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Protein

Interferon-induced protein with tetratricopeptide repeats 1

Gene

IFIT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Interferon-induced antiviral RNA-binding protein that specifically binds single-stranded RNA bearing a 5'-triphosphate group (PPP-RNA), thereby acting as a sensor of viral single-stranded RNAs and inhibiting expression of viral messenger RNAs. Single-stranded PPP-RNAs, which lack 2'-O-methylation of the 5' cap and bear a 5'-triphosphate group instead, are specific from viruses, providing a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Directly binds PPP-RNA in a non-sequence-specific manner. Viruses evolved several ways to evade this restriction system such as encoding their own 2'-O-methylase for their mRNAs or by stealing host cap containing the 2'-O-methylation (cap snatching mechanism). Exhibits antiviral activity against several viruses including human papilloma and hepatitis C viruses.4 Publications

GO - Molecular functioni

  • RNA binding Source: UniProtKB

GO - Biological processi

  • cellular response to exogenous dsRNA Source: BHF-UCL
  • cellular response to type I interferon Source: BHF-UCL
  • defense response to virus Source: UniProtKB-KW
  • intracellular transport of viral protein in host cell Source: BHF-UCL
  • negative regulation of defense response to virus by host Source: BHF-UCL
  • negative regulation of helicase activity Source: BHF-UCL
  • negative regulation of protein binding Source: BHF-UCL
  • negative regulation of viral genome replication Source: UniProtKB
  • positive regulation of viral genome replication Source: BHF-UCL
  • response to virus Source: UniProtKB
  • type I interferon signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Antiviral defense, Host-virus interaction, Immunity, Innate immunity

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciZFISH:G66-31035-MONOMER.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-909733. Interferon alpha/beta signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon-induced protein with tetratricopeptide repeats 1
Short name:
IFIT-1
Alternative name(s):
Interferon-induced 56 kDa protein
Short name:
IFI-56K
Short name:
P56
Gene namesi
Name:IFIT1
Synonyms:G10P1, IFI56, IFNAI1, ISG56
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:5407. IFIT1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • host cell Source: GOC
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi34D → A: Abolishes PPP-RNA-binding. 1 Publication1
Mutagenesisi38R → M: Abolishes PPP-RNA-binding. 1 Publication1
Mutagenesisi42Q → E: Reduced PPP-RNA-binding. 1 Publication1
Mutagenesisi151K → M: Abolishes PPP-RNA-binding. 1 Publication1
Mutagenesisi157Y → F: Reduced PPP-RNA-binding. 1 Publication1
Mutagenesisi187R → H: Abolishes PPP-RNA-binding. 1 Publication1
Mutagenesisi255R → M: Abolishes PPP-RNA-binding. 1 Publication1

Organism-specific databases

DisGeNETi3434.
OpenTargetsiENSG00000185745.
PharmGKBiPA29648.

Polymorphism and mutation databases

DMDMi116242522.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001063441 – 478Interferon-induced protein with tetratricopeptide repeats 1Add BLAST478

Post-translational modificationi

Phosphorylated.1 Publication
ISGylated.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP09914.
PaxDbiP09914.
PeptideAtlasiP09914.
PRIDEiP09914.

PTM databases

iPTMnetiP09914.
PhosphoSitePlusiP09914.

Expressioni

Inductioni

By type I interferons, dsRNAs and viruses.1 Publication

Gene expression databases

BgeeiENSG00000185745.
CleanExiHS_IFIT1.
GenevisibleiP09914. HS.

Organism-specific databases

HPAiCAB045980.
HPA055380.

Interactioni

Subunit structurei

Component of an interferon-dependent multiprotein complex, at least composed of IFIT1, IFIT2 and IFIT3. Interacts (via TPR repeats 4-7) with EEF1A1 (By similarity). Interacts with EIF3C (By similarity). Interacts with IFIT2 and IFIT3. Interacts (via TPR repeats 1-4) with RPL15. Interacts with TMEM173/MITA and disrupts its interaction with MAVS or TBK1. Interacts with EIF3E. Interacts (via TPR repeat 2) with E1 proteins of HPV types 11, 18 and 3 and this interaction blocks E1 helicase activity and viral replication.By similarity6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei34Interaction with PPP-RNABy similarity1
Sitei42Interaction with PPP-RNABy similarity1
Sitei151Interaction with PPP-RNABy similarity1
Sitei187Interaction with PPP-RNABy similarity1
Sitei252Interaction with PPP-RNABy similarity1
Sitei290Interaction with the 5'-triphosphate group of PPP-RNABy similarity1

Binary interactionsi

WithEntry#Exp.IntActNotes
E1P067898EBI-745117,EBI-7015660From a different organism.
IFIT2P099135EBI-745117,EBI-3507167
IFIT3O1487910EBI-745117,EBI-745127

Protein-protein interaction databases

BioGridi109659. 48 interactors.
DIPiDIP-37898N.
IntActiP09914. 39 interactors.
MINTiMINT-153827.
STRINGi9606.ENSP00000360869.

