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Q9BYX4

- IFIH1_HUMAN

UniProt

Q9BYX4 - IFIH1_HUMAN

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Protein

Interferon-induced helicase C domain-containing protein 1

Gene

IFIH1

Organism
Homo sapiens (Human)
Status
Reviewed - 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) and mengo encephalomyocarditis virus (ENMG). 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.

Cofactori

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei208 – 2092CleavageBy similarity
Sitei216 – 2172CleavageBy similarity
Sitei251 – 2522CleavageBy similarity
Metal bindingi907 – 9071Zinc
Metal bindingi910 – 9101Zinc
Metal bindingi962 – 9621Zinc
Metal bindingi964 – 9641Zinc

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. DNA binding Source: InterPro
  3. double-stranded RNA binding Source: UniProtKB
  4. helicase activity Source: UniProtKB-KW
  5. ribonucleoprotein complex binding Source: UniProtKB
  6. single-stranded RNA binding Source: UniProtKB
  7. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. cytoplasmic pattern recognition receptor signaling pathway in response to virus Source: UniProtKB
  2. detection of virus Source: BHF-UCL
  3. innate immune response Source: UniProtKB
  4. negative regulation of type I interferon production Source: Reactome
  5. positive regulation of interferon-alpha production Source: UniProtKB
  6. positive regulation of interferon-beta production Source: UniProtKB
  7. protein sumoylation Source: UniProtKB
  8. regulation of apoptotic process Source: InterPro
  9. regulation of type III interferon production Source: UniProtKB
  10. response to virus Source: UniProtKB
  11. viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase

Keywords - Biological processi

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

Keywords - Ligandi

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

Enzyme and pathway databases

ReactomeiREACT_24938. TRAF6 mediated IRF7 activation.
REACT_24969. TRAF6 mediated NF-kB activation.
REACT_25026. TRAF3-dependent IRF activation pathway.
REACT_25039. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon-induced helicase C domain-containing protein 1 (EC:3.6.4.13)
Alternative name(s):
Clinically amyopathic dermatomyositis autoantigen 140 kDa
Short name:
CADM-140 autoantigen
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
Murabutide down-regulated protein
RIG-I-like receptor 2
Short name:
RLR-2
RNA helicase-DEAD box protein 116
Gene namesi
Name:IFIH1
Synonyms:MDA5, RH116
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:18873. IFIH1.

Subcellular locationi

Cytoplasm 2 Publications. Nucleus Curated
Note: May be found in the nucleus, during apoptosis.

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. nucleus Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Diabetes mellitus, insulin-dependent, 19 (IDDM19) [MIM:610155]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti337 – 3371R → G in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; no loss of ATP hydrolysis. 1 Publication
VAR_071375
Natural varianti372 – 3721L → F in IDDM19; enhances IFNB1 promoter activation; loss of ligand-induced responsiveness. 1 Publication
VAR_071376
Natural varianti393 – 3931D → V in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; no loss of ATP hydrolysis. 1 Publication
VAR_071377
Natural varianti452 – 4521A → T in IDDM19; enhances IFNB1 promoter activation; loss of ligand-induced responsiveness. 1 Publication
VAR_071378
Natural varianti495 – 4951G → R in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; no loss of ATP hydrolysis. 1 Publication
VAR_071379
Natural varianti720 – 7201R → Q in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; no loss of ATP hydrolysis. 1 Publication
VAR_071380
Natural varianti779 – 7791R → C in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; no loss of ATP hydrolysis. 1 Publication
VAR_071381
Natural varianti779 – 7791R → H in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; enhances IFNB1 promoter activation; no loss of ATP hydrolysis. 2 Publications
VAR_071382
Natural varianti946 – 9461A → T Associated with susceptibility to IDDM19. 3 Publications
Corresponds to variant rs1990760 [ dbSNP | Ensembl ].
VAR_021595
IFIH1 is the CADM-140 autoantigen, involved in clinically amyopathic dermatomyositis (CADM). This is a chronic inflammatory disorder that shows typical skin manifestations of dermatomyositis but has no or little evidence of clinical myositis. Anti-CADM-140 antibodies appear to be specific to dermatomyositis, especially CADM. Patients with anti-CADM-140 antibodies frequently develop life-threatening acute progressive interstitial lung disease (ILD).
Aicardi-Goutieres syndrome 7 (AGS7) [MIM:615846]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi251 – 2511D → A: No cleavage and no acceleration of DNA degradation. 1 Publication
Mutagenesisi444 – 4441E → A: No acceleration of DNA degradation, no binding to ATP, and no helicase activity. 1 Publication

Keywords - Diseasei

Aicardi-Goutieres syndrome, Diabetes mellitus, Disease mutation

Organism-specific databases

MIMi610155. phenotype.
615846. phenotype.
Orphaneti51. Aicardi-Goutieres syndrome.
PharmGKBiPA134889215.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10251025Interferon-induced helicase C domain-containing protein 1PRO_0000102012Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei645 – 6451PhosphoserineBy similarity

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 (By similarity).By similarity
Sumoylated. Sumoylation positively regulates its role in type I interferon induction and is enhanced by PIAS2-beta.1 Publication
Ubiquitinated. USP17/UPS17L2-dependent deubiquitination positively regulates the receptor.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9BYX4.
PaxDbiQ9BYX4.
PRIDEiQ9BYX4.

PTM databases

PhosphoSiteiQ9BYX4.

Expressioni

Tissue specificityi

Widely expressed, at a low level. Expression is detected at slightly highest levels in placenta, pancreas and spleen and at barely levels in detectable brain, testis and lung.3 Publications

Inductioni

By interferon (IFN) and TNF.1 Publication

Gene expression databases

BgeeiQ9BYX4.
CleanExiHS_IFIH1.
ExpressionAtlasiQ9BYX4. baseline and differential.
GenevestigatoriQ9BYX4.

Organism-specific databases

HPAiHPA002656.

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 Simian virus 5, Human parainfluenza virus 2, Mumps virus, Sendai virus and Hendra 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 DDX60.10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAVSQ7Z4345EBI-6115771,EBI-995373
P/VP112072EBI-6115771,EBI-6148694From a different organism.
P/VP309272EBI-6115771,EBI-6599165From a different organism.
P/VQ9EMA92EBI-6115771,EBI-6598728From a different organism.
US11P044874EBI-6115771,EBI-6150681From a different organism.

Protein-protein interaction databases

BioGridi122082. 11 interactions.
DIPiDIP-42607N.
IntActiQ9BYX4. 15 interactions.
MINTiMINT-3381993.
STRINGi9606.ENSP00000263642.

Structurei

Secondary structure

1
1025
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi293 – 2997Combined sources
Helixi310 – 32011Combined sources
Beta strandi325 – 3284Combined sources
Helixi332 – 35221Combined sources
Beta strandi359 – 3657Combined sources
Helixi366 – 37510Combined sources
Helixi377 – 3815Combined sources
Turni382 – 3843Combined sources
Beta strandi387 – 3893Combined sources
Helixi400 – 4067Combined sources
Beta strandi408 – 4136Combined sources
Helixi414 – 4229Combined sources
Helixi434 – 4363Combined sources
Beta strandi438 – 4425Combined sources
Helixi454 – 47320Combined sources
Beta strandi483 – 4886Combined sources
Helixi900 – 9023Combined sources
Beta strandi903 – 9075Combined sources
Turni908 – 9103Combined sources
Beta strandi913 – 9164Combined sources
Helixi917 – 9193Combined sources
Beta strandi921 – 9233Combined sources
Turni924 – 9263Combined sources
Beta strandi927 – 9293Combined sources
Helixi934 – 9374Combined sources
Beta strandi938 – 9425Combined sources
Turni945 – 9473Combined sources
Beta strandi955 – 9628Combined sources
Beta strandi967 – 9748Combined sources
Beta strandi977 – 9826Combined sources
Helixi984 – 9863Combined sources
Beta strandi987 – 9915Combined sources
Turni992 – 9954Combined sources
Beta strandi996 – 9983Combined sources
Helixi1003 – 10053Combined sources
Helixi1015 – 10173Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2RQBNMR-A896-1025[»]
3B6EX-ray1.60A277-490[»]
3GA3X-ray1.45A893-1017[»]
4GL2X-ray3.56A/B306-1017[»]
ProteinModelPortaliQ9BYX4.
SMRiQ9BYX4. Positions 5-201, 292-1025.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BYX4.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini7 – 9791CARD 1Add
BLAST
Domaini110 – 19081CARD 2Add
BLAST
Domaini316 – 509194Helicase ATP-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini700 – 882183Helicase C-terminalPROSITE-ProRule annotationAdd
BLAST

