Ifi204

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003690 double-stranded DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function of Ifi204. The tandem HIN-200 OB-fold domains bind dsDNA in a non-sequence-specific manner, confirmed by crystal structures of the HINab:DNA complex and fluorescence polarization assays. Reason: dsDNA binding is the central biochemical activity of Ifi204 HIN domains, directly demonstrated by structural and biochemical studies. Supporting Evidence: PMID:33619523 p204 HINab binds dsDNA mainly through alpha2 helix of HINa and HINb, and the linker between them, revealing a similar HIN:DNA binding mode file:mouse/Ifi204/Ifi204-deep-research-bioreason-sft.md The tandem OB-fold HIN region binds duplex DNA directly, supporting GO:0003690 double-stranded DNA binding file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005730 nucleolus	IBA GO_REF:0000033	ACCEPT	Summary: Well-supported localization. p204 is primarily nucleolar in proliferating cells, confirmed by immunofluorescence. Reason: Nucleolar localization is directly demonstrated by immunofluorescence in multiple studies, and p204 inhibits rRNA transcription through nucleolar interaction with UBF1. Supporting Evidence: PMID:10329630 p204, a member of the interferon-inducible p200 family of murine proteins, is primarily nucleolar file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0035458 cellular response to interferon-beta	IBA GO_REF:0000033	MODIFY	Summary: The supporting evidence establishes Ifi204 as a DNA sensor that promotes type I IFN/IFN-beta production, not specifically as a gene product responding to IFN-beta stimulation. Reason: Replace the response-to-IFN-beta term with production/regulation terms that match the accessible Ifi204 evidence from Francisella and mycobacterial infection models. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN001385751 SUPPORTS TRANSFER Node in PTHR12200, PANTHER family name "INTERFERON-INDUCIBLE PROTEIN AIM2 FAMILY MEMBER", the family UniProt also assigns to the target (PTHR12200:SF25). All seeds are mouse PYHIN proteins, so the target sits squarely inside the clade and the node placement is not in question; the issue is which side of the interferon circuit the term names. MGI:MGI:96429 · mouse Ifi204 (the review target itself) SUPPORTS TRANSFER The target's own MGI record is one of the IBD seeds, the expected marker that experimental grounding exists on the target itself: Ifi204 carries an IDA at this same term (GO:0035458, PMID:19158679), which is among the descendant evidences behind the IBD and which stands on its own regardless of how this IBA row is re-scoped. MGI:MGI:96428 · mouse Ifi203 (interferon activated gene 203) SUPPORTS TRANSFER Closely related mouse HIN-200 paralog; like the target it is interferon-inducible, which is how the family acquired response-to-interferon terms. MGI:MGI:2686159 · mouse Aim2 (absent in melanoma 2) SUPPORTS TRANSFER Cytosolic dsDNA sensor of the same family. The shared, informative property across these seeds is DNA sensing that drives type I interferon output, so the propagation itself is sound; annotating the target as a responder to IFN-beta rather than an upstream inducer of its production is the role conflation the MODIFY corrects. Neither GO:0032728 nor GO:0032481 is a descendant of GO:0035458, so this is a re-scope onto the correct role, not a narrowing. MGI:MGI:101847 · mouse Ifi205 (interferon activated gene 205) SUPPORTS TRANSFER IBD seed in the local PAINT cache for this node but not listed in the GOA WITH/FROM; same mouse PYHIN cluster. MGI:MGI:2138243 · mouse Ifi209 (interferon activated gene 209) SUPPORTS TRANSFER IBD seed in the local PAINT cache for this node but not listed in the GOA WITH/FROM; same mouse PYHIN cluster. Proposed replacements: positive regulation of interferon-beta production positive regulation of type I interferon production Supporting Evidence: PMID:25710914 cGAS and Ifi204 cooperate to sense cytosolic dsDNA and F. novicida infection to produce a strong type I IFN response file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0002218 activation of innate immune response	IBA GO_REF:0000033	ACCEPT	Summary: Core biological process. Ifi204 senses cytosolic dsDNA and activates the STING-TBK1-IRF3 innate immune signaling pathway. KO mice show impaired innate immune responses to bacterial infection. Reason: Multiple studies demonstrate Ifi204 is required for innate immune activation via the STING pathway in response to bacterial DNA. Supporting Evidence: PMID:30936875 IFI204 deficiency results in decreased survival, increased bacterial loads, severe organs damage, and decreased recruitment of neutrophils and macrophages file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005654 nucleoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Ifi204 is nuclear in proliferating cells, present in nucleoplasm as well as nucleolus and nuclear bodies. Reason: Nuclear/nucleoplasmic localization is well-documented by immunofluorescence and consistent with its transcriptional regulatory roles. Supporting Evidence: PMID:12513910 When superimposed on optical sections obtained with anti-p204 Abs, these colocalized, with the sole exception of the nucleolar compartment stained by the anti-p204 Abs only file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Ifi204 translocates to the cytosol during differentiation and upon bacterial infection, where it functions as a DNA sensor cooperating with cGAS to activate the STING pathway. Reason: Cytosolic localization is well-documented during infection (after acetylation) and during differentiation, and is functionally important for DNA sensing. Supporting Evidence: PMID:28529930 IFI204 first undergoes acetylation and then translocates from nucleus into cytoplasm to recruit STING for activation of TBK1-dependent IRF3 nuclear translocation file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0002218 activation of innate immune response	IEA GO_REF:0000002	ACCEPT	Summary: Redundant with the IBA annotation for the same term. The InterPro-based annotation from the HIN-200 family domain is consistent with experimental evidence. Reason: Correct annotation from InterPro HIN-200 family classification, supported by extensive experimental evidence for innate immune activation. Supporting Evidence: file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Ifi204 is nuclear in proliferating cells, consistent with UniProt subcellular location annotation. Reason: Nuclear localization is well-established by multiple experimental studies. Supporting Evidence: file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005730 nucleolus	IEA GO_REF:0000044	ACCEPT	Summary: Redundant with IBA and IDA annotations for the same term. Consistent with experimental evidence. Reason: Correct annotation supported by direct experimental evidence. Supporting Evidence: file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Ifi204 translocates to cytoplasm during differentiation and infection. This annotation is more general than cytosol but still correct. Reason: Cytoplasmic localization is well-documented during differentiation and bacterial infection. Supporting Evidence: file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0035458 cellular response to interferon-beta	IEA GO_REF:0000120	MODIFY	Summary: Redundant with the IBA response-to-IFN-beta annotation, but the available Ifi204 evidence supports type I IFN/IFN-beta production rather than cellular response to IFN-beta. Reason: Replace with production/regulation terms that capture Ifi204-dependent activation of the STING/type I interferon response. Proposed replacements: positive regulation of interferon-beta production positive regulation of type I interferon production Supporting Evidence: PMID:25710914 cGAS and Ifi204 cooperate to sense cytosolic dsDNA and F. novicida infection to produce a strong type I IFN response
GO:0005654 nucleoplasm	ISO GO_REF:0000119	ACCEPT	Summary: ISO transfer from human IFI16. Nucleoplasmic localization is confirmed by direct studies of Ifi204. Reason: Consistent with direct experimental evidence for Ifi204 nuclear localization. Supporting Evidence: file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005730 nucleolus	ISO GO_REF:0000119	ACCEPT	Summary: ISO transfer from human IFI16. Nucleolar localization is directly demonstrated for Ifi204. Reason: Redundant with IDA evidence but correct. Supporting Evidence: file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005829 cytosol	ISO GO_REF:0000119	ACCEPT	Summary: ISO transfer from human IFI16. Cytosolic localization during infection is directly demonstrated for Ifi204. Reason: Consistent with direct experimental evidence. Supporting Evidence: file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0031625 ubiquitin protein ligase binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: ISO transfer from human ortholog. While p204 promotes ubiquitination and degradation of Id proteins, this appears to be indirect (p204 sequesters Id proteins and promotes their ubiquitination by other ligases rather than