Structurei

Secondary structure

1478
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi11 – 16Combined sources6
Helixi20 – 22Combined sources3
Turni29 – 31Combined sources3
Helixi32 – 41Combined sources10
Helixi48 – 64Combined sources17
Helixi68 – 82Combined sources15
Helixi92 – 94Combined sources3
Helixi95 – 107Combined sources13
Helixi111 – 125Combined sources15
Helixi139 – 151Combined sources13
Helixi154 – 156Combined sources3
Helixi157 – 170Combined sources14
Helixi175 – 191Combined sources17
Turni200 – 203Combined sources4
Helixi204 – 212Combined sources9
Helixi217 – 229Combined sources13
Helixi233 – 246Combined sources14
Helixi253 – 264Combined sources12
Helixi267 – 277Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HOUX-ray1.95A/B7-279[»]
ProteinModelPortaliP09914.
SMRiP09914.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati52 – 85TPR 1Add BLAST34
Repeati95 – 128TPR 2Add BLAST34
Repeati139 – 174TPR 3Add BLAST36
Repeati183 – 216TPR 4Add BLAST34
Repeati218 – 249TPR 5Add BLAST32
Repeati251 – 284TPR 6Add BLAST34
Repeati305 – 339TPR 7Add BLAST35
Repeati340 – 373TPR 8Add BLAST34
Repeati378 – 412TPR 9Add BLAST35
Repeati437 – 470TPR 10Add BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni256 – 262Interaction with the 5'-triphosphate group of PPP-RNABy similarity7

Domaini

RNA recognition is mediated by a convoluted intramolecular fold of the TPR repeats (TPR eddy), which scaffolds unique additional helices that form an RNA binding cleft.By similarity

Sequence similaritiesi

Belongs to the IFIT family.Curated
Contains 10 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG1124. Eukaryota.
COG0457. LUCA.
GeneTreeiENSGT00390000013876.
HOGENOMiHOG000001558.
HOVERGENiHBG066330.
InParanoidiP09914.
KOiK14217.
OMAiTWELSID.
OrthoDBiEOG091G06GX.
PhylomeDBiP09914.
TreeFamiTF342671.

Family and domain databases

Gene3Di1.25.40.10. 2 hits.
InterProiIPR024121. Interferon-induced_IFIT1.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10271:SF16. PTHR10271:SF16. 1 hit.
PfamiPF13181. TPR_8. 2 hits.
[Graphical view]
SMARTiSM00028. TPR. 6 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 3 hits.
PROSITEiPS50005. TPR. 6 hits.
PS50293. TPR_REGION. 3 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P09914-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSTNGDDHQV KDSLEQLRCH FTWELSIDDD EMPDLENRVL DQIEFLDTKY
60 70 80 90 100
SVGIHNLLAY VKHLKGQNEE ALKSLKEAEN LMQEEHDNQA NVRSLVTWGN
110 120 130 140 150
FAWMYYHMGR LAEAQTYLDK VENICKKLSN PFRYRMECPE IDCEEGWALL
160 170 180 190 200
KCGGKNYERA KACFEKVLEV DPENPESSAG YAISAYRLDG FKLATKNHKP
210 220 230 240 250
FSLLPLRQAV RLNPDNGYIK VLLALKLQDE GQEAEGEKYI EEALANMSSQ
260 270 280 290 300
TYVFRYAAKF YRRKGSVDKA LELLKKALQE TPTSVLLHHQ IGLCYKAQMI
310 320 330 340 350
QIKEATKGQP RGQNREKLDK MIRSAIFHFE SAVEKKPTFE VAHLDLARMY
360 370 380 390 400
IEAGNHRKAE ENFQKLLCMK PVVEETMQDI HFHYGRFQEF QKKSDVNAII
410 420 430 440 450
HYLKAIKIEQ ASLTRDKSIN SLKKLVLRKL RRKALDLESL SLLGFVYKLE
460 470
GNMNEALEYY ERALRLAADF ENSVRQGP
Length:478
Mass (Da):55,360
Last modified:October 17, 2006 - v2
Checksum:iEF46E652A366E721
GO
Isoform 2 (identifier: P09914-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-31: Missing.

