Details for: IFIT5

Gene ID: 24138

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: IFIT5

Ensembl ID: ENSG00000152778

Description: interferon induced protein with tetratricopeptide repeats 5

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • neural progenitor cell CL0011020
    CSI 5.8
    rCSI 25.51%
    PRS 78.79
  • unswitched memory B cell CL0000970
    CSI 5.64
    rCSI 4.75%
    PRS 96.73
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 3.54
    rCSI 2.54%
    PRS 97.18
  • epithelial cell of lung CL0000082
    CSI 3.14
    rCSI 2.6%
    PRS 90.2
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.61
    rCSI 2.01%
    PRS 92.41
  • retina horizontal cell CL0000745
    CSI 2.61
    rCSI 3.97%
    PRS 86.3
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 2.47
    rCSI 7.28%
    PRS 89.67
  • ciliated epithelial cell CL0000067
    CSI 2.34
    rCSI 2.05%
    PRS 80.57
  • mature alpha-beta T cell CL0000791
    CSI 2.27
    rCSI 8.22%
    PRS 97.96
  • vascular associated smooth muscle cell CL0000359
    CSI 2.12
    rCSI 6.88%
    PRS 87.49
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.07
    rCSI 2.66%
    PRS 85.96
  • radial glial cell CL0000681
    CSI 2.05
    rCSI 2.85%
    PRS 87.96
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 1.99
    rCSI 2.3%
    PRS 82.27
  • bronchus fibroblast of lung CL2000093
    CSI 1.95
    rCSI 1.58%
    PRS 88.58
  • retinal blood vessel endothelial cell CL0002585
    CSI 1.91
    rCSI 3.04%
    PRS 91.85
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.89
    rCSI 2.43%
    PRS 76.83
  • peripheral nervous system neuron CL2000032
    CSI 1.74
    rCSI 2.38%
    PRS 82.9
  • glioblast CL0000030
    CSI 1.69
    rCSI 2.69%
    PRS 81.86
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.68
    rCSI 2.09%
    PRS 73.51
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.46
    rCSI 2.91%
    PRS 96
  • mesenchymal cell CL0008019
    CSI 1.27
    rCSI 3.23%
    PRS 84.19

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [IFIT5](/details-gene/24138) (Interferon Induced Protein With Tetratricopeptide Repeats 5) is a protein-coding gene located on chromosome 10q23.31. As a member of the IFIT gene family, it plays a crucial role in the innate immune system as an interferon-stimulated gene (ISG). Its primary function is in the defense response to viruses, where it recognizes specific RNA structures characteristic of viral replication intermediates, thereby inhibiting viral propagation [Link](https://doi.org/10.1038/ni.2048), [Link](https://doi.org/10.1073/pnas.1412842111). **Overall**, expression data reveals its significance not only in canonical immune cells such as [unswitched memory B cells](/details-cell/CL0000970) and [T cells](/details-cell/CL0000084), but also highlights a pronounced role in non-immune cell types, most notably [neural progenitor cells](/details-cell/CL0011020), suggesting functions that may extend beyond classical antiviral immunity. ## Cellular Roles and Expression Landscape The expression profile of [IFIT5](/details-gene/24138) indicates its importance across multiple biological systems, particularly in contexts of host defense and cellular development. Its significance is highest in [neural progenitor cells](/details-cell/CL0011020) (CSI: 5.80), a finding that suggests a potential role in neurodevelopment or the protection of neural stem cell niches from viral threats. The gene is also a key marker in several immune cell populations. It shows high significance in [unswitched memory B cells](/details-cell/CL0000970) (CSI: 5.64), [CD4-positive, alpha-beta memory T cells](/details-cell/CL0000897) (CSI: 3.54), and [CD14-low, CD16-positive monocytes](/details-cell/CL0002396) (CSI: 2.61). This pattern suggests [IFIT5](/details-gene/24138) is an active component of both the adaptive and innate immune responses following interferon stimulation. Furthermore, [IFIT5](/details-gene/24138) is significantly expressed in barrier tissues, such as in [epithelial cells of the lung](/details-cell/CL0000082) (CSI: 3.14) and [ciliated epithelial cells](/details-cell/CL0000067) (CSI: 2.34). This localization is consistent with its function as a first-line antiviral defender at common sites of pathogen entry. The broad, yet specific, expression pattern across immune, neural, and epithelial lineages underscores its role as a versatile effector of the interferon-mediated innate immune response. ## Pathways and Molecular Function The functional annotations for [IFIT5](/details-gene/24138) confirm its central role in host-pathogen interactions. Gene Ontology (GO) analysis places it squarely within the [defense response to virus](/details-go/GO:0051607) and the broader [innate immune response](/details-go/GO:0045087). Mechanistically, this is achieved through its molecular function as an [RNA binding](/details-go/GO:0003723) protein. Specifically, [IFIT5](/details-gene/24138) can recognize and bind various RNA structures, including [poly(U) RNA](/details-go/GO:0008266), [tRNA](/details-go/GO:0000049), and RNA with 5'-triphosphate ends, a common feature of viral RNA, which leads to the [negative regulation of viral genome replication](/details-go/GO:0045071) [Link](https://doi.org/10.1038/nature11783), [Link](https://doi.org/10.1016/j.molcel.2012.12.015). According to Reactome pathway analysis, [IFIT5](/details-gene/24138) is a key component of the [Interferon signaling](/details-reactome/R-HSA-913531) pathway, particularly [Interferon alpha/beta signaling](/details-reactome/R-HSA-909733). In addition to its direct antiviral actions, [IFIT5](/details-gene/24138) has been shown to positively regulate pro-inflammatory signaling by facilitating the recruitment of the IKK complex, a key step in [positive regulation of canonical NF-kappaB signal transduction](/details-go/GO:0043123) [Link](https://doi.org/10.1016/j.cellsig.2015.08.018). This dual function of direct viral inhibition and amplification of inflammatory signals makes it a critical effector of the innate immune response. ## Research Directions The diverse expression pattern of [IFIT5](/details-gene/24138) provides fertile ground for several novel research avenues. The data prompts the formulation of several testable hypotheses: 1. The high significance of [IFIT5](/details-gene/24138) in [neural progenitor cells](/details-cell/CL0011020) suggests a primary role in protecting this critical cell population from neurotropic viruses, or alternatively, a secondary role in regulating neurogenesis or cell fate decisions, possibly through its RNA-binding capabilities. 2. Given its expression in both innate ([monocytes](/details-cell/CL0000576)) and adaptive ([B](/details-cell/CL0000236) and [T cells](/details-cell/CL0000084)) lymphocytes, [IFIT5](/details-gene/24138) may function as a molecular link that helps coordinate the transition from an early innate response to a mature adaptive response during viral infections. 3. The role of [IFIT5](/details-gene/24138) in positively regulating NF-kappaB signaling suggests that its dysregulation in [epithelial cells of the lung](/details-cell/CL0000082) could contribute to the hyperinflammatory state (cytokine storm) observed in severe respiratory viral infections like influenza or SARS-CoV-2. To explore the first hypothesis, a compelling experimental approach would be to investigate the role of [IFIT5](/details-gene/24138) in neural development and defense. Using a human iPSC-derived neural progenitor cell (NPC) model, a CRISPR-Cas9 knockout of [IFIT5](/details-gene/24138) could be generated. The impact of its absence on NPC proliferation, differentiation into neurons and glia, and transcriptome profile could be assessed via high-content imaging and RNA-seq. Subsequently, these knockout and wild-type NPCs could be challenged with a neurotropic virus, such as Zika virus, to directly measure the gene's contribution to antiviral defense by quantifying viral load and cell apoptosis. From a therapeutic perspective, [IFIT5](/details-gene/24138) is an attractive candidate for modulation rather than simple inhibition or activation. As a natural host defense protein, strategies aimed at augmenting its expression or activity could be beneficial for treating acute viral infections. Development of small-molecule agonists or mimetics that enhance its viral RNA recognition capabilities could represent a novel class of host-directed antiviral therapies. However, its pro-inflammatory role via NF-kappaB signaling necessitates caution, as untargeted activation could exacerbate inflammatory damage. A targeted delivery mechanism to sites of infection, such as the respiratory tract, would be critical for any therapeutic application.