directly binding ubiquitin ligases). Evidence is limited for direct ubiquitin ligase binding. Reason: The ISO transfer is plausible but the direct evidence for p204 binding ubiquitin ligases is limited. The ubiquitination of Id proteins promoted by p204 may be indirect. Supporting Evidence: file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0032991 protein-containing complex	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Generic complex annotation. Ifi204 forms complexes with multiple partners including UBF1, Runx2, Id proteins, Tpr, and STING, but this term is too vague to be informative. Reason: While Ifi204 participates in multiple protein complexes, the term protein-containing complex is too generic to be useful. More specific complex annotations would be preferable. Supporting Evidence: file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0009617 response to bacterium	IEP PMID:23012479 Impact of lactobacilli on orally acquired listeriosis.	MODIFY	Summary: Based on expression change during Listeria infection in a lactobacilli study. Ifi204 is one of many ISGs affected. While the annotation is not wrong (Ifi204 does respond to bacterial infection), this specific paper provides only weak expression evidence. Reason: While expression-based evidence from PMID:23012479 is weak, much stronger evidence from PMID:30936875 (IFI204-KO mice with S. aureus) and PMID:25710914 (Francisella response) directly demonstrates a role in defense response to bacterium, which is more specific and appropriate. Proposed replacements: defense response to bacterium Supporting Evidence: PMID:23012479 IFN-stimulated genes (ISGs) being the most affected by both lactobacilli file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005515 protein binding	IPI PMID:12513910 The mouse interferon-inducible gene Ifi204 product interacts...	REMOVE	Summary: Based on interaction with Tpr (nucleoporin). Per curation guidelines, protein binding is too generic and should be replaced with a more informative MF term. The interaction with Tpr is relevant to nuclear-cytoplasmic transport of p204. Reason: Per curation guidelines, GO:0005515 protein binding is uninformative. The Tpr interaction is better captured by noting Tpr as a transport partner rather than a generic protein binding annotation. Supporting Evidence: PMID:12513910 in vivo interaction was demonstrated by coimmunoprecipitation experiments file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005730 nucleolus	IDA PMID:12513910 The mouse interferon-inducible gene Ifi204 product interacts...	ACCEPT	Summary: Direct demonstration of nucleolar localization by immunofluorescence. Anti-p204 antibodies stained the nucleolar compartment. Reason: Direct experimental evidence for nucleolar localization, consistent with p204's function in inhibiting rRNA transcription. Supporting Evidence: PMID:12513910 the sole exception of the nucleolar compartment stained by the anti-p204 Abs only file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0035457 cellular response to interferon-alpha	IDA PMID:12513910 The mouse interferon-inducible gene Ifi204 product interacts...	ACCEPT	Summary: p204 expression is induced by interferon treatment. The study shows p204 translocates to the nucleus after IFN treatment, mediated by Tpr interaction. Reason: Direct evidence that Ifi204 responds to interferon treatment with nuclear translocation mediated by Tpr. Supporting Evidence: PMID:12513910 Although the specific function of Tpr is not defined, it appears to mediate p204 translocation from the cytoplasmic to the nuclear compartment following IFN treatment file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0042405 nuclear inclusion body	IDA PMID:12513910 The mouse interferon-inducible gene Ifi204 product interacts...	ACCEPT	Summary: p204 localizes to discrete nuclear foci/inclusion bodies as shown by immunofluorescence, colocalizing with Tpr in the nuclear interior. Reason: Direct immunofluorescence evidence for localization to nuclear inclusion bodies. Supporting Evidence: PMID:12513910 The intranuclear Tpr occurred in apparently discrete foci. When superimposed on optical sections obtained with anti-p204 Abs, these colocalized file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0048839 inner ear development	IDA PMID:21795542 Developmental profiling of spiral ganglion neurons reveals i...	