Note: No experimental confirmation available.
Show »
Length:447
Mass (Da):51,713
Checksum:i3CB6ECE609D546E7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti198H → Y in BAG52612 (PubMed:14702039).Curated1
Sequence conflicti383H → Y in CAA27244 (PubMed:3753936).Curated1
Sequence conflicti401H → R in BAG52612 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052614131P → H.Corresponds to variant rs11553019dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0548311 – 31Missing in isoform 2. 1 PublicationAdd BLAST31

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03557 mRNA. Translation: CAA27244.1.
BT006667 mRNA. Translation: AAP35313.1.
AK092813 mRNA. Translation: BAG52612.1.
AK314588 mRNA. Translation: BAG37163.1.
AL353146 Genomic DNA. Translation: CAI12379.1.
CH471066 Genomic DNA. Translation: EAW50136.1.
CH471066 Genomic DNA. Translation: EAW50137.1.
CH471066 Genomic DNA. Translation: EAW50138.1.
BC007091 mRNA. Translation: AAH07091.1.
X06559 Genomic DNA. Translation: CAA29802.1.
CCDSiCCDS31243.1. [P09914-1]
CCDS59220.1. [P09914-2]
PIRiA25407.
RefSeqiNP_001257857.1. NM_001270928.1. [P09914-2]
NP_001257858.1. NM_001270929.1. [P09914-2]
NP_001257859.1. NM_001270930.1. [P09914-2]
NP_001539.3. NM_001548.4. [P09914-1]
UniGeneiHs.20315.

Genome annotation databases

EnsembliENST00000371804; ENSP00000360869; ENSG00000185745. [P09914-1]
ENST00000546318; ENSP00000441968; ENSG00000185745. [P09914-2]
GeneIDi3434.
KEGGihsa:3434.
UCSCiuc001kgi.5. human. [P09914-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03557 mRNA. Translation: CAA27244.1.
BT006667 mRNA. Translation: AAP35313.1.
AK092813 mRNA. Translation: BAG52612.1.
AK314588 mRNA. Translation: BAG37163.1.
AL353146 Genomic DNA. Translation: CAI12379.1.
CH471066 Genomic DNA. Translation: EAW50136.1.
CH471066 Genomic DNA. Translation: EAW50137.1.
CH471066 Genomic DNA. Translation: EAW50138.1.
BC007091 mRNA. Translation: AAH07091.1.
X06559 Genomic DNA. Translation: CAA29802.1.
CCDSiCCDS31243.1. [P09914-1]
CCDS59220.1. [P09914-2]
PIRiA25407.
RefSeqiNP_001257857.1. NM_001270928.1. [P09914-2]
NP_001257858.1. NM_001270929.1. [P09914-2]
NP_001257859.1. NM_001270930.1. [P09914-2]
NP_001539.3. NM_001548.4. [P09914-1]
UniGeneiHs.20315.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HOUX-ray1.95A/B7-279[»]
ProteinModelPortaliP09914.
SMRiP09914.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109659. 48 interactors.
DIPiDIP-37898N.
IntActiP09914. 39 interactors.
MINTiMINT-153827.
STRINGi9606.ENSP00000360869.

PTM databases

iPTMnetiP09914.
PhosphoSitePlusiP09914.

Polymorphism and mutation databases

DMDMi116242522.

Proteomic databases

EPDiP09914.
PaxDbiP09914.
PeptideAtlasiP09914.
PRIDEiP09914.

Protocols and materials databases

DNASUi3434.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371804; ENSP00000360869; ENSG00000185745. [P09914-1]
ENST00000546318; ENSP00000441968; ENSG00000185745. [P09914-2]
GeneIDi3434.
KEGGihsa:3434.
UCSCiuc001kgi.5. human. [P09914-1]

Organism-specific databases

CTDi3434.
DisGeNETi3434.
GeneCardsiIFIT1.
HGNCiHGNC:5407. IFIT1.
HPAiCAB045980.
HPA055380.
MIMi147690. gene.
neXtProtiNX_P09914.
OpenTargetsiENSG00000185745.
PharmGKBiPA29648.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1124. Eukaryota.
COG0457. LUCA.
GeneTreeiENSGT00390000013876.
HOGENOMiHOG000001558.
HOVERGENiHBG066330.
InParanoidiP09914.
KOiK14217.
OMAiTWELSID.
OrthoDBiEOG091G06GX.
PhylomeDBiP09914.
TreeFamiTF342671.

Enzyme and pathway databases

BioCyciZFISH:G66-31035-MONOMER.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-909733. Interferon alpha/beta signaling.

Miscellaneous databases

GeneWikiiIFIT1.
GenomeRNAii3434.
PROiP09914.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185745.
CleanExiHS_IFIT1.
GenevisibleiP09914. HS.

Family and domain databases

Gene3Di1.25.40.10. 2 hits.
InterProiIPR024121. Interferon-induced_IFIT1.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10271:SF16. PTHR10271:SF16. 1 hit.
PfamiPF13181. TPR_8. 2 hits.
[Graphical view]
SMARTiSM00028. TPR. 6 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 3 hits.
PROSITEiPS50005. TPR. 6 hits.
PS50293. TPR_REGION. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIFIT1_HUMAN
AccessioniPrimary (citable) accession number: P09914
Secondary accession number(s): B3KS50
, D3DR31, Q5T7J1, Q96QM5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: October 17, 2006
Last modified: November 2, 2016
This is version 163 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.