Sox2 is a SOXB1 HMG-box transcription factor and pioneer factor that binds sequence-specific cis-regulatory DNA to regulate RNA polymerase II transcriptional programs controlling pluripotency, early lineage decisions, and stem/progenitor maintenance. In mouse, Sox2 is essential for early embryonic pluripotent cells and for maintaining neural stem/progenitor identity. Its core site of action is the nucleus/chromatin, while reported cytoplasmic localization reflects regulated trafficking rather than the primary location of function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: Sox2 functions as a sequence-specific transcriptional activator binding to Sox motifs (WWCAAW consensus). Reason: This annotation accurately represents Sox2's core molecular function. The HMG-box domain binds sequence-specifically to Sox motifs and activates transcription. This is supported by IBA phylogenetic inference and extensive experimental evidence. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007420 brain development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Sox2 plays essential roles in brain development through maintaining neural progenitor populations and regulating neural fate specification. Reason: While Sox2 is indeed involved in brain development, this term is very broad and captures pleiotropy rather than core molecular function. The more specific neural stem cell maintenance and neural specification functions are better representations of Sox2's primary roles. This annotation is not incorrect but represents a higher-level developmental outcome rather than the core cellular function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030900 forebrain development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Sox2 expression and function in forebrain development is well-documented. Reason: This is a more specific developmental process than general brain development, but still represents a regional/developmental outcome rather than core molecular function. Sox2 functions the same way (maintaining neural progenitors) across brain regions. The forebrain-specific annotation reflects where Sox2 is expressed and important, but the core function is neural progenitor maintenance regardless of brain region. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Sox2 functions as both a transcriptional activator and repressor depending on context. SUMOylation of Sox2 enables transcriptional repression of centrosome/centromere and cell-cycle genes in neural stem cells, providing proliferative restraint. Reason: This annotation accurately represents a documented function of Sox2. The deep research shows SUMOylation-dependent repression of cell-cycle genes in neural stem cells. While Sox2 is primarily an activator, its repressor function is well-established and represents a core regulatory mechanism for controlling neural stem cell proliferation. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030182 neuron differentiation | IBA GO_REF:0000033 | MODIFY | Summary: Sox2 is involved in neuronal differentiation primarily by maintaining neural progenitor identity and preventing premature neuronal differentiation. Reason: The generic neuron differentiation term is ambiguous and can imply promotion of differentiation. Mouse Sox2 evidence and Falcon synthesis better support negative regulation of neuron differentiation/neural progenitor maintenance. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN008496689 SUPPORTS TRANSFER Node in PTHR10270, PANTHER family name "SOX TRANSCRIPTION FACTOR", the family UniProt also assigns to the target (PTHR10270:SF231 "TRANSCRIPTION FACTOR SOX-2"). The seeds span SoxB and SoxC group members whose relationships to neurogenesis differ in direction, which is why the node could only carry the unsigned participation term; the target's descent from the node is not in question. MGI:MGI:98364 · mouse Sox2 (the review target itself) SUPPORTS TRANSFER The target's own MGI record is among the IBD seeds, the expected marker that experimental grounding exists on the target itself: Sox2 carries an IDA at GO:0045665 negative regulation of neuron differentiation (PMID:16631155) - the term proposed as the replacement - along with IMP annotations for neuron fate commitment and forebrain neuron differentiation, and these are among the descendant evidences behind the IBD. MGI:MGI:98357 · mouse Sox1 (SoxB1 group, like the target) SUPPORTS TRANSFER Same SoxB1 group as Sox2, with the same neural-progenitor role, so the transfer of neurogenic involvement itself is sound. MGI:MGI:98359 · mouse Sox11 (SoxC group) SUPPORTS SOURCE BUT NOT TARGET A SoxC-group factor acting at the neuronal-differentiation step rather than in progenitor maintenance; the unsigned term reads as participation in differentiation for it, but the target's own evidence is for restraining that step. MGI:MGI:98366 · mouse Sox4 (SoxC group) SUPPORTS SOURCE BUT NOT TARGET Second SoxC-group seed with the same directionality problem. Because the family mixes members that drive differentiation with SoxB1 members that hold it back, the unsigned parent is the only term the node can assert - and it is what makes the row ambiguous for the target. GO:0045665 is not a descendant of GO:0030182 (regulation terms are not is_a children of the process they regulate), so the MODIFY is a re-scope from participant to regulator, not a narrowing, and no granularity failure mode is asserted. FB:FBgn0029123 · Drosophila SoxN (SoxNeuro) SUPPORTS TRANSFER Invertebrate SoxB seed; anchors the neurogenic role of the SoxB branch deep in the bilaterian tree. FB:FBgn0000411 · Drosophila Dichaete (D) SUPPORTS TRANSFER Second invertebrate SoxB seed with a neurogenic role. FB:FBgn0005612 · Drosophila Sox14 (Sox box protein 14) SUPPORTS SOURCE BUT NOT TARGET More distant Sox seed outside the SoxB1 group; contributes to the node's breadth rather than to a directional claim about the target. Proposed replacements: negative regulation of neuron differentiation Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048839 inner ear development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Sox2 expression and function in inner ear development. Reason: Sox2 plays roles in sensory organ development including inner ear, but this represents tissue-specific developmental pleiotropy rather than core function. The core function is maintaining progenitor populations; inner ear development is one of many developmental contexts where this occurs. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Sox2 binds to cis-regulatory enhancer regions through sequence-specific recognition of Sox motifs. Reason: This annotation accurately captures Sox2's binding to enhancer elements. Deep research shows Sox2 binds thousands of enhancers and recognizes specific DNA sequences. This represents a core molecular function of the HMG-box domain. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic annotation based on UniProtKB subcellular location vocabulary. Reason: Sox2 acts primarily as a nuclear/chromatin transcription factor. Cytoplasmic localization is supported as regulated shuttling/export and turnover, but it is secondary to the core site of function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md SOX2 acts primarily in the **nucleus** |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic annotation based on InterPro domain IPR022097 (SOX family). Reason: This is a valid high-level annotation based on domain architecture. All SOX family transcription factors regulate transcription, and this annotation is appropriately general. While less specific than the positive/negative regulation terms, it is not incorrect. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:19139101 A positive regulatory role for the mSin3A-HDAC complex in pl... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:19536159 The pluripotency factor Oct4 interacts with Ctcf and also co... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:20362541 An Oct4-centered protein interaction network in embryonic st... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:23108051 Cdk1 interplays with Oct4 to repress differentiation of embr... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:23892456 A direct physical interaction between Nanog and Sox2 regulat... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000976 transcription cis-regulatory region binding | ISO GO_REF:0000119 | ACCEPT | Summary: Electronic annotation for cis-regulatory region binding. Reason: This is a parent term of sequence-specific cis-regulatory binding and is supported by extensive evidence of Sox2 binding to enhancers. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001649 osteoblast differentiation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: IDA evidence for Sox2 role in osteoblast differentiation when ectopically expressed in mesenchymal stem cells. Reason: This represents an experimental manipulation (forced Sox2 expression in mesenchymal stem cells) rather than Sox2's endogenous core function. While experimentally valid, osteoblast differentiation is not a physiological context where Sox2 normally functions and represents experimental pleiotropy. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003677 DNA binding | ISO GO_REF:0000119 | ACCEPT | Summary: Electronic annotation based on UniProtKB keyword mapping. Reason: This high-level term is appropriate for describing Sox2's DNA-binding capacity. While very general, it is not incorrect and is supported by HMG-box domain annotation. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003700 DNA-binding transcription factor activity | ISO GO_REF:0000119 | ACCEPT | Summary: IDA evidence for general transcription factor activity. Reason: This is a high-level parent term accurately describing Sox2's molecular function. Multiple IDA studies support this classification. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | ISO GO_REF:0000119 | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | ISO GO_REF:0000119 | ACCEPT | Summary: IDA evidence based on immunofluorescence localization. Reason: Nucleoplasm is a more specific cellular component than nucleus, indicating Sox2 is soluble within the nuclear compartment rather than associated with nuclear envelope or other nuclear structures. This is appropriate for a transcription factor. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005737 cytoplasm | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Electronic annotation based on UniProtKB subcellular location vocabulary. Reason: Sox2 acts primarily as a nuclear/chromatin transcription factor. Cytoplasmic localization is supported as regulated shuttling/export and turnover, but it is secondary to the core site of function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md SOX2 acts primarily in the **nucleus** |
| GO:0005829 cytosol | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: IDA evidence for cytosolic localization. Reason: The local evidence supports occasional cytoplasmic signal/shuttling, not a specific stable cytosolic site of Sox2 function. Cytosol overstates the localization beyond the core nuclear/chromatin function and beyond the broader cytoplasm evidence. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md SOX2 acts primarily in the **nucleus** |
| GO:0006355 regulation of DNA-templated transcription | ISO GO_REF:0000119 | ACCEPT | Summary: Electronic annotation based on InterPro domain IPR022097 (SOX family). Reason: This is a valid high-level annotation based on domain architecture. All SOX family transcription factors regulate transcription, and this annotation is appropriately general. While less specific than the positive/negative regulation terms, it is not incorrect. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010468 regulation of gene expression | ISO GO_REF:0000119 | ACCEPT | Summary: IMP evidence showing mutant phenotype affecting gene expression regulation. Reason: This is a valid high-level annotation demonstrating Sox2's role in gene expression control through mutant phenotype analysis. While very general, it is appropriate as a parent term encompassing transcriptional regulation. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035019 somatic stem cell population maintenance | ISO GO_REF:0000119 | ACCEPT | Summary: IMP evidence showing Sox2 is required for maintaining somatic stem cell populations, particularly neural stem cells. Reason: This annotation represents a core function of Sox2. Multiple independent IMP and IDA studies demonstrate Sox2's essential role in maintaining stem cell populations. This encompasses both embryonic and neural stem cell maintenance and represents a fundamental cellular function of Sox2. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035198 miRNA binding | ISO GO_REF:0000119 | REMOVE | Summary: The miRNA binding transfer is not supported as a core Sox2 molecular activity in mouse. Reason: The relevant Sox2 literature primarily supports DNA/chromatin binding and transcriptional regulation; promoter regulation of miRNA genes should not be converted into direct miRNA binding without direct evidence. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043410 positive regulation of MAPK cascade | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: IDA evidence for Sox2 involvement in MAPK signaling. Reason: While experimentally supported, MAPK cascade regulation represents a context-specific signaling outcome rather than a core molecular function. Sox2's primary function is as a transcription factor; MAPK regulation may be an indirect consequence or occur in specific cellular contexts (e.g., mesenchymal stem cells in this study). This is valid but peripheral to core transcriptional regulatory function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000119 | ACCEPT | Summary: IDA evidence for positive regulation of transcription. Reason: This is a parent term of RNA pol II-specific transcriptional activation and accurately represents Sox2's core function. The term is at an appropriate level of specificity for general transcriptional activation function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000119 | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070848 response to growth factor | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: IDA evidence for Sox2 response to growth factor stimulation. Reason: This represents an upstream regulatory input rather than Sox2's core function. Growth factors can regulate Sox2 expression or activity, but this does not define what Sox2 itself does. This is valid annotation but describes regulation of Sox2 rather than Sox2's function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: IDA evidence for Sox2 regulation of Wnt signaling. Reason: While experimentally supported, Wnt pathway regulation represents cross-talk between Sox2's transcriptional program and developmental signaling rather than a core molecular function. This is a valid regulatory connection but peripheral to Sox2's primary role as a transcriptional regulator of pluripotency and neural fate. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1902807 negative regulation of cell cycle G1/S phase transition | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: IDA evidence for Sox2 role in cell cycle regulation. Reason: Negative regulation of G1/S transition is plausible Sox2-associated biology, but the underlying transferred evidence is from non-mouse cancer/overexpression contexts and the local notes classify Wnt/cell-cycle ISO terms as secondary outputs rather than conserved core Sox2 function. Supporting Evidence: file:mouse/Sox2/Sox2-notes.md Wnt and cell-cycle ISO terms are plausible secondary outputs but still not central to mouse Sox2's conserved function |
| GO:0005634 nucleus | ISO GO_REF:0000096 | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0022409 positive regulation of cell-cell adhesion | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in positive regulation of cell-cell adhesion, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045597 positive regulation of cell differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in positive regulation of cell differentiation, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000096 | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050998 nitric-oxide synthase binding | ISO GO_REF:0000096 | REMOVE | Summary: Nitric-oxide synthase binding is not supported as a conserved or informative Sox2 function. Reason: Compared with the strong nuclear transcription-factor evidence, this rat-to-mouse transfer is implausibly specific and lacks corroborating support in the mouse Sox2 literature. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0090649 response to oxygen-glucose deprivation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in response to oxygen-glucose deprivation, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1904520 regulation of myofibroblast cell apoptotic process | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in regulation of myofibroblast cell apoptotic process, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010467 gene expression | IMP PMID:21874018 lincRNAs act in the circuitry controlling pluripotency and d... | ACCEPT | Summary: gene expression is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:30442713 Proteolysis of methylated SOX2 protein is regulated by L3MBT... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:25901318 Functional and mechanistic studies of XPC DNA-repair complex... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:25901318 Functional and mechanistic studies of XPC DNA-repair complex... | ACCEPT | Summary: RNA polymerase II-specific DNA-binding transcription factor binding is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010467 gene expression | IMP PMID:17267691 Zic3 is required for maintenance of pluripotency in embryoni... | ACCEPT | Summary: gene expression is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010467 gene expression | IMP PMID:26005002 Expression patterns of long noncoding RNAs from Dlk1-Dio3 im... | ACCEPT | Summary: gene expression is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000785 chromatin | IDA PMID:23798425 Acetylated histone H3K56 interacts with Oct4 to promote mous... | ACCEPT | Summary: ISA evidence from TFClass database indicating Sox2 associates with chromatin. Reason: This annotation is highly appropriate for Sox2 as a pioneer factor. Deep research shows Sox2 engages nucleosomal DNA and maintains chromatin accessibility. Chromatin localization is essential for Sox2's function as a pioneer transcription factor that can bind DNA in chromatin context. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003677 DNA binding | IDA PMID:23798425 Acetylated histone H3K56 interacts with Oct4 to promote mous... | ACCEPT | Summary: Electronic annotation based on UniProtKB keyword mapping. Reason: This high-level term is appropriate for describing Sox2's DNA-binding capacity. While very general, it is not incorrect and is supported by HMG-box domain annotation. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:21076177 Core transcription factors, Oct4, Sox2 and Nanog, individual... | ACCEPT | Summary: DNA-binding transcription factor binding is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:19816951 Klf4 interacts directly with Oct4 and Sox2 to promote reprog... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:31481660 Nucleoporin insufficiency disrupts a pluripotent regulatory ... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:32127020 Tsukushi is essential for the development of the inner ear. | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0071276 cellular response to cadmium ion | IDA PMID:15219627 Disturbing endoderm signaling to anterior neural plate of ve... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in cellular response to cadmium ion, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005737 cytoplasm | IDA PMID:9512512 Sox1 directly regulates the gamma-crystallin genes and is es... | KEEP AS NON CORE | Summary: Electronic annotation based on UniProtKB subcellular location vocabulary. Reason: Sox2 acts primarily as a nuclear/chromatin transcription factor. Cytoplasmic localization is supported as regulated shuttling/export and turnover, but it is secondary to the core site of function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md SOX2 acts primarily in the **nucleus** |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:12665572 Fbx15 is a novel target of Oct3/4 but is dispensable for emb... | ACCEPT | Summary: Sox2 binds to cis-regulatory enhancer regions through sequence-specific recognition of Sox motifs. Reason: This annotation accurately captures Sox2's binding to enhancer elements. Deep research shows Sox2 binds thousands of enhancers and recognizes specific DNA sequences. This represents a core molecular function of the HMG-box domain. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:15082719 SOX7 and GATA-4 are competitive activators of Fgf-3 transcri... | ACCEPT | Summary: Sox2 binds to cis-regulatory enhancer regions through sequence-specific recognition of Sox motifs. Reason: This annotation accurately captures Sox2's binding to enhancer elements. Deep research shows Sox2 binds thousands of enhancers and recognizes specific DNA sequences. This represents a core molecular function of the HMG-box domain. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IGI PMID:15863505 Differential roles for Sox15 and Sox2 in transcriptional con... | ACCEPT | Summary: Sox2 binds to cis-regulatory enhancer regions through sequence-specific recognition of Sox motifs. Reason: This annotation accurately captures Sox2's binding to enhancer elements. Deep research shows Sox2 binds thousands of enhancers and recognizes specific DNA sequences. This represents a core molecular function of the HMG-box domain. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:22344693 Deciphering the Sox-Oct partner code by quantitative coopera... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:25901318 Functional and mechanistic studies of XPC DNA-repair complex... | ACCEPT | Summary: Electronic annotation for cis-regulatory region binding. Reason: This is a parent term of sequence-specific cis-regulatory binding and is supported by extensive evidence of Sox2 binding to enhancers. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:26691508 Physical Interactions and Functional Coordination between th... | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:26523946 Combined Overexpression of JARID2, PRDM14, ESRRB, and SALL4A... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:23169531 Co-motif discovery identifies an Esrrb-Sox2-DNA ternary comp... | ACCEPT | Summary: IDA evidence for general transcription factor activity. Reason: This is a high-level parent term accurately describing Sox2's molecular function. Multiple IDA studies support this classification. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019827 stem cell population maintenance | IMP PMID:23169531 Co-motif discovery identifies an Esrrb-Sox2-DNA ternary comp... | ACCEPT | Summary: stem cell population maintenance is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043565 sequence-specific DNA binding | IDA PMID:23169531 Co-motif discovery identifies an Esrrb-Sox2-DNA ternary comp... | ACCEPT | Summary: IDA evidence for sequence-specific DNA binding. Reason: This annotation accurately describes the fundamental DNA-binding property of the Sox2 HMG-box domain, which recognizes specific Sox motif sequences. This is a core molecular function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:18448678 ES cell pluripotency and germ-layer formation require the SW... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-9615549 | ACCEPT | Summary: IDA evidence based on immunofluorescence localization. Reason: Nucleoplasm is a more specific cellular component than nucleus, indicating Sox2 is soluble within the nuclear compartment rather than associated with nuclear envelope or other nuclear structures. This is appropriate for a transcription factor. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-9832812 | ACCEPT | Summary: IDA evidence based on immunofluorescence localization. Reason: Nucleoplasm is a more specific cellular component than nucleus, indicating Sox2 is soluble within the nuclear compartment rather than associated with nuclear envelope or other nuclear structures. This is appropriate for a transcription factor. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-9833004 | ACCEPT | Summary: IDA evidence based on immunofluorescence localization. Reason: Nucleoplasm is a more specific cellular component than nucleus, indicating Sox2 is soluble within the nuclear compartment rather than associated with nuclear envelope or other nuclear structures. This is appropriate for a transcription factor. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:25335925 Pwp1 is required for the differentiation potential of mouse ... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:21300049 Cooperative functions of Hes/Hey genes in auditory hair cell... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:25535395 Notch inhibition induces mitotically generated hair cells in... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031490 chromatin DNA binding | IDA PMID:24268575 Tsix RNA and the germline factor, PRDM14, link X reactivatio... | ACCEPT | Summary: chromatin DNA binding is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:23447615 Paired related homeobox protein 1 is a regulator of stemness... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:23447615 Paired related homeobox protein 1 is a regulator of stemness... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:20531390 Suppression of the novel ER protein Maxer by mutant ataxin-1... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:24036311 CTR9/PAF1c regulates molecular lineage identity, histone H3K... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:23056351 The mammalian DM domain transcription factor Dmrta2 is requi... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:24191021 Sox9 plays multiple roles in the lung epithelium during bran... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:23284756 Ascl1 (Mash1) knockout perturbs differentiation of nonneuron... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:22344693 Deciphering the Sox-Oct partner code by quantitative coopera... | ACCEPT | Summary: ISA evidence from TFClass database classification of Sox2 as a sequence-specific DNA-binding transcription factor. Reason: This is a parent term of DNA-binding transcription activator activity and accurately describes Sox2's molecular function class. The ISA evidence from TFClass is appropriate for classifying Sox2 within the transcription factor family. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005667 transcription regulator complex | IDA PMID:22344693 Deciphering the Sox-Oct partner code by quantitative coopera... | ACCEPT | Summary: TAS evidence for Sox2 participation in transcriptional regulatory complexes, particularly with OCT4. Reason: Sox2 forms complexes with OCT4 and other transcription factors to regulate gene expression. This is well-documented and represents an important aspect of Sox2 function - it does not act alone but cooperates with partner factors in multi-protein complexes. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:22232070 Genome-wide analysis of N1ICD/RBPJ targets in vivo reveals d... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:22992956 Transcriptional regulatory networks in epiblast cells and du... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050767 regulation of neurogenesis | IGI PMID:22513373 EYA1 and SIX1 drive the neuronal developmental program in co... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in regulation of neurogenesis, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019827 stem cell population maintenance | IMP PMID:20720539 Mediator and cohesin connect gene expression and chromatin a... | ACCEPT | Summary: stem cell population maintenance is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0097150 neuronal stem cell population maintenance | IGI PMID:22198669 Ars2 maintains neural stem-cell identity through direct tran... | ACCEPT | Summary: Sox2 is essential for maintaining neural stem cell identity and self-renewal. This is one of its core functions in the nervous system. Reason: This annotation represents a core function of Sox2 in neural biology. Deep research shows Sox2 is critical for neural stem cell maintenance, and UniProt (not the deep-research synthesis, which does not contain the phrase) describes it as a factor that "Keeps neural cells undifferentiated by counteracting the activity of proneural proteins". The term accurately captures Sox2's essential role in maintaining the neural stem cell pool. Supporting Evidence: file:mouse/Sox2/Sox2-uniprot.txt Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:19796622 Uncovering early response of gene regulatory networks in ESC... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006357 regulation of transcription by RNA polymerase II | IDA PMID:19796622 Uncovering early response of gene regulatory networks in ESC... | ACCEPT | Summary: regulation of transcription by RNA polymerase II is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO PMID:21245162 Pluripotency factors regulate definitive endoderm specificat... | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001714 endodermal cell fate specification | ISO PMID:21245162 Pluripotency factors regulate definitive endoderm specificat... | KEEP AS NON CORE | Summary: IDA evidence for role in endoderm specification. Reason: Sox2 with OCT4 regulates germ layer specification including endoderm fate. While experimentally supported, this represents one developmental context among many. Sox2's core function is maintaining pluripotency and regulating lineage choice; endoderm specification is one specific outcome. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043565 sequence-specific DNA binding | ISO PMID:21245162 Pluripotency factors regulate definitive endoderm specificat... | ACCEPT | Summary: IDA evidence for sequence-specific DNA binding. Reason: This annotation accurately describes the fundamental DNA-binding property of the Sox2 HMG-box domain, which recognizes specific Sox motif sequences. This is a core molecular function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:19490090 Expression of Sox11 in adult neurogenic niches suggests a st... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:20123909 Sox17 promotes differentiation in mouse embryonic stem cells... | ACCEPT | Summary: Electronic annotation for cis-regulatory region binding. Reason: This is a parent term of sequence-specific cis-regulatory binding and is supported by extensive evidence of Sox2 binding to enhancers. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:20123909 Sox17 promotes differentiation in mouse embryonic stem cells... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048863 stem cell differentiation | IDA PMID:20123909 Sox17 promotes differentiation in mouse embryonic stem cells... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in stem cell differentiation, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IDA PMID:17875931 Sox17 and Sox4 differentially regulate beta-catenin/T-cell f... | KEEP AS NON CORE | Summary: IDA evidence for Sox2 regulation of Wnt signaling. Reason: While experimentally supported, Wnt pathway regulation represents cross-talk between Sox2's transcriptional program and developmental signaling rather than a core molecular function. This is a valid regulatory connection but peripheral to Sox2's primary role as a transcriptional regulator of pluripotency and neural fate. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:21062744 Sall1 regulates embryonic stem cell differentiation in assoc... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:21076177 Core transcription factors, Oct4, Sox2 and Nanog, individual... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:19328208 The structure of Sox17 bound to DNA reveals a conserved bend... | ACCEPT | Summary: Electronic annotation for cis-regulatory region binding. Reason: This is a parent term of sequence-specific cis-regulatory binding and is supported by extensive evidence of Sox2 binding to enhancers. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:7628452 Involvement of SOX proteins in lens-specific activation of c... | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:19740739 Zfp206, Oct4, and Sox2 are integrated components of a transc... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030858 positive regulation of epithelial cell differentiation | IDA PMID:18374910 Sox2 is important for two crucial processes in lung developm... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in positive regulation of epithelial cell differentiation, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045165 cell fate commitment | IDA PMID:18374910 Sox2 is important for two crucial processes in lung developm... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in cell fate commitment, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048286 lung alveolus development | IDA PMID:18374910 Sox2 is important for two crucial processes in lung developm... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in lung alveolus development, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060441 epithelial tube branching involved in lung morphogenesis | IDA PMID:18374910 Sox2 is important for two crucial processes in lung developm... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in epithelial tube branching involved in lung morphogenesis, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032526 response to retinoic acid | IDA PMID:18400104 Detailed characterization of the mouse embryonic stem cell t... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in response to retinoic acid, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043565 sequence-specific DNA binding | IDA PMID:18400104 Detailed characterization of the mouse embryonic stem cell t... | ACCEPT | Summary: IDA evidence for sequence-specific DNA binding. Reason: This annotation accurately describes the fundamental DNA-binding property of the Sox2 HMG-box domain, which recognizes specific Sox motif sequences. This is a core molecular function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003682 chromatin binding | IDA PMID:15988017 Reciprocal transcriptional regulation of Pou5f1 and Sox2 via... | ACCEPT | Summary: chromatin binding is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:15988017 Reciprocal transcriptional regulation of Pou5f1 and Sox2 via... | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:18287078 SOX2-expressing progenitor cells generate all of the major c... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:17097055 Inhibition of DNA binding of Sox2 by the SUMO conjugation. | ACCEPT | Summary: IDA evidence for general transcription factor activity. Reason: This is a high-level parent term accurately describing Sox2's molecular function. Multiple IDA studies support this classification. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:17507372 A dominant-negative form of mouse SOX2 induces trophectoderm... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:17507372 A dominant-negative form of mouse SOX2 induces trophectoderm... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005667 transcription regulator complex | IDA PMID:17507372 A dominant-negative form of mouse SOX2 induces trophectoderm... | ACCEPT | Summary: TAS evidence for Sox2 participation in transcriptional regulatory complexes, particularly with OCT4. Reason: Sox2 forms complexes with OCT4 and other transcription factors to regulate gene expression. This is well-documented and represents an important aspect of Sox2 function - it does not act alone but cooperates with partner factors in multi-protein complexes. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030910 olfactory placode formation | IGI PMID:17140559 Sox2 and Pou2f1 interact to control lens and olfactory placo... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in olfactory placode formation, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045596 negative regulation of cell differentiation | IMP PMID:17507372 A dominant-negative form of mouse SOX2 induces trophectoderm... | ACCEPT | Summary: negative regulation of cell differentiation is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:17097055 Inhibition of DNA binding of Sox2 by the SUMO conjugation. | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:17097055 Inhibition of DNA binding of Sox2 by the SUMO conjugation. | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:17140559 Sox2 and Pou2f1 interact to control lens and olfactory placo... | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:17507372 A dominant-negative form of mouse SOX2 induces trophectoderm... | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:17507372 A dominant-negative form of mouse SOX2 induces trophectoderm... | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060235 lens induction in camera-type eye | IGI PMID:17140559 Sox2 and Pou2f1 interact to control lens and olfactory placo... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in lens induction in camera-type eye, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:16932809 Mutations within Sox2/SOX2 are associated with abnormalities... | ACCEPT | Summary: IDA evidence for general transcription factor activity. Reason: This is a high-level parent term accurately describing Sox2's molecular function. Multiple IDA studies support this classification. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:16631155 Role of Sox2 in the development of the mouse neocortex. | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:16932809 Mutations within Sox2/SOX2 are associated with abnormalities... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0021984 adenohypophysis development | IMP PMID:16932809 Mutations within Sox2/SOX2 are associated with abnormalities... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in adenohypophysis development, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030539 male genitalia development | IMP PMID:16932809 Mutations within Sox2/SOX2 are associated with abnormalities... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in male genitalia development, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045665 negative regulation of neuron differentiation | IDA PMID:16631155 Role of Sox2 in the development of the mouse neocortex. | ACCEPT | Summary: Sox2 actively suppresses neuronal differentiation to maintain neural progenitor cells in an undifferentiated state. This is a core function in neural development. Reason: This annotation accurately captures Sox2's essential role in preventing premature neuronal differentiation. UniProt states that Sox2 "keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation." This is central to its function in neural stem cell maintenance and represents a core activity. Supporting Evidence: file:mouse/Sox2/Sox2-uniprot.txt Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045747 positive regulation of Notch signaling pathway | IDA PMID:16631155 Role of Sox2 in the development of the mouse neocortex. | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in positive regulation of Notch signaling pathway, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16932809 Mutations within Sox2/SOX2 are associated with abnormalities... | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002052 positive regulation of neuroblast proliferation | IMP PMID:15240551 Sox2 deficiency causes neurodegeneration and impaired neurog... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in positive regulation of neuroblast proliferation, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002052 positive regulation of neuroblast proliferation | IMP PMID:16651659 SOX2 is a dose-dependent regulator of retinal neural progeni... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in positive regulation of neuroblast proliferation, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:15781477 Sox2 induction by FGF and FGFR2 activating mutations inhibit... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0021879 forebrain neuron differentiation | IMP PMID:15240551 Sox2 deficiency causes neurodegeneration and impaired neurog... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in forebrain neuron differentiation, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0021987 cerebral cortex development | IMP PMID:15240551 Sox2 deficiency causes neurodegeneration and impaired neurog... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in cerebral cortex development, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030178 negative regulation of Wnt signaling pathway | IGI PMID:15781477 Sox2 induction by FGF and FGFR2 activating mutations inhibit... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in negative regulation of Wnt signaling pathway, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045666 positive regulation of neuron differentiation | IMP PMID:16651659 SOX2 is a dose-dependent regulator of retinal neural progeni... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in positive regulation of neuron differentiation, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045668 negative regulation of osteoblast differentiation | IDA PMID:15781477 Sox2 induction by FGF and FGFR2 activating mutations inhibit... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in negative regulation of osteoblast differentiation, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048852 diencephalon morphogenesis | IMP PMID:15240551 Sox2 deficiency causes neurodegeneration and impaired neurog... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in diencephalon morphogenesis, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060042 retina morphogenesis in camera-type eye | IMP PMID:16651659 SOX2 is a dose-dependent regulator of retinal neural progeni... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in retina morphogenesis in camera-type eye, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:7628452 Involvement of SOX proteins in lens-specific activation of c... | ACCEPT | Summary: IDA evidence for general transcription factor activity. Reason: This is a high-level parent term accurately describing Sox2's molecular function. Multiple IDA studies support this classification. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:9669521 Role of the transcription factor Sox-2 in the expression of ... | ACCEPT | Summary: IDA evidence for general transcription factor activity. Reason: This is a high-level parent term accurately describing Sox2's molecular function. Multiple IDA studies support this classification. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | ISO GO_REF:0000008 | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:9512512 Sox1 directly regulates the gamma-crystallin genes and is es... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043565 sequence-specific DNA binding | IDA PMID:7628452 Involvement of SOX proteins in lens-specific activation of c... | ACCEPT | Summary: IDA evidence for sequence-specific DNA binding. Reason: This annotation accurately describes the fundamental DNA-binding property of the Sox2 HMG-box domain, which recognizes specific Sox motif sequences. This is a core molecular function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043565 sequence-specific DNA binding | IDA PMID:9669521 Role of the transcription factor Sox-2 in the expression of ... | ACCEPT | Summary: IDA evidence for sequence-specific DNA binding. Reason: This annotation accurately describes the fundamental DNA-binding property of the Sox2 HMG-box domain, which recognizes specific Sox motif sequences. This is a core molecular function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048646 anatomical structure formation involved in morphogenesis | IMP PMID:9851841 The amn gene product is required in extraembryonic tissues f... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in anatomical structure formation involved in morphogenesis, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IGI PMID:9649510 New POU dimer configuration mediates antagonistic control of... | ACCEPT | Summary: Sox2 functions as both a transcriptional activator and repressor depending on context. SUMOylation of Sox2 enables transcriptional repression of centrosome/centromere and cell-cycle genes in neural stem cells, providing proliferative restraint. Reason: This annotation accurately represents a documented function of Sox2. The deep research shows SUMOylation-dependent repression of cell-cycle genes in neural stem cells. While Sox2 is primarily an activator, its repressor function is well-established and represents a core regulatory mechanism for controlling neural stem cell proliferation. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:7590241 Developmental-specific activity of the FGF-4 enhancer requir... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043565 sequence-specific DNA binding | IDA PMID:9649510 New POU dimer configuration mediates antagonistic control of... | ACCEPT | Summary: IDA evidence for sequence-specific DNA binding. Reason: This annotation accurately describes the fundamental DNA-binding property of the Sox2 HMG-box domain, which recognizes specific Sox motif sequences. This is a core molecular function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:7590241 Developmental-specific activity of the FGF-4 enhancer requir... | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019827 stem cell population maintenance | IMP PMID:16767105 Dissecting self-renewal in stem cells with RNA interference. | ACCEPT | Summary: stem cell population maintenance is consistent with Sox2 core function as an HMG-box DNA-binding transcription factor and pioneer factor. Reason: Falcon synthesis supports sequence-specific DNA binding, chromatin/pioneer activity, nuclear localization, OCT4/cofactor partnership, transcriptional activation/repression, and stem/neural progenitor maintenance as central Sox2 functions. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043586 tongue development | IMP PMID:17015430 Sox2 is required for development of taste bud sensory cells. | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in tongue development, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048663 neuron fate commitment | IMP PMID:17015430 Sox2 is required for development of taste bud sensory cells. | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in neuron fate commitment, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:17522155 Multiple dose-dependent roles for Sox2 in the patterning and... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048568 embryonic organ development | IMP PMID:17522155 Multiple dose-dependent roles for Sox2 in the patterning and... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in embryonic organ development, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048646 anatomical structure formation involved in morphogenesis | IMP PMID:17522155 Multiple dose-dependent roles for Sox2 in the patterning and... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in anatomical structure formation involved in morphogenesis, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003677 DNA binding | IDA PMID:8625802 A comparison of the properties of Sox-3 with Sry and two rel... | ACCEPT | Summary: Electronic annotation based on UniProtKB keyword mapping. Reason: This high-level term is appropriate for describing Sox2's DNA-binding capacity. While very general, it is not incorrect and is supported by HMG-box domain annotation. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:15863505 Differential roles for Sox15 and Sox2 in transcriptional con... | REMOVE | Summary: The protein binding annotation captures a physical interaction but is too generic for Sox2 curation. Reason: Sox2 partner interactions should be represented by more informative terms such as DNA-binding transcription factor binding, transcription regulator complex, or specific transcriptional regulatory activities; generic protein binding is not informative. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:15863505 Differential roles for Sox15 and Sox2 in transcriptional con... | ACCEPT | Summary: Sox2 is fundamentally a transcriptional activator that cooperates with OCT4 to activate thousands of enhancers controlling pluripotency and neural fate genes. This is the primary and core molecular function of Sox2. Reason: This annotation represents the core function of Sox2 as a transcriptional activator. Deep research shows Sox2 and OCT4 co-occupy thousands of OSN enhancers in pluripotent cells and activate genes essential for pluripotency and neural specification. Multiple IBA, IDA, and IEA annotations converge on this fundamental activity. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042472 inner ear morphogenesis | IMP PMID:15846349 Sox2 is required for sensory organ development in the mammal... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in inner ear morphogenesis, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050910 detection of mechanical stimulus involved in sensory perception of sound | IMP PMID:15846349 Sox2 is required for sensory organ development in the mammal... | MARK AS OVER ANNOTATED | Summary: detection of mechanical stimulus involved in sensory perception of sound is an organismal/tissue phenotype downstream of Sox2 developmental roles rather than a direct Sox2 molecular or cellular function. Reason: Sox2 is essential in sensory and pigment-related developmental contexts, but Falcon synthesis supports its core action as an HMG-box transcription factor/pioneer factor controlling enhancer accessibility and stem/progenitor programs. This term overstates downstream phenotypes as direct gene-product function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050973 detection of mechanical stimulus involved in equilibrioception | IMP PMID:15846349 Sox2 is required for sensory organ development in the mammal... | MARK AS OVER ANNOTATED | Summary: detection of mechanical stimulus involved in equilibrioception is an organismal/tissue phenotype downstream of Sox2 developmental roles rather than a direct Sox2 molecular or cellular function. Reason: Sox2 is essential in sensory and pigment-related developmental contexts, but Falcon synthesis supports its core action as an HMG-box transcription factor/pioneer factor controlling enhancer accessibility and stem/progenitor programs. This term overstates downstream phenotypes as direct gene-product function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001708 cell fate specification | IMP PMID:12514105 Multipotent cell lineages in early mouse development depend ... | KEEP AS NON CORE | Summary: Sox2 has evidence for involvement in cell fate specification, but this is a tissue-specific developmental or stress-response context rather than the core molecular activity. Reason: The conserved core function is enhancer/chromatin binding and transcriptional control of pluripotency and neural progenitor programs. Retain this annotation as supported non-core developmental biology. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:12514105 Multipotent cell lineages in early mouse development depend ... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005737 cytoplasm | IDA PMID:12514105 Multipotent cell lineages in early mouse development depend ... | KEEP AS NON CORE | Summary: Electronic annotation based on UniProtKB subcellular location vocabulary. Reason: Sox2 acts primarily as a nuclear/chromatin transcription factor. Cytoplasmic localization is supported as regulated shuttling/export and turnover, but it is secondary to the core site of function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md SOX2 acts primarily in the **nucleus** |
| GO:0005634 nucleus | IC PMID:12665572 Fbx15 is a novel target of Oct3/4 but is dispensable for emb... | ACCEPT | Summary: Sox2 is a nuclear transcription factor with NLS sequences directing nuclear localization. Reason: Nuclear localization is essential for Sox2 function as a transcription factor. This annotation accurately represents where Sox2 performs its core function. UniProt describes nuclear localization regulated by NLS/NES sequences, and deep research confirms Sox2 is "predominantly nuclear." Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:12665572 Fbx15 is a novel target of Oct3/4 but is dispensable for emb... | ACCEPT | Summary: IDA evidence for general transcription factor activity. Reason: This is a high-level parent term accurately describing Sox2's molecular function. Multiple IDA studies support this classification. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:12665572 Fbx15 is a novel target of Oct3/4 but is dispensable for emb... | ACCEPT | Summary: Electronic annotation based on InterPro domain IPR022097 (SOX family). Reason: This is a valid high-level annotation based on domain architecture. All SOX family transcription factors regulate transcription, and this annotation is appropriately general. While less specific than the positive/negative regulation terms, it is not incorrect. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007605 sensory perception of sound | IMP PMID:12036291 Circling, deafness, and yellow coat displayed by yellow subm... | MARK AS OVER ANNOTATED | Summary: sensory perception of sound is an organismal/tissue phenotype downstream of Sox2 developmental roles rather than a direct Sox2 molecular or cellular function. Reason: Sox2 is essential in sensory and pigment-related developmental contexts, but Falcon synthesis supports its core action as an HMG-box transcription factor/pioneer factor controlling enhancer accessibility and stem/progenitor programs. This term overstates downstream phenotypes as direct gene-product function. Supporting Evidence: file:mouse/Sox2/Sox2-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0046148 pigment biosynthetic process | IMP PMID:12036291 Circling, deafness, and yellow coat displayed by yellow subm... | UNDECIDED | Summary: Cannot be adjudicated here: PMID:12036291 is cached abstract-only. Prior observation, not a verdict: 'The underlying mutant mapping paper reports yellow coat phenotypes from chromosomal rearrangements, not direct Sox2 gene-product involvement in pigment biosynthesis.' Reason: PMID:12036291 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: Pigment biosynthesis is not supported as a Sox2 molecular or cellular function. PMID:12036291 maps Ysb/Lcc chromosomal rearrangements with pigmentation phenotypes and does not establish Sox2 as functioning in pigment biosynthesis. Supporting Evidence: PMID:12036291 Chromosomal mapping and genomic characterization showed the Ysb and Lcc mutations involve complex chromosomal rearrangements |
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Download this section (compressed HTML)Q: Should GO represent Sox2's pioneer-factor/chromatin-opening activity more explicitly than the current generic DNA-binding transcription factor terms?
Q: Which specialized transferred Sox2 terms from rat or human stress/pathology contexts are truly conserved direct functions versus secondary downstream consequences?
Experiment: Perform endogenous Sox2 CUT&Tag/ChIP-seq across mouse ESCs, neural stem cells, and selected injury models to separate conserved direct targets from context-specific downstream programs behind the transferred ISO terms.
Experiment: Use endogenous epitope tagging plus live-cell imaging/fractionation to resolve when Sox2 genuinely occupies cytoplasmic compartments versus merely transiting during regulated trafficking or turnover.
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