developmental outputs of a pleiotropic signalling regulator. Supporting Evidence: PMID:10559945 Functionally, SUFUH inhibits transcriptional activation by GLI-1, as well as osteogenic differentiation in response to signalling from Sonic hedgehog. |
| GO:0045879 negative regulation of smoothened signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference from PTHR10928 node PTN000859153, with IBD support seeded by Drosophila Su(fu) (FB:FBgn0005355), mouse Sufu (MGI:MGI:1345643), zebrafish sufu and human SUFU. Reason: Accepted as the core biological process. This is the term that every independent line of evidence converges on: eight GOA rows spanning IBA, IDA, IEA, IMP and TAS; an IBD at the PTHR10928 ancestral node PTN000859153 seeded by fly, mouse, zebrafish and human; the sufu_sequestration annoton of the hedgehog_signaling module; and all five curated human GO-CAM models that contain SUFU. Nothing in the literature reviewed here contradicts it. As a node assertion this IBA says something the experimental rows do not: that negative regulation of Smoothened signalling is ancestral within the family rather than a vertebrate innovation. That is a meaningful additional claim given that the fly protein is dispensable for embryogenesis while the mammalian one is essential - the difference is in phenotypic weight, not in mechanism. Human SUFU in the WITH/FROM is expected: its own experimental annotations are among the descendant evidences behind the IBD. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000859153 · PTN000859153 SUPPORTS TRANSFER PTHR10928 node PTN000859153, placed at taxon:6072 with IBD support seeded by Drosophila Su(fu) (FB:FBgn0005355), mouse Sufu (MGI:MGI:1345643) and human SUFU. Human SUFU appearing among the seeds is expected, not circular: its own experimental annotations are part of the descendant evidence the PAINT curator used to place the node. Supporting Evidence: file:human/SUFU/SUFU-notes.md those experimental rows file:human/SUFU/SUFU-notes.md then says something *additional* |
| GO:0045879 negative regulation of smoothened signaling pathway | IDA PMID:10559945 Mammalian suppressor-of-fused modulates nuclear-cytoplasmic ... | ACCEPT | Summary: Kogerman et al. showed that SUFU inhibits GLI1-driven transcription and osteogenic differentiation downstream of Sonic hedgehog, and concluded that it is a conserved negative regulator of GLI1 signalling. Reason: Accepted as the core biological process. This is the term that every independent line of evidence converges on: eight GOA rows spanning IBA, IDA, IEA, IMP and TAS; an IBD at the PTHR10928 ancestral node PTN000859153 seeded by fly, mouse, zebrafish and human; the sufu_sequestration annoton of the hedgehog_signaling module; and all five curated human GO-CAM models that contain SUFU. Nothing in the literature reviewed here contradicts it. Supporting Evidence: PMID:10559945 These results show that SUFUH is a conserved negative regulator of GLI-1 signalling that may affect nuclear-cytoplasmic shuttling of GLI-1 or the activity of GLI-1 in the nucleus and thereby modulate cellular responses. PMID:10559945 Functionally, SUFUH inhibits transcriptional activation by GLI-1, as well as osteogenic differentiation in response to signalling from Sonic hedgehog. |
| GO:0045879 negative regulation of smoothened signaling pathway | IDA PMID:35831023 ERK2 MAP kinase regulates SUFU binding by multisite phosphor... | ACCEPT | Summary: Bardwell et al. showed that ERK2-mediated phosphorylation of GLI1 on three conserved sites weakens GLI1-SUFU binding by more than 25-fold, and that phosphomimetic GLI1 drives more transcription - a quantitative demonstration that the SUFU-GLI1 interaction is what holds pathway output down. Reason: Accepted as the core biological process. This is the term that every independent line of evidence converges on: eight GOA rows spanning IBA, IDA, IEA, IMP and TAS; an IBD at the PTHR10928 ancestral node PTN000859153 seeded by fly, mouse, zebrafish and human; the sufu_sequestration annoton of the hedgehog_signaling module; and all five curated human GO-CAM models that contain SUFU. Nothing in the literature reviewed here contradicts it. The paper's title foregrounds ERK2, but SUFU is directly assayed throughout: the binding affinity being measured is SUFU's, and the curator's IDA reflects that. This is the kind of case where the title names one partner while the experiments characterise both. Supporting Evidence: PMID:35831023 Here we show that MAP kinase-mediated phosphorylation weakens the binding of the GLI1 transcription factor to its negative regulator SUFU. PMID:35831023 these phosphorylations cooperate to weaken the affinity of GLI1-SUFU binding by over 25-fold |
