GATA6 is a GATA-family zinc-finger transcription factor that binds GATA regulatory elements and activates or represses RNA polymerase II target genes. It acts in nuclear regulatory complexes with context-dependent cofactors, including MED1, and helps establish and maintain epithelial, endodermal and cardiovascular cell programs. Its downstream effects include lineage differentiation, cardiac patterning and specialized responses controlling proliferation and survival. Haploinsufficiency can cause pancreatic agenesis in humans. Alternative translation initiation produces 595- and 449-residue proteins that retain the zinc-finger region; their transcriptional output can differ with promoter and cellular context.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Retain conserved PolII repression. Reason: The target inherits the actual AN0 repression IBD. Independent target support is linked; self-evidence does not make the placement circular. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:18177748 GATA-6 is a novel transcriptional repressor of the human Ten... | ACCEPT | Summary: Retain direct PolII repression. Reason: Functional promoter mutation and endogenous occupancy support TNC repression, with coding-construct provenance bounded. Supporting Evidence: |
| GO:0000785 chromatin | ISA GO_REF:0000113 | KEEP AS NON CORE | Summary: Retain contextual chromatin association. Reason: Independent occupancy evidence supports association, without implying a stable architectural role or a separate molecular activity. |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:18177748 GATA-6 is a novel transcriptional repressor of the human Ten... | MODIFY | Summary: Refine TNC regulatory-site binding. Reason: GATA-site dependence and endogenous ChIP support specific PolII cis-regulatory recognition. Construct provenance remains bounded; see the source guide. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:19666519 GATA6 mutations cause human cardiac outflow tract defects by... | MODIFY | Summary: Refine human regulatory DNA binding. Reason: Human EMSA supports PolII cis-regulatory specificity. Binding and activation are separable; no natural-product-exclusive claim follows. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:20206639 The transcription factor GATA-4 regulates cytochrome P4502C1... | MODIFY | Summary: GATA6 binds a sequence-specific site in the CYP2C19 promoter. Reason: Although the paper title foregrounds GATA4, the authentic abstract explicitly reports sequence-specific GATA6 binding by EMSA. Its reporter activation and ChIP claims are stated for GATA4/GATA2 or GATA4 and are not silently reassigned to GATA6. Refine the positive GATA6 binding assertion to PolII cis-regulatory sequence-specific DNA binding, also supported independently by direct human GATA6 promoter work. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:9566909 Distinct functions are implicated for the GATA-4, -5, and -6... | MODIFY | Summary: Refine conserved regulatory DNA recognition. Reason: The historical Xenopus assays and human antibody limits remain explicit. Independent human evidence supports GO:0000978; see the shared source guide. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000117 | MODIFY | Summary: Refine regulatory DNA recognition. Reason: Independent human evidence supports the verified GO:0000978 descendant. Preserve ARBA provenance; see the guideβs shared DNA-recognition evidence and construct limits. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Retain conserved regulatory DNA recognition. Reason: Actual AN0/PTN001600628 ancestry supports transfer to AN20/PTN002467704. Independent target support is linked; donor count does not determine validity. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the grounded ortholog inference. Reason: Preserve Q61169 and its direct experimental grounding. Independent target support is linked without converting donor experiments into human-product assays. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: Retain conserved PolII transcription-factor activity. Reason: The exact target inherits the AN0 assertion with no target-path NOT. Target self-evidence is legitimate; tissue-specific outputs need separate assessment. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: Retain orthologous PolII transcription-factor activity. Reason: The donor transfer agrees with independent target evidence linked here. Preserve species and construct distinctions documented in the source guide. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IMP PMID:21127043 GATA6 promotes angiogenic function and survival in endotheli... | ACCEPT | Summary: Retain endothelial transcription-factor activity. Reason: Human functional promoter assays support this activity; rescue uses mouse Gata6. Supporting Evidence: |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: Retain the supported transcription-factor classification. Reason: TFClass agrees with the established specific molecular activity. This does not make every downstream phenotype a core function. |
