Protein: Interferon-induced transmembrane protein 3 (Dispanin subfamily A member 2b) (DSPA2b) (Interferon-inducible protein 1-8U) (Q01628)
Organism: Homo sapiens (Human)
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). 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. 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. 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. 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.
Subcellular location: Cell membrane {ECO:0000269|PubMed:20943977, ECO:0000269|PubMed:22511783, ECO:0000269|PubMed:26354436}; Single-pass type II membrane protein {ECO:0000269|PubMed:20943977, ECO:0000269|PubMed:22511783}. Late endosome membrane {ECO:0000269|PubMed:22046135}; Single-pass type II membrane protein {ECO:0000305}. Early endosome membrane {ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33270927}; Single-pass type II membrane protein. Lysosome membrane {ECO:0000269|PubMed:22046135, ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33270927}; Single-pass type II membrane protein {ECO:0000305}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:30983867}. Note=Co-localizes with BRI3 isoform 1 at the perinuclear region. {ECO:0000269|PubMed:30983867}.
Sequence: MNHTVQTFFSPVNSGQPPNYEMLKEEHEVAVLGAPHNPAPPTSTVIHIRSETSVPDHVVWSLFNTLFMNPCCLGFIAFAYSVKSRDRKMVGDVTGAQAYASTAKCLNIWALILGILMTILLIVIPVLIFQAYG
InterPro domains: - IPR007593: CD225/Dispanin family (family) [55-120]
- IPR051517: Interferon-induced transmembrane antiviral protein (family) [17-128]
Interaction partners: - Interferon-induced protein with tetratricopeptide repeats 3
- Ubiquitin-like protein ISG15
- Interferon-induced GTP-binding protein Mx1
- Interferon regulatory factor 9
- Interferon-induced transmembrane protein 1
- Antiviral innate immune response effector IFIT1
- Interferon alpha-inducible protein 6
- Interferon-induced 35 kDa protein
- Interferon-induced protein 44-like
- Vesicle-associated membrane protein-associated protein A
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0043903 (regulation of biological process involved in symbiotic interaction), GO:0042221 (response to chemical), GO:0009607 (response to biotic stimulus), GO:0006955 (immune response), GO:0051716 (cellular response to stimulus), GO:0050792 (regulation of viral process), GO:0006950 (response to stress), GO:0048525 (negative regulation of viral process), GO:0051707 (response to other organism), GO:0045069 (regulation of viral genome replication), GO:1903900 (regulation of viral life cycle), GO:0043207 (response to external biotic stimulus), GO:0070887 (cellular response to chemical stimulus), GO:0006952 (defense response), GO:0045071 (negative regulation of viral genome replication), GO:0052372 (modulation by symbiont of entry into host), GO:0009615 (response to virus), GO:1903901 (negative regulation of viral life cycle), GO:0010033 (response to organic substance), GO:0045087 (innate immune response), GO:0098542 (defense response to other organism), GO:0046596 (regulation of viral entry into host cell), GO:0034097 (response to cytokine), GO:0071310 (cellular response to organic substance), GO:0034341 (response to type II interferon), GO:0046597 (negative regulation of viral entry into host cell), GO:0035456 (response to interferon-beta), GO:0035455 (response to interferon-alpha), GO:0071345 (cellular response to cytokine stimulus), GO:0035458 (cellular response to interferon-beta)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0031974 (membrane-enclosed lumen), GO:0071944 (cell periphery), GO:0030054 (cell junction), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005654 (nucleoplasm), GO:0031090 (organelle membrane), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0005773 (vacuole), GO:0043233 (organelle lumen), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0000323 (lytic vacuole), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0012506 (vesicle membrane), GO:0005770 (late endosome), GO:0005774 (vacuolar membrane), GO:0010008 (endosome membrane), GO:0031982 (vesicle), GO:0070013 (intracellular organelle lumen), GO:0030659 (cytoplasmic vesicle membrane), GO:0005764 (lysosome), GO:0097708 (intracellular vesicle), GO:0005634 (nucleus), GO:0031981 (nuclear lumen), GO:0031902 (late endosome membrane), GO:0098852 (lytic vacuole membrane), GO:0005765 (lysosomal membrane)