IFITM3
entrez
10410
canonical
uniprot
Q01628
canonical
ensembl
ENSG00000142089
resolver
ensp
ENSP00000382707
resolver
enst
ENST00000399808
resolver
genesymbol
IFITM3
resolver
hgnc
HGNC:5414
resolver
uniprot
Q53Y76
resolver
uniprot
Q96HK8
resolver
uniprot
Q96J15
resolver
uniprot_entry
IFM3_HUMAN
resolver
uniprot_sec
Q53Y76
resolver
uniprot_sec
Q96HK8
resolver
uniprot_sec
Q96J15
resolver
amino_acid_sequence
MNHTVQTFFSPVNSGQPPNYEMLKEEHEVAVLGAPHNPAPPTSTVIHIRSETSVPDHVVWSLFNTLFMNPCCLGFIAFAYSVKSRDRKMVGDVTGAQAYASTAKCLNIWALILGILMTILLIVIPVLIFQAYG
uniprot
proteins
function
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). {ECO:0000269|PubMed:20064371, ECO:0000269|PubMed:20534863, ECO:0000269|PubMed:20943977, ECO:0000269|PubMed:21177806, ECO:0000269|PubMed:21253575, ECO:0000269|PubMed:22046135, ECO:0000269|PubMed:22479637, ECO:0000269|PubMed:23601107, ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33239446, ECO:0000269|PubMed:33270927}.
uniprot
proteins
mass_dalton
14632
uniprot
proteins
mutagenesis
MUTAGEN 20; /note="Y->A: Loss of phosphorylation. Accumulates at the plasma membrane. Increases anti-HCV properties. Loss of anti-SARS-CoV-2 activity by enhancing Spike-mediated cell-to-cell fusion."; /evidence="ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33270927"; MUTAGEN 23; /note="L->Q: Accumulates at the plasma membrane. Loss of anti-SARS-CoV-2 activity by enhancing Spike-mediated cell-to-cell fusion."; /evidence="ECO:0000269|PubMed:33270927"; MUTAGEN 59..68; /note="Missing: Slightly enhances infection by SARS-CoV-2."; /evidence="ECO:0000269|PubMed:33270927"; MUTAGEN 61..65; /note="SLFNT->ALFAA: Decreases anti-SARS-CoV-2 activity."; /evidence="ECO:0000269|PubMed:33270927"; MUTAGEN 71..72; /note="CC->AA: Loss of anti-HCV activity. Only localizes at the lysosome. No effect on SARS-CoV-2 infection; when associated with A-105. Loss of anti-influenza A virus activity; when associated with A-105."; /evidence="ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33270927"; MUTAGEN 105; /note="C->A: Loss of anti-HCV activity. Only localizes at the lysosome. No effect on SARS-CoV-2 infection; when associated with 71-A-A-72. Loss of anti-influenza A virus activity; when associated with 71-A-A-72."; /evidence="ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33270927
uniprot
proteins
post_translational_modification
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. {ECO:0000269|PubMed:20601941, ECO:0000269|PubMed:22511783, ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:33270927}.; 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. {ECO:0000269|PubMed:22511783}.; PTM: Phosphorylation at Tyr-20 is required for endosomal and lysosomal location. {ECO:0000269|PubMed:26354436}.
uniprot
proteins
protein_family
CD225/Dispanin family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
1906403
uniprot
proteins
pubmed
19901966
uniprot
proteins
pubmed
20064371
uniprot
proteins
pubmed
20534863
uniprot
proteins
pubmed
20601941
uniprot
proteins
pubmed
20943977
uniprot
proteins
pubmed
21166591
uniprot
proteins
pubmed
21177806
uniprot
proteins
pubmed
21253575
uniprot
proteins
pubmed
22046135
uniprot
proteins
pubmed
22363774
uniprot
proteins
pubmed
22446628
uniprot
proteins
pubmed
22479637
uniprot
proteins
pubmed
22511783
uniprot
proteins
pubmed
23601107
uniprot
proteins
pubmed
26354436
uniprot
proteins
pubmed
30983867
uniprot
proteins
pubmed
33239446
uniprot
proteins
pubmed
33270927
uniprot
proteins
sequence_length
133
uniprot
proteins
subcellular_location
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}.
uniprot
proteins
transmembrane_region
TRANSMEM 108..128; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins