Details for: IFIT1

Gene ID: 3434

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: IFIT1

Ensembl ID: ENSG00000185745

Description: interferon induced protein with tetratricopeptide repeats 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • T follicular helper cell CL0002038
    CSI 26.69
    rCSI 19.98%
    PRS 94.67
  • fallopian tube secretory epithelial cell CL4030006
    CSI 10.83
    rCSI 10.42%
    PRS 84.4
  • multi-ciliated epithelial cell CL0005012
    CSI 6.24
    rCSI 6.23%
    PRS 79.59
  • myofibroblast cell CL0000186
    CSI 5.78
    rCSI 8%
    PRS 81.66
  • glioblast CL0000030
    CSI 5.66
    rCSI 9.03%
    PRS 77.17
  • fibroblast of lung CL0002553
    CSI 5.54
    rCSI 5.16%
    PRS 86.25
  • retinal cone cell CL0000573
    CSI 5.25
    rCSI 8.45%
    PRS 76.38
  • epithelial cell of lung CL0000082
    CSI 5.1
    rCSI 4.23%
    PRS 86.33
  • mononuclear phagocyte CL0000113
    CSI 3.89
    rCSI 8.56%
    PRS 88.22
  • elicited macrophage CL0000861
    CSI 3.67
    rCSI 3.37%
    PRS 91.48
  • alternatively activated macrophage CL0000890
    CSI 3.43
    rCSI 4.31%
    PRS 92.53
  • cerebral cortex endothelial cell CL1001602
    CSI 3.27
    rCSI 5.65%
    PRS 78.09
  • ciliated epithelial cell CL0000067
    CSI 3.03
    rCSI 2.66%
    PRS 75.49
  • secretory cell CL0000151
    CSI 2.86
    rCSI 2.99%
    PRS 84.53
  • mesodermal cell CL0000222
    CSI 2.81
    rCSI 3.37%
    PRS 83.55
  • rod bipolar cell CL0000751
    CSI 2.76
    rCSI 4.96%
    PRS 79.43
  • non-classical monocyte CL0000875
    CSI 2.74
    rCSI 4.39%
    PRS 92.18
  • ionocyte CL0005006
    CSI 2.71
    rCSI 2.91%
    PRS 87.23
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.53
    rCSI 4.05%
    PRS 88.46
  • blood vessel endothelial cell CL0000071
    CSI 2.52
    rCSI 5.24%
    PRS 82.59
  • extravillous trophoblast CL0008036
    CSI 2.36
    rCSI 2.92%
    PRS 83.62
  • vein endothelial cell CL0002543
    CSI 2.27
    rCSI 6.2%
    PRS 89.99
  • alveolar adventitial fibroblast CL4028006
    CSI 2.12
    rCSI 3.34%
    PRS 86.33
  • monocyte CL0000576
    CSI 2.07
    rCSI 3.75%
    PRS 88.21
  • retina horizontal cell CL0000745
    CSI 2
    rCSI 3.04%
    PRS 82.39
  • mesenchymal cell CL0008019
    CSI 1.9
    rCSI 4.83%
    PRS 79.05
  • duct epithelial cell CL0000068
    CSI 1.89
    rCSI 2.76%
    PRS 89.45
  • lung ciliated cell CL1000271
    CSI 1.84
    rCSI 2.13%
    PRS 78.69
  • vascular associated smooth muscle cell CL0000359
    CSI 1.72
    rCSI 5.57%
    PRS 83.21
  • enteroendocrine cell CL0000164
    CSI 1.7
    rCSI 2.32%
    PRS 84.33
  • ciliated cell CL0000064
    CSI 1.65
    rCSI 2.67%
    PRS 80.18
  • Hofbauer cell CL3000001
    CSI 1.57
    rCSI 2.97%
    PRS 91.6
  • alveolar macrophage CL0000583
    CSI 1.49
    rCSI 2.46%
    PRS 88.38
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.23
    rCSI 2.06%
    PRS 69.25
  • squamous epithelial cell CL0000076
    CSI 1.13
    rCSI 2.68%
    PRS 84.17
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.1
    rCSI 3.19%
    PRS 84.37
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.05
    rCSI 2.4%
    PRS 78.69
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.96
    rCSI 2.34%
    PRS 67.11
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 0.76
    rCSI 4.61%
    PRS 93.3
  • endothelial cell of vascular tree CL0002139
    CSI 0.67
    rCSI 3.68%
    PRS 81.59
  • odontoblast CL0000060
    CSI 0.3
    rCSI 6.9%
    PRS 92.11

