Affinage

IFITM1

Interferon-induced transmembrane protein 1 · UniProt P13164

Length
125 aa
Mass
14.0 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IFITM1 is an interferon-stimulated transmembrane protein with diverse roles in antiviral defense, immune surveillance, cell migration, and proliferation control. Its antiviral activity against HCV, HBV, HIV-1, VSV, and influenza depends on S-palmitoylation of conserved cysteines—written by DHHC enzymes and erased by ABHD16A (itself regulated by ABHD17A and RNF5-mediated ubiquitination)—and on a C-terminal dibasic KRXX sorting signal that governs AP-3-dependent subcellular distribution between plasma membrane and endosomal compartments (PMID:26354436, PMID:25527505, PMID:23804635, PMID:40434075, PMID:39601593). At the plasma membrane, IFITM1 interacts with caveolin-1 to inhibit ERK signaling and p53 degradation, and with tight-junction proteins CD81 and occludin to block HCV entry; it also associates with SRSF1 and HLA-B mRNA to facilitate ribosomal translation of MHC class I, promoting immune surveillance including complement C3-mediated microglial activation and CD8+ T cell cytotoxicity against metastatic tumor cells (PMID:22996292, PMID:19499152, PMID:36008984, PMID:36799040). In development, mouse IFITM1 acts as a repulsive cue directing primordial germ cell migration via its N-terminal extracellular domain, and in adult tissues it regulates trophoblast invasion and limbal stem cell expansion (PMID:16326387, PMID:37434700, PMID:40372397).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1993 Medium

    The initial discovery that IFITM1 binds RNA and inhibits HIV-1 Rev-dependent post-transcriptional gene expression established it as an interferon-induced antiviral effector, but left its mechanism of action and breadth of viral targets unknown.

    Evidence cDNA library screen for RRE-binding proteins with in vitro RNA-binding and HIV-1 expression assays in human cells

    PMID:7680491

    Open questions at the time
    • RNA-binding activity not confirmed by orthogonal methods
    • unclear whether antiviral effect requires direct RNA binding or operates via another mechanism
    • breadth of viral targets untested
  2. 1996 Medium

    Constitutive expression showed IFITM1 has intrinsic antiviral activity against VSV (but not influenza) and localizes like cytoskeleton-associated proteins, indicating virus-specific restriction independent of the broader IFN response.

    Evidence Constitutive cDNA expression in mouse cells with viral plaque assays and immunofluorescence

    PMID:8727077

    Open questions at the time
    • mechanism of VSV restriction unresolved
    • apparent lack of influenza restriction later contradicted for mouse IFITM1 orthologue
  3. 2005 High

    Discovery that mouse Ifitm1 directs primordial germ cell migration via a repulsive mechanism mediated by its N-terminal extracellular domain revealed a developmental function entirely distinct from antiviral activity.

    Evidence Mouse genetic loss-of-function and domain-swap experiments with in vivo PGC migration assays

    PMID:16326387

    Open questions at the time
    • molecular receptor for IFITM1 repulsive signal unknown
    • whether human IFITM1 retains PGC guidance function untested
  4. 2006 High

    Mechanistic dissection in hepatocytes showed IFITM1 mediates IFN-γ antiproliferative signaling by inhibiting ERK, enhancing p53 transcriptional activity, and stabilizing p53 through inhibition of Thr55 phosphorylation, establishing a tumor-suppressive signaling role.

    Evidence Overexpression/siRNA knockdown with ERK activity, p53 reporter, phospho-p53 assays, and nude mouse tumorigenicity

    PMID:16847454

    Open questions at the time
    • direct biochemical target linking IFITM1 to ERK inhibition not identified
    • generalizability beyond hepatocytes unknown
  5. 2009 Medium

    The finding that IFITM1 localizes to caveolae and physically interacts with caveolin-1 via its transmembrane domains to enhance ERK inhibition provided a molecular platform for its antiproliferative signaling.

    Evidence Co-IP with deletion mutagenesis, immunofluorescence co-localization, and ERK phosphorylation assay

    PMID:19499152

    Open questions at the time
    • stoichiometry and structural basis of IFITM1-CAV1 interaction unknown
    • single lab without reciprocal Co-IP validation
  6. 2012 High

    Identification of IFITM1 as a tight-junction protein interacting with HCV co-receptors CD81 and occludin established that its anti-HCV activity operates by disrupting viral entry at the plasma membrane, validated in patient liver during IFN therapy.

    Evidence Reciprocal Co-IP with CD81/occludin, immunofluorescence at tight junctions, HCV entry assay, and patient liver immunohistochemistry

    PMID:22996292

    Open questions at the time
    • precise stoichiometry or structural basis of CD81/occludin disruption unknown
    • whether other tight-junction-tropic viruses are affected untested
  7. 2013 High

    Two studies resolved key post-translational regulatory mechanisms: palmitoylation of conserved cysteines is essential for antiviral activity and protein stability, while the C-terminal KRXX dibasic motif controls AP-3-dependent trafficking between plasma membrane and endosomal compartments, tuning antiviral breadth.

    Evidence Palmitoylation assay with cysteine mutagenesis and influenza assay; SCAM topology mapping, AP-3 Co-IP, and mutagenesis with pseudovirus assays

    PMID:23804635 PMID:25527505

    Open questions at the time
    • identity of DHHC palmitoyltransferase(s) writing IFITM1 palmitoylation not determined
    • dual topology not yet integrated into structural model
  8. 2014 Medium

    The C-terminal 9 residues of human IFITM1 were shown to suppress antiviral restriction of HIV-1 by controlling localization; independently, HIV-1 evolved resistance via Vpu/Env mutations enhancing cell-to-cell transmission, defining an evolutionary arms race.