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG1111.
GeneTreeiENSGT00510000046789.
HOGENOMiHOG000230992.
HOVERGENiHBG106019.
InParanoidiQ9BYX4.
KOiK12647.
OMAiKCGQAWG.
OrthoDBiEOG7RV9FC.
PhylomeDBiQ9BYX4.
TreeFamiTF330258.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR006935. Helicase/UvrB_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR021673. RIG-I_C-RD.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
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]
SUPFAMiSSF52540. SSF52540. 6 hits.
PROSITEiPS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9BYX4-1) [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
MSNGYSTDEN FRYLISCFRA RVKMYIQVEP VLDYLTFLPA EVKEQIQRTV
60 70 80 90 100
ATSGNMQAVE LLLSTLEKGV WHLGWTREFV EALRRTGSPL AARYMNPELT
110 120 130 140 150
DLPSPSFENA HDEYLQLLNL LQPTLVDKLL VRDVLDKCME EELLTIEDRN
160 170 180 190 200
RIAAAENNGN ESGVRELLKR IVQKENWFSA FLNVLRQTGN NELVQELTGS
210 220 230 240 250
DCSESNAEIE NLSQVDGPQV EEQLLSTTVQ PNLEKEVWGM ENNSSESSFA
260 270 280 290 300
DSSVVSESDT SLAEGSVSCL DESLGHNSNM GSDSGTMGSD SDEENVAARA
310 320 330 340 350
SPEPELQLRP YQMEVAQPAL EGKNIIICLP TGSGKTRVAV YIAKDHLDKK
360 370 380 390 400
KKASEPGKVI VLVNKVLLVE QLFRKEFQPF LKKWYRVIGL SGDTQLKISF
410 420 430 440 450
PEVVKSCDII ISTAQILENS LLNLENGEDA GVQLSDFSLI IIDECHHTNK
460 470 480 490 500
EAVYNNIMRH YLMQKLKNNR LKKENKPVIP LPQILGLTAS PGVGGATKQA
510 520 530 540 550
KAEEHILKLC ANLDAFTIKT VKENLDQLKN QIQEPCKKFA IADATREDPF
560 570 580 590 600
KEKLLEIMTR IQTYCQMSPM SDFGTQPYEQ WAIQMEKKAA KEGNRKERVC
610 620 630 640 650
AEHLRKYNEA LQINDTIRMI DAYTHLETFY NEEKDKKFAV IEDDSDEGGD
660 670 680 690 700
DEYCDGDEDE DDLKKPLKLD ETDRFLMTLF FENNKMLKRL AENPEYENEK
710 720 730 740 750
LTKLRNTIME QYTRTEESAR GIIFTKTRQS AYALSQWITE NEKFAEVGVK
760 770 780 790 800
AHHLIGAGHS SEFKPMTQNE QKEVISKFRT GKINLLIATT VAEEGLDIKE
810 820 830 840 850
CNIVIRYGLV TNEIAMVQAR GRARADESTY VLVAHSGSGV IEHETVNDFR
860 870 880 890 900
EKMMYKAIHC VQNMKPEEYA HKILELQMQS IMEKKMKTKR NIAKHYKNNP
910 920 930 940 950
SLITFLCKNC SVLACSGEDI HVIEKMHHVN MTPEFKELYI VRENKALQKK
960 970 980 990 1000
CADYQINGEI ICKCGQAWGT MMVHKGLDLP CLKIRNFVVV FKNNSTKKQY
1010 1020
KKWVELPITF PNLDYSECCL FSDED
Length:1,025
Mass (Da):116,689
Last modified:March 20, 2007 - v3
Checksum:i789CFB4824B92DC9
GO
Isoform 2 (identifier: Q9BYX4-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     208-221: EIENLSQVDGPQVE → GICNFTEEDSSNSA
     222-1025: Missing.