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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Comma-separated if multiple.
Legend:
  • 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 Interferon-induced protein with tetratricopeptide repeats 1 ([IFIT1](/details-gene/3434)) is a well-characterized protein-coding gene located on chromosome 10q23.31. As a member of the IFIT gene family, it is a primary interferon-stimulated gene (ISG) that plays a crucial role in the innate immune system's defense against viral pathogens. Its protein product functions by binding viral RNA and interacting with various host and viral proteins, thereby inhibiting viral replication and modulating cellular signaling pathways. **Overall**, expression data reveals an exceptionally high significance of [IFIT1](/details-gene/3434) in [T follicular helper cells](/details-cell/CL0002038), suggesting a specialized function in this T cell subset. Consistent with its role as a first-line antiviral defender, it is also highly significant in various epithelial cells of barrier tissues, such as the fallopian tube and lung, as well as in professional immune cells like macrophages and phagocytes. ## Cellular Roles and Expression Landscape The expression profile of [IFIT1](/details-gene/3434) underscores its central role in host defense, particularly at mucosal surfaces and within the immune system. The most striking observation is its remarkably high cell significance index (CSI: 26.69) in [T follicular helper cells](/details-cell/CL0002038), which far exceeds its significance in other cell types. This suggests that beyond its canonical role as a broadly-acting antiviral protein, [IFIT1](/details-gene/3434) may have a highly specific and critical function within the germinal center reaction, potentially influencing Tfh differentiation, cytokine production, or interaction with B cells. Consistent with its function as an interferon-stimulated gene, [IFIT1](/details-gene/3434) is also a significant marker in cell types that form the initial line of defense against pathogens. This includes high significance in [fallopian tube secretory epithelial cells](/details-cell/CL4030006), [multi-ciliated epithelial cells](/details-cell/CL0005012), and [epithelial cells of the lung](/details-cell/CL0000082). This pattern indicates its importance in establishing an antiviral state at mucosal barriers. Furthermore, its notable significance in stromal and myeloid cells, including [myofibroblast cells](/details-cell/CL0000186), [fibroblasts of the lung](/details-cell/CL0002553), [mononuclear phagocytes](/details-cell/CL0000113), and [elicited macrophages](/details-cell/CL0000861), highlights its widespread involvement in the cellular response to inflammatory and viral signals across diverse tissue compartments. ## Pathways and Molecular Function The functional annotations for [IFIT1](/details-gene/3434) firmly place it within the interferon-mediated antiviral response. It is a key component of several Reactome pathways, including [Antiviral mechanism by ifn-stimulated genes](/content/detail/R-HSA-1169410), [Interferon alpha/beta signaling](/content/detail/R-HSA-909733), and the broader [Immune System](/content/detail/R-HSA-168256) pathway. Its involvement is further supported by Gene Ontology (GO) annotations, which link it to biological processes such as [defense response to virus](/QuickGO/term/GO:0051607), [cellular response to type I interferon](/QuickGO/term/GO:0071357), and [antiviral innate immune response](/QuickGO/term/GO:0140374). Located primarily in the [cytoplasm](/QuickGO/term/GO:0005737), the IFIT1 protein exerts its function through its ability to bind both [RNA](/QuickGO/term/GO:0003723) and other [proteins](/QuickGO/term/GO:0005515). It can directly recognize specific viral RNA structures, such as those with 5'-triphosphates, to sequester them and prevent translation. Additionally, it has been shown to inhibit viral replication by interacting with viral proteins, such as the E1 helicase of HPV [Link](https://doi.org/10.1038/emboj.2008.241). Research also indicates a regulatory role, where it can act as a negative-feedback regulator of virus-triggered signaling pathways to prevent excessive inflammation [Link](https://doi.org/10.1073/pnas.0900818106). ## Research Directions The available data points toward novel functions for [IFIT1](/details-gene/3434) beyond its well-established role in general antiviral immunity, presenting several avenues for future investigation. **Proposed Hypotheses:** 1. The uniquely high significance of [IFIT1](/details-gene/3434) in [T follicular helper cells](/details-cell/CL0002038) suggests it plays a specialized role in regulating the germinal center response. It may modulate the translation of specific mRNAs that control Tfh differentiation, cytokine profiles (e.g., IL-21), or survival, thereby fine-tuning high-affinity antibody production during viral infections or vaccination. 2. In barrier tissues like the lung and fallopian tube, [IFIT1](/details-gene/3434) may function as a critical rheostat for the local inflammatory milieu. Its induction could serve not only to directly inhibit viral replication but also to negatively regulate signaling pathways that would otherwise lead to excessive tissue damage from an over-exuberant immune response. **Experimental Approach:** To test the first hypothesis regarding the role of [IFIT1](/details-gene/3434) in Tfh cell function, a conditional knockout mouse model could be employed. Specifically, *Ifit1*fl/fl mice could be crossed with *Cd4*-Cre or *Bcl6*-CreERT2 mice to achieve T cell-specific or Tfh-specific deletion of the gene, respectively. Following immunization with a T-dependent antigen (e.g., NP-CGG), the germinal center reaction would be analyzed. Key readouts would include quantification of Tfh cells (CXCR5+PD-1hi) and germinal center B cells by flow cytometry, assessment of antigen-specific antibody titers and affinity by ELISA, and single-cell RNA sequencing of sorted Tfh cells from knockout and control animals to define the downstream molecular pathways regulated by [IFIT1](/details-gene/3434). **Therapeutic Potential:** Directly targeting the intracellular [IFIT1](/details-gene/3434) protein with small molecules or biologics is challenging. However, its expression level serves as a robust biomarker for type I interferon activity. In the context of viral diseases, strategies to augment the interferon pathway and thereby enhance [IFIT1](/details-gene/3434) expression could be a viable therapeutic approach to boost antiviral immunity. Conversely, in autoimmune disorders characterized by a pathological interferon signature (e.g., systemic lupus erythematosus), inhibiting upstream signaling nodes that lead to [IFIT1](/details-gene/3434) induction, such as JAK/STAT pathways, represents a more practical therapeutic strategy than targeting [IFIT1](/details-gene/3434) itself.