    Evidence C-terminal deletion mutagenesis with HIV-1 entry assay; serial passage/whole-genome sequencing with transmission assays

    PMID:24725927 PMID:25738301

    Open questions at the time
    • structural basis for C-terminal autoinhibition unresolved
    • Vpu stop-codon mechanism not fully understood
  9. 2015 High

    Confirmation that palmitoylation is essential for anti-HCV activity and that IFITM1 localizes to tight junctions/plasma membrane to block HCV entry unified the palmitoylation and tight-junction interaction models.

    Evidence Palmitoylation inhibition and mutagenesis with HCV entry/replication assays and confocal localization

    PMID:26354436

    Open questions at the time
    • which specific palmitoylation sites are most critical for HCV restriction not dissected
  10. 2017 High

    Multiple studies expanded IFITM1 beyond antiviral restriction: a distal IFN-responsive enhancer was shown to coordinate IFITM locus expression via STAT1-dependent chromatin looping; SWATH-IP proteomics identified ISG15 and HLA-B as major IFITM1-associated proteins; and IFITM1 KO in hESCs derepressed endogenous retroviruses with loss of H3K9me3, revealing epigenetic regulatory capacity.

    Evidence ChIP, 3C, CRISPR enhancer deletion with influenza assay; SWATH-IP MS with PLA and CRISPR double-KO; CRISPR IFITM1 KO in hESCs with qRT-PCR and H3K9me3 ChIP

    PMID:28511927 PMID:28781951 PMID:30951861

    Open questions at the time
    • mechanism linking IFITM1 to H3K9 methyltransferase recruitment unknown
    • functional consequence of ISG15 association for antiviral activity untested
  11. 2019 Medium

    The transcriptional regulation of IFITM1 was further elaborated: MUC1-STAT1 interaction drives IFITM1 expression in breast cancer, BAF200/PBAF chromatin remodeling controls basal expression in hepatocytes, and HBV core protein antagonizes IFITM1 induction by destabilizing PBAF.

    Evidence Co-IP of MUC1-STAT1 with siRNA/drug in tumor models; yeast two-hybrid and Co-IP of HBc-BAF200 with siRNA and HBV replication assays

    PMID:30655323 PMID:31075894

    Open questions at the time
    • direct STAT1 binding sites in IFITM1 promoter for MUC1-dependent activation not mapped
    • whether PBAF disruption by HBc is specific to IFITM1 or affects other ISGs
  12. 2022 High

    The mechanism by which IFITM1 promotes MHC class I surface expression was resolved: IFITM1 associates with splicing factor SRSF1 and HLA-B mRNA in the cytosol, facilitating ribosomal translation without altering mRNA levels, as demonstrated by ribosome profiling showing reduced 80S fraction in IFITM1/3-null cells.

    Evidence SBP-tagged pulldown/MS, RNA-protein PLA, ribosome profiling by sucrose gradient, isogenic CRISPR rescue

    PMID:36008984

    Open questions at the time
    • specificity for HLA-B vs. other mRNAs not fully defined
    • structural basis of IFITM1-SRSF1-mRNA ternary complex unknown
  13. 2023 High

    Multiple discoveries broadened IFITM1 biology: it mediates immune surveillance of brain-metastatic cells via C3 secretion and MHC-I upregulation; it enhances non-enveloped Aichi virus replication by facilitating cholesterol transport to the Golgi; and it reduces extracellular vesicle uptake in colorectal cancer cells.

    Evidence In vivo CRISPR screen with C3/MHC-I/T cell assays; Co-IP of IFITM1 with ACBD3/PI4KB/OSBP, cholesterol imaging; organoid IFITM1 KD with EV uptake quantification

    PMID:34609520 PMID:36799040 PMID:37252940

    Open questions at the time
    • mechanism by which IFITM1 promotes C3 secretion unknown
    • proviral cholesterol transport role potentially contradicts canonical antiviral paradigm—generalizability unclear
    • EV uptake mechanism not structurally resolved
  14. 2024 Medium

    The palmitoylation cycle was mechanistically resolved: ABHD16A was identified as the depalmitoylase of IFITM1, and RNF5 ubiquitinates ABHD16A at K3/K452 for proteasomal degradation, creating a ubiquitin-palmitoylation regulatory circuit that tunes antiviral potency. Biophysical characterization also revealed IFITM1 forms monomers, dimers, and highly stable oligomers with N-terminal region involvement.

    Evidence Co-IP, APEGS palmitoylation assay, CRISPR KO of ABHD16A with HBV assays; ubiquitination assay with K→R mutagenesis; SEC, CD, HDX-MS of recombinant IFITM1

    PMID:38379409 PMID:39601593 PMID:40434075

    Open questions at the time
    • whether RNF5-ABHD16A axis operates in human cells (studied in swine)
    • functional significance of oligomeric states for antiviral activity or signaling unknown
    • identity of DHHC writer enzymes for IFITM1 still not established
  15. 2025 Medium

    ABHD17A was shown to physically interact with IFITM1 and enhance its palmitoylation by downregulating ABHD16A, adding another layer to the palmitoylation regulatory network; separately, IFITM1 was identified as a regulator of limbal epithelial stem cell expansion via OVOL1 inhibition after corneal injury.