| GO:0045879 negative regulation of smoothened signaling pathway | IDA PMID:38968120 Positive regulation of Hedgehog signaling via phosphorylatio... | ACCEPT | Summary: Yoshida et al. showed that DYRK2 phosphorylates conserved serines in GLI2 and GLI3 at the ciliary base in a SMO-activation-dependent manner, that this triggers their dissociation from SUFU and nuclear translocation, and - by surface plasmon resonance on phosphorylated and unphosphorylated GLI3 peptides - that the phosphorylation directly weakens SUFU binding. Reason: Accepted as the core biological process. This is the term that every independent line of evidence converges on: eight GOA rows spanning IBA, IDA, IEA, IMP and TAS; an IBD at the PTHR10928 ancestral node PTN000859153 seeded by fly, mouse, zebrafish and human; the sufu_sequestration annoton of the hedgehog_signaling module; and all five curated human GO-CAM models that contain SUFU. Nothing in the literature reviewed here contradicts it. Again the title names the kinase, but SUFU is measured directly: SUFU is the analyte in the SPR experiments and the co-immunoprecipitation readout throughout. Supporting Evidence: PMID:38968120 Another negative regulator, SUFU, inhibits Hh signaling by retaining GLI2 and GLI3 in the cytoplasm and blocking their nuclear translocation. PMID:38968120 This phosphorylation induces the dissociation of GLI2/GLI3 from suppressor, SUFU, and their translocation into the nucleus. PMID:38968120 As previously reported (17, 25), the level of SUFU coimmunoprecipitated with GLI3 in wild-type MEFs was substantially decreased by SAG treatment |
| GO:0045879 negative regulation of smoothened signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation (GO_REF:0000120) assigning negative regulation of the smoothened signaling pathway, drawing on an ARBA rule and the mouse orthologue Sufu. Reason: Accepted as the core biological process. This is the term that every independent line of evidence converges on: eight GOA rows spanning IBA, IDA, IEA, IMP and TAS; an IBD at the PTHR10928 ancestral node PTN000859153 seeded by fly, mouse, zebrafish and human; the sufu_sequestration annoton of the hedgehog_signaling module; and all five curated human GO-CAM models that contain SUFU. Nothing in the literature reviewed here contradicts it. The electronic call reproduces a term with five independent experimental rows on the human protein, so it carries no inferential risk. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z0P7 · Sufu SUPPORTS TRANSFER Mouse Sufu is the single-copy orthologue and the pathway role is identical. ARBA:ARBA00086554 SUPPORTS TRANSFER Rule output coincides with direct human experimental evidence and with the ancestral IBD. |
| GO:0045879 negative regulation of smoothened signaling pathway | IMP PMID:27234298 SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signa... | ACCEPT | Summary: Raducu et al. showed that FBXL17-mediated ubiquitylation of SUFU releases GLI1 for signalling, that depleting FBXL17 gives defective Hedgehog signalling with impaired proliferation and medulloblastoma growth, and that a Gorlin-syndrome SUFU mutation which accelerates SUFU turnover produces sustained pathway activation - loss of SUFU raising pathway output is the defining behaviour of a negative regulator. Reason: Accepted as the core biological process. This is the term that every independent line of evidence converges on: eight GOA rows spanning IBA, IDA, IEA, IMP and TAS; an IBD at the PTHR10928 ancestral node PTN000859153 seeded by fly, mouse, zebrafish and human; the sufu_sequestration annoton of the hedgehog_signaling module; and all five curated human GO-CAM models that contain SUFU. Nothing in the literature reviewed here contradicts it. Supporting Evidence: PMID:27234298 Sufu (Suppressor of fused) is a central regulator of Hh (Hedgehog) signaling and acts as a tumor suppressor by maintaining the Gli (Glioma-associated oncogene homolog) transcription factors inactive. PMID:27234298 Depletion of Fbxl17 leads to defective Hh signaling associated with an impaired cancer cell proliferation and medulloblastoma tumor growth. PMID:27234298 we identify a mutation in Sufu, occurring in medulloblastoma of patients with Gorlin syndrome, which increases Sufu turnover through Fbxl17-mediated polyubiquitylation and leads to a sustained Hh signaling activation |
| GO:0045879 negative regulation of smoothened signaling pathway | IMP PMID:28965847 Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedg... | ACCEPT | Summary: De Mori et al. identified homozygous hypomorphic SUFU missense variants in children with Joubert syndrome, showed that the variants reduce SUFU stability and GLI3 binding, and demonstrated the resulting loss of SHH-pathway repression by target-gene expression. Reason: Accepted as the core biological process. This is the term that every independent line of evidence converges on: eight GOA rows spanning IBA, IDA, IEA, IMP and TAS; an IBD at the PTHR10928 ancestral node PTN000859153 seeded by fly, mouse, zebrafish and human; the sufu_sequestration annoton of the hedgehog_signaling module; and all five curated human GO-CAM models that contain SUFU. Nothing in the literature reviewed here contradicts it. This is the strongest human genetic evidence in the record: germline loss-of-function in the negative regulator produces a phenotype with both SHH-pathway and ciliopathy features. Supporting Evidence: PMID:28965847 SUFU is the main negative regulator of the SHH pathway and is essential during development. PMID:28965847 Functional studies on cellular models and fibroblasts showed that both variants significantly reduced SUFU stability and its capacity to bind GLI3 and promote its cleavage into the repressor form GLI3R. PMID:28965847 In turn, this impaired SUFU-mediated repression of the SHH pathway, as shown by altered expression levels of several target genes. |
