Q01628 (IFM3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interferon-induced transmembrane protein 3

Alternative name(s):
Dispanin subfamily A member 2b
Short name=DSPA2b
Interferon-inducible protein 1-8U

Gene names

Name:

IFITM3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	133 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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), 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. Ref.8 Ref.9 Ref.10 Ref.14 Ref.16 Ref.17 Ref.19
Subunit structure	Interacts with SPP1; the interaction reduces OPN expression. Interacts with ATP6V0B and CD81 By similarity. Ref.11
Subcellular location	Cell membrane; Single-pass type II membrane protein. Late endosome membrane; Single-pass type II membrane protein. Lysosome membrane; Single-pass type II membrane protein Ref.10 Ref.16 Ref.18.
Induction	By IFN-alpha and IFNG/IFN-gamma.
Post-translational modification	Palmitoylation on membrane-proximal cysteines controls clustering in membrane compartments and antiviral activity against influenza virus. Ref.12 Ref.18 Not glycosylated. Ref.18 Polyubiquitinated with both 'Lys-48' and 'Lys-63' linkages. Ubiqutination negatively regulates antiviral activity. Lys-24 is the most prevalent ubiquitination site.
Polymorphism	Genetic variations in IFITM3 are responsible for susceptibility to severe influenza virus infection [MIM:614680].
Sequence similarities	Belongs to the CD225/Dispanin family.