Note: No experimental confirmation available.

Show »
Length:221
Mass (Da):25,129
Checksum:i3C7139ECAC564BB5
GO

Sequence cautioni

The sequence AAH78180.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.Curated
The sequence BAB71141.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti439 – 4391L → F in AAG54076. (PubMed:14645903)Curated
Sequence conflicti475 – 4751N → H in BAB71141. (PubMed:14702039)Curated
Sequence conflicti592 – 5921E → K in AAG34368. (PubMed:11805321)Curated
Sequence conflicti598 – 5981R → S in AAG54076. (PubMed:14645903)Curated
Sequence conflicti609 – 6091E → K in AAG54076. (PubMed:14645903)Curated
Sequence conflicti782 – 7821K → R in BAB71141. (PubMed:14702039)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti337 – 3371R → G in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; no loss of ATP hydrolysis. 1 Publication
VAR_071375
Natural varianti372 – 3721L → F in IDDM19; enhances IFNB1 promoter activation; loss of ligand-induced responsiveness. 1 Publication
VAR_071376
Natural varianti393 – 3931D → V in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; no loss of ATP hydrolysis. 1 Publication
VAR_071377
Natural varianti452 – 4521A → T in IDDM19; enhances IFNB1 promoter activation; loss of ligand-induced responsiveness. 1 Publication
VAR_071378
Natural varianti460 – 4601H → R.
Corresponds to variant rs10930046 [ dbSNP | Ensembl ].
VAR_031226
Natural varianti495 – 4951G → R in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; no loss of ATP hydrolysis. 1 Publication
VAR_071379
Natural varianti720 – 7201R → Q in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; no loss of ATP hydrolysis. 1 Publication
VAR_071380
Natural varianti779 – 7791R → C in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; no loss of ATP hydrolysis. 1 Publication
VAR_071381
Natural varianti779 – 7791R → H in IDDM19; enhances the interferon signaling pathway activation; enhances the stability of filament formation; enhances dsRNA binding activity; enhances IFNB1 promoter activation; no loss of ATP hydrolysis. 2 Publications
VAR_071382
Natural varianti843 – 8431H → R.3 Publications
Corresponds to variant rs3747517 [ dbSNP | Ensembl ].
VAR_021594
Natural varianti946 – 9461A → T Associated with susceptibility to IDDM19. 3 Publications
Corresponds to variant rs1990760 [ dbSNP | Ensembl ].
VAR_021595

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei208 – 22114EIENL…GPQVE → GICNFTEEDSSNSA in isoform 2. 1 PublicationVSP_013337Add
BLAST
Alternative sequencei222 – 1025804Missing in isoform 2. 1 PublicationVSP_013338Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF095844 mRNA. Translation: AAG34368.1.
AY017378 mRNA. Translation: AAG54076.1.
BC046208 mRNA. Translation: AAH46208.1.
BC078180 mRNA. Translation: AAH78180.1. Sequence problems.
BC111750 mRNA. Translation: AAI11751.1.
AK056293 mRNA. Translation: BAB71141.1. Different initiation.
CCDSiCCDS2217.1. [Q9BYX4-1]
RefSeqiNP_071451.2. NM_022168.3. [Q9BYX4-1]
UniGeneiHs.163173.

Genome annotation databases

EnsembliENST00000263642; ENSP00000263642; ENSG00000115267. [Q9BYX4-1]
ENST00000421365; ENSP00000408450; ENSG00000115267. [Q9BYX4-2]
GeneIDi64135.
KEGGihsa:64135.
UCSCiuc002uce.4. human. [Q9BYX4-1]
uc002ucf.4. human. [Q9BYX4-2]

