GLIS2 is a GLIS-family protein with five C2H2 zinc fingers. It binds regulatory DNA and acts predominantly in the nucleus. Promoter context permits activation or repression. Corepressor and beta-catenin interactions contribute to its regulatory activity. GLIS2 supports renal epithelial homeostasis, and biallelic disruption is associated with nephronophthisis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Retain context-dependent transcriptional repression. Reason: Human GLIS2 descends from Bilateria AN224/PTN008571319. Mouse Glis2 grounds this assertion; primary evidence supports reporter repression. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Reason: Reporter repression supports the mouse transfer; preserve the Gli1-stimulated GlisBS context. Supporting Evidence: |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Reason: Reporter repression supports the mouse transfer; preserve the Gli1-stimulated GlisBS context. Supporting Evidence: |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | TOO GENERAL | Reason: The existing polymerase-II cis-regulatory binding term is a verified descendant; retain the orthology context at that specific resolution. |
| GO:0000976 transcription cis-regulatory region binding | ISS GO_REF:0000024 | TOO GENERAL | Reason: The existing polymerase-II cis-regulatory binding term is a verified descendant; retain the orthology context at that specific resolution. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IEA GO_REF:0000120 | TOO GENERAL | Summary: Broader regulatory-DNA binding is already covered. Reason: Accepted GO:0000978 is a verified is_a descendant. This broader polymerase-II regulatory-DNA label adds no distinct coverage; retain all mouse, Ensembl and InterPro supports. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Retain inherited regulatory-DNA recognition. Reason: The actual Eukaryota AN0/PTN001803442 assertion includes GLIS2 on its descendant path. The inspected tree, alignment and donor mappings support transfer; no target-path loss annotation was found. Supporting Evidence: GO_REF:0000033 |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: Retain inherited transcription-factor activity. Reason: GLIS2 inherits AN0/PTN001803442 in the actual PAINT tree. This direction-neutral molecular function accommodates activation and repression; current UniProt family assignment is kept distinct from the historical PAINT family. Retain this term as the functional summary for a dual-direction regulator. Its children resolve promoter-dependent outputs; generic DNA-binding and process ancestors add no distinct functional account. Supporting Evidence: GO_REF:0000033 |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Reason: The mouse donor represses Gli1-stimulated GlisBS reporters; preserve promoter-dependent activity and orthology. Supporting Evidence: |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Reason: The mouse donor represses Gli1-stimulated GlisBS reporters; preserve promoter-dependent activity and orthology. Supporting Evidence: |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Reason: Mouse-donor assays show Ins2-promoter activation via Glis-binding elements; retain this promoter-specific transfer. Supporting Evidence: |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Reason: Mouse-donor assays show Ins2-promoter activation via Glis-binding elements; retain this promoter-specific transfer. Supporting Evidence: |
| GO:0003677 DNA binding | IEA GO_REF:0000107 | TOO GENERAL | Summary: Generic DNA binding is already covered. Reason: Accepted GO:0000978 entails DNA binding through verified is_a ancestry. Preserve the orthology evidence while preferring that established specific function. |
| GO:0005515 protein binding | IPI PMID:17289029 The KrΓΌppel-like zinc finger protein Glis2 functions as a ne... | MODIFY | Summary: Replace generic binding with beta-catenin binding. Reason: Two-hybrid, co-immunoprecipitation and GST-pulldown experiments support beta-catenin association with reporter consequences. GO:0008013 captures this specific interaction. Human assay hosts do not establish the tagged Glis2 construct species; historical 520/522 boundaries are not mapped onto the current 524-residue human product. Preserve the curated human IPI context. Proposed replacements: beta-catenin binding Supporting Evidence: PMID:17289029 Ξ²-catenin and Glis2 physically interact with each other |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: The FAM168B contact remains in the evidence record. Generic binding does not define a specific GLIS2 molecular role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the GOLGA6L9 contact as interaction evidence; the generic label is not an informative GLIS2 activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the SHOX interaction and its literal partner isoform. A contact alone does not establish a shared transcriptional mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the CRX contact without assigning a regulatory complex from the partner identity. The generic function label adds no useful specificity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Keep the OIP5 interaction in the evidence record; it does not justify assigning GLIS2 a specific chromatin-associated activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the GMNN contact. The generic binding term does not distinguish a demonstrated GLIS2 molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the VENTX contact. Its presence does not establish a shared transcriptional role sufficient for a functional replacement. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Keep the PRKAR1B interaction as evidence; a specific regulatory activity for GLIS2 is not established by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the FOSB contact without assigning GLIS2 an AP-1 regulatory role. The generic binding label is uninformative. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the CTBP2 contact and literal isoform. The row alone does not establish a functional GLIS2 corepressor complex. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Keep the BCAR1 contact as physical evidence; the generic term supplies no specific GLIS2 activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the RBM11 interaction without transferring an RNA-processing role to GLIS2 from its partner. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Keep the VBP1 contact in the evidence record; generic binding does not specify the molecular contribution made by GLIS2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the CSNK2B contact without inferring a kinase-regulatory function for GLIS2 from partner identity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the POU6F2 contact; a specific transcriptional partnership has not been established by this interaction row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the PRR20D interaction while removing the generic label, which does not resolve a GLIS2 molecular activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Keep the CREM contact and literal partner isoform. The interaction alone does not specify a shared transcriptional mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the ARID5A contact; the generic term does not establish a functional transcriptional partnership. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the ACTN3 interaction without assigning a cytoskeletal molecular function to GLIS2 from its partner. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the TLE5 contact and literal isoform. A functional corepressor relationship requires evidence beyond this interaction row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Keep the VAC14 contact without assigning GLIS2 a phosphoinositide-regulatory activity from the partner identity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the KRTAP6-1 interaction as physical evidence. The generic binding label does not describe GLIS2 function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the KRTAP6-2 contact and all source records; repeated assay records do not supply a functional replacement term. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the KRTAP19-5 contact and its source records. The generic binding annotation remains uninformative. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the KRTAP19-7 contact while removing the generic label, which does not identify a specific GLIS2 activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the ACTMAP contact and literal isoform in the evidence record; no GLIS2 enzymatic role follows from partner identity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the AKAP9 contact without inferring a scaffold activity for GLIS2. The generic term lacks functional specificity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Keep the KRTAP19-3 interaction as evidence; generic binding does not distinguish a GLIS2 molecular role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the TSC1 contact without assigning GLIS2 an mTOR-regulatory activity from the partner identity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the GPSM1 contact and literal isoform; the row does not establish a specific signaling activity of GLIS2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the KRTAP8-1 interaction in the evidence record while removing the uninformative generic label. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Keep the ANKRD36B contact and its literal isoform. A specific molecular contribution by GLIS2 is not resolved by this row. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the TWIST2 contact; physical association alone does not demonstrate a shared transcriptional mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the RBPMS contact and literal partner isoform without transferring an RNA-binding activity to GLIS2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the PLEKHB2 contact and all source records; generic binding supplies no specific GLIS2 molecular activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Retain the WWOX contact and literal isoform. The interaction does not establish a functional enzymatic role for GLIS2. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the PLEKHB1 contact and current literal isoform while retaining the distinct historical isoform label in the source audit. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Keep the ZRANB1 interaction without transferring a deubiquitinase function to GLIS2 from its partner. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic binding is uninformative. Reason: Preserve the NME7 contact; the generic term does not establish a specific GLIS2 molecular activity. Supporting Evidence: |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Retain nuclear activity. Reason: The actual AN0/PTN001803442 nuclear assertion covers GLIS2. Preserve is_active_in and the conserved nuclear transcriptional context; this does not imply exclusive localization or that every nuclear molecule is active. Supporting Evidence: GO_REF:0000033 |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Reason: Mouse Glis2βEGFP is nuclear in CV-1 cells; retain located_in separately from the nuclear-activity IBA. Supporting Evidence: |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Reason: Mouse Glis2βEGFP is nuclear in CV-1 cells; retain located_in separately from the nuclear-activity IBA. Supporting Evidence: |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain a contextual cytoplasmic pool. Reason: EGFP-Glis2 is present in both cytoplasm and nucleus in a minority of transfected CHO cells. This supports a contextual pool alongside predominant nuclear localization, without assigning cytoplasmic transcriptional activity or claiming an endogenous-human assay. |
| GO:0016607 nuclear speck | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Reason: Tagged Glis2 forms nuclear puncta with CtBP1. Without splicing-factor markers, these experiments do not establish the transferred nuclear-speck specificity. |
| GO:0016607 nuclear speck | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Reason: Tagged Glis2 forms nuclear puncta with CtBP1. Without splicing-factor markers, these experiments do not establish the transferred nuclear-speck specificity. |
| GO:0045879 negative regulation of smoothened signaling pathway | IEA GO_REF:0000107 | ACCEPT | Reason: Mouse Glis2 opposes Gli1 through Snai1/Wnt4 regulatory-DNA binding, directly suppressing postnatal renal Hedgehog output. This specific transcriptional mechanism supports a conserved core role; human activity is inferred from the mouse evidence. Supporting Evidence: |
| GO:0045879 negative regulation of smoothened signaling pathway | ISS GO_REF:0000024 | ACCEPT | Reason: Mouse Glis2 opposes Gli1 through Snai1/Wnt4 regulatory-DNA binding, directly suppressing postnatal renal Hedgehog output. This specific transcriptional mechanism supports a conserved core role; human activity is inferred from the mouse evidence. Supporting Evidence: |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000107 | TOO GENERAL | Reason: The existing polymerase-II repression term is a verified descendant; preserve the mouse transfer at that more informative resolution. |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | TOO GENERAL | Reason: The existing polymerase-II repression term is a verified descendant; preserve the mouse transfer at that more informative resolution. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | TOO GENERAL | Reason: The existing polymerase-II activation term is a verified descendant; preserve the mouse transfer at that more informative resolution. |
| GO:0045893 positive regulation of DNA-templated transcription | ISS GO_REF:0000024 | TOO GENERAL | Reason: The existing polymerase-II activation term is a verified descendant; preserve the mouse transfer at that more informative resolution. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Retain context-dependent transcriptional activation. Reason: AN224/PTN008571319 also carries activation grounded in mouse Glis2. Human GLIS2 inherits this node; primary evidence supports Ins2-promoter activation. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Reason: Ins2-promoter activation supports this mouse transfer, without establishing endogenous human insulin regulation. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Reason: Ins2-promoter activation supports this mouse transfer, without establishing endogenous human insulin regulation. Supporting Evidence: |
| GO:0097730 non-motile cilium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain contextual localization to primary cilia. Reason: The primary study detects GLIS2 along acetylated-tubulin-positive MDCK-II axonemes and separately examines GFP-GLIS2/P100 colocalization in HEK293T cells. This supports the orthology-based ciliary pool; it does not establish a particular ciliary molecular activity or the tagged construct species from its host. Supporting Evidence: |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | TOO GENERAL | Summary: The retained claim is covered by accepted regulatory-DNA recognition. Reason: Retain the curatorβs broad DNA-binding claim: independently established GO:0000978 entails it. The specific source construct and methylation result remain unverified because the target supplement was inaccessible. Supporting Evidence: |
| GO:1990837 sequence-specific double-stranded DNA binding | IEA GO_REF:0000117 | TOO GENERAL | Summary: Broader sequence-specific DNA binding is already covered. Reason: Accepted GO:0000978 is a verified is_a descendant of GO:1990837. The ARBA-supported row remains true at broad resolution but adds no distinct functional coverage. |
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Download this section (compressed HTML)Q: Which endogenous human target promoters distinguish GLIS2-mediated activation from repression in renal epithelial cells?
Suggested experts: GLIS transcription-factor researchers, Renal epithelial biologists
Q: Do endogenous human GLIS2 puncta occupy marker-defined nuclear speckles, and how does any ciliary pool relate to nuclear activity?
Q: Which exact GLIS2 construct and result underlie the incoming methyl-SELEX annotation?
Q: Does the demonstrated beta-catenin interaction warrant a distinct physiological process annotation, beyond the supported binding refinement?
Q: Should the reviewer-raised CBFA2T3βGLIS2 fusion product receive a separate review before comparing its activities with intact GLIS2?
Experiment: Combine endogenous GLIS2 occupancy mapping with acute perturbation and nascent transcription measurements in human renal epithelial cells; distinguish occupied promoters from indirect expression responses.
Experiment: Assess endogenous GLIS2 localization with nuclear-speckle and ciliary markers, validated loss-of-signal controls and separate nuclear and ciliary measurements.
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