Ontologies

Keywords
Biological process	Antiviral defense Immunity Innate immunity
Cellular component	Cell membrane Endosome Lysosome Membrane
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
PTM	Isopeptide bond Lipoprotein Palmitate Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of viral entry into host cell Inferred from direct assay Ref.10Ref.17. Source: UniProtKB negative regulation of viral genome replication Inferred from direct assay Ref.10Ref.17. Source: UniProtKB negative regulation of viral transcription Inferred from direct assay Ref.10. Source: UniProtKB response to interferon-alpha Inferred from direct assay Ref.19. Source: UniProtKB response to interferon-beta Inferred from direct assay Ref.17. Source: UniProtKB response to interferon-gamma Inferred from direct assay Ref.17. Source: UniProtKB response to virus Inferred from direct assay Ref.10Ref.17Ref.19. Source: UniProtKB type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW late endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 133	133	Interferon-induced transmembrane protein 3		PRO_0000153729
Regions
	Topological domain	1 – 57	57	Cytoplasmic Potential
	Intramembrane	58 – 78	21	Helical; Potential
	Topological domain	79 – 107	29	Cytoplasmic Potential
	Transmembrane	108 – 128	21	Helical; Potential
	Topological domain	129 – 133	5	Extracellular Potential
	Region	60 – 93	34	Interaction with SPP1
Amino acid modifications
	Lipidation	71	1	S-palmitoyl cysteine Ref.12 Ref.18
	Lipidation	72	1	S-palmitoyl cysteine Ref.12 Ref.18
	Lipidation	105	1	S-palmitoyl cysteine Ref.12 Ref.18
	Cross-link	24		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.18
	Cross-link	83		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.18
	Cross-link	88		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.18
	Cross-link	104		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.18
Natural variations
	Natural variant	3	1	H → Q. Ref.7 Corresponds to variant rs1136853 [ dbSNP | Ensembl ].		VAR_053810
Experimental info
	Sequence conflict	2	1	N → S in CAA40626. Ref.1
	Sequence conflict	34	1	A → G in CAA40626. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q01628 [UniParc]. Last modified April 16, 2002. Version 2. Checksum: 9FFB2E4623F7A1DD	FASTA	133	14,632
	10 20 30 40 50 60 MNHTVQTFFS PVNSGQPPNY EMLKEEHEVA VLGAPHNPAP PTSTVIHIRS ETSVPDHVVW 70 80 90 100 110 120 SLFNTLFMNP CCLGFIAFAY SVKSRDRKMV GDVTGAQAYA STAKCLNIWA LILGILMTIL 130 LIVIPVLIFQ AYG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular analysis of a human interferon-inducible gene family." Lewin A.R., Reid L.E., McMahon M., Stark G.R., Kerr I.M. Eur. J. Biochem. 199:417-423(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"IFITM3 restricts the morbidity and mortality associated with influenza." Everitt A.R., Clare S., Pertel T., John S.P., Wash R.S., Smith S.E., Chin C.R., Feeley E.M., Sims J.S., Adams D.J., Wise H.M., Kane L., Goulding D., Digard P., Anttila V., Baillie J.K., Walsh T.S., Hume D.A. , Palotie A., Xue Y., Colonna V., Tyler-Smith C., Dunning J., Gordon S.B., Smyth R.L., Openshaw P.J., Dougan G., Brass A.L., Kellam P. Nature 484:519-523(2012) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], INVOLVEMENT IN SUSCEPTIBILITY TO SEVERE INFLUENZA INFECTION.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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], VARIANT GLN-3. Tissue: Brain, Cervix and Vascular endothelial cell.
[8]	"The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus." Brass A.L., Huang I.C., Benita Y., John S.P., Krishnan M.N., Feeley E.M., Ryan B.J., Weyer J.L., van der Weyden L., Fikrig E., Adams D.J., Xavier R.J., Farzan M., Elledge S.J. Cell 139:1243-1254(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN VIRAL RESISTANCE.
[9]	"Identification of five interferon-induced cellular proteins that inhibit west nile virus and dengue virus infections." Jiang D., Weidner J.M., Qing M., Pan X.B., Guo H., Xu C., Zhang X., Birk A., Chang J., Shi P.Y., Block T.M., Guo J.T. J. Virol. 84:8332-8341(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Interferon-induced cell membrane proteins, IFITM3 and tetherin, inhibit vesicular stomatitis virus infection via distinct mechanisms." Weidner J.M., Jiang D., Pan X.B., Chang J., Block T.M., Guo J.T. J. Virol. 84:12646-12657(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]	"Interferon-induced transmembrane 3 binds osteopontin in vitro: expressed in vivo IFITM3 reduced OPN expression." El-Tanani M.K., Jin D., Campbell F.C., Johnston P.G. Oncogene 29:752-762(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SPP1.
[12]	"Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3." Yount J.S., Moltedo B., Yang Y.Y., Charron G., Moran T.M., Lopez C.B., Hang H.C. Nat. Chem. Biol. 6:610-614(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT CYS-71; CYS-72 AND CYS-105.
[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]	"The IFITM proteins inhibit HIV-1 infection." Lu J., Pan Q., Rong L., He W., Liu S.L., Liang C. J. Virol. 85:2126-2137(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	Erratum Lu J., Pan Q., Rong L., He W., Liu S.L., Liang C. J. Virol. 85:4043-4043(2011)
[16]	"IFITM3 inhibits influenza A virus infection by preventing cytosolic entry." Feeley E.M., Sims J.S., John S.P., Chin C.R., Pertel T., Chen L.M., Gaiha G.D., Ryan B.J., Donis R.O., Elledge S.J., Brass A.L. PLoS Pathog. 7:E1002337-E1002337(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[17]	"Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus." Huang I.C., Bailey C.C., Weyer J.L., Radoshitzky S.R., Becker M.M., Chiang J.J., Brass A.L., Ahmed A.A., Chi X., Dong L., Longobardi L.E., Boltz D., Kuhn J.H., Elledge S.J., Bavari S., Denison M.R., Choe H., Farzan M. PLoS Pathog. 7:E1001258-E1001258(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[18]	"S-palmitoylation and ubiquitination differentially regulate interferon-induced transmembrane protein 3 (IFITM3)-mediated resistance to influenza virus." Yount J.S., Karssemeijer R.A., Hang H.C. J. Biol. Chem. 287:19631-19641(2012) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-24; LYS-83; LYS-88 AND LYS-104, PALMITOYLATION, TOPOLOGY, ABSENCE OF GLYCOSYLATION, SUBCELLULAR LOCATION.
[19]	"IFITM proteins restrict antibody-dependent enhancement of dengue virus infection." Chan Y.K., Huang I.C., Farzan M. PLoS ONE 7:E34508-E34508(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[20]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00303726.
PIR	S17182.
RefSeq	NP_066362.2. NM_021034.2.
UniGene	Hs.374650.
3D structure databases
ProteinModelPortal	Q01628.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-2805186.
STRING	9606.ENSP00000382707.
PTM databases
PhosphoSite	Q01628.
Polymorphism databases
DMDM	20178301.
Proteomic databases
PaxDb	Q01628.
PRIDE	Q01628.
Protocols and materials databases
DNASU	10410.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000399808; ENSP00000382707; ENSG00000142089.
GeneID	10410.
KEGG	hsa:10410.
UCSC	uc001lpa.2. human.
Organism-specific databases
CTD	10410.
GeneCards	GC11M000319.
HGNC	HGNC:5414. IFITM3.
HPA	HPA004337.
MIM	605579. gene. 614680. phenotype.
neXtProt	NX_Q01628.
PharmGKB	PA29655.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG26698.
HOGENOM	HOG000115781.
HOVERGEN	HBG001182.
KO	K06566.
OMA	VLIFQAY.
PhylomeDB	Q01628.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q01628.
Bgee	Q01628.
CleanEx	HS_IFITM3.
Genevestigator	Q01628.
Family and domain databases
InterPro	IPR007593. Interferon-induced_TM_protein. [Graphical view]
Pfam	PF04505. CD225. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	10410.
NextBio	39457.
SOURCE	Search...

Entry information

Entry name

IFM3_HUMAN

Accession

Primary (citable) accession number: Q01628
Secondary accession number(s): Q53Y76, Q96HK8, Q96J15

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	April 16, 2002
Last modified:	April 3, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.