Polymorphism databases

DMDMi134047802.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF095844 mRNA. Translation: AAG34368.1 .
AY017378 mRNA. Translation: AAG54076.1 .
BC046208 mRNA. Translation: AAH46208.1 .
BC078180 mRNA. Translation: AAH78180.1 . Sequence problems.
BC111750 mRNA. Translation: AAI11751.1 .
AK056293 mRNA. Translation: BAB71141.1 . Different initiation.
CCDSi CCDS2217.1. [Q9BYX4-1 ]
RefSeqi NP_071451.2. NM_022168.3. [Q9BYX4-1 ]
UniGenei Hs.163173.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2RQB NMR - A 896-1025 [» ]
3B6E X-ray 1.60 A 277-490 [» ]
3GA3 X-ray 1.45 A 893-1017 [» ]
4GL2 X-ray 3.56 A/B 306-1017 [» ]
ProteinModelPortali Q9BYX4.
SMRi Q9BYX4. Positions 5-201, 292-1025.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 122082. 11 interactions.
DIPi DIP-42607N.
IntActi Q9BYX4. 15 interactions.
MINTi MINT-3381993.
STRINGi 9606.ENSP00000263642.

PTM databases

PhosphoSitei Q9BYX4.

Polymorphism databases

DMDMi 134047802.

Proteomic databases

MaxQBi Q9BYX4.
PaxDbi Q9BYX4.
PRIDEi Q9BYX4.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000263642 ; ENSP00000263642 ; ENSG00000115267 . [Q9BYX4-1 ]
ENST00000421365 ; ENSP00000408450 ; ENSG00000115267 . [Q9BYX4-2 ]
GeneIDi 64135.
KEGGi hsa:64135.
UCSCi uc002uce.4. human. [Q9BYX4-1 ]
uc002ucf.4. human. [Q9BYX4-2 ]

Organism-specific databases

CTDi 64135.
GeneCardsi GC02M163123.
HGNCi HGNC:18873. IFIH1.
HPAi HPA002656.
MIMi 606951. gene.
610155. phenotype.
615846. phenotype.
neXtProti NX_Q9BYX4.
Orphaneti 51. Aicardi-Goutieres syndrome.
PharmGKBi PA134889215.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1111.
GeneTreei ENSGT00510000046789.
HOGENOMi HOG000230992.
HOVERGENi HBG106019.
InParanoidi Q9BYX4.
KOi K12647.
OMAi KCGQAWG.
OrthoDBi EOG7RV9FC.
PhylomeDBi Q9BYX4.
TreeFami TF330258.

Enzyme and pathway databases

Reactomei REACT_24938. TRAF6 mediated IRF7 activation.
REACT_24969. TRAF6 mediated NF-kB activation.
REACT_25026. TRAF3-dependent IRF activation pathway.
REACT_25039. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
REACT_25271. Negative regulators of RIG-I/MDA5 signaling.
REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.

Miscellaneous databases

ChiTaRSi IFIH1. human.
EvolutionaryTracei Q9BYX4.
GeneWikii MDA5.
GenomeRNAii 64135.
NextBioi 66034.
PROi Q9BYX4.
SOURCEi Search...

Gene expression databases

Bgeei Q9BYX4.
CleanExi HS_IFIH1.
ExpressionAtlasi Q9BYX4. baseline and differential.
Genevestigatori Q9BYX4.