| GO:0045879 negative regulation of smoothened signaling pathway | TAS PMID:11001584 The sonic hedgehog-patched-gli pathway in human development ... | ACCEPT | Summary: A GOA row from the Villavicencio et al. review, asserting SUFU's negative role in the sonic hedgehog-patched-gli pathway. Reason: Accepted as the core biological process. This is the term that every independent line of evidence converges on: eight GOA rows spanning IBA, IDA, IEA, IMP and TAS; an IBD at the PTHR10928 ancestral node PTN000859153 seeded by fly, mouse, zebrafish and human; the sufu_sequestration annoton of the hedgehog_signaling module; and all five curated human GO-CAM models that contain SUFU. Nothing in the literature reviewed here contradicts it. The cached record for this review holds citation metadata only, so no author statement can be quoted; the row is redundant with seven better-evidenced rows for the same term rather than load-bearing. |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5610766 | ACCEPT | Summary: Reactome places SUFU at the ciliary tip as a participant in the curated reaction "The intraflagellar transport A (IFT-A) complex is required for the transit of GLI:SUFU complexes to the ciliary base". Reason: Accepted. In the vertebrate implementation of this pathway the GLI:SUFU complex is carried by anterograde intraflagellar transport to the ciliary tip on pathway activation, and it is there that the complex disassembles and GLI is released. Reactome curates these as explicit reactions with SUFU as a participant, and UniProt records that SUFU is recruited to cilia in response to Smoothened signalling, leading to dissociation from GLI. The location is therefore where a discrete step of the core mechanism happens, not incidental presence. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Recruited to cilia in response to file:human/SUFU/SUFU-uniprot.txt smoothened signaling, the SUFU-GLI3 complex is recruited to cilia, |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5610767 | ACCEPT | Summary: Reactome places SUFU at the ciliary tip as a participant in the curated reaction "The intraflagellar transport B (IFT-B) complex is required for the transit of GLI:SUFU complexes to the ciliary tip". Reason: Accepted. In the vertebrate implementation of this pathway the GLI:SUFU complex is carried by anterograde intraflagellar transport to the ciliary tip on pathway activation, and it is there that the complex disassembles and GLI is released. Reactome curates these as explicit reactions with SUFU as a participant, and UniProt records that SUFU is recruited to cilia in response to Smoothened signalling, leading to dissociation from GLI. The location is therefore where a discrete step of the core mechanism happens, not incidental presence. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Recruited to cilia in response to file:human/SUFU/SUFU-uniprot.txt smoothened signaling, the SUFU-GLI3 complex is recruited to cilia, |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5635839 | ACCEPT | Summary: Reactome places SUFU at the ciliary tip as a participant in the curated reaction "ULK3:SUFU dissociates". Reason: Accepted. In the vertebrate implementation of this pathway the GLI:SUFU complex is carried by anterograde intraflagellar transport to the ciliary tip on pathway activation, and it is there that the complex disassembles and GLI is released. Reactome curates these as explicit reactions with SUFU as a participant, and UniProt records that SUFU is recruited to cilia in response to Smoothened signalling, leading to dissociation from GLI. The location is therefore where a discrete step of the core mechanism happens, not incidental presence. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Recruited to cilia in response to file:human/SUFU/SUFU-uniprot.txt smoothened signaling, the SUFU-GLI3 complex is recruited to cilia, |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5635859 | ACCEPT | Summary: Reactome places SUFU at the ciliary tip as a participant in the curated reaction "GLI:SUFU dissociates". Reason: Accepted. In the vertebrate implementation of this pathway the GLI:SUFU complex is carried by anterograde intraflagellar transport to the ciliary tip on pathway activation, and it is there that the complex disassembles and GLI is released. Reactome curates these as explicit reactions with SUFU as a participant, and UniProt records that SUFU is recruited to cilia in response to Smoothened signalling, leading to dissociation from GLI. The location is therefore where a discrete step of the core mechanism happens, not incidental presence. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Recruited to cilia in response to file:human/SUFU/SUFU-uniprot.txt smoothened signaling, the SUFU-GLI3 complex is recruited to cilia, |
