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Protein

Interferon-induced helicase C domain-containing protein 1

Gene

Ifih1

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

Functioni

Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV), mengo encephalomyocarditis virus (ENMG), and theiler's murine encephalomyelitis virus (TMEV). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines.5 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi907ZincPROSITE-ProRule annotation1
Metal bindingi910ZincPROSITE-ProRule annotation1
Metal bindingi962ZincPROSITE-ProRule annotation1
Metal bindingi964ZincPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • innate immune response Source: UniProtKB
  • MDA-5 signaling pathway Source: UniProtKB
  • positive regulation of interferon-alpha production Source: UniProtKB
  • positive regulation of interferon-beta production Source: UniProtKB
  • protein sumoylation Source: UniProtKB
  • response to virus Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, RNA-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-5689880. Ub-specific processing proteases.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon-induced helicase C domain-containing protein 1 (EC:3.6.4.13)
Alternative name(s):
Helicase with 2 CARD domains
Short name:
Helicard
Interferon induced with helicase C domain protein 1
Melanoma differentiation-associated protein 5
Short name:
MDA-5
RIG-I-like receptor 2
Short name:
RLR-2
Gene namesi
Name:Ifih1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1918836. Ifih1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001020131 – 1025Interferon-induced helicase C domain-containing protein 1Add BLAST1025

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei289PhosphoserineCombined sources1
Modified residuei291PhosphoserineCombined sources1
Modified residuei302PhosphoserineCombined sources1
Modified residuei645PhosphoserineCombined sources1
Modified residuei648PhosphoserineCombined sources1

Post-translational modificationi

During apoptosis, processed into 3 cleavage products. The helicase-containing fragment, once liberated from the CARD domains, translocate from the cytoplasm to the nucleus. The processed protein significantly sensitizes cells to DNA degradation.1 Publication
Sumoylated. Sumoylation positively regulates its role in type I interferon induction and is enhanced by PIAS2-beta (By similarity).By similarity
Ubiquitinated. USP17L2/USP17-dependent deubiquitination positively regulates the receptor (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei208 – 209Cleavage2
Sitei216 – 217Cleavage2
Sitei251 – 252Cleavage2

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8R5F7.
PeptideAtlasiQ8R5F7.
PRIDEiQ8R5F7.

PTM databases

iPTMnetiQ8R5F7.
PhosphoSitePlusiQ8R5F7.

Expressioni

Tissue specificityi

Expression is prominent in lung, liver, kidney, heart and spleen (at protein level). Widely expressed at low level.1 Publication

Inductioni

By interferon (IFN).

Gene expression databases

BgeeiENSMUSG00000026896.
CleanExiMM_IFIH1.
ExpressionAtlasiQ8R5F7. baseline and differential.
GenevisibleiQ8R5F7. MM.

Interactioni

Subunit structurei

Monomer in the absence of ligands and homodimerizes in the presence of dsRNA ligands. Can assemble into helical or linear polymeric filaments on long dsRNA. Interacts with MAVS/IPS1. Interacts with V protein of Sendai virus. Binding to paramyxoviruses V proteins prevents IFN-beta induction, and the further establishment of an antiviral state. Interacts with PCBP2. Interacts with NLRC5. Interacts with PIAS2-beta. Interacts with DDX60. Interacts with ANKRD17. Interacts with IKBKE. Interacts (via the CARD domains) with TKFC, the interaction is inhibited by viral infection (By similarity).By similarity

Protein-protein interaction databases

BioGridi214799. 2 interactors.
DIPiDIP-60085N.
IntActiQ8R5F7. 1 interactor.
MINTiMINT-4118007.
STRINGi10090.ENSMUSP00000028259.

Structurei

Secondary structure

11025
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi550 – 565Combined sources16
Helixi577 – 593Combined sources17
Helixi596 – 617Combined sources22
Helixi620 – 640Combined sources21
Helixi671 – 691Combined sources21
Helixi694 – 696Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3TS9X-ray2.00A545-697[»]
ProteinModelPortaliQ8R5F7.
SMRiQ8R5F7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini7 – 97CARD 1Add BLAST91
Domaini110 – 190CARD 2Add BLAST81
Domaini317 – 510Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST194
Domaini700 – 872Helicase C-terminalPROSITE-ProRule annotationAdd BLAST173
Domaini893 – 1020RLR CTRPROSITE-ProRule annotationAdd BLAST128