    Evidence Co-IP and APEGS palmitoylation assay with antiviral assays; scRNA-seq with AAV-mediated in vivo KD and OVOL1 epistasis

    PMID:40372397 PMID:40723864

    Open questions at the time
    • ABHD17A mechanism of ABHD16A downregulation not fully elucidated
    • OVOL1 inhibition mechanism (direct or indirect) not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of IFITM1 membrane fusion inhibition, the identity of DHHC palmitoyltransferases that write IFITM1 palmitoylation, the molecular receptor mediating its developmental repulsive cue, reconciliation of proviral (Aichi virus) versus antiviral roles, and whether oligomeric states have distinct functional outputs.
  • no high-resolution structure of IFITM1 in membrane context
  • DHHC writer enzymes unidentified
  • proviral vs. antiviral duality mechanism unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0003723 RNA binding 2 GO:0005198 structural molecule activity 2 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 5 GO:0005768 endosome 2 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 9 R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ABHD16AABHD17AACBD3AP3B1CAV1CD81OCLNSRSF1

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Mouse Ifitm1 acts via a repulsive mechanism to direct primordial germ cell (PGC) transit from mesoderm into endoderm; this repulsive activity is mediated by the N-terminal extracellular domain of IFITM1 and cannot be substituted by the N-terminal domain of another family member. Mouse genetic loss-of-function and domain-swap experiments; in vivo cell migration assays Developmental cell High 16326387
1993 IFITM1 (RBP9-27) binds RNA in vitro and inhibits HIV-1 Rev-dependent posttranscriptional steps of viral gene expression after transfection into human cells, identifying an interferon-induced antiviral mechanism targeting Rev function. cDNA library screen for RRE-binding proteins, in vitro RNA-binding assay, transfection + HIV-1 expression assay Science Medium 7680491
1996 Human IFITM1 (9-27 protein) has intrinsic antiviral activity against vesicular stomatitis virus (VSV) when constitutively expressed; its intracellular distribution resembles cytoskeleton-associated proteins. No significant inhibition of influenza virus was observed. Constitutive cDNA expression in mouse cells; single-cell immunofluorescence; virus infection assays Journal of interferon & cytokine research Medium 8727077
2006 IFITM1 is required for the antiproliferative action of IFN-γ downstream of STAT1; it inhibits ERK activity, enhances p53 transcriptional activity, and stabilizes p53 by inhibiting phosphorylation of p53 on Thr55. Suppression of IFITM1 blocks IFN-γ antiproliferation and confers tumorigenicity. Overexpression and siRNA knockdown in hepatocytes; ERK activity assay; p53 transcriptional reporter; p53 phosphorylation assay; nude mouse tumor assay Oncogene High 16847454
2009 IFITM1 localizes to caveolae of the plasma membrane and physically interacts with caveolin-1 (CAV-1) via its hydrophobic transmembrane domains; this interaction enhances CAV-1's inhibitory effect on ERK phosphorylation and downstream transcription. Immunofluorescence co-localization; Co-IP; deletion mutagenesis; ERK phosphorylation assay; CAV-1 siRNA knockdown Acta biochimica et biophysica Sinica Medium 19499152
2010 CD147 activation by Cyclophilin A induces IFITM1 expression via ERK, PI3K, and NF-κB signaling pathways; cross-linking of IFITM1 with a monoclonal antibody induces pro-inflammatory mediators IL-8 and MMP-9, indicating IFITM1 mediates inflammatory activation of macrophages. Pharmacological inhibition of signaling pathways; RT-PCR; Western blot; IFITM1 cross-linking with mAb Mediators of inflammation Medium 20847954
2012 IFITM1 is a hepatocyte tight junction protein that interacts with HCV co-receptors CD81 and occludin to disrupt viral entry; IFITM1 accumulates at hepatic tight junctions during IFN therapy in HCV-infected patient liver. Co-IP of IFITM1 with CD81 and occludin; immunofluorescence localization; gain/loss-of-function in hepatocytes; patient liver IHC during IFN therapy Hepatology High 22996292
2013 IFITM1 adopts more than one membrane topology co-existing in cellular membranes; its antiviral breadth is regulated by a unique C-terminal non-canonical dibasic sorting signal (KRXX) that governs intracellular distribution by binding to adaptor protein complex 3 (AP-3). Mutating this motif (KR/AA) increases restriction of certain retroviruses and redistributes IFITM1 to CD63-positive multivesicular bodies away from LAMP1-positive lysosomes. Deconvolution microscopy; substituted cysteine accessibility method (SCAM) for topology; Co-IP with AP-3; AP-3 knockdown; mutagenesis; pseudovirus infection assays Journal of biological chemistry High 25527505
2013 Murine IFITM1 is palmitoylated on one nonconserved cysteine and three conserved cysteines; palmitoylation is required for anti-influenza A virus activity and regulates protein stability by preventing proteasomal degradation. Modification of the nonconserved C-terminal cysteine supports an intramembrane topology. Palmitoylation assay; cysteine mutagenesis; proteasome inhibitor assay; influenza A virus infection assay Journal of virology High 23804635
2015 S-palmitoylation of IFITM1 (and IFITM2/3) is essential for anti-HCV activity in hepatocytes. IFITM1 localizes at the plasma membrane/tight junctions and co-localizes with CD81, and its anti-HCV activity operates at the entry level. Mutation of the conserved N-terminal tyrosine of IFITM2/3 results in an IFITM1-like phenotype with plasma membrane localization and retained anti-HCV activity. Palmitoylation inhibition; site-directed mutagenesis; subcellular fractionation; confocal localization; HCV entry/replication assays Journal of biological chemistry High 26354436
2014 The C-terminal 9 amino acids of human IFITM1 suppress antiviral restriction of some viruses by controlling subcellular localization; a deletion mutant (Δ117-125) shifts IFITM1 predominantly to the plasma membrane and inhibits HIV-1 entry. Mouse IFITM1, which naturally lacks 19 C-terminal amino acids relative to human IFITM1, similarly restricts HIV-1 entry. C-terminal deletion mutagenesis; subcellular localization by microscopy; HIV-1 entry assay; comparison of human vs. mouse IFITM1 PloS one Medium 25738301
