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Protein

Interferon-induced transmembrane protein 3

Gene

IFITM3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 coronavirus (SARS-CoV), Marburg virus (MARV) and Ebola virus (EBOV), Dengue virus (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry, SARS-CoV 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.8 Publications

GO - Biological processi

  • defense response to virus Source: UniProtKB
  • immune response Source: ProtInc
  • negative regulation of viral entry into host cell Source: UniProtKB
  • negative regulation of viral genome replication Source: UniProtKB
  • negative regulation of viral transcription Source: UniProtKB
  • response to interferon-alpha Source: UniProtKB
  • response to interferon-beta Source: UniProtKB
  • response to interferon-gamma Source: UniProtKB
  • response to virus Source: UniProtKB
  • type I interferon signaling pathway Source: Reactome

Keywordsi

Biological processAntiviral defense, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-909733 Interferon alpha/beta signaling

Protein family/group databases

TCDBi8.A.58.1.3 the dispanin (dispanin) family

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon-induced transmembrane protein 3
Alternative name(s):
Dispanin subfamily A member 2b
Short name:
DSPA2b
Interferon-inducible protein 1-8U
Gene namesi
Name:IFITM3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000142089.15
HGNCiHGNC:5414 IFITM3
MIMi605579 gene
neXtProtiNX_Q01628

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 57CytoplasmicSequence analysisAdd BLAST57
Intramembranei58 – 78HelicalSequence analysisAdd BLAST21
Topological domaini79 – 107CytoplasmicSequence analysisAdd BLAST29
Transmembranei108 – 128HelicalSequence analysisAdd BLAST21
Topological domaini129 – 133ExtracellularSequence analysis5

Keywords - Cellular componenti

Cell membrane, Endosome, Lysosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi10410
MalaCardsiIFITM3
MIMi614680 phenotype
OpenTargetsiENSG00000142089
PharmGKBiPA29655

Polymorphism and mutation databases

BioMutaiIFITM3
DMDMi20178301

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001537291 – 133Interferon-induced transmembrane protein 3Add BLAST133

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki24Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Lipidationi71S-palmitoyl cysteine1 Publication1
Lipidationi72S-palmitoyl cysteine1 Publication1
Cross-linki83Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki88Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki104Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Lipidationi105S-palmitoyl cysteine1 Publication1

Post-translational modificationi

Palmitoylation on membrane-proximal cysteines controls clustering in membrane compartments and antiviral activity against influenza virus.2 Publications
Not glycosylated.
Polyubiquitinated with both 'Lys-48' and 'Lys-63' linkages. Ubiquitination negatively regulates antiviral activity. Lys-24 is the most prevalent ubiquitination site.1 Publication

Keywords - PTMi

Isopeptide bond, Lipoprotein, Palmitate, Ubl conjugation

Proteomic databases

EPDiQ01628
PaxDbiQ01628
PeptideAtlasiQ01628
PRIDEiQ01628
TopDownProteomicsiQ01628

PTM databases

iPTMnetiQ01628
PhosphoSitePlusiQ01628
SwissPalmiQ01628

Expressioni

Inductioni

By IFN-alpha and IFNG/IFN-gamma.

Gene expression databases

BgeeiENSG00000142089
CleanExiHS_IFITM3
ExpressionAtlasiQ01628 baseline and differential
GenevisibleiQ01628 HS

Organism-specific databases

HPAiHPA004337

Interactioni

Subunit structurei

Interacts with ATP6V0B and CD81 (By similarity). Interacts with SPP1; the interaction reduces OPN expression. Interacts with VAPA.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NAMPTP434903EBI-7932862,EBI-2829310

Protein-protein interaction databases

BioGridi115681, 6 interactors
IntActiQ01628, 4 interactors
MINTiQ01628
STRINGi9606.ENSP00000382707

Structurei

3D structure databases

ProteinModelPortaliQ01628
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni60 – 93Interaction with SPP11 PublicationAdd BLAST34
Regioni108 – 133Interaction with VAPA1 PublicationAdd BLAST26

Sequence similaritiesi

Belongs to the CD225/Dispanin family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J2DU Eukaryota
ENOG4112C1U LUCA
GeneTreeiENSGT00390000003476
HOGENOMiHOG000115781
HOVERGENiHBG001182
InParanoidiQ01628
KOiK06566
OMAiVLIFQAY
OrthoDBiEOG091G1143
PhylomeDBiQ01628
TreeFamiTF334894

Family and domain databases

InterProiView protein in InterPro
IPR007593 CD225/Dispanin_fam
PfamiView protein in Pfam
PF04505 CD225, 1 hit

Sequencei

Sequence statusi: Complete.