| GO:0001223 transcription coactivator binding | IEA GO_REF:0000107 | ACCEPT | Summary: Retain coactivator binding. Reason: Human MED1 association independently supports the ortholog inference; preserve Q61169. |
| GO:0001223 transcription coactivator binding | IPI PMID:19497978 The mediator complex subunit 1 enhances transcription of gen... | ACCEPT | Summary: Retain MED1 binding. Reason: Endogenous association supports the coactivator-partner claim; product and perturbation limits are centralized in the guide. Supporting Evidence: |
| GO:0001949 sebaceous gland cell differentiation | IDA PMID:33082341 Contribution of GATA6 to homeostasis of the human upper pilo... | KEEP AS NON CORE | Summary: Retain contextual sebocyte differentiation. Reason: GATA6 promotes early lineage markers while terminal lipid output falls; this is not uniform maturation. Supporting Evidence: PMID:33082341 GATA6 triggers a junctional zone and sebaceous differentiation program |
| GO:0002759 regulation of antimicrobial humoral response | IDA PMID:33082341 Contribution of GATA6 to homeostasis of the human upper pilo... | KEEP AS NON CORE | Summary: Retain contextual antimicrobial response. Reason: Human expression and microbial-stimulus responses support the process; mixed mediator effects do not establish direct bacterial killing. Supporting Evidence: |
| GO:0003148 outflow tract septum morphogenesis | IMP PMID:19666519 GATA6 mutations cause human cardiac outflow tract defects by... | KEEP AS NON CORE | Summary: Retain contextual outflow morphogenesis. Reason: Human variants and target regulation support developmental participation; enhancer-site experiments do not establish GATA6-specific mouse necessity. Supporting Evidence: |
| GO:0003162 atrioventricular node development | NAS PMID:26786210 The formation and function of the cardiac conduction system. | KEEP AS NON CORE | Summary: GATA6 contributes to atrioventricular-node development. Reason: The actual cited review discusses mouse myocardial Gata6 deletion, reduced conduction-lineage markers and cell-cycle exit, fewer AV-node cells and prolonged PR intervals. This supports the NAS developmental attribution at its proper mouse-derived review scope. It is not a new direct human AV-node assay or an inference from expression of a Gata6 enhancer reporter alone. Supporting Evidence: |
| GO:0003163 sinoatrial node development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain contextual SAN development. Reason: Mouse lineage deletion supports pacemaker programming; preserve donor species and unresolved construct details rather than imply a human experiment. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: Refine generic DNA binding. Reason: GO:0000978 is the verified specific descendant supported independently on the target. Preserve electronic provenance; linked source details are centralized in the guide. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | MODIFY | Summary: Replace broad chromatin binding with resolved specificity. Reason: Endogenous ChIP supports chromatin association, not its absence. GATA-site mutation and DNA-recognition assays resolve the functional contact as sequence-specific PolII regulatory DNA binding. This lateral replacement states that molecular specificity; it does not claim GO:0000978 is a chromatin-binding descendant or deny chromatin occupancy. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:19497978 The mediator complex subunit 1 enhances transcription of gen... | MODIFY | Summary: Specify PolII activity. Reason: Adrenal promoter experiments support GO:0000981; MED1 perturbation is distinct from GATA6 catalytic activity. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:19666519 GATA6 mutations cause human cardiac outflow tract defects by... | MODIFY | Summary: Specify PolII transcription-factor activity. Reason: Direct human target-promoter experiments establish the specific activity. Mouse enhancer-site tests are not GATA6-specific knockouts. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | MODIFY | Summary: Specify PolII transcription-factor activity. Reason: The verified GO:0000981 descendant matches independent target evidence. Preserve the combined electronic provenance. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| GO:0005515 protein binding | IPI PMID:16199874 Hey basic helix-loop-helix transcription factors are repress... | MODIFY | Summary: Specify HEYL transcription-factor binding. Reason: CoIP supports the literal mouse Q9DBX7 partner. HEYL is a DNA-binding repressor, not a non-DNA-binding corepressor; construct limits remain in the guide. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16199874 Hey basic helix-loop-helix transcription factors are repress... | MODIFY | Summary: Specify HEY2 transcription-factor binding. Reason: CoIP supports mouse Q9QUS4. Its verified DNA-binding partner role supports GO:0061629, without an affinity or natural-product claim. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16199874 Hey basic helix-loop-helix transcription factors are repress... | MODIFY | Summary: Specify HEY1 transcription-factor binding. Reason: CoIP supports mouse Q9WV93. Its DNA-binding partner role supports the refinement; retain the sourceβs construct limitations. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Retain conserved nuclear residence. Reason: The verified AN0 nuclear IBD reaches this target. Independent support is linked; retain the root organelle alongside its more specific compartment. |
