DegronMD - Q01628(IFITM3)

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:33270927, PubMed:33239446). 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}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.F8L	TCGA-E2-A154	BRCA	TCGA	PPNY	ITCH	17:20	Mutation rewiring degron network	0.0833
p.F8L	DO1966	BRCA	ICGC	PPNY	ITCH	17:20	Mutation rewiring degron network	0.0833
p.A30V	TCGA-W3-A824	SKCM	TCGA	PPNY	ITCH	17:20	Mutation rewiring degron network	0.0556
p.V10M	DO229022	LICA	ICGC	PPNY	ITCH	17:20	Mutation blocking phosphorylation signal	0.5833
p.V10M	DO229009	LICA	ICGC	PPNY	ITCH	17:20	Mutation blocking phosphorylation signal	0.5833
p.V10M	DO229259	THCA	ICGC	PPNY	ITCH	17:20	Mutation blocking phosphorylation signal	0.5833
p.V10M	DO229232	THCA	ICGC	PPNY	ITCH	17:20	Mutation blocking phosphorylation signal	0.5833
p.V10M	DO229240	THCA	ICGC	PPNY	ITCH	17:20	Mutation blocking phosphorylation signal	0.5833
p.K24Q	DO45293	LIRI	ICGC	PPNY	ITCH	17:20	Mutation blocking ubiquitination signal	0.6667
p.E25G	DO45293	LIRI	ICGC	PPNY	ITCH	17:20	Mutation rewiring degron network	0.1944
p.A9V	DO51271	SKCM	ICGC	PPNY	ITCH	17:20	Mutation rewiring degron network	0.1111
p.E28Q	SIDM00138	Non-Small Cell Lung Carcinoma	GDSC	PPNY	ITCH	17:20	Mutation rewiring degron network	0.1111
p.E28Q	ACH-000900	Lung Cancer	CCLE	PPNY	ITCH	17:20	Mutation rewiring degron network	0.1111
p.E28Q	NCI-H23	lung	COSMIC	PPNY	ITCH	17:20	Mutation rewiring degron network	0.1111
p.H27Q	ACH-000038	Lymphoma	CCLE	PPNY	ITCH	17:20	Mutation rewiring degron network	0.1389
p.H27Q	ACH-000641	Leukemia	CCLE	PPNY	ITCH	17:20	Mutation rewiring degron network	0.1389
p.H27Q	ACH-000783	Breast Cancer	CCLE	PPNY	ITCH	17:20	Mutation rewiring degron network	0.1389
p.H27Q	ACH-000918	Leukemia	CCLE	PPNY	ITCH	17:20	Mutation rewiring degron network	0.1389
p.P17H	ACH-000221	Liver Cancer	CCLE	PPNY	ITCH	17:20	Mutation altering degron motif	0.7694
p.E7Q	NCI-H23	lung	COSMIC	PPNY	ITCH	17:20	Mutation rewiring degron network	0.0556
p.R28H	CTV-1	haematopoietic and lymphoid tissue	COSMIC	PPNY	ITCH	17:20	Mutation rewiring degron network	0.1111

Kaplan plot for IFITM3 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

IFITM3

UniProt ID: Q01628

Entrez ID: 10410

Protein name: Interferon-induced transmembrane protein 3 (Dispanin subfamily A member 2b) (DSPA2b) (Interferon-inducible protein 1-8U)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for IFITM3 in