Family and domain databases

Gene3Di 1.10.533.10. 1 hit.
3.40.50.300. 2 hits.
InterProi IPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR006935. Helicase/UvrB_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR021673. RIG-I_C-RD.
[Graphical view ]
Pfami PF00619. CARD. 1 hit.
PF00271. Helicase_C. 1 hit.
PF04851. ResIII. 1 hit.
PF11648. RIG-I_C-RD. 1 hit.
[Graphical view ]
SMARTi SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 6 hits.
PROSITEi PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "mda-5: an interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties."
    Kang D.-C., Gopalkrishnan R.V., Wu Q., Jankowsky E., Pyle A.M., Fisher P.B.
    Proc. Natl. Acad. Sci. U.S.A. 99:637-642(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Tissue: Melanoma.
  2. "A novel cellular RNA helicase, RH116, differentially regulates cell growth, programmed cell death and human immunodeficiency virus type 1 replication."
    Cocude C., Truong M.-J., Billaut-Mulot O., Delsart V., Darcissac E., Capron A., Mouton Y., Bahr G.M.
    J. Gen. Virol. 84:3215-3225(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT ARG-843.
    Tissue: Spleen.
  3. "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] (ISOFORMS 1 AND 2), VARIANTS ARG-843 AND THR-946.
    Tissue: Uterus.
  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 [MRNA] OF 475-1025 (ISOFORM 1), VARIANTS ARG-843 AND THR-946.
  5. "Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation."
    Kovacsovics M., Martinon F., Micheau O., Bodmer J.-L., Hofmann K., Tschopp J.
    Curr. Biol. 12:838-843(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ASP-251 AND GLU-444, TISSUE SPECIFICITY.
  6. Erratum
    Kovacsovics M., Martinon F., Micheau O., Bodmer J.-L., Hofmann K., Tschopp J.
    Curr. Biol. 12:1633-1633(2002)
  7. "The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter."
    Andrejeva J., Childs K.S., Young D.F., Carlos T.S., Stock N., Goodbourn S., Randall R.E.
    Proc. Natl. Acad. Sci. U.S.A. 101:17264-17269(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PARAMYXOVIRUSES V PROTEIN.
  8. "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction."
    Kawai T., Takahashi K., Sato S., Coban C., Kumar H., Kato H., Ishii K.J., Takeuchi O., Akira S.
    Nat. Immunol. 6:981-988(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAVS/IPS1.
  9. "Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus."
    Meylan E., Curran J., Hofmann K., Moradpour D., Binder M., Bartenschlager R., Tschopp J.
    Nature 437:1167-1172(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAVS/IPS1.
  10. "RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease."
    Sato S., Hoshino K., Satoh T., Fujita T., Kawakami Y., Fujita T., Kuwana M.
    Arthritis Rheum. 60:2193-2200(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CLINICALLY AMYOPATHIC DERMATOMYOSITIS, IDENTIFICATION AS CADM-140 AUTOANTIGEN.
  11. "Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2."
    Bamming D., Horvath C.M.
    J. Biol. Chem. 284:9700-9712(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  12. "Activation of MDA5 requires higher-order RNA structures generated during virus infection."
    Pichlmair A., Schulz O., Tan C.P., Rehwinkel J., Kato H., Takeuchi O., Akira S., Way M., Schiavo G., Reis e Sousa C.
    J. Virol. 83:10761-10769(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4."
    You F., Sun H., Zhou X., Sun W., Liang S., Zhai Z., Jiang Z.
    Nat. Immunol. 10:1300-1308(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PCBP2.
  14. "NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways."
    Cui J., Zhu L., Xia X., Wang H.Y., Legras X., Hong J., Ji J., Shen P., Zheng S., Chen Z.J., Wang R.F.
    Cell 141:483-496(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NLRC5.
  15. "The ubiquitin-specific protease 17 is involved in virus-triggered type I IFN signaling."
    Chen R., Zhang L., Zhong B., Tan B., Liu Y., Shu H.B.
    Cell Res. 20:802-811(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP17L2.
  16. "The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody."
    Nakashima R., Imura Y., Kobayashi S., Yukawa N., Yoshifuji H., Nojima T., Kawabata D., Ohmura K., Usui T., Fujii T., Okawa K., Mimori T.
    Rheumatology 49:433-440(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CLINICALLY AMYOPATHIC DERMATOMYOSITIS, IDENTIFICATION AS CADM-140 AUTOANTIGEN, IDENTIFICATION BY MASS SPECTROMETRY.
  17. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  19. "Immune signaling by RIG-I-like receptors."
    Loo Y.M., Gale M. Jr.
    Immunity 34:680-692(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  20. "RIG-I-like receptors: cytoplasmic sensors for non-self RNA."