2014 HIV-1 can evolve to evade IFITM1 restriction through mutations in Vpu (introducing a premature stop at position 35) and Env (G367E at the CD4-binding site); these mutations enhance cell-to-cell virus transmission rather than overcoming p24 downregulation caused by IFITM1. Serial passage of HIV-1 in IFITM1-expressing cells; whole-genome sequencing; functional cell-to-cell transmission assays Virology Medium 24725927
2015 IFITM1 promotes colorectal cancer cell migration/invasion via Caveolin-1 (CAV1) as a downstream target; CAV1 knockdown abrogates the siIFITM1-mediated inhibition of cell invasion, and IFITM1 expression inversely correlates with CAV1 in patient tumors. siRNA knockdown of IFITM1 and CAV1; cell migration/invasion assays; correlation analysis in patient tumor cohort Cancer letters Medium 26259513
2016 IFITM1 overexpression enhances the aggressive phenotype of SUM149 inflammatory breast cancer cells in a STAT2-dependent manner; STAT2 activates IFITM1 promoter activity via the chromatin remodeler BRG1, and loss of STAT2 abolishes IFITM1 expression and reduces proliferation, migration, and invasion. siRNA/shRNA knockdown; luciferase promoter assay; STAT2/BRG1 interaction studies; migration/invasion assays Breast cancer research Medium 26897526
2017 Loss of IFITM1 in AI-resistant MCF-7:5C breast cancer cells induces p21 transcription, expression, and nuclear localization via JAK/STAT pathway activation, suppressing tumor growth and invasion in vivo. Lentiviral shRNA knockdown; orthotopic and mammary intraductal mouse models; p21 quantification; JAK/STAT inhibitor studies Cancer letters Medium 28411130
2017 IFITM1 coordinates with IFITM3 to regulate IFNγ-stimulated protein synthesis; SWATH-IP mass spectrometry of SBP-tagged IFITM1 identified ISG15 and HLA-B as dominant co-associated proteins. Proximity ligation assays confirmed IFITM1/3 interaction with HLA-B. Loss of IFITM1/3 attenuates ISG15ylation and reduces cell surface HLA-B expression. SWATH-IP mass spectrometry; pulse SILAC; proximity ligation assay; CRISPR-Cas9 double knockout; flow cytometry for surface HLA-B Cellular signalling High 30951861
2017 STAT1 binds to an IFN-responsive enhancer located 35 kb upstream of the IFITM3 gene promoter upon IFN treatment; this enhancer physically clusters with IFITM1, 2, and 3 gene loci via long-range chromatin interactions and is required for coordinated IFN-induced expression of all three IFITM genes and antiviral resistance to influenza A virus. ChIP; EMSA; luciferase reporter; CRISPR-Cas9 enhancer truncation; chromosome conformation capture (3C) Biochimica et biophysica acta. Gene regulatory mechanisms High 28511927
2017 IFITM1 suppresses human endogenous retroviruses (HERVs) in human embryonic stem cells by regulating epigenetic modifications; IFITM1 KO leads to higher HERV expression and reduced trimethylation of H3K9 at HERV loci. CRISPR/Cas9 IFITM1 knockout in hESCs; qRT-PCR; ChIP for H3K9me3 FEBS open bio Medium 28781951
2019 MUC1 interacts with STAT1 via JAK/STAT signaling to stimulate IFITM1 transcription in AI-resistant breast cancer cells; siRNA knockdown or pharmacological inhibition of MUC1 abrogates IFITM1 expression and induces cell death. In vivo, estrogen and ruxolitinib reduce MUC1, P-STAT1, and IFITM1 expression. siRNA knockdown; pharmacological inhibition; Co-IP of MUC1-STAT1; in vivo tumor model; Western blot Molecular cancer research Medium 30655323
2019 G3BP1 and G3BP2 are essential for accumulation of IFITM1, IFITM2, and IFITM3 proteins; they regulate IFITM1-3 translation through the MEK pathway and through interaction with the 3'-UTRs of IFITM transcripts. G3BP knockdown; MEK pathway inhibition; 3'-UTR interaction assays; Western blot Molecular and cellular biochemistry Low 31172368
2019 IFITM1 overexpression promotes VSMC proliferation, migration, and macrophage-like transdifferentiation via the c-Src/MAPK/GATA2/E2F2 signaling pathway; IFITM1 overexpression in ApoE-/- mice accelerates atherosclerotic plaque formation. Overexpression/knockdown; Western blot for p-Src, p-MAPK, p-GATA2, E2F2; cell viability, wound healing, transwell assays; ApoE-/- mouse model Biochemical pharmacology Medium 40466954
2021 IFITM1 knockdown in triple-negative breast cancer cells activates NF-κB as a downstream target, as revealed by RNA-seq. IFITM1 loss reduces proliferation, colony formation, migration, and invasion in vitro and in vivo; the NF-κB inhibitor parthenolide suppresses both IFITM1 expression and TNBC tumor growth. siRNA/CRISPR-Cas9 KO; RNA-seq; NF-κB functional assays; orthotopic mouse model; drug treatment Cancer letters Medium 34022283
2021 IFITM1 expression (induced by APC mutation/Wnt activation) reduces extracellular vesicle (EV) uptake by colorectal cancer cells; IFITM1 inactivation enhances EV uptake and eliminates proliferation differences between IFITM1-high and IFITM1-low CRC subpopulations. Mouse and patient-derived organoids; IFITM1 knockdown; EV uptake quantification; proliferation assays Cellular and molecular life sciences Medium 34609520
2022 IFITM1 SRSF1 (splicing factor) and HLA-B as interaction partners in cervical cancer cells; IFITM1/3 associate with SRSF1 in the cytosol and with HLA-B mRNA in response to IFNγ, facilitating ribosomal translation of HLA-B without altering mRNA levels. IFITM1/3 double-null cells show reduced 80S ribosomal fraction, partially reversed by IFITM1/3 complementation. SBP-tagged IFITM1 pulldown/MS; in situ proximity ligation assay; RNA-protein PLA; ribosome profiling by sucrose gradient sedimentation; RNA-seq; RT-qPCR Biomolecules High 36008984
2022 CircVPS13C decreases IFITM1 mRNA stability by competitively interacting with RRBP1 (a ribosome-binding protein of the ER membrane), thereby suppressing IFITM1 expression and activating MAPK and apoptosis-associated downstream signaling in pituitary adenoma cells. CircRNA pulldown; RNA-seq; gain/loss-of-function; rescue experiments; in vivo mouse model Oncogene Medium 35091683