Sequence similaritiesi

Belongs to the helicase family. RLR subfamily.Curated
Contains 2 CARD domains.Curated
Contains 1 helicase ATP-binding domain.PROSITE-ProRule annotation
Contains 1 helicase C-terminal domain.PROSITE-ProRule annotation
Contains 1 RLR CTR (RLR C-terminal regulatory) domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0354. Eukaryota.
COG1111. LUCA.
GeneTreeiENSGT00510000046789.
HOVERGENiHBG106019.
InParanoidiQ8R5F7.
KOiK12647.
OMAiEIICKCG.
OrthoDBiEOG091G01PQ.
PhylomeDBiQ8R5F7.
TreeFamiTF330258.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR031964. CARD_dom.
IPR011029. DEATH-like_dom.
IPR006935. Helicase/UvrB_N.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR021673. RIG-I_C-RD.
[Graphical view]
PfamiPF16739. CARD_2. 2 hits.
PF00271. Helicase_C. 1 hit.
PF04851. ResIII. 1 hit.
PF11648. RIG-I_C-RD. 1 hit.
[Graphical view]
SMARTiSM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51789. RLR_CTR. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q8R5F7-1) [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
MSIVCSAEDS FRNLILFFRP RLKMYIQVEP VLDHLIFLSA ETKEQILKKI
60 70 80 90 100
NTCGNTSAAE LLLSTLEQGQ WPLGWTQMFV EALEHSGNPL AARYVKPTLT
110 120 130 140 150
DLPSPSSETA HDECLHLLTL LQPTLVDKLL INDVLDTCFE KGLLTVEDRN
160 170 180 190 200
RISAAGNSGN ESGVRELLRR IVQKENWFST FLDVLRQTGN DALFQELTGG
210 220 230 240 250
GCPEDNTDLA NSSHRDGPAA NECLLPAVDE SSLETEAWNV DDILPEASCT
260 270 280 290 300
DSSVTTESDT SLAEGSVSCF DESLGHNSNM GRDSGTMGSD SDESVIQTKR
310 320 330 340 350
VSPEPELQLR PYQMEVAQPA LDGKNIIICL PTGSGKTRVA VYITKDHLDK
360 370 380 390 400
KKQASESGKV IVLVNKVMLA EQLFRKEFNP YLKKWYRIIG LSGDTQLKIS
410 420 430 440 450
FPEVVKSYDV IISTAQILEN SLLNLESGDD DGVQLSDFSL IIIDECHHTN
460 470 480 490 500
KEAVYNNIMR RYLKQKLRNN DLKKQNKPAI PLPQILGLTA SPGVGAAKKQ
510 520 530 540 550
SEAEKHILNI CANLDAFTIK TVKENLGQLK HQIKEPCKKF VIADDTRENP
560 570 580 590 600
FKEKLLEIMA SIQTYCQKSP MSDFGTQHYE QWAIQMEKKA AKDGNRKDRV
610 620 630 640 650
CAEHLRKYNE ALQINDTIRM IDAYSHLETF YTDEKEKKFA VLNDSDKSDD
660 670 680 690 700
EASSCNDQLK GDVKKSLKLD ETDEFLMNLF FDNKKMLKKL AENPKYENEK
710 720 730 740 750
LIKLRNTILE QFTRSEESSR GIIFTKTRQS TYALSQWIME NAKFAEVGVK
760 770 780 790 800
AHHLIGAGHS SEVKPMTQTE QKEVISKFRT GEINLLIATT VAEEGLDIKE
810 820 830 840 850
CNIVIRYGLV TNEIAMVQAR GRARADESTY VLVTSSGSGV TEREIVNDFR
860 870 880 890 900
EKMMYKAINR VQNMKPEEYA HKILELQVQS ILEKKMKVKR SIAKQYNDNP
910 920 930 940 950
SLITLLCKNC SMLVCSGENI HVIEKMHHVN MTPEFKGLYI VRENKALQKK
960 970 980 990 1000
FADYQTNGEI ICKCGQAWGT MMVHKGLDLP CLKIRNFVVN FKNNSPKKQY
1010 1020
KKWVELPIRF PDLDYSEYCL YSDED
Length:1,025
Mass (Da):115,971
Last modified:June 1, 2002 - v1
Checksum:i708FCAC690C9F6D8
GO
Isoform 2 (identifier: Q8R5F7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     207-255: Missing.

Note: No experimental confirmation available.
Show »
Length:976
Mass (Da):110,842
Checksum:iB9F6D84C207F1031
GO

Sequence cautioni

The sequence AAH25508 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti100T → I in AAH80200 (PubMed:15489334).Curated1
Sequence conflicti339V → E in BAE31652 (PubMed:16141072).Curated1
Sequence conflicti412 – 414IST → TRP in AAH25508 (PubMed:15489334).Curated3
Sequence conflicti624Y → H in AAH25508 (PubMed:15489334).Curated1
Sequence conflicti629T → A in AAM21359 (PubMed:11805321).Curated1
Sequence conflicti647K → E in AAH25508 (PubMed:15489334).Curated1
Sequence conflicti647K → E in AAH04031 (PubMed:15489334).Curated1
Sequence conflicti647K → E in AAH80200 (PubMed:15489334).Curated1
Sequence conflicti889K → E in BAB31303 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013339207 – 255Missing in isoform 2. 1 PublicationAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY075132 mRNA. Translation: AAL77205.1.
AF374384 mRNA. Translation: AAM21359.1.
AK018602 mRNA. Translation: BAB31303.2.
AK037057 mRNA. Translation: BAC29687.2.
AK040519 mRNA. Translation: BAC30614.1.
AK153018 mRNA. Translation: BAE31652.1.
AL929246 Genomic DNA. Translation: CAM21790.1.
BC004031 mRNA. Translation: AAH04031.1.
BC019605 mRNA. Translation: AAH19605.1.
BC025508 mRNA. Translation: AAH25508.1. Different initiation.
BC080200 mRNA. Translation: AAH80200.1.
CCDSiCCDS16068.1. [Q8R5F7-1]
CCDS50594.1. [Q8R5F7-2]
RefSeqiNP_001157949.1. NM_001164477.1. [Q8R5F7-2]
NP_082111.2. NM_027835.3. [Q8R5F7-1]
UniGeneiMm.136224.

