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Protein

Interferon-induced transmembrane protein 3

Gene

Ifitm3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

IFN-induced antiviral protein which inhibits the entry of viruses to the host cell cytoplasm, permitting endocytosis, but preventing subsequent viral fusion and release of viral contents into the cytosol. 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) and human immunodeficiency virus type 1 (HIV-1). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry and SARS-CoV S 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. Involved in initiating germ cell competence and specification, and in the demarcation of PGCs from their somatic neighbors.4 Publications

GO - Biological processi

  • defense response to virus Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of viral entry into host cell Source: UniProtKB
  • negative regulation of viral genome replication Source: MGI
  • negative regulation of viral transcription Source: MGI
  • receptor-mediated endocytosis Source: MGI
  • response to interferon-alpha Source: MGI
  • response to interferon-beta Source: MGI
  • response to interferon-gamma Source: MGI
  • response to virus Source: UniProtKB
  • type I interferon signaling pathway Source: MGI
Complete GO annotation...

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon-induced transmembrane protein 3
Alternative name(s):
Dispanin subfamily A member 2b
Short name:
DSPA2b
Fragilis protein
Interferon-inducible protein 15
Mouse ifitm-like protein 1
Short name:
Mil-1
Gene namesi
Name:Ifitm3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1913391. Ifitm3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5757CytoplasmicSequence analysisAdd
BLAST
Intramembranei58 – 7821HelicalSequence analysisAdd
BLAST
Topological domaini79 – 10931CytoplasmicSequence analysisAdd
BLAST
Transmembranei110 – 13021HelicalSequence analysisAdd
BLAST
Topological domaini131 – 1377ExtracellularSequence analysis

GO - Cellular componenti

  • apical part of cell Source: MGI
  • cell surface Source: MGI
  • cytoplasm Source: MGI
  • cytoplasmic, membrane-bounded vesicle Source: MGI
  • endoplasmic reticulum Source: MGI
  • extracellular exosome Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • late endosome membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: UniProtKB-SubCell
  • nucleus Source: MGI
  • plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Lysosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 137137Interferon-induced transmembrane protein 3PRO_0000398567Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki24 – 24Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei27 – 271PhosphotyrosineCombined sources
Lipidationi71 – 711S-palmitoyl cysteineBy similarity
Lipidationi72 – 721S-palmitoyl cysteineBy similarity
Cross-linki83 – 83Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki88 – 88Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki104 – 104Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Lipidationi105 – 1051S-palmitoyl cysteineBy similarity

Post-translational modificationi

Polyubiquitinated with both 'Lys-48' and 'Lys-63' linkages. Ubiqutination negatively regulates antiviral activity. Lys-24 is the most prevalent ubiquitination site (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9CQW9.
MaxQBiQ9CQW9.
PaxDbiQ9CQW9.
PRIDEiQ9CQW9.

PTM databases

iPTMnetiQ9CQW9.
PhosphoSiteiQ9CQW9.
SwissPalmiQ9CQW9.

Expressioni

Tissue specificityi

Expressed in acinar cell. Predominantly expressed in nascent primordial germ cells, as well as in gonadal germ cells.2 Publications

Developmental stagei

At E7.25 strong expression is found at the base of the incipient allantois and weak expression in the mesodermal portion of the posterior amnion, and, importantly, the expression did not extend to the allantois. Expression persisted until the late bud stage (E7.5), but gradually faded around the early head fold stage (E7.75). At an earlier stage, only weak expression is seen throughout the epiblast in E6.0. But around E6.25-E6.5 (before gastrulation), marked expression is evident within the most proximal layer of the epiblast that is in intimate contact with the extraembryonic ectoderm. Expression is indeed induced by extraembryonic ectoderm through signaling molecules. During germ cell formation, is expressed in putative PGC ancestors in embryos at 6.5-7.5 dpc. In migrating PGCs, expression is continuous. After the beginning of gastrulation, the expression migrates to the posterior end of the developing primitive streak at the early/mid streak stage and became very intense in the position where PGCs (Primordial germ cells) differentiate from late streak stage onward.3 Publications

Inductioni

By alpha interferon. Induced in pancreas during caerulein-induced pancreatitis. Induced in pancreas under systemic-lipopolysaccharide treatment and in intestine under Salmonella infection.1 Publication

Gene expression databases

BgeeiQ9CQW9.
GenevisibleiQ9CQW9. MM.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi211244. 2 interactions.
IntActiQ9CQW9. 3 interactions.
MINTiMINT-1870107.
STRINGi10090.ENSMUSP00000026565.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni60 – 9334Interaction with SPP1By similarityAdd
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.
InParanoidiQ9CQW9.
KOiK06566.
OMAiVLIFQAY.
OrthoDBiEOG7288T5.
PhylomeDBiQ9CQW9.
TreeFamiTF334894.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

Q9CQW9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNHTSQAFIT AASGGQPPNY ERIKEEYEVA EMGAPHGSAS VRTTVINMPR
60 70 80 90 100
EVSVPDHVVW SLFNTLFMNF CCLGFIAYAY SVKSRDRKMV GDVTGAQAYA
110 120 130
STAKCLNIST LVLSILMVVI TIVSVIIIVL NAQNLHT
Length:137
Mass (Da):14,954
Last modified:June 1, 2001 - v1
Checksum:i4BEBED26E38D3511
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti130 – 1301L → F in BAB25347 (PubMed:15184081).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY082484 mRNA. Translation: AAM03316.1.
AY594690 mRNA. Translation: AAT06089.1.
AK003407 mRNA. Translation: BAB22771.1.
AK007916 mRNA. Translation: BAB25347.1.
AK007919 mRNA. Translation: BAB25350.1.
AK151890 mRNA. Translation: BAE30774.1.
CH466531 Genomic DNA. Translation: EDL17977.1.
BC010291 mRNA. Translation: AAH10291.1.
CCDSiCCDS21996.1.
RefSeqiNP_079654.1. NM_025378.2.
UniGeneiMm.141021.