| GO:0097542 ciliary tip | TAS Reactome:R-HSA-5635860 | ACCEPT | Summary: Reactome places SUFU at the ciliary tip as a participant in the curated reaction "GLI:SUFU translocates to the ciliary tip in response to Hh signaling". Reason: Accepted. In the vertebrate implementation of this pathway the GLI:SUFU complex is carried by anterograde intraflagellar transport to the ciliary tip on pathway activation, and it is there that the complex disassembles and GLI is released. Reactome curates these as explicit reactions with SUFU as a participant, and UniProt records that SUFU is recruited to cilia in response to Smoothened signalling, leading to dissociation from GLI. The location is therefore where a discrete step of the core mechanism happens, not incidental presence. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Recruited to cilia in response to file:human/SUFU/SUFU-uniprot.txt smoothened signaling, the SUFU-GLI3 complex is recruited to cilia, |
| GO:0097546 ciliary base | TAS Reactome:R-HSA-5610720 | ACCEPT | Summary: Reactome places SUFU at the ciliary base as a participant in the curated reaction "PKA phosphorylates GLI3". Reason: Accepted. The ciliary base is where the pathway-off processing cassette operates on the GLI:SUFU complex: retrograde IFT-A transport returns the complex there, the PKA/CK1/GSK3 phosphorylation and beta-TrCP-dependent partial proteolysis that generate GLI3R are curated at that location, and SUFU is a participant in each of those reactions because it is what holds GLI while the kinases act. Independent work places the SMO-dependent DYRK2 phosphorylation of GLI2/GLI3 at the ciliary base as well. This is the compartment in which SUFU's adaptor contribution to GLI3 processing is executed. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 file:human/SUFU/SUFU-uniprot.txt leading to the efficient processing of full-length GLI3 into |
| GO:0097546 ciliary base | TAS Reactome:R-HSA-5610722 | ACCEPT | Summary: Reactome places SUFU at the ciliary base as a participant in the curated reaction "CK1 phosphorylates p-GLI3". Reason: Accepted. The ciliary base is where the pathway-off processing cassette operates on the GLI:SUFU complex: retrograde IFT-A transport returns the complex there, the PKA/CK1/GSK3 phosphorylation and beta-TrCP-dependent partial proteolysis that generate GLI3R are curated at that location, and SUFU is a participant in each of those reactions because it is what holds GLI while the kinases act. Independent work places the SMO-dependent DYRK2 phosphorylation of GLI2/GLI3 at the ciliary base as well. This is the compartment in which SUFU's adaptor contribution to GLI3 processing is executed. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 file:human/SUFU/SUFU-uniprot.txt leading to the efficient processing of full-length GLI3 into |
| GO:0097546 ciliary base | TAS Reactome:R-HSA-5610732 | ACCEPT | Summary: Reactome places SUFU at the ciliary base as a participant in the curated reaction "GSK3 phosphorylates p-GLI3". Reason: Accepted. The ciliary base is where the pathway-off processing cassette operates on the GLI:SUFU complex: retrograde IFT-A transport returns the complex there, the PKA/CK1/GSK3 phosphorylation and beta-TrCP-dependent partial proteolysis that generate GLI3R are curated at that location, and SUFU is a participant in each of those reactions because it is what holds GLI while the kinases act. Independent work places the SMO-dependent DYRK2 phosphorylation of GLI2/GLI3 at the ciliary base as well. This is the compartment in which SUFU's adaptor contribution to GLI3 processing is executed. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 file:human/SUFU/SUFU-uniprot.txt leading to the efficient processing of full-length GLI3 into |
| GO:0097546 ciliary base | TAS Reactome:R-HSA-5610737 | ACCEPT | Summary: Reactome places SUFU at the ciliary base as a participant in the curated reaction "NUMB:ITCH bind and ubiquitnate GLI1". Reason: Accepted. The ciliary base is where the pathway-off processing cassette operates on the GLI:SUFU complex: retrograde IFT-A transport returns the complex there, the PKA/CK1/GSK3 phosphorylation and beta-TrCP-dependent partial proteolysis that generate GLI3R are curated at that location, and SUFU is a participant in each of those reactions because it is what holds GLI while the kinases act. Independent work places the SMO-dependent DYRK2 phosphorylation of GLI2/GLI3 at the ciliary base as well. This is the compartment in which SUFU's adaptor contribution to GLI3 processing is executed. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 file:human/SUFU/SUFU-uniprot.txt leading to the efficient processing of full-length GLI3 into |
