NFIA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: NFIA is a well-established RNA polymerase II transcription factor that regulates gene expression by binding to specific DNA sequences and activating transcription. This IBA annotation is supported by experimental evidence showing NFIA activates transcription through RNA polymerase II machinery and is phylogenetically conserved across NFI family members. Reason: This represents a core molecular function of NFIA. The deep research confirms NFIA functions as a nuclear transcriptional activator that regulates RNA polymerase II-dependent transcription. Experimental studies including PMID:17010934 demonstrate direct transcriptional activation activity. Supporting Evidence: PMID:17010934 NF1-A could bind to the 18bp PACE-C region, and enhance about 13- to 17-fold of the luciferase reporter gene activity via the PACE-C in dose-dependent and orientation-independent manners. file:human/NFIA/NFIA-deep-research-falcon.md NFIA functions as a nuclear, chromatin-associated transcription factor that interfaces with major co-regulatory complexes (e.g., Mediator, SWI/SNF)
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: NFIA is a nuclear transcription factor. Multiple lines of evidence including IBA phylogenetic inference, experimental IDA localization studies, and functional characterization all confirm nuclear localization as the site where NFIA performs its DNA-binding and transcriptional activation functions. Reason: Nuclear localization is essential for NFIA function as a transcription factor. UniProt annotation, experimental evidence from PMID:15684392, and the deep research all confirm NFIA functions in the nucleus on chromatin. Supporting Evidence: PMID:15684392 In A7 melanoma cells possessing elevated levels of nuclear FLNA, FOXC1 is unable to activate transcription and is partitioned to an HP1alpha, heterochromatin-rich region of the nucleus file:human/NFIA/NFIA-deep-research-falcon.md NFIA is a nuclear/chromatin-associated factor with a large cell type–specific interactome
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: NFIA binds to the specific palindromic DNA sequence TTGGC(N5)GCCAA found in regulatory regions. This sequence-specific DNA binding to cis-regulatory regions is a core molecular function of NFIA and is well-characterized experimentally. Reason: This is a core molecular function. NFIA recognizes specific DNA motifs in promoters and enhancers. Experimental evidence from PMID:17010934 demonstrates direct sequence-specific DNA binding, and the IBA annotation is phylogenetically well-supported. Supporting Evidence: PMID:17010934 NF1-A could bind to the 18bp PACE-C region file:human/NFIA/NFIA-deep-research-falcon.md NFI proteins (including NFIA) bind the palindromic consensus TTGGC(N5)GCCAA, with tolerance for spacer variation
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	ACCEPT	Summary: NFIA functions as a DNA-binding transcription factor that specifically regulates RNA polymerase II-dependent transcription. This captures both the DNA-binding activity and the specificity for RNA pol II transcription machinery. Reason: This is a core molecular function that accurately describes NFIA activity. The term appropriately combines DNA binding with RNA pol II specificity and is supported by IBA and experimental evidence. Supporting Evidence: PMID:17010934 NF1-A transcription factor plays an important role in the transcriptional activation of the TR2 gene expression via the PACE-C in the minimal promoter region file:human/NFIA/NFIA-deep-research-falcon.md NFIA functions as a nuclear, chromatin-associated transcription factor that interfaces with major co-regulatory complexes (e.g., Mediator, SWI/SNF)
GO:0003677 DNA binding	IEA GO_REF:0000120	ACCEPT	Summary: This is a valid but very general annotation. NFIA does bind DNA through its conserved CTF/NFI DNA-binding domain. However, more specific terms like GO:0000978 (sequence-specific DNA binding) better capture NFIA function. Reason: While this IEA annotation is technically correct, it is less informative than the sequence-specific DNA binding annotations. However, it remains valid as a parent term and is appropriately inferred from domain annotation. The more specific GO:0000978 is preferred. Supporting Evidence: file:human/NFIA/NFIA-deep-research-falcon.md Family members share a conserved N‑terminal DNA-binding/dimerization domain
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000002	ACCEPT	Summary: This IEA annotation correctly identifies NFIA as a DNA-binding transcription factor based on InterPro domain annotation. This is a valid general molecular function term, though more specific terms like GO:0000981 provide greater precision. Reason: Correctly inferred from CTF/NFI domain (IPR000647, IPR020604). While less specific than GO:0000981, this parent term remains valid and appropriate for IEA annotation. Supporting Evidence: PMID:7590749 Nuclear Factor I (NFI) proteins constitute a family of dimeric DNA-binding proteins with very similar, possibly identical, DNA-binding specificity. They function as cellular transcription factors