Q01628-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNHTVQTFFS PVNSGQPPNY EMLKEEHEVA VLGAPHNPAP PTSTVIHIRS
60 70 80 90 100
ETSVPDHVVW SLFNTLFMNP CCLGFIAFAY SVKSRDRKMV GDVTGAQAYA
110 120 130
STAKCLNIWA LILGILMTIL LIVIPVLIFQ AYG
Length:133
Mass (Da):14,632
Last modified:April 16, 2002 - v2
Checksum:i9FFB2E4623F7A1DD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2N → S in CAA40626 (PubMed:1906403).Curated1
Sequence conflicti34A → G in CAA40626 (PubMed:1906403).Curated1

Polymorphismi

Genetic variations in IFITM3 are responsible for susceptibility to severe influenza virus infection [MIMi:614680].2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0538103H → Q1 PublicationCorresponds to variant dbSNP:rs1136853Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57352 mRNA Translation: CAA40626.1
JQ610571 Genomic DNA Translation: AFF60305.1
JQ610572 Genomic DNA Translation: AFF60306.1
JQ610573 Genomic DNA Translation: AFF60307.1
JQ610574 Genomic DNA Translation: AFF60308.1
JQ610575 Genomic DNA Translation: AFF60309.1
JQ610576 Genomic DNA Translation: AFF60310.1
JQ610577 Genomic DNA Translation: AFF60311.1
JQ610578 Genomic DNA Translation: AFF60312.1
JQ610579 Genomic DNA Translation: AFF60313.1
JQ610580 Genomic DNA Translation: AFF60314.1
JQ610581 Genomic DNA Translation: AFF60315.1
JQ610582 Genomic DNA Translation: AFF60316.1
JQ610583 Genomic DNA Translation: AFF60317.1
JQ610585 Genomic DNA Translation: AFF60319.1
JQ610586 Genomic DNA Translation: AFF60320.1
JQ610587 Genomic DNA Translation: AFF60321.1
JQ610588 Genomic DNA Translation: AFF60322.1
JQ610589 Genomic DNA Translation: AFF60323.1
JQ610590 Genomic DNA Translation: AFF60324.1
JQ610591 Genomic DNA Translation: AFF60325.1
JQ610592 Genomic DNA Translation: AFF60326.1
JQ610593 Genomic DNA Translation: AFF60327.1
JQ610594 Genomic DNA Translation: AFF60328.1
JQ610595 Genomic DNA Translation: AFF60329.1
JQ610596 Genomic DNA Translation: AFF60330.1
JQ610597 Genomic DNA Translation: AFF60331.1
JQ610598 Genomic DNA Translation: AFF60332.1
JQ610599 Genomic DNA Translation: AFF60333.1
JQ610600 Genomic DNA Translation: AFF60334.1
JQ610601 Genomic DNA Translation: AFF60335.1
JQ610602 Genomic DNA Translation: AFF60336.1
JQ610603 Genomic DNA Translation: AFF60337.1
JQ610604 Genomic DNA Translation: AFF60338.1
JQ610605 Genomic DNA Translation: AFF60339.1
JQ610606 Genomic DNA Translation: AFF60340.1
JQ610607 Genomic DNA Translation: AFF60341.1
JQ610608 Genomic DNA Translation: AFF60342.1
JQ610609 Genomic DNA Translation: AFF60343.1
JQ610610 Genomic DNA Translation: AFF60344.1
JQ610611 Genomic DNA Translation: AFF60345.1
JQ610613 Genomic DNA Translation: AFF60347.1
JQ610614 Genomic DNA Translation: AFF60348.1
JQ610615 Genomic DNA Translation: AFF60349.1
JQ610616 Genomic DNA Translation: AFF60350.1
JQ610617 Genomic DNA Translation: AFF60351.1
JQ610618 Genomic DNA Translation: AFF60352.1
JQ610620 Genomic DNA Translation: AFF60354.1
JQ610621 Genomic DNA Translation: AFF60355.1
BT006892 mRNA Translation: AAP35538.1
AK292173 mRNA Translation: BAF84862.1
AC136475 Genomic DNA No translation available.
CH891444 Genomic DNA Translation: EAW50866.1
BC006794 mRNA Translation: AAH06794.1
BC008417 mRNA Translation: AAH08417.1
BC022439 mRNA Translation: AAH22439.1
BC070243 mRNA Translation: AAH70243.1
CCDSiCCDS41585.1
PIRiS17182
RefSeqiNP_066362.2, NM_021034.2
UniGeneiHs.374650

Genome annotation databases

EnsembliENST00000399808; ENSP00000382707; ENSG00000142089
GeneIDi10410
KEGGihsa:10410
UCSCiuc001lpa.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIFM3_HUMAN
AccessioniPrimary (citable) accession number: Q01628
Secondary accession number(s): Q53Y76, Q96HK8, Q96J15
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: April 16, 2002
Last modified: May 23, 2018
This is version 151 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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