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Protein

Interferon-induced transmembrane protein 3

Gene

IFITM3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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-KW
  • 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
Complete GO annotation...

Keywords - Biological processi

Antiviral 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 interferon-induced transmembrane protein (ifitm) 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

HGNCiHGNC:5414. IFITM3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5757CytoplasmicSequence analysisAdd
BLAST
Intramembranei58 – 7821HelicalSequence analysisAdd
BLAST
Topological domaini79 – 10729CytoplasmicSequence analysisAdd
BLAST
Transmembranei108 – 12821HelicalSequence analysisAdd
BLAST
Topological domaini129 – 1335ExtracellularSequence analysis

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • late endosome membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Lysosome, Membrane

Pathology & Biotechi

Organism-specific databases

MalaCardsiIFITM3.
MIMi614680. phenotype.
PharmGKBiPA29655.

Polymorphism and mutation databases

BioMutaiIFITM3.
DMDMi20178301.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 133133Interferon-induced transmembrane protein 3PRO_0000153729Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki24 – 24Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Lipidationi71 – 711S-palmitoyl cysteine1 Publication
Lipidationi72 – 721S-palmitoyl cysteine1 Publication
Cross-linki83 – 83Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki88 – 88Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki104 – 104Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Lipidationi105 – 1051S-palmitoyl cysteine1 Publication

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. Ubiqutination 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.
PhosphoSiteiQ01628.
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. 5 interactions.
IntActiQ01628. 3 interactions.
MINTiMINT-2805186.
STRINGi9606.ENSP00000382707.

Structurei

3D structure databases

ProteinModelPortaliQ01628.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni60 – 9334Interaction with SPP1Add
BLAST
Regioni108 – 13326Interaction with VAPAAdd
BLAST

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

InterProiIPR007593. CD225/Dispanin_fam.
[Graphical view]
PfamiPF04505. CD225. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti2 – 21N → S in CAA40626 (PubMed:1906403).Curated
Sequence conflicti34 – 341A → G in CAA40626 (PubMed:1906403).Curated

Polymorphismi

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti3 – 31H → Q.1 Publication
Corresponds to variant rs1136853 [ dbSNP | Ensembl ].
VAR_053810

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ01628.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115681. 5 interactions.
IntActiQ01628. 3 interactions.
MINTiMINT-2805186.
STRINGi9606.ENSP00000382707.

Protein family/group databases

TCDBi8.A.58.1.3. the interferon-induced transmembrane protein (ifitm) family.

PTM databases

iPTMnetiQ01628.
PhosphoSiteiQ01628.
SwissPalmiQ01628.

Polymorphism and mutation databases

BioMutaiIFITM3.
DMDMi20178301.

Proteomic databases

EPDiQ01628.
PaxDbiQ01628.
PeptideAtlasiQ01628.
PRIDEiQ01628.
TopDownProteomicsiQ01628.

Protocols and materials databases

DNASUi10410.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10410.
GeneCardsiIFITM3.
HGNCiHGNC:5414. IFITM3.
HPAiHPA004337.
MalaCardsiIFITM3.
MIMi605579. gene.
614680. phenotype.
neXtProtiNX_Q01628.
PharmGKBiPA29655.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-909733. Interferon alpha/beta signaling.

Miscellaneous databases

GeneWikiiIFITM3.
GenomeRNAii10410.
PROiQ01628.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000142089.
CleanExiHS_IFITM3.
ExpressionAtlasiQ01628. baseline and differential.
GenevisibleiQ01628. HS.

Family and domain databases

InterProiIPR007593. CD225/Dispanin_fam.
[Graphical view]
PfamiPF04505. CD225. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIFM3_HUMAN
AccessioniPrimary (citable) accession number: Q01628
Secondary accession number(s): Q53Y76, Q96HK8, Q96J15
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: April 16, 2002
Last modified: September 7, 2016
This is version 139 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.