IFITM3 interferon induced transmembrane protein 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: IFITM3provided by HGNC
Official Full Name: interferon induced transmembrane protein 3provided by HGNC
Primary source: HGNC:HGNC:5414
See related: Ensembl:ENSG00000142089 MIM:605579; AllianceGenome:HGNC:5414
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: 1-8U; IP15; DSPA2b
Summary: Interferon-induced transmembrane (IFITM) proteins are a family of interferon induced antiviral proteins. The family contains five members, including IFITM1, IFITM2 and IFITM3 and belong to the CD225 superfamily. The protein encoded by this gene restricts cellular entry by diverse viral pathogens, such as influenza A virus, Ebola virus and Sars-CoV-2. [provided by RefSeq, Nov 2021]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
Expression: Ubiquitous expression in liver (RPKM 370.9), placenta (RPKM 358.2) and 25 other tissues See more
Orthologs: all
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Genomic context

Location:: 11p15.5

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (319676..320860, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (360910..362094, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (319676..320860, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TYK2, IFITM3, IFNAR2 and OAS3 single-nucleotide polymorphisms among severe COVID-19 ICU patients in Morocco.
Title: TYK2, IFITM3, IFNAR2 and OAS3 single-nucleotide polymorphisms among severe COVID-19 ICU patients in Morocco.
Interferon-Induced Transmembrane Protein-3 Rs12252-G Variant Increases COVID-19 Mortality Potential in Egyptian Population.
Title: Interferon-Induced Transmembrane Protein-3 Rs12252-G Variant Increases COVID-19 Mortality Potential in Egyptian Population.
Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB-dependent IFITM3 expression.
Title: Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB-dependent IFITM3 expression.
IFITM3 inhibits severe fever with thrombocytopenia syndrome virus entry and interacts with viral Gc protein.
Title: IFITM3 inhibits severe fever with thrombocytopenia syndrome virus entry and interacts with viral Gc protein.
Inflammatory Polymorphisms (IL-6 rs1800796, IL-10 rs1800896, TNF-alpha rs1800629, and IFITM3 rs12252) Are Not Associated with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors.
Title: Inflammatory Polymorphisms (IL-6 rs1800796, IL-10 rs1800896, TNF-α rs1800629, and IFITM3 rs12252) Are Not Associated with Post-COVID Symptoms in Previously Hospitalized COVID-19 Survivors.
A Knockout of the IFITM3 Gene Increases the Sensitivity of WI-38 VA13 Cells to the Influenza A Virus.
Title: A Knockout of the IFITM3 Gene Increases the Sensitivity of WI-38 VA13 Cells to the Influenza A Virus.
Evaluation of long non-coding RNAs EGOT, NRAV, NRIR and mRNAs ISG15 and IFITM3 expressions in COVID-19 patients.
Title: Evaluation of long non-coding RNAs EGOT, NRAV, NRIR and mRNAs ISG15 and IFITM3 expressions in COVID-19 patients.
IFITM1 and IFITM3 Proteins Inhibit the Infectivity of Progeny HIV-1 without Disrupting Envelope Glycoprotein Clusters.
Title: IFITM1 and IFITM3 Proteins Inhibit the Infectivity of Progeny HIV-1 without Disrupting Envelope Glycoprotein Clusters.
IFITM3-mediated activation of TRAF6/MAPK/AP-1 pathways induces acquired TKI resistance in clear cell renal cell carcinoma.
Title: IFITM3-mediated activation of TRAF6/MAPK/AP-1 pathways induces acquired TKI resistance in clear cell renal cell carcinoma.
Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFalpha genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis.
Title: Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFα genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis.