| GO:0097546 ciliary base | TAS Reactome:R-HSA-5610742 | ACCEPT | Summary: Reactome places SUFU at the ciliary base as a participant in the curated reaction "SCF(beta-TrCP) ubiquitinates p-GLI1". Reason: Accepted. The ciliary base is where the pathway-off processing cassette operates on the GLI:SUFU complex: retrograde IFT-A transport returns the complex there, the PKA/CK1/GSK3 phosphorylation and beta-TrCP-dependent partial proteolysis that generate GLI3R are curated at that location, and SUFU is a participant in each of those reactions because it is what holds GLI while the kinases act. Independent work places the SMO-dependent DYRK2 phosphorylation of GLI2/GLI3 at the ciliary base as well. This is the compartment in which SUFU's adaptor contribution to GLI3 processing is executed. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 file:human/SUFU/SUFU-uniprot.txt leading to the efficient processing of full-length GLI3 into |
| GO:0097546 ciliary base | TAS Reactome:R-HSA-5610746 | ACCEPT | Summary: Reactome places SUFU at the ciliary base as a participant in the curated reaction "SCF(beta-TrCP) ubiquitinates p-GLI3". Reason: Accepted. The ciliary base is where the pathway-off processing cassette operates on the GLI:SUFU complex: retrograde IFT-A transport returns the complex there, the PKA/CK1/GSK3 phosphorylation and beta-TrCP-dependent partial proteolysis that generate GLI3R are curated at that location, and SUFU is a participant in each of those reactions because it is what holds GLI while the kinases act. Independent work places the SMO-dependent DYRK2 phosphorylation of GLI2/GLI3 at the ciliary base as well. This is the compartment in which SUFU's adaptor contribution to GLI3 processing is executed. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 file:human/SUFU/SUFU-uniprot.txt leading to the efficient processing of full-length GLI3 into |
| GO:0097546 ciliary base | TAS Reactome:R-HSA-5610754 | ACCEPT | Summary: Reactome places SUFU at the ciliary base as a participant in the curated reaction "GLI3 is partially degraded by the proteasome to yield the GLI3 repressor". Reason: Accepted. The ciliary base is where the pathway-off processing cassette operates on the GLI:SUFU complex: retrograde IFT-A transport returns the complex there, the PKA/CK1/GSK3 phosphorylation and beta-TrCP-dependent partial proteolysis that generate GLI3R are curated at that location, and SUFU is a participant in each of those reactions because it is what holds GLI while the kinases act. Independent work places the SMO-dependent DYRK2 phosphorylation of GLI2/GLI3 at the ciliary base as well. This is the compartment in which SUFU's adaptor contribution to GLI3 processing is executed. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 file:human/SUFU/SUFU-uniprot.txt leading to the efficient processing of full-length GLI3 into |
| GO:0097546 ciliary base | TAS Reactome:R-HSA-5610758 | ACCEPT | Summary: Reactome places SUFU at the ciliary base as a participant in the curated reaction "GLI1 is degraded by the proteasome after ubiquitination by beta-TrCP". Reason: Accepted. The ciliary base is where the pathway-off processing cassette operates on the GLI:SUFU complex: retrograde IFT-A transport returns the complex there, the PKA/CK1/GSK3 phosphorylation and beta-TrCP-dependent partial proteolysis that generate GLI3R are curated at that location, and SUFU is a participant in each of those reactions because it is what holds GLI while the kinases act. Independent work places the SMO-dependent DYRK2 phosphorylation of GLI2/GLI3 at the ciliary base as well. This is the compartment in which SUFU's adaptor contribution to GLI3 processing is executed. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 file:human/SUFU/SUFU-uniprot.txt leading to the efficient processing of full-length GLI3 into |
| GO:0097546 ciliary base | TAS Reactome:R-HSA-5610760 | ACCEPT | Summary: Reactome places SUFU at the ciliary base as a participant in the curated reaction "GLI1 is degraded by the proteasome after ubiquitination by ITCH". Reason: Accepted. The ciliary base is where the pathway-off processing cassette operates on the GLI:SUFU complex: retrograde IFT-A transport returns the complex there, the PKA/CK1/GSK3 phosphorylation and beta-TrCP-dependent partial proteolysis that generate GLI3R are curated at that location, and SUFU is a participant in each of those reactions because it is what holds GLI while the kinases act. Independent work places the SMO-dependent DYRK2 phosphorylation of GLI2/GLI3 at the ciliary base as well. This is the compartment in which SUFU's adaptor contribution to GLI3 processing is executed. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 file:human/SUFU/SUFU-uniprot.txt leading to the efficient processing of full-length GLI3 into |