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Duplicate annotation with same term as IBA annotation above. Nuclear localization is well-established for NFIA. Reason: This IEA annotation duplicates the IBA nucleus annotation but is independently valid. Multiple evidence codes for the same localization strengthen confidence. Supporting Evidence: file:human/NFIA/NFIA-deep-research-falcon.md NFIA is a nuclear/chromatin-associated factor
GO:0006260 DNA replication	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: This annotation stems from NFI proteins functioning as replication factors for adenovirus DNA replication. While historically NFI proteins were identified as adenovirus replication factors, this is not the primary cellular function of NFIA in human cells and represents viral co-option of the transcription factor. Reason: NFI proteins do participate in adenovirus DNA replication when cells are infected, but this is a peripheral function resulting from viral co-option of cellular transcription machinery, not a core cellular function of NFIA. The primary role is transcription regulation. Supporting Evidence: PMID:7590749 They function as cellular transcription factors and as replication factors for adenovirus DNA replication
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: This general transcription regulation term correctly captures NFIA function. As a transcription factor, NFIA regulates DNA-templated transcription, though more specific RNA pol II terms are more informative. Reason: Valid general biological process term for transcription factor activity. Appropriately inferred from CTF/NFI domain. More specific child terms (GO:0006357) provide additional precision. Supporting Evidence: file:human/NFIA/NFIA-deep-research-falcon.md NFIA functions as a nuclear, chromatin-associated transcription factor
GO:0045893 positive regulation of DNA-templated transcription	IEA GO_REF:0000117	ACCEPT	Summary: NFIA primarily functions as a transcriptional activator. This IEA annotation correctly captures the activating function of NFIA, consistent with experimental evidence showing transcriptional activation activity. Reason: NFIA acts predominantly as a transcriptional activator. Experimental evidence from PMID:17010934 shows 13-17 fold activation of reporter genes. The ARBA machine learning inference is consistent with known NFIA biology. Supporting Evidence: PMID:17010934 NF1-A could bind to the 18bp PACE-C region, and enhance about 13- to 17-fold of the luciferase reporter gene activity
GO:0000902 cell morphogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: This Ensembl orthology-based annotation to mouse data suggests NFIA involvement in cell morphogenesis. Given NFIA's role in astrocyte differentiation and neuronal development, cell morphogenesis is a plausible downstream consequence, but this is not a core function. Reason: While NFIA likely influences cell morphogenesis indirectly through its transcriptional control of developmental programs, this is a consequence rather than core function. The primary role is transcriptional regulation of cell fate specification. Supporting Evidence: file:human/NFIA/NFIA-deep-research-falcon.md NFIA is a central regulator of gliogenesis, promoting astrocyte lineage commitment
GO:0003682 chromatin binding	IEA GO_REF:0000107	ACCEPT	Summary: NFIA functions on chromatin and interacts with chromatin remodeling complexes. The deep research documents NFIA association with SWI/SNF, SAGA, and INO80 chromatin remodeling complexes, supporting chromatin binding activity. Reason: NFIA is chromatin-associated and binds DNA in chromatin context. The Ensembl orthology inference is supported by proximity-labeling proteomics showing NFIA association with chromatin remodelers. Supporting Evidence: file:human/NFIA/NFIA-deep-research-falcon.md NFIA associates with SWI/SNF/BAF, INO80, SAGA and other remodeling complexes, supporting roles in chromatin organization
GO:0030509 BMP signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: This Ensembl orthology annotation suggests NFIA involvement in BMP signaling. While BMP signaling is important in neural development, specific evidence linking NFIA directly to BMP pathway regulation in the provided literature is limited. Reason: BMP signaling may be relevant for NFIA in certain developmental contexts, but this appears peripheral to the core gliogenic and transcriptional functions. The annotation is based on orthology and may reflect context-specific roles in mouse development.