MARK AS OVER ANNOTATED	Summary: Based on transcriptomic profiling of spiral ganglion neurons. Ifi204 is one of many genes with altered expression during auditory development. The paper is a large-scale profiling study, not a functional study of Ifi204. Expression in a developing tissue does not demonstrate functional involvement. Reason: This annotation is based solely on expression profiling data from a transcriptomics screen. There is no functional evidence (knockdown, knockout, or other perturbation) that Ifi204 plays a role in inner ear development. The expression change likely reflects the interferon-responsive nature of Ifi204 during immune gene upregulation in maturing neurons, not a specific developmental function. Supporting Evidence: PMID:21795542 We catalogued gene expression in mouse SG neurons from embryonic day 12 ...exhibit a dramatic increase in immune gene expression file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005634 nucleus	ISO PMID:19158679 An orthogonal proteomic-genomic screen identifies AIM2 as a ...	ACCEPT	Summary: ISO transfer from human IFI16 based on an AIM2-focused paper is weak, but nuclear localization itself is supported by direct p204/Ifi204 localization evidence. Reason: Nuclear localization is well-established for Ifi204 by direct studies, making this ISO annotation consistent with known biology. Supporting Evidence: PMID:12513910 When superimposed on optical sections obtained with anti-p204 Abs, these colocalized, with the sole exception of the nucleolar compartment stained by the anti-p204 Abs only file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0016607 nuclear speck	ISO PMID:19158679 An orthogonal proteomic-genomic screen identifies AIM2 as a ...	REMOVE	Summary: The cited AIM2 paper describes cytoplasmic ASC inflammasome speckles, not nuclear speckles, and direct Ifi204 evidence supports p204/Tpr intranuclear foci and nucleolus rather than GO nuclear speck. Reason: The ISO transfer is not adequately supported for this specific cellular component. ASC speckles are inflammasome structures, and p204 intranuclear foci should not be equated with nuclear speckles without direct evidence. Supporting Evidence: PMID:19158679 AIM2 showed specificity for double-stranded DNA. It also recruited the inflammasome adaptor ASC and localized to ASC 'speckles' PMID:12513910 The intranuclear Tpr occurred in apparently discrete foci file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0003690 double-stranded DNA binding	IDA PMID:19158679 An orthogonal proteomic-genomic screen identifies AIM2 as a ...	ACCEPT	Summary: While PMID:19158679 is primarily about AIM2, dsDNA binding by Ifi204/p204 is directly supported by structural and biochemical studies of p204 HIN domains. Reason: dsDNA binding is the core molecular function of Ifi204 HIN domains, extensively validated by crystal structures and biochemical assays. Supporting Evidence: PMID:33619523 p204 HINab binds dsDNA mainly through α2 helix of HINa and HINb, and the linker between them, revealing a similar HIN:DNA binding mode file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0035458 cellular response to interferon-beta	IDA PMID:19158679 An orthogonal proteomic-genomic screen identifies AIM2 as a ...	MODIFY	Summary: PMID:19158679 is AIM2-focused and does not support Ifi204 cellular response to IFN-beta. Ifi204 evidence instead supports DNA-sensor-dependent IFN-beta/type I interferon production. Reason: Replace this term with production/regulation terms matching the direct Ifi204 evidence. The accessible studies show Ifi204 is required for STING-dependent type I IFN or IFN-beta production after bacterial DNA sensing, not simply response to IFN-beta. Proposed replacements: positive regulation of interferon-beta production positive regulation of type I interferon production Supporting Evidence: PMID:25710914 cGAS and Ifi204 cooperate to sense cytosolic dsDNA and F. novicida infection to produce a strong type I IFN response PMID:28529930 IFI204 plays an important role in IFN-β release during M. bovis infection in murine macrophage model file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0003712 transcription coregulator activity	IGI PMID:15557274 The interferon-inducible p204 protein acts as a transcriptio...	ACCEPT	Summary: p204 acts as a transcriptional coactivator of Cbfa1/Runx2 during osteoblast differentiation. High p204 levels augment Runx2-dependent transcription; low levels decrease it. p204 associates with Runx2 both in vitro and in vivo. Reason: Core molecular function demonstrated by direct biochemical evidence. p204 enhances Runx2-dependent transcription as a coactivator. Supporting Evidence: PMID:15557274 high levels of p204 augment, whereas the lowering of p204 level decreases, the Cbfa1-dependent transcription, and...p204 associates with Cbfa1 both in vitro and in vivo file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005515 protein binding	IPI PMID:15557274 The interferon-inducible p204 protein acts as a transcriptio...	