2023 IFITM1 mediates immune surveillance of brain-metastatic lung cancer cells: high IFITM1 expression causes cancer cells to secrete complement component 3 (C3), which activates microglia, and increases MHC class I surface expression to enhance CD8+ T cell cytolytic activity. IFITM1 loss promotes brain colonization in vivo genome-wide CRISPR screen. In vivo genome-wide CRISPR-Cas9 screen; C3 secretion assay; flow cytometry for MHC-I; microglia phagocytosis and CD8+ T cell killing assays; mouse brain metastasis model EMBO journal High 36799040
2023 IFITM1 inhibits trophoblast invasion; IFN-β treatment upregulates IFITMs and reduces invasive ability of extravillous cytotrophoblasts, and transduction experiments confirmed IFITM1 specifically contributes to decreased cell invasion. High IFITM1 is found in CMV- and bacterial-infected human placentas. In vitro/ex vivo trophoblast invasion models; lentiviral IFITM1 transduction; poly(I:C) in vivo mouse model; human pathological placental sections iScience Medium 37434700
2023 IFITM1 enhances non-enveloped Aichi virus (AiV) RNA replication by facilitating cholesterol transport to the Golgi; IFITM1 localizes to viral RNA replication sites, interacts with viral proteins and host Golgi proteins ACBD3, PI4KB, and OSBP, and overexpressed IFITM1 facilitates late endosome-to-Golgi cholesterol transport. Co-IP of IFITM1 with viral and host proteins; immunofluorescence localization; IFITM1 knockdown; pharmacological inhibition of cholesterol transport; cholesterol imaging PLoS pathogens High 37252940
2023 IFITM1 and IFITM3 reduce HIV-1 infectivity when incorporated into progeny virions; IFITM3 additionally reduces HIV-1 Env processing and incorporation into virions, whereas IFITM1 does not affect Env clustering (shown by super-resolution imaging). Pseudovirus infectivity assays; super-resolution imaging of Env distribution; Western blot for Env processing Viruses Medium 38140631
2023 Oncostatin M induces IFITM1 expression via JAK-STAT signaling (STAT1-IRF9 transcription factor complex), and IFITM1 acts as an HBV restriction factor mediating OSM's anti-HBV activity in vitro and in vivo. RNA-seq; JAK-STAT pathway analysis; HBV replication assays in cells and rAAV8-HBV mice; ELISA Cellular and molecular gastroenterology and hepatology Medium 37879404
2019 HBV core protein (HBc) inhibits IFNα-induced IFITM1 expression by interacting with BAF200, disrupting stability of the PBAF chromatin remodeling complex; basal IFITM1 expression depends on BAF200 rather than the JAK-STAT1 pathway. Yeast two-hybrid; Co-IP in 293T, HepG2 and HepG2-NTCP cells; siRNA knockdown; HBV replication assays Viruses Medium 31075894
2025 ABHD17A physically interacts with IFITM1 and increases IFITM1 S-palmitoylation by downregulating the depalmitoylase ABHD16A, thereby enhancing IFITM1 antiviral activity; ABHD16A catalyzes depalmitoylation of IFITM1 and negatively regulates its antiviral function. Co-IP; acyl-PEGyl exchange gel-shift (APEGS) palmitoylation assay; siRNA/CRISPR KO; antiviral assays Biomolecules Medium 40723864
2024 ABHD16A catalyzes depalmitoylation of IFITM1 and negatively regulates its anti-HBV activity; CRISPR KO of ABHD16A in HepG2.215 cells increases IFITM1 palmitoylation and enhances HBV restriction. Co-IP; APEGS palmitoylation assay; CRISPR/Cas9 KO of IFITM1 and ABHD16A; HBV replication assays Microbiology spectrum Medium 40434075
2024 Swine RNF5 ubiquitinates ABHD16A at residues K3 and K452, targeting it for proteasomal degradation; this prevents ABHD16A-mediated depalmitoylation of IFITM1, thereby restoring IFITM1 antiviral activity. This regulatory axis balances antiviral immune responses. AlphaFold2-based PPI prediction; immunofluorescence; Co-IP; ubiquitination assay; site-directed mutagenesis of K3/K452; IFITM1 palmitoylation assay; antiviral assays Journal of virology Medium 39601593
2024 Biochemical characterization of recombinant IFITM1 reveals three conformational variants: monomer, dimer, and highly stable oligomer. The N-terminal region contains a structural motif important for oligomer formation, identified by HDX mass spectrometry and two-site ELISA. Dimer is less stable than oligomer to reducing agents and thermal denaturation. Size exclusion chromatography; circular dichroism thermal denaturation; reducing agent treatment; two-site ELISA; HDX mass spectrometry Biological chemistry Medium 38379409
2025 IFITM1 is predominantly expressed in limbal epithelial stem/early transient amplifying (eTA) cells and positively regulates their proliferation and expansion after corneal wounding via inhibition of OVOL1 (a negative regulator of epithelial cell proliferation). AAV-mediated in vivo IFITM1 knockdown attenuates stem/eTA cell expansion after corneal injury. Single-cell RNA-seq; AAV-mediated in vivo knockdown; IFITM1 overexpression in human limbal epithelial cells; OVOL1 expression analysis FASEB journal Medium 40372397
2024 Hydroquinone (benzene metabolite) impairs trophoblast migration and invasion via activation of the AhR pathway, which reduces Twist1 and subsequently IFITM1 expression; IFITM1 overexpression rescues impaired trophoblast migration, establishing the AhR-Twist1-IFITM1 axis as a regulator of trophoblast invasion. 3D invasion/migration model; AhR pathway activation; Twist1 and IFITM1 qPCR and Western blot; IFITM1 overexpression rescue Placenta Medium 39173312
2023 Invasive FoxM1 phosphorylated at Ser25 by PLK1 upregulates IFITM1 expression through the STING-TBK1-IRF3 signaling axis in lung adenocarcinoma cells with phosphomimetic FoxM1. Immunoprecipitation; LC-MS/MS; kinase assay; site-directed mutagenesis; chromatin immunoprecipitation; microarray analysis Journal of experimental & clinical cancer research Medium 37968723
2018 PITX2 transcriptionally activates IFITM1, and the resulting PITX2/IFITM1 cascade enhances IFNα-induced AKT activation, mediating letrozole resistance in breast cancer; siRNA ablation of IFITM1 abolishes IFNα-elicited AKT phosphorylation even in PITX2-overexpressing cells. Luciferase transcription assay; siRNA knockdown; AKT phosphorylation assay; xenograft model; Western blot Cancer research and treatment Medium 30025446