| GO:0097546 ciliary base | TAS Reactome:R-HSA-5610766 | ACCEPT | Summary: Reactome places SUFU at the ciliary base as a participant in the curated reaction "The intraflagellar transport A (IFT-A) complex is required for the transit of GLI:SUFU complexes to the ciliary base". Reason: Accepted. The ciliary base is where the pathway-off processing cassette operates on the GLI:SUFU complex: retrograde IFT-A transport returns the complex there, the PKA/CK1/GSK3 phosphorylation and beta-TrCP-dependent partial proteolysis that generate GLI3R are curated at that location, and SUFU is a participant in each of those reactions because it is what holds GLI while the kinases act. Independent work places the SMO-dependent DYRK2 phosphorylation of GLI2/GLI3 at the ciliary base as well. This is the compartment in which SUFU's adaptor contribution to GLI3 processing is executed. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt promoting recruitment of GSK3B to GLI3 file:human/SUFU/SUFU-uniprot.txt leading to the efficient processing of full-length GLI3 into |
| GO:0097730 non-motile cilium | IEA GO_REF:0000107 | ACCEPT | Summary: An Ensembl Compara projection (GO_REF:0000107) of non-motile cilium onto human SUFU from the mouse orthologue Sufu (Q9Z0P7). Reason: Accepted. This is the correct refinement of the parent cilium annotation: Hedgehog signalling in vertebrates runs through the primary cilium, which is non-motile, and the SUFU-relevant events - IFT transport of GLI:SUFU, ciliary-base GLI3 processing, tip dissociation - are all primary-cilium biology. The SUFU-related ciliopathy phenotype (Joubert syndrome with the molar tooth sign) is itself a primary-cilium disorder, which is independent human support for the compartment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9Z0P7 · Sufu SUPPORTS TRANSFER Mouse Sufu is the donor; the refinement from cilium to non-motile cilium is consistent with the vertebrate primary-cilium implementation of the pathway in both species. Supporting Evidence: file:human/SUFU/SUFU-uniprot.txt Cell projection, cilium file:human/SUFU/SUFU-uniprot.txt smoothened signaling, the SUFU-GLI3 complex is recruited to cilia, |
| GO:0140311 protein sequestering activity | IDA PMID:10559945 Mammalian suppressor-of-fused modulates nuclear-cytoplasmic ... | ACCEPT | Summary: Kogerman et al. showed that human SUFU binds GLI1 and can sequester it in the cytoplasm, the observation that named the activity. Reason: Accepted as the core molecular function. SUFU has no catalytic domain and no enzymatic activity; what it does is bind full-length GLI1/GLI2/GLI3 through a defined interface and hold them out of productive service. Zhang et al. showed that disrupting that single interface simultaneously abolishes transcriptional repression, cytoplasmic tethering and protection from proteasomal degradation, which establishes that these are three readouts of one sequestering event rather than three separate activities. The term carries an IBD at the PTHR10928 ancestral node, is the molecular function of the sufu_sequestration annoton in the hedgehog_signaling module, and is the molecular function assigned to SUFU in all five curated human GO-CAM models. Supporting Evidence: PMID:10559945 the gene product interacts physically with the transcriptional effector GLI-1, can sequester GLI-1 in the cytoplasm, but can also interact with GLI-1 on DNA PMID:24217340 Mutations of critical interface residues disrupt the Sufu-Gli complex and prevent Sufu from repressing Gli-mediated transcription, tethering Gli in the cytoplasm and protecting Gli from the 26S proteasome-mediated degradation. |
| GO:0140311 protein sequestering activity | IDA PMID:24311597 Structural basis of SUFU-GLI interaction in human Hedgehog s... | ACCEPT | Summary: Cherry et al. determined the crystal and SAXS structures of full-length human SUFU alone and bound to the conserved GLI SYGHL motif, showing that GLI binding drives a large conformational change in which the N- and C-terminal domains clamp the GLI peptide. Reason: Accepted as the core molecular function. SUFU has no catalytic domain and no enzymatic activity; what it does is bind full-length GLI1/GLI2/GLI3 through a defined interface and hold them out of productive service. Zhang et al. showed that disrupting that single interface simultaneously abolishes transcriptional repression, cytoplasmic tethering and protection from proteasomal degradation, which establishes that these are three readouts of one sequestering event rather than three separate activities. The term carries an IBD at the PTHR10928 ancestral node, is the molecular function of the sufu_sequestration annoton in the hedgehog_signaling module, and is the molecular function assigned to SUFU in all five curated human GO-CAM models. This row supplies the structural basis: sequestration here is a physical clamp around a short conserved motif, not a vague association. Supporting Evidence: PMID:24311597 SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. PMID:24311597 Upon GLI binding, SUFU undergoes a large conformational change in which the N- and C-terminal domains come together to clamp highly conserved GLI residues PMID:24311597 the minimal SUFU binding motif in GLI encompasses the amino acids SYGHL |