REMOVE	Summary: Based on interaction with Runx2/Cbfa1. Per curation guidelines, protein binding is too generic. The interaction with Runx2 is better captured by the transcription coregulator activity annotation. Reason: Per curation guidelines, GO:0005515 protein binding is uninformative. The functionally relevant interaction is captured by GO:0003712 transcription coregulator activity. Supporting Evidence: PMID:15557274 p204 associates with Cbfa1 both in vitro and in vivo. Two nonoverlapping segments in p204 bind to Cbfa1 file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0006357 regulation of transcription by RNA polymerase II	IDA PMID:15557274 The interferon-inducible p204 protein acts as a transcriptio...	ACCEPT	Summary: p204 modulates Runx2-dependent transcription from RNA Pol II promoters during osteoblast differentiation. Also shown to regulate transcription of rRNA (via UBF1) and other target genes. Reason: Direct evidence for regulation of Pol II transcription through coactivation of Runx2 and modulation of other transcription factors. Supporting Evidence: PMID:15557274 p204 acts as a cofactor of Cbfa1...high levels of p204 augment...the Cbfa1-dependent transcription file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0045669 positive regulation of osteoblast differentiation	IGI PMID:15557274 The interferon-inducible p204 protein acts as a transcriptio...	KEEP AS NON CORE	Summary: p204 overexpression enhances BMP-2-induced osteoblast differentiation in vitro, with elevated alkaline phosphatase activity and osteocalcin production. Expressed in embryonic osteoblasts and growth plate chondrocytes. Reason: Valid annotation but represents a non-core, context-dependent function. Osteoblast differentiation is one of several differentiation programs p204 participates in (also myoblast and cardiac), reflecting its general role in overcoming Id protein inhibition rather than a specific osteoblast function. Supporting Evidence: PMID:15557274 Overexpression of p204 enhances the BMP-2-induced osteoblast differentiation in vitro, as revealed by elevated alkaline phosphatase activity and osteocalcin production file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005654 nucleoplasm	ISO PMID:14654789 A member of the Pyrin family, IFI16, is a novel BRCA1-associ...	ACCEPT	Summary: ISO from human IFI16. Nucleoplasmic localization of IFI16 is demonstrated by immunofluorescence. Consistent with direct evidence for Ifi204. Reason: Consistent with direct experimental evidence for Ifi204. Supporting Evidence: PMID:14654789 We found that IFI16 was localized in the nucleoplasm and nucleoli file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0005730 nucleolus	ISO PMID:14654789 A member of the Pyrin family, IFI16, is a novel BRCA1-associ...	ACCEPT	Summary: ISO from human IFI16. IFI16 nucleolar localization is demonstrated. Consistent with direct evidence for Ifi204. Reason: Redundant with IDA evidence but correct. Supporting Evidence: PMID:14654789 We found that IFI16 was localized in the nucleoplasm and nucleoli file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	ISO PMID:14654789 A member of the Pyrin family, IFI16, is a novel BRCA1-associ...	KEEP AS NON CORE	Summary: ISO from human IFI16. PMID:14654789 shows IFI16 interacts with BRCA1 and collaborates in p53-mediated apoptosis after DNA damage. p204 is known to inhibit cell growth via p53-dependent pathways, but direct evidence for p53-mediated apoptotic signaling in response to DNA damage is limited for mouse Ifi204 specifically. Reason: The ISO transfer from IFI16 is plausible given that p204 also interacts with p53 and modulates cell growth. However, the specific apoptotic signaling pathway in response to DNA damage has not been directly demonstrated for mouse Ifi204. Keep as non-core pending direct evidence. Supporting Evidence: PMID:14654789 Coexpression of IFI16 and BRCA1 enhanced DNA damage-induced apoptosis in mouse embryonic fibroblasts from BRCA1 mutant mice expressing wild-type p53 file:mouse/Ifi204/Ifi204-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.]

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Tags

Deep Research

Bioreason Pro

Falcon

📚 Additional Documentation

Notes

Bioreason Sft Review

📄 View Raw YAML