Genome annotation databases

EnsembliENSMUST00000026565; ENSMUSP00000026565; ENSMUSG00000025492.
GeneIDi66141.
KEGGimmu:66141.
UCSCiuc009kjc.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY082484 mRNA. Translation: AAM03316.1.
AY594690 mRNA. Translation: AAT06089.1.
AK003407 mRNA. Translation: BAB22771.1.
AK007916 mRNA. Translation: BAB25347.1.
AK007919 mRNA. Translation: BAB25350.1.
AK151890 mRNA. Translation: BAE30774.1.
CH466531 Genomic DNA. Translation: EDL17977.1.
BC010291 mRNA. Translation: AAH10291.1.
CCDSiCCDS21996.1.
RefSeqiNP_079654.1. NM_025378.2.
UniGeneiMm.141021.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi211244. 2 interactions.
IntActiQ9CQW9. 3 interactions.
MINTiMINT-1870107.
STRINGi10090.ENSMUSP00000026565.

PTM databases

iPTMnetiQ9CQW9.
PhosphoSiteiQ9CQW9.
SwissPalmiQ9CQW9.

Proteomic databases

EPDiQ9CQW9.
MaxQBiQ9CQW9.
PaxDbiQ9CQW9.
PRIDEiQ9CQW9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026565; ENSMUSP00000026565; ENSMUSG00000025492.
GeneIDi66141.
KEGGimmu:66141.
UCSCiuc009kjc.1. mouse.

Organism-specific databases

CTDi10410.
MGIiMGI:1913391. Ifitm3.

Phylogenomic databases

eggNOGiENOG410J2DU. Eukaryota.
ENOG4112C1U. LUCA.
GeneTreeiENSGT00390000003476.
HOGENOMiHOG000115781.
HOVERGENiHBG001182.
InParanoidiQ9CQW9.
KOiK06566.
OMAiVLIFQAY.
OrthoDBiEOG7288T5.
PhylomeDBiQ9CQW9.
TreeFamiTF334894.

Enzyme and pathway databases

ReactomeiR-MMU-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

Miscellaneous databases

ChiTaRSiIfitm3. mouse.
NextBioi320750.
PROiQ9CQW9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9CQW9.
GenevisibleiQ9CQW9. MM.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  1. "Developmentally regulated expression of mil-1 and mil-2, mouse interferon-induced transmembrane protein like genes, during formation and differentiation of primordial germ cells."
    Tanaka S.S., Matsui Y.
    Mech. Dev. 119:S261-S267(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
  2. "A molecular programme for the specification of germ cell fate in mice."
    Saitou M., Barton S.C., Surani M.A.
    Nature 418:293-300(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
    Strain: 129/SvEv.
  3. "Cloning of IP15, a pancreatitis-induced gene whose expression inhibits cell growth."
    Ropolo A., Tomasini R., Grasso D., Dusetti N.J., Cerquetti M.C., Iovanna J.L., Vaccaro M.I.
    Biochem. Biophys. Res. Commun. 319:1001-1009(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION.
    Strain: BALB/cJ.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Bone marrow, Embryo and Pancreas.
  5. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N-3.
    Tissue: Mammary tumor.
  7. "The fragilis interferon-inducible gene family of transmembrane proteins is associated with germ cell specification in mice."
    Lange U.C., Saitou M., Western P.S., Barton S.C., Surani M.A.
    BMC Dev. Biol. 3:1-1(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  8. "IFITM/Mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primordial germ cell homing and repulsion."
    Tanaka S.S., Yamaguchi Y.L., Tsoi B., Lickert H., Tam P.P.
    Dev. Cell 9:745-756(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
  9. "Expression of the mouse fragilis gene products in immune cells and association with receptor signaling complexes."
    Smith R.A., Young J., Weis J.J., Weis J.H.
    Genes Immun. 7:113-121(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CD81.
  10. "Normal germ line establishment in mice carrying a deletion of the Ifitm/Fragilis gene family cluster."
    Lange U.C., Adams D.J., Lee C., Barton S., Schneider R., Bradley A., Surani M.A.
    Mol. Cell. Biol. 28:4688-4696(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-27, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.
  13. "The small interferon-induced transmembrane genes and proteins."
    Siegrist F., Ebeling M., Certa U.
    J. Interferon Cytokine Res. 31:183-197(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  14. Cited for: FUNCTION.
  15. "Interferon-inducible transmembrane proteins of the innate immune response act as membrane organizers by influencing clathrin and v-ATPase localization and function."
    Wee Y.S., Roundy K.M., Weis J.J., Weis J.H.
    Inn. Immun. 18:834-845(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ATP6V0B.
  16. Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SEVERE INFLUENZA INFECTION.
  17. "The dispanins: a novel gene family of ancient origin that contains 14 human members."
    Sallman Almen M., Bringeland N., Fredriksson R., Schioth H.B.
    PLoS ONE 7:E31961-E31961(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: GENE FAMILY.

Entry informationi

Entry nameiIFM3_MOUSE
AccessioniPrimary (citable) accession number: Q9CQW9
Secondary accession number(s): Q9D8L6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 5, 2010
Last sequence update: June 1, 2001
Last modified: March 16, 2016
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

It has been previously shown that mediates migration of early primordial germ cells (PGCs) (PubMed:16326387). But according to PubMed:16326387, have no detectable effects on development of the germ line or on the generation of live young, hence, is not essential for PGC migration.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.