Genome annotation databases

EnsembliENSMUST00000028259; ENSMUSP00000028259; ENSMUSG00000026896. [Q8R5F7-1]
ENSMUST00000112459; ENSMUSP00000108078; ENSMUSG00000026896. [Q8R5F7-2]
GeneIDi71586.
KEGGimmu:71586.
UCSCiuc008jvm.2. mouse. [Q8R5F7-1]
uc012bvy.1. mouse. [Q8R5F7-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY075132 mRNA. Translation: AAL77205.1.
AF374384 mRNA. Translation: AAM21359.1.
AK018602 mRNA. Translation: BAB31303.2.
AK037057 mRNA. Translation: BAC29687.2.
AK040519 mRNA. Translation: BAC30614.1.
AK153018 mRNA. Translation: BAE31652.1.
AL929246 Genomic DNA. Translation: CAM21790.1.
BC004031 mRNA. Translation: AAH04031.1.
BC019605 mRNA. Translation: AAH19605.1.
BC025508 mRNA. Translation: AAH25508.1. Different initiation.
BC080200 mRNA. Translation: AAH80200.1.
CCDSiCCDS16068.1. [Q8R5F7-1]
CCDS50594.1. [Q8R5F7-2]
RefSeqiNP_001157949.1. NM_001164477.1. [Q8R5F7-2]
NP_082111.2. NM_027835.3. [Q8R5F7-1]
UniGeneiMm.136224.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3TS9X-ray2.00A545-697[»]
ProteinModelPortaliQ8R5F7.
SMRiQ8R5F7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi214799. 2 interactors.
DIPiDIP-60085N.
IntActiQ8R5F7. 1 interactor.
MINTiMINT-4118007.
STRINGi10090.ENSMUSP00000028259.

PTM databases

iPTMnetiQ8R5F7.
PhosphoSitePlusiQ8R5F7.

Proteomic databases

PaxDbiQ8R5F7.
PeptideAtlasiQ8R5F7.
PRIDEiQ8R5F7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028259; ENSMUSP00000028259; ENSMUSG00000026896. [Q8R5F7-1]
ENSMUST00000112459; ENSMUSP00000108078; ENSMUSG00000026896. [Q8R5F7-2]
GeneIDi71586.
KEGGimmu:71586.
UCSCiuc008jvm.2. mouse. [Q8R5F7-1]
uc012bvy.1. mouse. [Q8R5F7-2]

Organism-specific databases

CTDi64135.
MGIiMGI:1918836. Ifih1.

Phylogenomic databases

eggNOGiKOG0354. Eukaryota.
COG1111. LUCA.
GeneTreeiENSGT00510000046789.
HOVERGENiHBG106019.
InParanoidiQ8R5F7.
KOiK12647.
OMAiEIICKCG.
OrthoDBiEOG091G01PQ.
PhylomeDBiQ8R5F7.
TreeFamiTF330258.

Enzyme and pathway databases

ReactomeiR-MMU-5689880. Ub-specific processing proteases.

Miscellaneous databases

PROiQ8R5F7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000026896.
CleanExiMM_IFIH1.
ExpressionAtlasiQ8R5F7. baseline and differential.
GenevisibleiQ8R5F7. MM.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR031964. CARD_dom.
IPR011029. DEATH-like_dom.
IPR006935. Helicase/UvrB_N.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR021673. RIG-I_C-RD.
[Graphical view]
PfamiPF16739. CARD_2. 2 hits.
PF00271. Helicase_C. 1 hit.
PF04851. ResIII. 1 hit.
PF11648. RIG-I_C-RD. 1 hit.
[Graphical view]
SMARTiSM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51789. RLR_CTR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIFIH1_MOUSE
AccessioniPrimary (citable) accession number: Q8R5F7
Secondary accession number(s): A2AUY7
, Q3U6S2, Q68EM4, Q8BYC9, Q8BZ01, Q8K5C7, Q8R144, Q8VE79, Q99KS4, Q9D2Z5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: June 1, 2002
Last modified: November 2, 2016
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.