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 IFITM/Mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primordial germ cell homing and repulsion. Developmental cell 163 16326387
2013 The CD225 domain of IFITM3 is required for both IFITM protein association and inhibition of influenza A virus and dengue virus replication. Journal of virology 156 23658454
2015 The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3 Inhibit Hepatitis C Virus Entry. The Journal of biological chemistry 148 26354436
2012 IFITM1 is a tight junction protein that inhibits hepatitis C virus entry. Hepatology (Baltimore, Md.) 133 22996292
2011 ISG56 and IFITM1 proteins inhibit hepatitis C virus replication. Journal of virology 128 21976647
2013 IFITM-2 and IFITM-3 but not IFITM-1 restrict Rift Valley fever virus. Journal of virology 109 23720721
2006 IFITM1 plays an essential role in the antiproliferative action of interferon-gamma. Oncogene 108 16847454
2012 Hepatitis C virus infection modulates expression of interferon stimulatory gene IFITM1 by upregulating miR-130A. Journal of virology 82 22787204
2013 Palmitoylation on conserved and nonconserved cysteines of murine IFITM1 regulates its stability and anti-influenza A virus activity. Journal of virology 72 23804635
2015 IFITM1 promotes the metastasis of human colorectal cancer via CAV-1. Cancer letters 69 26259513
2010 Knockdown of interferon-induced transmembrane protein 1 (IFITM1) inhibits proliferation, migration, and invasion of glioma cells. Journal of neuro-oncology 68 20838853
2016 Interferon-induced transmembrane protein 1 (IFITM1) overexpression enhances the aggressive phenotype of SUM149 inflammatory breast cancer cells in a signal transducer and activator of transcription 2 (STAT2)-dependent manner. Breast cancer research : BCR 67 26897526
2014 The antiviral restriction factors IFITM1, 2 and 3 do not inhibit infection of human papillomavirus, cytomegalovirus and adenovirus. PloS one 66 24827144
2005 The interferon-inducible 9-27 gene modulates the susceptibility to natural killer cells and the invasiveness of gastric cancer cells. Cancer letters 61 15808405
2017 IFITM1 suppression blocks proliferation and invasion of aromatase inhibitor-resistant breast cancer in vivo by JAK/STAT-mediated induction of p21. Cancer letters 48 28411130
2012 Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is regulated by an epigenetic mechanism. The American journal of pathology 48 22609115
1993 Inhibition of Rev-mediated HIV-1 expression by an RNA binding protein encoded by the interferon-inducible 9-27 gene. Science (New York, N.Y.) 48 7680491
1996 Partial inhibition of vesicular stomatitis virus by the interferon-induced human 9-27 protein. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 43 8727077
1991 Differential response of the human 6-16 and 9-27 genes to alpha and gamma interferons. Nucleic acids research 43 1901407
2014 A sorting signal suppresses IFITM1 restriction of viral entry. The Journal of biological chemistry 39 25527505
2016 Interferon-induced transmembrane protein 1 (IFITM1) is required for the progression of colorectal cancer. Oncotarget 37 27852071
2019 Inhibiting of Proliferation, Migration, and Invasion in Lung Cancer Induced by Silencing Interferon-Induced Transmembrane Protein 1 (IFITM1). BioMed research international 36 31205947
2014 HIV-1 mutates to evade IFITM1 restriction. Virology 36 24725927
2019 Bat IFITM3 restriction depends on S-palmitoylation and a polymorphic site within the CD225 domain. Life science alliance 35 31826928
2005 Expression of IFITM1 in chronic myeloid leukemia patients. Leukemia research 35 15661263
2023 Invasive FoxM1 phosphorylated by PLK1 induces the polarization of tumor-associated macrophages to promote immune escape and metastasis, amplified by IFITM1. Journal of experimental & clinical cancer research : CR 34 37968723
2020 Deciphering the Roles of IFITM1 in Tumors. Molecular diagnosis & therapy 34 32394410
2019 Porcine IFITM1 is a host restriction factor that inhibits pseudorabies virus infection. International journal of biological macromolecules 34 31743714
2019 The effects of IFITM1 and IFITM3 gene deletion on IFNγ stimulated protein synthesis. Cellular signalling 33 30951861
2015 The C-terminal sequence of IFITM1 regulates its anti-HIV-1 activity. PloS one 33 25738301
2014 Porcine reproductive and respiratory syndrome virus counteracts the porcine intrinsic virus restriction factors-IFITM1 and Tetherin in MARC-145 cells. Virus research 33 25102331
2018 Combination of IFITM1 knockdown and radiotherapy inhibits the growth of oral cancer. Cancer science 31 29770536
2010 Activation of CD147 with cyclophilin a induces the expression of IFITM1 through ERK and PI3K in THP-1 cells. Mediators of inflammation 30 20847954
2008 Selection of a novel drug-response predictor in esophageal cancer: a novel screening method using microarray and identification of IFITM1 as a potent marker gene of CDDP response. International journal of oncology 29 18202764
2018 IFITM1 Outperforms CD10 in Differentiating Low-grade Endometrial Stromal Sarcomas From Smooth Muscle Neoplasms of the Uterus. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 28 28700435