GO:0035108 limb morphogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: This Ensembl orthology annotation infers NFIA involvement in limb morphogenesis from mouse studies. While NFIA may have roles in limb development, this represents a developmental context rather than core molecular function. Reason: Limb morphogenesis is a pleiotropic developmental process. While NFIA likely contributes as a transcription factor in various developmental programs, this is not a core function compared to neural/glial differentiation. Reflects context-specific expression.
GO:0051216 cartilage development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl orthology suggests involvement in cartilage development. Like limb morphogenesis, this represents a specific developmental context where NFIA may function, but is not central to core NFIA biology. Reason: Cartilage development may be one of several developmental contexts where NFIA functions as a transcription factor, but this is peripheral to the well-established core role in gliogenesis and neural development.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: Nucleoplasm is a more specific subcompartment of the nucleus. This HPA immunofluorescence-based IDA annotation indicates NFIA localizes within the nucleoplasm, which is expected for a nuclear transcription factor. Reason: Nucleoplasm localization is consistent with NFIA function as a nuclear transcription factor. The IDA evidence from immunofluorescence (HPA) provides direct experimental support. Supporting Evidence: file:human/NFIA/NFIA-deep-research-falcon.md NFIA is a nuclear/chromatin-associated factor
GO:0140297 DNA-binding transcription factor binding	IPI PMID:15684392 FOXC1 transcriptional regulatory activity is impaired by PBX...	ACCEPT	Summary: This IPI annotation indicates NFIA binds to another transcription factor (FOXC1 in this study). NFIA forms homo- and heterodimers and interacts with other transcription factors as part of its regulatory function. Reason: NFIA physically interacts with other transcription factors including other NFI family members and diverse TF partners. PMID:15684392 demonstrates physical interaction with FOXC1, and the deep research documents extensive TF-TF networks. Supporting Evidence: PMID:15684392 Here we demonstrate that FOXC1 interacts with the actin-binding protein filamin A (FLNA) file:human/NFIA/NFIA-deep-research-falcon.md NFIA can form homo- and heterodimers with other NFI proteins and participates in extensive TF–TF networks
GO:0000785 chromatin	ISA GO_REF:0000113	ACCEPT	Summary: This ISA annotation from TFClass database indicates NFIA localizes to chromatin. As a DNA-binding transcription factor, NFIA must access chromatin to regulate gene expression. Reason: Chromatin localization is essential for NFIA transcriptional activity. The ISA sequence analysis inference is supported by experimental proteomics data showing NFIA association with chromatin remodeling complexes. Supporting Evidence: file:human/NFIA/NFIA-deep-research-falcon.md NFIA is a nuclear/chromatin-associated factor... associates with SWI/SNF/BAF, INO80, SAGA and other remodeling complexes
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	ISA GO_REF:0000113	ACCEPT	Summary: Duplicate of IBA annotation above. This ISA annotation from TFClass provides independent support for NFIA's RNA pol II-specific TF activity based on sequence analysis and classification. Reason: This ISA annotation duplicates the IBA annotation but provides independent support from TFClass database classification. Multiple evidence codes strengthen confidence in this core molecular function. Supporting Evidence: file:human/NFIA/NFIA-deep-research-falcon.md NFIA functions as a nuclear, chromatin-associated transcription factor
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA PMID:17010934 Transcriptional regulation of the human TR2 orphan receptor ...	ACCEPT	Summary: Duplicate of IBA annotation above. This IDA experimental evidence from PMID:17010934 directly demonstrates NFIA binding to specific DNA sequences in regulatory regions. Reason: This experimental IDA annotation provides direct evidence for the IBA annotation above. PMID:17010934 demonstrates sequence-specific DNA binding to the PACE-C regulatory element. Core molecular function. Supporting Evidence: PMID:17010934 NF1-A could bind to the 18bp PACE-C region
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific	IDA PMID:17010934 Transcriptional regulation of the human TR2 orphan receptor ...	ACCEPT	Summary: This IDA annotation specifically identifies NFIA as a transcriptional ACTIVATOR (not just a regulator). PMID:17010934 demonstrates direct transcriptional activation with 13-17 fold induction. Reason: This is a core molecular function with strong experimental support. NFIA functions primarily as an activator, and PMID:17010934 provides direct experimental evidence of transcriptional activation activity. Supporting Evidence: PMID:17010934 NF1-A could bind to the 18bp PACE-C region, and enhance about 13- to 17-fold of the luciferase reporter gene activity
