UniProt:Q01628 IFITM3

chain
  • chain:1-133
checksum 9FFB2E4623F7A1DD
comment
  • FUNCTION IFN-induced antiviral protein which disrupts intracellular cholesterol homeostasis. Inhibits the entry of viruses to the host cell cytoplasm by preventing viral fusion with cholesterol depleted endosomes. May inactivate new enveloped viruses which buds out of the infected cell, by letting them go out with a cholesterol depleted membrane. Active against multiple viruses, including influenza A virus, SARS coronaviruses (SARS-CoV and SARS-CoV-2), Marburg virus (MARV), Ebola virus (EBOV), Dengue virus (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV) and vesicular stomatitis virus (VSV) (PubMed:26354436, PubMed:33239446, PubMed:33270927). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry, SARS-CoV and SARS-CoV-2 S protein-mediated viral entry and VSV G protein-mediated viral entry (PubMed:33270927). Plays a critical role in the structural stability and function of vacuolar ATPase (v-ATPase). Establishes physical contact with the v-ATPase of endosomes which is critical for proper clathrin localization and is also required for the function of the v-ATPase to lower the pH in phagocytic endosomes thus establishing an antiviral state. In hepatocytes, IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation (PubMed:26354436). IFITM2 and IFITM3 display anti-HCV activity that may complement the anti-HCV activity of IFITM1 by inhibiting the late stages of HCV entry, possibly in a coordinated manner by trapping the virion in the endosomal pathway and targeting it for degradation at the lysosome (PubMed:26354436). Exerts opposing activities on SARS-CoV-2, including amphipathicity-dependent restriction of virus at endosomes and amphipathicity-independent enhancement of infection at the plasma membrane (PubMed:33270927).SUBUNIT Interacts with ATP6V0B (By similarity). Interacts with CD81 (By similarity). Interacts with SPP1; the interaction reduces OPN expression (PubMed:19901966). Interacts with VAPA (PubMed:23601107). Interacts with BRI3 (isoforms 1 and 2); the interaction with isoform 2 is weaker than with isoform 1 (PubMed:30983867).INTERACTION Co-localizes with BRI3 isoform 1 at the perinuclear region.INDUCTION By IFN-alpha and IFNG/IFN-gamma.PTM Palmitoylation on membrane-proximal cysteines controls clustering in membrane compartments and antiviral activity against influenza virus and hepatitis C virus (HCV). Has no effect on anti-SARS-CoV-2 activity.PTM Not glycosylated.PTM Polyubiquitinated with both 'Lys-48' and 'Lys-63' linkages. Ubiquitination negatively regulates antiviral activity. Lys-24 is the most prevalent ubiquitination site.PTM Phosphorylation at Tyr-20 is required for endosomal and lysosomal location.POLYMORPHISM Genetic variations in IFITM3 are responsible for susceptibility to severe influenza virus infection [MIM:614680].SIMILARITY Belongs to the CD225/Dispanin family.
crossReference
databaseName UniProt
dbId 57162
description
  • recommendedName: fullName evidence="20"Interferon-induced transmembrane protein 3 alternativeName: Dispanin subfamily A member 2b shortName: DSPA2b alternativeName: Interferon-inducible protein 1-8U
displayName UniProt:Q01628 IFITM3
geneName
  • IFITM3
identifier Q01628
isSequenceChanged false
keyword
  • Antiviral defense
  • Cell membrane
  • Cytoplasm
  • Endosome
  • Immunity
  • Innate immunity
  • Isopeptide bond
  • Lipoprotein
  • Lysosome
  • Membrane
  • Palmitate
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Signal-anchor
  • Transmembrane
  • Transmembrane helix
  • Ubl conjugation
modified [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType Protein
name
  • IFITM3
otherIdentifier
  • 10410
  • 11715239_x_at
  • 16733851
  • 212203_PM_x_at
  • 212203_x_at
  • 3315667
  • 3315668
  • 3315669
  • 3315670
  • 3315674
  • 3315676
  • 3315677
  • 3315683
  • 3357843
  • 3357844
  • 3357845
  • 3357846
  • 3357847
  • 3357848
  • 3357849
  • 3357850
  • 3357851
  • 3357852
  • 3357853
  • 3357858
  • 3357859
  • 3357861
  • 3357863
  • 3357865
  • 3357867
  • 3357869
  • 3357870
  • 3357871
  • 3357873
  • 3357875
  • 3357877
  • 41745_at
  • 676_g_at
  • 7945371
  • A_23_P87545
  • GE82581
  • GO:0002376
  • GO:0005515
  • GO:0005737
  • GO:0005764
  • GO:0005765
  • GO:0005768
  • GO:0005886
  • GO:0006955
  • GO:0009615
  • GO:0016020
  • GO:0031901
  • GO:0031902
  • GO:0032897
  • GO:0032991
  • GO:0034341
  • GO:0035455
  • GO:0035456
  • GO:0045071
  • GO:0045087
  • GO:0046597
  • GO:0048471
  • GO:0051607
  • GO:0060337
  • GO:0098542
  • HMNXSV003042131
  • Hs.182241.2.S1_3p_x_at
  • ILMN_1805750
  • TC11001230.hg
  • X57351_s_at
  • p2139
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • IFM3_HUMAN
  • Q53Y76
  • Q96HK8
  • Q96J15
sequenceLength 133
species [Species:48887] Homo sapiens
stId uniprot:Q01628
url http://purl.uniprot.org/uniprot/Q01628

Referrals

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