    Kato H., Takahasi K., Fujita T.
    Immunol. Rev. 243:91-98(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  21. "Innate immune responses in human monocyte-derived dendritic cells are highly dependent on the size and the 5' phosphorylation of RNA molecules."
    Jiang M., Osterlund P., Sarin L.P., Poranen M.M., Bamford D.H., Guo D., Julkunen I.
    J. Immunol. 187:1713-1721(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  22. Cited for: REVIEW ON FUNCTION.
  23. "DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling."
    Miyashita M., Oshiumi H., Matsumoto M., Seya T.
    Mol. Cell. Biol. 31:3802-3819(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DDX60.
  24. "MDA5 is SUMOylated by PIAS2? in the upregulation of type I interferon signaling."
    Fu J., Xiong Y., Xu Y., Cheng G., Tang H.
    Mol. Immunol. 48:415-422(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION, INTERACTION WITH PIAS2-BETA.
  25. "2 methylate or not 2 methylate: viral evasion of the type I interferon response."
    Garcia-Sastre A.
    Nat. Immunol. 12:114-115(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  26. "Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5."
    Zuest R., Cervantes-Barragan L., Habjan M., Maier R., Neuman B.W., Ziebuhr J., Szretter K.J., Baker S.C., Barchet W., Diamond M.S., Siddell S.G., Ludewig B., Thiel V.
    Nat. Immunol. 12:137-143(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  27. "Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition."
    Peisley A., Lin C., Wu B., Orme-Johnson M., Liu M., Walz T., Hur S.
    Proc. Natl. Acad. Sci. U.S.A. 108:21010-21015(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  28. "A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region."
    Smyth D.J., Cooper J.D., Bailey R., Field S., Burren O., Smink L.J., Guja C., Ionescu-Tirgoviste C., Widmer B., Dunger D.B., Savage D.A., Walker N.M., Clayton D.G., Todd J.A.
    Nat. Genet. 38:617-619(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT THR-946, ASSOCIATION WITH IDDM19.
  29. Cited for: INVOLVEMENT IN IDDM19, VARIANTS IDDM19 PHE-372; THR-452 AND HIS-779, CHARACTERIZATION OF VARIANTS IDDM19 PHE-372; THR-452 AND HIS-779.
  30. "Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling."
    Rice G.I., del Toro Duany Y., Jenkinson E.M., Forte G.M., Anderson B.H., Ariaudo G., Bader-Meunier B., Baildam E.M., Battini R., Beresford M.W., Casarano M., Chouchane M., Cimaz R., Collins A.E., Cordeiro N.J., Dale R.C., Davidson J.E., De Waele L.
    , Desguerre I., Faivre L., Fazzi E., Isidor B., Lagae L., Latchman A.R., Lebon P., Li C., Livingston J.H., Lourenco C.M., Mancardi M.M., Masurel-Paulet A., McInnes I.B., Menezes M.P., Mignot C., O'Sullivan J., Orcesi S., Picco P.P., Riva E., Robinson R.A., Rodriguez D., Salvatici E., Scott C., Szybowska M., Tolmie J.L., Vanderver A., Vanhulle C., Vieira J.P., Webb K., Whitney R.N., Williams S.G., Wolfe L.A., Zuberi S.M., Hur S., Crow Y.J.
    Nat. Genet. 46:503-509(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN IDDM19, VARIANTS IDDM19 GLY-337; VAL-393; ARG-495; GLN-720; HIS-779 AND CYS-779, CHARACTERIZATION OF VARIANTS IDDM19 GLY-337; VAL-393; ARG-495; GLN-720; HIS-779 AND CYS-779.
  31. "Structural basis of double-stranded RNA recognition by the RIG-I like receptor MDA5."
    Li X., Lu C., Stewart M., Xu H., Strong R.K., Igumenova T., Li P.
    Arch. Biochem. Biophys. 488:23-33(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 893-1017 IN COMPLEX WITH ZINC IONS.
  32. "Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors."
    Takahasi K., Kumeta H., Tsuduki N., Narita R., Shigemoto T., Hirai R., Yoneyama M., Horiuchi M., Ogura K., Fujita T., Inagaki F.
    J. Biol. Chem. 284:17465-17474(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 896-1025 IN COMPLEX WITH ZINC IONS.
  33. "Human dech-box RNA helicase mda5 (melanoma differentiation-associated protein 5), dech-domain."
    Structural genomics consortium (SGC)
    Submitted (FEB-2009) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 277-490.

Entry informationi

Entry nameiIFIH1_HUMAN
AccessioniPrimary (citable) accession number: Q9BYX4
Secondary accession number(s): Q2NKL6
, Q6DC96, Q86X56, Q96MX8, Q9H3G6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: March 20, 2007
Last modified: November 26, 2014
This is version 129 of the entry and version 3 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

Miscellaneous

In HIV-1 infected HeLa-CD4 cells, overexpression of IFIH1 results in a great increase in the level of secreted viral p24 protein.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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

External Data

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