Submit: New GeneRIF Correction See all GeneRIFs (139)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Influenza, severe, susceptibility to MedGen: C3553462 OMIM: 614680 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 incorporates IFITM3 into virions but this incorporation does not strictly correlate with the phenotype of IFITM inhibition of HIV-1 cell-to-cell infection	PubMed
HIV-1 CXCR4-tropic virus replication is restricted by IFITM2 and IFITM3 as shown through shRNA knockdown	PubMed
HIV-1 infectivity is inhibited when IFITM3 is expressed by the virus producing cell (293T cells)	PubMed
HIV-1 cell-to-cell transmission (Jurkat-to-Jurkat, 293T-to-Jurkat, PM1 to Jurkat, PBMCs to Jurkat) is inhibited by IFITM3 and this inhibition appears to be regulated by the IFITM protein C terminus, is IFITM-species specific and virus-strain specific	PubMed
Knockdown of IFITM1/2/3 by siRNA enhances virus transmission to target cells and the production of virions in CD4+ T cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 shedding is induced by IFITM3	PubMed
	env	HIV-1 gp120 interacts with IFITM3	PubMed
	env	HIV-1 Env processing from gp160 to gp120/41 is inhibited by IFITM3	PubMed
	env	The exposure to HIV-1 gp120 upregulates the IFITM3 level in HeLa cells	PubMed
	env	Tyrosine kinase Fyn-mediated phosphorylation of IFITM3 at position Y20 induces localization of IFITM3 at the endocytic compartments, which impairs inhibition of Env-mediated entry by IFITM3 delta(1-21) mutant	PubMed
	env	The expression of IFITM3 delta(1-21) mutant inhibits HIV-1 gp120/gp41 Env-mediated entry into human SupT1 cells, suggesting that the first 21 amino acids in IFITM3 are not required for inhibition of Env-mediated entry	PubMed
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 interacts with IFITM3	PubMed
	env	IFITM2/3 proteins are co-localize with HIV-1 Env in the cell interior, while surface-associated IFITM2/3 proteins are present at virus budding sites containing HIV-1 Gag and Env proteins in CD4+ T cells	PubMed
Envelope transmembrane glycoprotein gp41	env	HIV-1 Env processing from gp160 to gp120/41 is inhibited by IFITM3	PubMed
	env	HIV-1 gp41 interacts with IFITM3	PubMed
	env	Tyrosine kinase Fyn-mediated phosphorylation of IFITM3 at position Y20 induces localization of IFITM3 at the endocytic compartments, which impairs inhibition of Env-mediated entry by IFITM3 delta(1-21) mutant	PubMed
	env	The expression of IFITM3 delta(1-21) mutant inhibits HIV-1 gp120/gp41 Env-mediated entry into human SupT1 cells, suggesting that the first 21 amino acids in IFITM3 are not required for inhibition of Env-mediated entry	PubMed
Nef	nef	The small molecule PKR inhibitor C16 inhibits the IFITM3-induced suppression of HIV-1 Gag, Vif, and Nef protein expression	PubMed
	nef	IFITM3 significantly downregulates the expression of HIV-1 Nef by interfering with Tat/TAR-mediated expression	PubMed
Pr55(Gag)	gag	IFITM1, IFITM2, and IFITM3 proteins (IFITMs) co-localize with HIV-1 Gag in virus-producing cells and co-assemble with Gag into budding particles	PubMed
	gag	Endogenous IFITM3 inhibits virus infectivity by measuement of Gag+ target cells	PubMed
	gag	Endogenous IFITM1/2/3 proteins are upregulated in activated CD4+ T cells and incorporated into HIV-1 Gag/p24-associated virions during infection	PubMed
	gag	IFITM2/3 proteins are co-localize with HIV-1 Env in the cell interior, while surface-associated IFITM2/3 proteins are present at virus budding sites containing HIV-1 Gag and Env proteins in CD4+ T cells	PubMed
	gag	The small molecule PKR inhibitor C16 inhibits the IFITM3-induced suppression of HIV-1 Gag, Vif, and Nef protein expression	PubMed
	gag	IFITM3 significantly downregulates the expression of HIV-1 Gag and CA by interfering with both Rev/RRE- and Tat/TAR-mediated expression	PubMed
Vif	vif	The small molecule PKR inhibitor C16 inhibits the IFITM3-induced suppression of HIV-1 Gag, Vif, and Nef protein expression	PubMed
	vif	IFITM3 significantly downregulates the expression of HIV-1 Vif by interfering with both Rev/RRE- and Tat/TAR-mediated expression	PubMed
Vpr	vpr	HIV-1 Vpr upregulates the gene expression of IFITM3 in human monocyte-derived dendritic cells	PubMed
	vpr	IFITM1, 2 or 3 marginally inhibit the entry of HIV-1 NL4-3 and SIV Mac into TZM-bl by measuring the cleavage of CCF2 by BlaM-Vpr that enters the cytoplasm together with viral cores	PubMed
capsid	gag	IFITM1, IFITM2, and IFITM3 proteins (IFITMs) co-localize with HIV-1 CA in velocity gradients, indicating that IFITMs are virion-associated proteins	PubMed
	gag	Endogenous IFITM1/2/3 proteins are upregulated in activated CD4+ T cells and incorporated into HIV-1 Gag/p24-associated virions during infection	PubMed
	gag	IFITM3 significantly downregulates the expression of HIV-1 Gag and CA by interfering with both Rev/RRE- and Tat/TAR-mediated expression	PubMed
matrix	gag	IFITM3 associates with HIV-1 viral membrane-associated MA rather than with the core in virions	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SGC31615 (e-PCR)
- UniSTS:18300

PMC135632P3 (e-PCR)
- UniSTS:270760

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in defense response to virus	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of viral entry into host cell	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of viral entry into host cell	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of viral entry into host cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of viral genome replication	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of viral genome replication	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of viral transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in response to interferon-alpha	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to interferon-alpha	IDA Inferred from Direct Assay more info	PubMed
involved_in response to interferon-beta	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to interferon-beta	IDA Inferred from Direct Assay more info	PubMed
involved_in response to type II interferon	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to type II interferon	IDA Inferred from Direct Assay more info	PubMed
involved_in response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in type I interferon-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in early endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in late endosome membrane	IEA Inferred from Electronic Annotation more info
located_in lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: interferon-induced transmembrane protein 3

Names: dispanin subfamily A member 2b; interferon-inducible protein 1-8U

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_032755.1 RefSeqGene

Range

5055..6239

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_021034.3 → NP_066362.2 interferon-induced transmembrane protein 3

See identical proteins and their annotated locations for NP_066362.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer, protein-coding transcript.

Source sequence(s)

AI355192, DB261103

Consensus CDS

CCDS41585.1

UniProtKB/Swiss-Prot

Q01628, Q53Y76, Q96HK8, Q96J15

UniProtKB/TrEMBL

H9NL19

Related

ENSP00000382707.4, ENST00000399808.5

Conserved Domains (1) summary

pfam04505
Location:55 → 121

CD225; Interferon-induced transmembrane protein

RNA

NR_049759.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice junction at the 5' end of a coding exon compared to variant 1, that causes a frameshift. The resulting transcript is not thought to be protein-coding.

Source sequence(s)

BQ937265, DB261103

Related

ENST00000679382.1