| GO:0005634 nucleus | IDA PMID:17785913 Transcription factor GATA-6 in the human adrenocortex: assoc... | ACCEPT | Summary: GATA6 is a nuclear transcription factor in the adrenal context. Reason: The authentic source abstract describes immunohistochemistry of human fetal and postnatal adrenal glands. The detailed nuclear staining panels were not inspected here, so the exact source-specific assay is deferred to the experimental curator. Independent human GATA6 localization and adrenal promoter ChIP support the whole nuclear claim; expression correlations alone are not used to manufacture a new adrenal process annotation. |
| GO:0005634 nucleus | IDA PMID:19666519 GATA6 mutations cause human cardiac outflow tract defects by... | ACCEPT | Summary: Retain WT nuclear localization. Reason: Human FLAG-GATA6 is nuclear in COS1 cells; abnormal E486del intranuclear distribution is not complete exclusion. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:20206639 The transcription factor GATA-4 regulates cytochrome P4502C1... | ACCEPT | Summary: The nuclear annotation is consistent with GATA6 DNA-binding evidence and independent localization. Reason: The authentic abstract specifically includes GATA6 in EMSA binding to the CYP2C19 GATA element, whereas the transactivation and ChIP claims foreground GATA4/GATA2. The full original localization assay was not accessed; do not relabel those paralog experiments as GATA6 assays or reject the curator from that access limit. Independent direct human GATA6 localization supports retaining nucleus. |
| GO:0005634 nucleus | IDA PMID:21127043 GATA6 promotes angiogenic function and survival in endotheli... | ACCEPT | Summary: Retain endothelial nuclear residence. Reason: Direct human nuclear measurements support the literal endothelial-cell extension; abundance varies with conditions. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:21828274 HEB and E2A function as SMAD/FOXH1 cofactors. | ACCEPT | Summary: Nuclear residence remains well supported while the source-specific endoderm context is preserved. Reason: The authentic abstract describes human stem-cell/endoderm regulatory experiments but does not expose the GATA6 localization panel; the attempted PMC full text returned a browser challenge. Retain the experimental curator attribution and literal endoderm extension without inventing the inaccessible assay. Independent human GATA6 localization and promoter occupancy establish the nuclear claim; the HEB/E2A-focused title is not evidence of misattribution. |
| GO:0005634 nucleus | IDA PMID:27756709 Gain-of-function mutations in GATA6 lead to atrial fibrillat... | ACCEPT | Summary: GATA6 nuclear localization is compatible with the variant transcriptional study. Reason: The authentic abstract reports WT and mutant GATA6 reporter activity and transcription-factor cooperation, but does not expose a complete localization assay. Preserve the original experimental annotation and distinguish that access limit from biological uncertainty about nuclear GATA6, which is independently demonstrated with human constructs. No variant-specific redistribution or initiation-product exclusivity is inferred. |
| GO:0005634 nucleus | IDA PMID:9566909 Distinct functions are implicated for the GATA-4, -5, and -6... | ACCEPT | Summary: The conserved nuclear localization is supported despite the historical reagent limitation. Reason: Historical human nuclear binding has an antibody-specificity limitation. Independent human GATA6 localization supports the location; that evidence does not establish the separate intestinal differentiation claim. |
| GO:0005634 nucleus | IDA PMID:9593712 GATA-6 induces p21(Cip1) expression and G1 cell cycle arrest... | ACCEPT | Summary: The nuclear location agrees with the established transcriptional mechanism. Reason: The authentic abstract links GATA6 expression to p21 induction and growth arrest, but does not by itself expose the nuclear localization experiment or exact coding construct. Defer to the experimental curator for that source-specific panel and retain the biologically established nuclear claim using independent direct human localization evidence. The quiescence phenotype remains a separate contextual process. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Retain nuclear residence. Reason: Independent target support agrees with the combined electronic inputs. Preserve every incoming provenance path and avoid product-exclusive localization claims. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Retain nucleoplasmic localization. Reason: Preserve HPA attribution; its images were not reread. Independent localization and participant evidence are linked without product-exclusive claims. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Retain nucleoplasmic localization. Reason: Independent target evidence agrees with ARBA. Preserve the electronic provenance and nonexclusive scope. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683888 | ACCEPT | Summary: The LMCD1-binding record contains human GATA6 in the nucleoplasm. Reason: The actual official event has R-HSA-452902 as an input and places its LMCD1:GATA6 output complex in nucleoplasm. The target entity explicitly references human UniProt Q92908, chain1-595. This is direct curated target membership rather than inference from a pathway title; the database chain representation is not proof that every primary experiment uniquely tested the long natural product. Supporting Evidence: Reactome:R-HSA-5683888 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685296 | ACCEPT | Summary: The SFTPA promoter-binding record places the exact human GATA6 entity in nucleoplasm. Reason: The official event uses R-HSA-452902 as input and includes it in the GATA6:SFTPAs output. That entity is human Q92908, chain1-595, with nucleoplasmic location. Retain the TAS location without extending this participant check into an independently read primary-paper assay or a claim about all surfactant processes. Supporting Evidence: Reactome:R-HSA-5685296 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9823952 | ACCEPT | Summary: The CXCR4 regulatory-complex record contains nucleoplasmic human GATA6. Reason: The exact official input chain resolves to R-HSA-452902 and human Q92908, together with EOMES and SMAD regulators at CXCR4. The record explicitly draws on human pluripotent-cell contexts. This supports the existing compartment annotation; it does not establish that every displayed combination was tested in an intact human embryo. Supporting Evidence: Reactome:R-HSA-9823952 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9823977 | ACCEPT | Summary: The expression record identifies the produced GATA6 protein as nucleoplasmic. Reason: The official R-HSA-9823977 event is marked uncertain and lists R-HSA-452902, human Q92908 chain1-595, as output in nucleoplasm. The location is consistent with independent GATA6 evidence. Being the output of its expression event does not make GATA6 the catalyst of its own synthesis or justify an additional process annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-996755 | ACCEPT | Summary: GATA6 is an explicit nucleoplasmic member of the GATA-protein input set. Reason: The actual chain R-HSA-996755 to input set R-HSA-996770 to member R-HSA-452902 resolves to human Q92908, chain1-595. This verifies the target underlying the TAS nucleoplasm row. Set membership does not show that every GATA/ZFPM paralog pairing or natural product was independently tested. Supporting Evidence: Reactome:R-HSA-996755 |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000107 | ACCEPT | Summary: Retain regulatory-complex membership. Reason: MED1 association supports the ortholog inference; no universal simultaneous-partner complex is asserted. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: Specify PolII transcriptional regulation. Reason: The verified GO:0006357 descendant captures independently established target activity. Domain provenance remains unchanged; primary evidence is linked. Proposed replacements: regulation of transcription by RNA polymerase II |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000002 | ACCEPT | Summary: Retain PolII transcriptional regulation. Reason: This process matches the established molecular activity, independently supported on the target. Domain evidence remains distinct from experiments. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Zinc coordination supports the GATA DNA-binding fold. Reason: The InterPro-supported GATA zinc-finger architecture and conserved zinc-coordinating features support metal binding. This structural property contributes to the transcription-factor fold but is not the most informative stand-alone core molecular activity. It is retained without proposing zinc catalysis or a distinct metal-homeostasis process. Supporting Evidence: GO_REF:0000002 |
| GO:0008584 male gonad development | IEP PMID:17848411 Developmental changes in human fetal testicular cell numbers... | MARK AS OVER ANNOTATED | Summary: The cited human fetal-testis data establish developmental expression rather than a functional gonadal-development role. Reason: The original Methods and Results measure normal fetal cell numbers, transcripts and testosterone. GATA6 RNA increases per testis during the second trimester, but this observational design does not test GATA6-dependent gonadal morphogenesis or differentiation. Preserve the positive expression finding and incoming IEP assertion; the process claim exceeds what this source directly establishes, without asserting that GATA6 lacks any gonadal function. Supporting Evidence: |