2021 Disrupting interferon-alpha and NF-kappaB crosstalk suppresses IFITM1 expression attenuating triple-negative breast cancer progression. Cancer letters 27 34022283
2017 miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1). Scientific reports 27 29269892
2019 Interaction Between MUC1 and STAT1 Drives IFITM1 Overexpression in Aromatase Inhibitor-Resistant Breast Cancer Cells and Mediates Estrogen-Induced Apoptosis. Molecular cancer research : MCR 25 30655323
2016 Human Papillomavirus Downregulates the Expression of IFITM1 and RIPK3 to Escape from IFNγ- and TNFα-Mediated Antiproliferative Effects and Necroptosis. Frontiers in immunology 25 27920775
2022 CircVPS13C promotes pituitary adenoma growth by decreasing the stability of IFITM1 mRNA via interacting with RRBP1. Oncogene 24 35091683
2021 Long Non-coding RNA LINC00847 Induced by E2F1 Accelerates Non-small Cell Lung Cancer Progression Through Targeting miR-147a/IFITM1 Axis. Frontiers in medicine 24 33968966
2014 Aberrant DNA methylation in the IFITM1 promoter enhances the metastatic phenotype in an intraperitoneal xenograft model of human ovarian cancer. Oncology reports 24 24676393
2013 Targeted development of specific biomarkers of endometrial stromal cell differentiation using bioinformatics: the IFITM1 model. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 24 24072182
2009 Binding of IFITM1 enhances the inhibiting effect of caveolin-1 on ERK activation. Acta biochimica et biophysica Sinica 24 19499152
2012 Interferons induce the expression of IFITM1 and IFITM3 and suppress the proliferation of rat neonatal cardiomyocytes. Journal of cellular biochemistry 23 22021094
1998 The rat gene homologous to the human gene 9-27 is involved in the development of the mammary gland. Proceedings of the National Academy of Sciences of the United States of America 23 9448288
2013 Evidence for Paralichthys olivaceus IFITM1 antiviral effect by impeding viral entry into target cells. Fish & shellfish immunology 21 23850425
2012 IFITM1 increases osteogenesis through Runx2 in human alveolar-derived bone marrow stromal cells. Bone 21 22634173
2021 CD225 Proteins: A Family Portrait of Fusion Regulators. Trends in genetics : TIG 20 33518406
2019 G3BP1 and G3BP2 regulate translation of interferon-stimulated genes: IFITM1, IFITM2 and IFITM3 in the cancer cell line MCF7. Molecular and cellular biochemistry 20 31172368
2021 IFITM1 expression determines extracellular vesicle uptake in colorectal cancer. Cellular and molecular life sciences : CMLS 19 34609520
2018 Upregulation of PITX2 Promotes Letrozole Resistance Via Transcriptional Activation of IFITM1 Signaling in Breast Cancer Cells. Cancer research and treatment 19 30025446
2020 Interferon-Induced Transmembrane Protein 1 (IFITM1) Promotes Distant Metastasis of Small Cell Lung Cancer. International journal of molecular sciences 18 32668617
2019 Human Hepatitis B Virus Core Protein Inhibits IFNα-Induced IFITM1 Expression by Interacting with BAF200. Viruses 18 31075894
2017 Down-regulation of IFITM1 and its growth inhibitory role in cervical squamous cell carcinoma. Cancer cell international 18 29051711
2021 Transgenic Chicks Expressing Interferon-Inducible Transmembrane Protein 1 (IFITM1) Restrict Highly Pathogenic H5N1 Influenza Viruses. International journal of molecular sciences 17 34445163
2017 Coordinated regulation of IFITM1, 2 and 3 genes by an IFN-responsive enhancer through long-range chromatin interactions. Biochimica et biophysica acta. Gene regulatory mechanisms 17 28511927
2024 Identification of core immune-related genes CTSK, C3, and IFITM1 for diagnosing Helicobacter pylori infection-associated gastric cancer through transcriptomic analysis. International journal of biological macromolecules 16 39667460
2023 Immune surveillance of brain metastatic cancer cells is mediated by IFITM1. The EMBO journal 15 36799040
2023 IFITM1 inhibits trophoblast invasion and is induced in placentas associated with IFN-mediated pregnancy diseases. iScience 15 37434700
2021 IFITM1, CD10, SMA, and h-caldesmon as a helpful combination in differential diagnosis between endometrial stromal tumor and cellular leiomyoma. BMC cancer 14 34556086
2017 Identification of IFITM1 and IFITM3 in Goose: Gene Structure, Expression Patterns, and Immune Reponses against Tembusu Virus Infection. BioMed research international 14 28386554
2018 IFITM1 expression is crucial to gammaherpesvirus infection, in vivo. Scientific reports 13 30237526
2017 IFITM1 suppresses expression of human endogenous retroviruses in human embryonic stem cells. FEBS open bio 13 28781951
2012 In vivo functional requirement of the mouse Ifitm1 gene for germ cell development, interferon mediated immune response and somitogenesis. PloS one 13 23115618
2022 Co-expression of DDR2 and IFITM1 promotes breast cancer cell proliferation, migration and invasion and inhibits apoptosis. Journal of cancer research and clinical oncology 12 35761108
2020 Epigenetic regulation of IFITM1 expression in lipopolysaccharide-stimulated human mesenchymal stromal cells. Stem cell research & therapy 12 31910882