Genular Protein ID: 3662513422

Symbol: IFIT1_HUMAN

Name: Interferon-induced protein with tetratricopeptide repeats 1

UniProtKB Accession Codes:

P09914 B3KS50 D3DR31 Q5T7J1 Q96QM5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CPTC 1 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 10 Ensembl 2 EvolutionaryTrace 1 GO 14 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 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 8 PDBsum 8 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 2 RefSeq 4 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3753936

Title: Molecular cloning, full-length sequence and preliminary characterization of a 56-kDa protein induced by human interferons.

PubMed ID: 3753936

DOI: 10.1111/j.1432-1033.1986.tb09452.x

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: 6186990

Title: Interferon-induced 56,000 Mr protein and its mRNA in human cells: molecular cloning and partial sequence of the cDNA.

PubMed ID: 6186990

DOI: 10.1093/nar/11.5.1213

PubMed ID: 3121313

Title: New inducers revealed by the promoter sequence analysis of two interferon-activated human genes.

PubMed ID: 3121313

DOI: 10.1111/j.1432-1033.1987.tb13614.x

PubMed ID: 3360121

Title: The IFI-56K and IFI-54K interferon-inducible human genes belong to the same gene family.

PubMed ID: 3360121

DOI: 10.1016/0014-5793(88)80724-5

PubMed ID: 16009940

Title: Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways.

PubMed ID: 16009940

DOI: 10.1073/pnas.0504754102

PubMed ID: 16023166

Title: Induction and mode of action of the viral stress-inducible murine proteins, P56 and P54.

PubMed ID: 16023166

DOI: 10.1016/j.virol.2005.06.011

PubMed ID: 19008854

Title: Interferon-inducible protein, P56, inhibits HPV DNA replication by binding to the viral protein E1.

PubMed ID: 19008854

DOI: 10.1038/emboj.2008.241

PubMed ID: 19416887

Title: ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response.

PubMed ID: 19416887

DOI: 10.1073/pnas.0900818106

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21612406

Title: A novel interaction between interferon-inducible protein p56 and ribosomal protein L15 in gastric cancer cells.

PubMed ID: 21612406

DOI: 10.1089/dna.2010.1149

PubMed ID: 21190939

Title: The interferon stimulated gene 54 promotes apoptosis.

PubMed ID: 21190939

DOI: 10.1074/jbc.m110.207068

PubMed ID: 20950130

Title: The ISG56/IFIT1 gene family.

PubMed ID: 20950130

DOI: 10.1089/jir.2010.0101

PubMed ID: 21976647

Title: ISG56 and IFITM1 proteins inhibit hepatitis C virus replication.

PubMed ID: 21976647

DOI: 10.1128/jvi.05633-11

PubMed ID: 21685951

Title: Where, in antiviral defense, does IFIT1 fit?

PubMed ID: 21685951

DOI: 10.1038/ni.2061

PubMed ID: 21642987

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

PubMed ID: 21642987

DOI: 10.1038/ni.2048

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: 478
  • Mass: 55360
  • Checksum: EF46E652A366E721
  • Sequence:
    • MSTNGDDHQV KDSLEQLRCH FTWELSIDDD EMPDLENRVL DQIEFLDTKY SVGIHNLLAY 
VKHLKGQNEE ALKSLKEAEN LMQEEHDNQA NVRSLVTWGN FAWMYYHMGR LAEAQTYLDK 
VENICKKLSN PFRYRMECPE IDCEEGWALL KCGGKNYERA KACFEKVLEV DPENPESSAG 
YAISAYRLDG FKLATKNHKP FSLLPLRQAV RLNPDNGYIK VLLALKLQDE GQEAEGEKYI 
EEALANMSSQ TYVFRYAAKF YRRKGSVDKA LELLKKALQE TPTSVLLHHQ IGLCYKAQMI 
QIKEATKGQP RGQNREKLDK MIRSAIFHFE SAVEKKPTFE VAHLDLARMY IEAGNHRKAE 
ENFQKLLCMK PVVEETMQDI HFHYGRFQEF QKKSDVNAII HYLKAIKIEQ ASLTRDKSIN 
SLKKLVLRKL RRKALDLESL SLLGFVYKLE GNMNEALEYY ERALRLAADF ENSVRQGP