| GO:0009410 response to xenobiotic stimulus | IMP PMID:18671946 Statins activate GATA-6 and induce differentiated vascular s... | KEEP AS NON CORE | Summary: GATA6 participates in a functional vascular response to statins. Reason: The authentic abstract reports statin-induced GATA6 DNA-binding activity, smooth-muscle marker expression and promoter output in human aortic VSMCs, with loss of reporter induction after mutation of the GATA site. This is more than altered GATA6 abundance and supports the existing xenobiotic-response annotation. Detailed original methods and exact product identity remain unverified; the response is contextual rather than a universal GATA6 function. Supporting Evidence: |
| GO:0009653 anatomical structure morphogenesis | IEA GO_REF:0000117 | TOO GENERAL | Summary: Mark the broad morphology claim redundant. Reason: Actual typed ancestry of retained outflow morphogenesis reaches GO:0009653. TOO_GENERAL preserves biological compatibility while avoiding duplicate coverage. |
| GO:0010467 gene expression | IEA GO_REF:0000107 | MODIFY | Summary: Replace general expression with resolved transcription. Reason: Independent target evidence establishes GO:0006357. This is a mechanistic lateral replacement, not an asserted descendant of GO:0010467. Proposed replacements: regulation of transcription by RNA polymerase II |
| GO:0019901 protein kinase binding | IPI PMID:20864106 PTEN differentially regulates expressions of ICAM-1 and VCAM... | KEEP AS NON CORE | Summary: GATA6 associates with GSK3 beta in stimulated endothelial signaling. Reason: The authentic abstract explicitly reports GATA6 association with GSK3 beta in human endothelial cells and links PTEN/Akt modulation to GATA6 occupancy at the VCAM1 promoter. The original IPI partner P49841 is retained. This supports specialized kinase binding, not kinase activity by GATA6; detailed full-text interaction geometry and natural-product specificity remain unverified. Supporting Evidence: |
| GO:0030154 cell differentiation | IEA GO_REF:0000117 | TOO GENERAL | Summary: The general cell-differentiation claim is covered by retained specific lineage programs. Reason: The verified ancestry of epithelial and smooth-muscle differentiation includes GO:0030154. Both specific programs are retained, grounded respectively in actual phylogenetic placement and direct human lineage experiments. The ARBA assertion is true at this level but uninformative beside those existing descendants; no source error or loss of differentiation function is asserted. |
| GO:0030855 epithelial cell differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Epithelial differentiation is a conserved developmental output of GATA6. Reason: The exact human target descends from AN10/PTN002560167, where the actual PAINT IBD for epithelial differentiation was placed. Human GATA6 appears among legitimate descendant evidence, not circular support. Independent human epithelial perturbation and lineage-programming experiments support the broader biological claim, while the intestinal source-specific uncertainty in raw0 is preserved separately. |
| GO:0032526 response to retinoic acid | IDA PMID:33082341 Contribution of GATA6 to homeostasis of the human upper pilo... | KEEP AS NON CORE | Summary: Retain functional retinoic-acid response. Reason: GATA6 depletion partially reverses RA-driven marker effects, supporting mediation beyond expression alone. Supporting Evidence: |
| GO:0032911 negative regulation of transforming growth factor beta1 production | IMP PMID:21127043 GATA6 promotes angiogenic function and survival in endotheli... | KEEP AS NON CORE | Summary: Retain contextual TGFΞ²1 suppression. Reason: Human depletion raises TGFB1 RNA; mouse-promoter testing occurs in rat cells. Supporting Evidence: |
| GO:0032912 negative regulation of transforming growth factor beta2 production | IMP PMID:21127043 GATA6 promotes angiogenic function and survival in endotheli... | KEEP AS NON CORE | Summary: Retain contextual TGFΞ²2 suppression. Reason: Human depletion raises TGFB2 RNA; do not equate transcriptional effects with direct processing. Supporting Evidence: |
| GO:0036302 atrioventricular canal development | NAS PMID:26786210 The formation and function of the cardiac conduction system. | KEEP AS NON CORE | Summary: GATA6 contributes to the atrioventricular developmental program. Reason: The actual cited review places Gata6 in AVC/AVN developmental regulation and distinguishes the broader network from individual Gata4 mechanisms and chicken Gata6 enhancer reporters. Retain the NAS canal-development claim at that curated synthesis scope. The mouse node-deletion results provide related positive context but are not relabeled as a direct human canal-specific perturbation. Supporting Evidence: |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:21127043 GATA6 promotes angiogenic function and survival in endotheli... | KEEP AS NON CORE | Summary: Retain conditional survival regulation. Reason: The antiapoptotic effect depends on growth-factor withdrawal, not all endothelial conditions. Supporting Evidence: |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: Specify PolII cis-regulatory recognition. Reason: The verified GO:0000978 descendant is supported independently on the target. Linked original-study details and donor distinctions are centralized in the guide. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| GO:0045165 cell fate commitment | IBA GO_REF:0000033 | ACCEPT | Summary: Retain conserved cell-fate commitment. Reason: The actual AN3 placement lies on the verified target path. Target-specific lineage evidence corroborates the inference without making all developmental effects core. |