2020 IFITM1 is a Novel, Highly Sensitive Marker for Endometriotic Stromal Cells in Ovarian and Extragenital Endometriosis. Reproductive sciences (Thousand Oaks, Calif.) 12 32436195
2017 IFITM1 targets HIV-1 latently infected cells for antibody-dependent cytolysis. JCI insight 12 28097226
2022 Differential Leukocyte Expression of IFITM1 and IFITM3 in Patients with Severe Pandemic Influenza A(H1N1) and COVID-19. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 11 35708622
2022 Comparative transcriptome reveals the effect of IFITM1 on differential resistance to duck hepatitis A virus genotype 3 in Pekin ducks. Virus research 11 36130655
2021 The first association study of single-nucleotide polymorphisms (SNPs) of the IFITM1 gene with influenza H1N1 2009 pandemic virus infection. Molecular & cellular toxicology 11 33613683
2005 IFITM1-mediated cell repulsion controls the initial steps of germ cell migration in the mouse. Developmental cell 11 16326382
2023 Oncostatin M Induces IFITM1 Expression to Inhibit Hepatitis B Virus Replication Via JAK-STAT Signaling. Cellular and molecular gastroenterology and hepatology 10 37879404
2016 IFITM1 Is Superior to CD10 as a Marker of Endometrial Stroma in the Evaluation of Myometrial Invasion by Endometrioid Adenocarcinoma. American journal of clinical pathology 10 27124937
2016 KLF5 is involved in regulation of IFITM1, 2, and 3 genes during H5N1 virus infection in A549 cells. Cellular and molecular biology (Noisy-le-Grand, France) 10 28040064
2013 Brahma‑related gene 1-associated expression of 9-27 and IFI-27 is involved in acquired cisplatin resistance of gastric cancer cells. Molecular medicine reports 10 23836109
2013 Identification of the polymorphisms in IFITM1 gene and their association in a Korean population with ulcerative colitis. Immunology letters 9 24120510
2024 SNARE mimicry by the CD225 domain of IFITM3 enables regulation of homotypic late endosome fusion. The EMBO journal 7 39653855
2023 Association of IFITM1 Promoter Methylation with Severity of SARS-CoV-2 Infection. Clinical laboratory 7 37057950
2022 Interaction of SERINC5 and IFITM1/2/3 regulates the autophagy-apoptosis-immune network under CSFV infection. Virulence 7 36205528
2019 IFITM1 is a Novel, Highly Sensitive Marker for Endometriotic Stromal Cells in Ovarian and Extragenital Endometriosis. Reproductive sciences (Thousand Oaks, Calif.) 7 30791812
2019 Comparative analysis of the chicken IFITM locus by targeted genome sequencing reveals evolution of the locus and positive selection in IFITM1 and IFITM3. BMC genomics 7 30952207
2025 The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16A. Biomolecules 6 40723864
2019 NP and NS1 proteins of H5N1 virus significantly upregulated IFITM1, IFITM2, and IFITM3 in A549 cells. African health sciences 6 31148967
2015 Cloning and characterization of ifitm1 and ifitm3 expression during early zebrafish development. Zygote (Cambridge, England) 6 25613417
2025 IFITM1 promotes proliferation, migration and macrophage-like transdifferentiation of vascular smooth muscle cells via c-Src/MAPK/GATA2/E2F2 pathway in atherosclerosis. Biochemical pharmacology 5 40466954
2024 IFITM1 and IFITM2 inhibit the replication of senecavirus A by positive feedback with RIG-I signaling pathway. Veterinary microbiology 5 38484578
2023 IFITM1 enhances nonenveloped viral RNA replication by facilitating cholesterol transport to the Golgi. PLoS pathogens 5 37252940
2022 Emergent Role of IFITM1/3 towards Splicing Factor (SRSF1) and Antigen-Presenting Molecule (HLA-B) in Cervical Cancer. Biomolecules 5 36008984
2022 MiR-504-3p Has Tumor-Suppressing Activity and Decreases IFITM1 Expression in Non-Small Cell Lung Cancer Cells. Genetic testing and molecular biomarkers 5 36027039
2018 Expression and Cellular Localization of IFITM1 in Normal and Injured Rat Spinal Cords. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 5 29300519
2017 WITHDRAWN: Silencing of Interferon-Induced Transmembrane Protein 1 (IFITM1) Inhibits Proliferation, Migration, and Invasion in Lung Cancer Cells. Oncology research 5 28109085
2024 The role and mechanism of IFITM1 in developing acquired cisplatin resistance in small cell lung cancer. Heliyon 4 38803858
2024 Swine RNF5 positively regulates the antiviral activity of IFITM1 by mediating the degradation of ABHD16A. Journal of virology 4 39601593
2023 IFITM1 and IFITM3 Proteins Inhibit the Infectivity of Progeny HIV-1 without Disrupting Envelope Glycoprotein Clusters. Viruses 4 38140631
2025 IFITM1/OVOL1 Axis Is a Novel Regulator of the Expansion of the Limbal Epithelial Stem/Early Transient Amplifying Cell Population. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 3 40372397
2025 Depalmitoylase ABHD16A negatively regulates the anti-hepatitis B virus activity of IFITM1. Microbiology spectrum 3 40434075
2024 Biochemical evidence for conformational variants in the anti-viral and pro-metastatic protein IFITM1. Biological chemistry 2 38379409
2024 Hydroquinone impairs trophoblast migration and invasion via AHR-twist-IFITM1 axis. Placenta 2 39173312