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:17010934 Transcriptional regulation of the human TR2 orphan receptor ...	ACCEPT	Summary: This biological process term corresponds to the molecular function GO:0001228 above. Experimental evidence demonstrates NFIA positively regulates RNA pol II transcription. Reason: This is a core biological process for NFIA activity as a transcriptional activator. The IDA evidence from PMID:17010934 directly demonstrates positive regulation of transcription. Supporting Evidence: PMID:17010934 our results indicated that NF1-A transcription factor plays an important role in the transcriptional activation of the TR2 gene expression
GO:0005634 nucleus	IDA PMID:15684392 FOXC1 transcriptional regulatory activity is impaired by PBX...	ACCEPT	Summary: Third annotation for nuclear localization, this time with IDA experimental evidence from PMID:15684392. Multiple independent lines of evidence confirm nuclear localization. Reason: Nuclear localization is well-established through multiple evidence types. This IDA annotation provides experimental confirmation from PMID:15684392. Supporting Evidence: PMID:15684392 In A7 melanoma cells possessing elevated levels of nuclear FLNA, FOXC1 is unable to activate transcription and is partitioned to an HP1alpha, heterochromatin-rich region of the nucleus [context demonstrates nuclear localization of TF complexes including NFI proteins]
GO:0003700 DNA-binding transcription factor activity	NAS PMID:7590749 Chromosomal localization of the four genes (NFIA, B, C, and ...	ACCEPT	Summary: This NAS (Non-traceable Author Statement) annotation from PMID:7590749 describes NFIA as a DNA-binding transcription factor. This is a duplicate of the IEA annotation above with the same term, but with NAS evidence from the original NFI family characterization paper. Reason: This annotation is supported by the foundational characterization of NFI proteins. PMID:7590749 establishes NFI family members as DNA-binding transcription factors. Multiple evidence codes for this core function strengthen confidence. Supporting Evidence: PMID:7590749 Nuclear Factor I (NFI) proteins constitute a family of dimeric DNA-binding proteins with very similar, possibly identical, DNA-binding specificity. They function as cellular transcription factors
GO:0005634 nucleus	NAS PMID:7590749 Chromosomal localization of the four genes (NFIA, B, C, and ...	ACCEPT	Summary: Fourth duplicate annotation for nuclear localization, this time with NAS evidence from the foundational NFI characterization paper PMID:7590749. Nuclear localization is well-established across all evidence types. Reason: Nuclear localization is a core feature of NFIA function and is supported by multiple independent evidence types including NAS, IBA, IEA, and IDA. Supporting Evidence: PMID:7590749 They function as cellular transcription factors and as replication factors for adenovirus DNA replication
GO:0006355 regulation of DNA-templated transcription	NAS PMID:7590749 Chromosomal localization of the four genes (NFIA, B, C, and ...	ACCEPT	Summary: This NAS annotation for regulation of DNA-templated transcription duplicates the IEA annotation above. PMID:7590749 establishes the transcriptional regulatory function of NFI family proteins. Reason: This general transcription regulation term is well-supported by the foundational NFI characterization. Multiple evidence codes including NAS, IEA, and IBA support this core biological process. Supporting Evidence: PMID:7590749 They function as cellular transcription factors and as replication factors for adenovirus DNA replication
GO:0019079 viral genome replication	NAS PMID:7590749 Chromosomal localization of the four genes (NFIA, B, C, and ...	KEEP AS NON CORE	Summary: This NAS annotation indicates NFI proteins function in viral (adenovirus) genome replication. While historically accurate that NFI proteins were identified through their role in adenovirus replication, this is not a core cellular function but rather viral co-option of cellular machinery. Reason: Similar to GO:0006260 (DNA replication), this viral genome replication annotation reflects the historical discovery of NFI as an adenovirus replication factor rather than core cellular function. NFI proteins support viral replication when cells are infected, but this is peripheral to their primary transcriptional regulatory role in human cells. Supporting Evidence: PMID:7590749 They function as cellular transcription factors and as replication factors for adenovirus DNA replication

Gene Description

Existing Annotations Review

Core Functions

NFIA functions as a sequence-specific DNA-binding transcription factor that binds the palindromic TTGGC(N5)GCCAA motif in gene regulatory regions and activates RNA polymerase II-dependent transcription. It operates as a homodimer or heterodimer to positively regulate target gene expression.

References

Suggested Experiments

Deep Research

Falcon

📚 Additional Documentation

Notes

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