| GO:0045766 positive regulation of angiogenesis | IDA PMID:21127043 GATA6 promotes angiogenic function and survival in endotheli... | KEEP AS NON CORE | Summary: Retain contextual angiogenic regulation. Reason: Perturbation and rescue support endothelial behavior; rescue species remains distinct. Supporting Evidence: |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:18177748 GATA-6 is a novel transcriptional repressor of the human Ten... | MODIFY | Summary: Specify PolII repression. Reason: The direct TNC transcriptional mechanism supports the verified GO:0000122 descendant. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: Specify positive PolII regulation. Reason: The verified GO:0045944 descendant matches independent target evidence. Preserve domain provenance and the separately retained repressive capability. Proposed replacements: positive regulation of transcription by RNA polymerase II |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:22750565 GATA6 loss-of-function mutation in atrial fibrillation. | MODIFY | Summary: The WT-versus-mutant transcriptional comparison supports PolII promoter activation. Reason: The authentic PMID22750565 abstract reports reduced reporter transactivation by Y235S compared with WT GATA6. Detailed construct and reporter provenance are not exposed there, so they remain bounded. Independent direct human GATA6 promoter experiments establish the specific PolII activating process; use that supported refinement without inferring a universal causal AF mechanism or a natural-product-exclusive effect. Proposed replacements: positive regulation of transcription by RNA polymerase II |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:22824924 Novel GATA6 loss-of-function mutation responsible for famili... | MODIFY | Summary: The G469V comparison is consistent with established PolII transcriptional activation by GATA6. Reason: The authentic abstract documents a WT-versus-mutant luciferase comparison with diminished activity for G469V. Full original assay details are not claimed. Direct human GATA6 promoter evidence independently supplies the PolII specificity for the replacement; the source-specific variant experiment and physiological disease inference remain distinct. Proposed replacements: positive regulation of transcription by RNA polymerase II |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:27756709 Gain-of-function mutations in GATA6 lead to atrial fibrillat... | MODIFY | Summary: GATA6 activates the assayed cardiac PolII promoters. Reason: The authentic abstract explicitly identifies ANP reporter activation by WT and mutant GATA6 and additional alpha-MHC/ANP comparisons with GATA4 and MEF2C. Refine the general positive transcription term to the established PolII process. Gain-of-function variant differences do not define the activity of every natural product, and inaccessible full methods are not presented as read. Proposed replacements: positive regulation of transcription by RNA polymerase II |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Retain conserved positive PolII regulation. Reason: The target inherits the AN0 IBD. Incoming-versus-family donor differences remain literal; legitimate target self-evidence is not circular. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:19497978 The mediator complex subunit 1 enhances transcription of gen... | ACCEPT | Summary: Retain PolII activation. Reason: MED1-potentiated promoter output supports transcriptional activation, not a steroid-synthesis enzyme assignment. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:19666519 GATA6 mutations cause human cardiac outflow tract defects by... | ACCEPT | Summary: Retain target-promoter activation. Reason: Human reporter experiments distinguish transcriptional activation from binding; product exclusivity is unproven. Supporting Evidence: PMID:19666519 both GATA6 mutant proteins failed to transactivate these genes |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000117 | ACCEPT | Summary: Retain positive PolII regulation. Reason: Independent target evidence supports the ARBA assertion. This does not imply universal activation; repression is retained separately. |
| GO:0048513 animal organ development | IEA GO_REF:0000117 | TOO GENERAL | Summary: Mark organ development redundant. Reason: Verified typed paths from retained outflow and nodal development reach GO:0048513. The term is compatible but less informative. |
| GO:0048731 system development | IEA GO_REF:0000117 | TOO GENERAL | Summary: Mark system development redundant. Reason: Verified typed paths from retained developmental descendants reach GO:0048731. GATA6 performs regulatory work; this is redundancy, not biological rejection. |