Genular Protein ID: 2441577733

Symbol: IFIT5_HUMAN

Name: Interferon-induced protein with tetratricopeptide repeats 5

UniProtKB Accession Codes:

Q13325 B2R5X9 B4DDV1 Q5T7I9 Q6IAX3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 2 EvolutionaryTrace 1 GO 15 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 6 PDBsum 6 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9398535

Title: A novel interferon-inducible gene expressed during myeloid differentiation.

PubMed ID: 9398535

DOI: 10.1006/bcmd.1997.0151

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 20950130

Title: The ISG56/IFIT1 gene family.

PubMed ID: 20950130

DOI: 10.1089/jir.2010.0101

PubMed ID: 21642987

Title: IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA.

PubMed ID: 21642987

DOI: 10.1038/ni.2048

PubMed ID: 25092312

Title: Broad and adaptable RNA structure recognition by the human interferon-induced tetratricopeptide repeat protein IFIT5.

PubMed ID: 25092312

DOI: 10.1073/pnas.1412842111

PubMed ID: 26334375

Title: IFIT5 positively regulates NF-kappaB signaling through synergizing the recruitment of IkappaB kinase (IKK) to TGF-beta-activated kinase 1 (TAK1).

PubMed ID: 26334375

DOI: 10.1016/j.cellsig.2015.08.018

PubMed ID: 23774268

Title: Crystal structure and nucleotide selectivity of human IFIT5/ISG58.

PubMed ID: 23774268

DOI: 10.1038/cr.2013.80

PubMed ID: 23317505

Title: tRNA binding, structure, and localization of the human interferon-induced protein IFIT5.

PubMed ID: 23317505

DOI: 10.1016/j.molcel.2012.12.015

PubMed ID: 23334420

Title: Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins.

PubMed ID: 23334420

DOI: 10.1038/nature11783

Sequence Information:

  • Length: 482
  • Mass: 55847
  • Checksum: 8045BC100384BE05
  • Sequence:
    • MSEIRKDTLK AILLELECHF TWNLLKEDID LFEVEDTIGQ QLEFLTTKSR LALYNLLAYV 
KHLKGQNKDA LECLEQAEEI IQQEHSDKEE VRSLVTWGNY AWVYYHMDQL EEAQKYTGKI 
GNVCKKLSSP SNYKLECPET DCEKGWALLK FGGKYYQKAK AAFEKALEVE PDNPEFNIGY 
AITVYRLDDS DREGSVKSFS LGPLRKAVTL NPDNSYIKVF LALKLQDVHA EAEGEKYIEE 
ILDQISSQPY VLRYAAKFYR RKNSWNKALE LLKKALEVTP TSSFLHHQMG LCYRAQMIQI 
KKATHNRPKG KDKLKVDELI SSAIFHFKAA MERDSMFAFA YTDLANMYAE GGQYSNAEDI 
FRKALRLENI TDDHKHQIHY HYGRFQEFHR KSENTAIHHY LEALKVKDRS PLRTKLTSAL 
KKLSTKRLCH NALDVQSLSA LGFVYKLEGE KRQAAEYYEK AQKIDPENAE FLTALCELRL 
SI