| GO:0140311 protein sequestering activity | IDA PMID:35831023 ERK2 MAP kinase regulates SUFU binding by multisite phosphor... | ACCEPT | Summary: Bardwell et al. measured the affinity of the GLI1-SUFU interaction directly and showed that ERK2 phosphorylation of three conserved GLI1 serines weakens it by over 25-fold, with a corresponding increase in GLI1-driven transcription. Reason: Accepted as the core molecular function. SUFU has no catalytic domain and no enzymatic activity; what it does is bind full-length GLI1/GLI2/GLI3 through a defined interface and hold them out of productive service. Zhang et al. showed that disrupting that single interface simultaneously abolishes transcriptional repression, cytoplasmic tethering and protection from proteasomal degradation, which establishes that these are three readouts of one sequestering event rather than three separate activities. The term carries an IBD at the PTHR10928 ancestral node, is the molecular function of the sufu_sequestration annoton in the hedgehog_signaling module, and is the molecular function assigned to SUFU in all five curated human GO-CAM models. Quantifying how much the interaction must be weakened to release GLI is a direct measurement of the sequestering activity itself. Supporting Evidence: PMID:35831023 Here we show that MAP kinase-mediated phosphorylation weakens the binding of the GLI1 transcription factor to its negative regulator SUFU. PMID:35831023 these phosphorylations cooperate to weaken the affinity of GLI1-SUFU binding by over 25-fold |
| GO:0140311 protein sequestering activity | IDA PMID:38968120 Positive regulation of Hedgehog signaling via phosphorylatio... | ACCEPT | Summary: Yoshida et al. measured SUFU binding to phosphorylated and unphosphorylated GLI3 peptides by surface plasmon resonance and followed SUFU-GLI3 co-immunoprecipitation on pathway activation, showing that SUFU retains GLI2/GLI3 in the cytoplasm until DYRK2 phosphorylation releases them. Reason: Accepted as the core molecular function. SUFU has no catalytic domain and no enzymatic activity; what it does is bind full-length GLI1/GLI2/GLI3 through a defined interface and hold them out of productive service. Zhang et al. showed that disrupting that single interface simultaneously abolishes transcriptional repression, cytoplasmic tethering and protection from proteasomal degradation, which establishes that these are three readouts of one sequestering event rather than three separate activities. The term carries an IBD at the PTHR10928 ancestral node, is the molecular function of the sufu_sequestration annoton in the hedgehog_signaling module, and is the molecular function assigned to SUFU in all five curated human GO-CAM models. Supporting Evidence: PMID:38968120 Another negative regulator, SUFU, inhibits Hh signaling by retaining GLI2 and GLI3 in the cytoplasm and blocking their nuclear translocation. PMID:38968120 As previously reported (17, 25), the level of SUFU coimmunoprecipitated with GLI3 in wild-type MEFs was substantially decreased by SAG treatment |
| GO:0140311 protein sequestering activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation (GO_REF:0000120) assigning protein sequestering activity, drawing on an ARBA rule and the mouse orthologue Sufu. Reason: Accepted as the core molecular function. SUFU has no catalytic domain and no enzymatic activity; what it does is bind full-length GLI1/GLI2/GLI3 through a defined interface and hold them out of productive service. Zhang et al. showed that disrupting that single interface simultaneously abolishes transcriptional repression, cytoplasmic tethering and protection from proteasomal degradation, which establishes that these are three readouts of one sequestering event rather than three separate activities. The term carries an IBD at the PTHR10928 ancestral node, is the molecular function of the sufu_sequestration annoton in the hedgehog_signaling module, and is the molecular function assigned to SUFU in all five curated human GO-CAM models. The electronic call reproduces a term with four independent human IDA rows and an ancestral IBD behind it. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9Z0P7 · Sufu SUPPORTS TRANSFER Mouse Sufu is the single-copy orthologue with the same activity. ARBA:ARBA00095259 SUPPORTS TRANSFER Rule output coincides with four human IDA rows for the same term. |
| GO:1990788 GLI-SUFU complex | IPI PMID:24311597 Structural basis of SUFU-GLI interaction in human Hedgehog s... | ACCEPT | Summary: Cherry et al. reconstituted and crystallised the human SUFU-GLI complex, defining the interface and the conserved SYGHL motif in GLI that SUFU clamps. Reason: Accepted. The GLI-SUFU complex is not an incidental co-purification but the physical entity through which SUFU acts: it is what Reactome transports between ciliary base and tip, what the kinases disassemble, and what the GO-CAM models instantiate. Two independent co-structures define it. Recording SUFU as part_of this complex is the cellular-component counterpart of its protein sequestering activity. Supporting Evidence: PMID:24311597 Upon GLI binding, SUFU undergoes a large conformational change in which the N- and C-terminal domains come together to clamp highly conserved GLI residues PMID:24311597 the minimal SUFU binding motif in GLI encompasses the amino acids SYGHL PMID:24217340 reveal that Sufu alternates between 'open' and 'closed' conformations |