| GO:0051145 smooth muscle cell differentiation | IMP PMID:17626241 GATA-6 mediates human bladder smooth muscle differentiation:... | KEEP AS NON CORE | Summary: GATA6 directly regulates human bladder smooth-muscle differentiation. Reason: The authentic abstract reports endogenous GATA6 knockdown reducing differentiation markers, loss of promoter recruitment after forskolin, and rescue by WT but not a DNA-binding-deficient engineered deletion. Mutation of the alpha-SMA GATA element abrogates activation. These positive human experiments support the existing smooth-muscle differentiation term; detailed full-text and modern natural-product mapping remain unclaimed. Supporting Evidence: |
| GO:0051525 NFAT protein binding | IPI PMID:11889139 Calcineurin-GATA-6 pathway is involved in smooth muscle-spec... | KEEP AS NON CORE | Summary: Retain contextual NFAT binding. Reason: Human GATA6 binds murine NFATc1. Rat promoter and engineered deletion experiments do not establish natural-product or heart-specific claims. Supporting Evidence: |
| GO:0060047 heart contraction | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Limit the heart-contraction attribution. Reason: The actual donor study establishes pacemaker development and electrical timing, not contractile work. Preserve the positive cardiac phenotype while marking this process-specific transfer overbroad. |
| GO:0060575 intestinal epithelial cell differentiation | IDA PMID:9566909 Distinct functions are implicated for the GATA-4, -5, and -6... | UNDECIDED | Summary: Human intestinal differentiation remains unresolved. Reason: Human HT29 expression/nuclear observations and Xenopus reporter activity do not establish the human differentiation process. The proposed transition role remains compatible with the findings; transcript decline is not negative functional evidence. Retain source-specific uncertainty pending a discriminating human perturbation. Supporting Evidence: |
| GO:0060947 cardiac vascular smooth muscle cell differentiation | IMP PMID:11889139 Calcineurin-GATA-6 pathway is involved in smooth muscle-spec... | MODIFY | Summary: Generalize the anatomical specificity. Reason: Human aortic assays support smooth-muscle differentiation, not specifically heart-vasculature cells. GO:0051145 is the verified ancestor; the interaction remains valid. Proposed replacements: smooth muscle cell differentiation Supporting Evidence: |
| GO:0060947 cardiac vascular smooth muscle cell differentiation | IMP PMID:12615657 GATA-6 is involved in PPARgamma-mediated activation of diffe... | MODIFY | Summary: PPAR-dependent GATA6 activity supports smooth-muscle differentiation in human aortic cells. Reason: The actual original Methods identify human aortic VSMCs and human GATA6 constructs; GATA-site mutation and endogenous binding assays support the differentiation mechanism. These data justify GO:0051145, the verified ancestor of the incoming heart-vascular subtype, without asserting that aortic cells are cardiac vascular smooth muscle. Reporter and endogenous-cell contexts are kept distinct. Proposed replacements: smooth muscle cell differentiation Supporting Evidence: |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Binding other PolII DNA-binding transcription factors is part of GATA6's regulatory function. Reason: The mouse-derived partner-binding assignment agrees with direct human GATA6-SP1 interaction evidence and independently retained GATA6 interaction assays with other verified DNA-binding TF partners. Partner-role binding does not require a newly demonstrated regulatory function of GATA6 on the partner itself. The literal donor remains unchanged, and complex/source/construct scopes are preserved. |
| GO:0070315 G1 to G0 transition involved in cell differentiation | IDA PMID:9593712 GATA-6 induces p21(Cip1) expression and G1 cell cycle arrest... | KEEP AS NON CORE | Summary: GATA6 can promote a quiescent cellular phenotype. Reason: The authentic abstract reports that GATA6 expression inhibits S-phase entry in vascular smooth-muscle cells and p53-null mouse fibroblasts, with p21 induction and loss of the growth-inhibitory response in p21-null cells. This supports a specialized G1-arrest/quiescence output of transcriptional regulation. It does not establish that all GATA6-expressing cells undergo this transition, and the abstract alone does not settle the exact GATA6 construct or natural product. Supporting Evidence: |
| GO:0070848 response to growth factor | IDA PMID:21127043 GATA6 promotes angiogenic function and survival in endotheli... | KEEP AS NON CORE | Summary: Retain functional growth-factor response. Reason: Nuclear, occupancy and reporter effects support mediation beyond expression alone. Supporting Evidence: |
| GO:0071456 cellular response to hypoxia | IDA PMID:21127043 GATA6 promotes angiogenic function and survival in endotheli... | KEEP AS NON CORE | Summary: Retain functional hypoxic response. Reason: Reporter dependence supports the process despite no enhanced occupancy at tested promoters. Supporting Evidence: |
| GO:0098773 skin epidermis development | IDA PMID:33082341 Contribution of GATA6 to homeostasis of the human upper pilo... | KEEP AS NON CORE | Summary: Retain epidermal programming context. Reason: Human explants and organoids support specialized lineage programming; no embryonic skin-development or uniform differentiation effect is claimed. Supporting Evidence: PMID:33082341 GATA6 controls keratinocyte proliferation and differentiation |
| GO:0110024 positive regulation of cardiac muscle myoblast proliferation | IDA PMID:25068583 miR-10a regulates proliferation of human cardiomyocyte proge... | KEEP AS NON CORE | Summary: GATA6 promotes proliferation of human cardiac progenitor cells. Reason: The original uses cells isolated from human fetal hearts and sorted with anti-Sca1, not an hESC differentiation model. Direct GATA6 siRNA reduces BrdU incorporation, and overexpression of the human NM_005257.4 coding region rescues the miR10a-associated proliferation defect. This supports the population-specific positive regulatory role. The exact modern initiation product was not aligned; the miR10a binding experiment concerns GATA6 RNA, and the reported differentiation-null result is not a GATA6 loss-of-function differentiation assay. Supporting Evidence: PMID:25068583 Over-expression of GATA6 greatly attenuated the miR-10a-mediated inhibitory effect |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:14988427 GATA-4 and GATA-6 modulate tissue-specific transcription of ... | MODIFY | Summary: GATA6 binds the PolII DNA-binding transcription factor SP1. Reason: The authentic abstract explicitly reports GATA6-SP1 GST pull-down and co-immunoprecipitation, with association at the P450c17 promoter in human adrenal cells; SP3 is distinguished. SP1 is a verified sequence-specific PolII transcription factor. The GO:0061629 descendant refines the broader incoming TF-binding term, without treating GATA6 as a steroidogenic enzyme or claiming the unavailable detailed construct mapping. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:15016828 Interaction between hex and GATA transcription factors in va... | MODIFY | Summary: GATA6 binds the DNA-binding transcription factor HHEX. Reason: The original selected Methods/Results identify human GATA6 as the initial bait and report full-length human Hex/GATA6 yeast reporter retesting. Official HHEX recognizes sequence-specific DNA and regulates transcription. Refine the broader TF-binding term to the PolII-specific partner role. Subsequent mammalian co-IP, endogenous HUVEC and VEGF functional experiments in this paper concern GATA2 and are not attributed to GATA6; no exact modern GATA6 product mapping is claimed. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: |
| GO:1904003 negative regulation of sebum secreting cell proliferation | IDA PMID:33082341 Contribution of GATA6 to homeostasis of the human upper pilo... | KEEP AS NON CORE | Summary: Retain sebocyte proliferation inhibition. Reason: Reduced S-phase and colony growth occur without increased TUNEL; the effect is tissue-specific. Supporting Evidence: |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | MODIFY | Summary: GATA6 sequence-specific double-stranded DNA recognition can be assigned its established regulatory context. Reason: The retained original SELEX tables identify a GATA6 extended DNA-binding-domain reagent and positive methylated and unmethylated sequence-selection rows. This is not a full-length natural-product assay, and the little-effect methylation classification has no bisulfite dataset for this entry. Independent direct human promoter experiments establish PolII cis-regulatory recognition, an actual descendant of the incoming broad sequence-specific double-stranded DNA-binding term. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding |
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Download this section (compressed HTML)Q: How do endogenous 595- and 449-residue GATA6 products differ in occupancy, cofactor recruitment and regulatory output across human cell types?
Q: Which direct human GATA6 perturbation and lineage measurements resolve the intestinal epithelial differentiation assertion associated with PMID:9566909?
Q: Which endogenous targets account for GATA6-dependent survival and proliferation responses, and how do their effects depend on growth-factor conditions?
Q: Can the precise mouse-donor SAN reporter construct and ChIP cell context be recovered to separate developmental transcriptional work from downstream electrical phenotypes?
Experiment: Compare sequence-verified long and short GATA6 products at matched expression in human lineage models using occupancy profiling and target RNA measurements, alongside endogenous initiation-site perturbations.
Experiment: Perturb endogenous GATA6 in human intestinal differentiation models with rescue by sequence-verified products and measure lineage markers, regulatory occupancy and differentiation outcomes.
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