| GO:2001040 positive regulation of cellular response to drug | IEA GO_REF:0000107 | REMOVE | Summary: An Ensembl Compara projection (GO_REF:0000107) onto human SUFU from the rat orthologue Sufu (UniProtKB:A0A8I6A606). Reason: Removed. Tracing the donor shows the rat annotation is an IEP - inferred from expression pattern - made from PMID:30790292, a study reporting that Oroxylin A increases the sensitivity of glioma cells to temozolomide via an HIF-1alpha/Hedgehog axis under hypoxia. That is a cell-line pharmacology observation, not a physiological function, and it has been propagated twice: first into a process annotation on the rat gene on expression evidence alone, then electronically into human. Nothing in the human record - no experimental row, no PAINT node term, no GO-CAM model, no UniProt statement - supports human SUFU having a role in drug response. This is distinct from the spermatid-development row, which is flagged rather than removed because a testis role is at least biologically coherent for a Hedgehog regulator; a positive role in cellular drug response is not a function this protein can be said to have. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:A0A8I6A606 · Sufu SOURCE WEAK OR INFERRED Rat donor annotation is IEP from PMID:30790292, a glioma chemosensitisation study; an expression change under drug treatment does not establish a regulatory function. Supporting Evidence: file:human/SUFU/SUFU-notes.md Tracing the donor annotations in QuickGO shows both rest on **IEP** |
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Download this section (compressed HTML)Q: Four kinases - STK36, ULK3, DYRK2 and ERK2 - plus S6K1 have each been shown to weaken the SUFU-GLI interface. Are these redundant, sequential, or cell-type-specific routes to the same release event, and which of them carries a normal Hedgehog response in a given human tissue?
Q: Is the DNA-bound corepressor role of SUFU, via the SAP18/SIN3 complex, a genuine human mechanism or an artefact of overexpression? The answer decides whether transcription corepressor activity is a secondary SUFU function or should be removed from the record.
Q: SUFU inhibits ULK3 kinase activity rather than being its substrate. Is inhibition of a Fused-family kinase a general SUFU activity that deserves its own molecular-function annotation, or is ULK3 a special case?
Q: Human SUFU has two abundant isoforms differing by a 52-residue C-terminal extension, with isoform 2 enriched in fetal testis. Do they differ in GLI affinity, ciliary recruitment, or susceptibility to SCF(FBXL17)? No GOA row is currently isoform-qualified.
Experiment: Use the interface and IDR mutants already characterised structurally (for example the Tyr147/Asp159/Glu376 interface substitutions and the IDR deletion) in SUFU-null cells, and score sequestration (GLI1 nuclear/cytoplasmic ratio, co-immunoprecipitation) and GLI3R production (GLI3FL:GLI3R ratio by immunoblot) as independent readouts. A mutant that preserves binding but loses GSK3B recruitment would establish the adaptor role as a distinct molecular function rather than a consequence of holding GLI3.
Hypothesis: The GLI3-processing (adaptor) function of SUFU is genetically separable from its GLI-sequestering function.
Type: structure-guided mutagenesis with paired functional readouts
Experiment: In a single cell background, combinatorially deplete STK36, ULK3, DYRK2 and ERK2 and measure endogenous SUFU-GLI1, SUFU-GLI2 and SUFU-GLI3 complex occupancy by proximity ligation and co-immunoprecipitation after SMO agonist stimulation, alongside phospho-site specific antibodies for the known target serines. Redundancy predicts that no single depletion blocks release; specialisation predicts paralog-selective effects.
Hypothesis: The four kinase routes to SUFU-GLI dissociation act on different GLI paralogs or in different cell contexts rather than redundantly.
Type: combinatorial depletion with endogenous complex quantification
Experiment: Perform SUFU and GLI1 ChIP or CUT&RUN in cells with an intact Hedgehog response, and repeat in cells expressing a SUFU variant that cannot be ubiquitylated at Lys-257. If SUFU occupies GLI target promoters independently of its turnover, the transcription corepressor annotation is supported directly in human cells; if SUFU occupancy tracks only with GLI1 abundance, the corepressor reading should be dropped.
Hypothesis: The nuclear pool of SUFU acts on chromatin-bound GLI rather than simply being a staging compartment for SCF(FBXL17)-mediated turnover.
Type: chromatin occupancy profiling
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