Reviewed,
UniProtKB/Swiss-Prot Q9BYX4 (IFIH1_HUMAN)
Last modified
June 16, 2009.
Version 70.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Interferon-induced helicase C domain-containing protein 1 EC=3.6.1.- Alternative name(s): Interferon-induced with helicase C domain protein 1 Helicase with 2 CARD domains Short name=Helicard Melanoma differentiation-associated protein 5 Short name=MDA-5 RNA helicase-DEAD box protein 116 Murabutide down-regulated protein | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1025 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | RNA helicase that, through its ATP-dependent unwinding of RNA, may function to promote message degradation by specific RNases. Seems to have growth suppressive properties. Involved in innate immune defense against viruses. Upon interaction with intracellular dsRNA produced during viral replication, triggers a transduction cascade involving MAVS/IPS1, which results in the activation of NF-kappa-B, IRF3 and IRF7 and the induction of the expression of antiviral cytokines such as IFN-beta and RANTES (CCL5). ATPase activity is specifically induced by dsRNA. Essential for the production of interferons in response to picornaviruses. Ref.2 |
| Subunit structure | Interacts with MAVS. 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. Ref.7 Ref.8 Ref.9 |
| Subcellular location | Cytoplasm. Nucleus Potential. Note: May be found in the nucleus, during apoptosis. |
| Tissue specificity | 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. Ref.2 Ref.1 Ref.5 |
| Induction | By IFN-beta and TNF-alpha. Ref.1 |
| Post-translational modification | 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. |
| Involvement in disease | Genetic variation in IFIH1 is associated with insulin-dependent diabetes mellitus 19 (IDDM19) [MIM:610155]. |
| Miscellaneous | In HIV-1 infected HeLa-CD4 cells, overexpression of IFIH1 results in a great increase in the level of secreted viral p24 protein. |
| Sequence similarities | Belongs to the helicase family. Contains 2 CARD domains. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain. |
| Sequence caution | The sequence AAH78180.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9BYX4-1) 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. | ||||||
| Isoform 2 (identifier: Q9BYX4-2) The sequence of this isoform differs from the canonical sequence as follows: 208-221: EIENLSQVDGPQVE → GICNFTEEDSSNSA 222-1025: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1025 | 1025 | Interferon-induced helicase C domain-containing protein 1 | PRO_0000102012 | ||||||||||||||||||||||||||||||||||
Regions | ||||||||||||||||||||||||||||||||||||||
| Domain | 7 – 97 | 91 | CARD 1 | |||||||||||||||||||||||||||||||||||
| Domain | 110 – 190 | 81 | CARD 2 | |||||||||||||||||||||||||||||||||||
| Domain | 316 – 509 | 194 | Helicase ATP-binding | |||||||||||||||||||||||||||||||||||
| Domain | 700 – 882 | 183 | Helicase C-terminal | |||||||||||||||||||||||||||||||||||
Sites | ||||||||||||||||||||||||||||||||||||||
| Site | 208 – 209 | 2 | Cleavage By similarity | |||||||||||||||||||||||||||||||||||
| Site | 216 – 217 | 2 | Cleavage By similarity | |||||||||||||||||||||||||||||||||||
| Site | 251 – 252 | 2 | Cleavage By similarity | |||||||||||||||||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||||||||||||||||
| Modified residue | 289 | 1 | Phosphoserine By similarity | |||||||||||||||||||||||||||||||||||
| Modified residue | 301 | 1 | Phosphoserine By similarity | |||||||||||||||||||||||||||||||||||
| Modified residue | 645 | 1 | Phosphoserine By similarity | |||||||||||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 208 – 221 | 14 | EIENL…GPQVE → GICNFTEEDSSNSA in isoform 2. | VSP_013337 | ||||||||||||||||||||||||||||||||||
| Alternative sequence | 222 – 1025 | 804 | Missing in isoform 2. | VSP_013338 | ||||||||||||||||||||||||||||||||||
| Natural variant | 460 | 1 | H → R: dbSNP rs10930046. | VAR_031226 | ||||||||||||||||||||||||||||||||||
| Natural variant | 843 | 1 | H → R: dbSNP rs3747517. Ref.2 Ref.3 Ref.4 | VAR_021594 | ||||||||||||||||||||||||||||||||||
| Natural variant | 946 | 1 | A → T Associated with susceptibility to insulin-dependent diabetes mellitus. dbSNP rs1990760. Ref.3 Ref.4 Ref.11 | VAR_021595 | ||||||||||||||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 251 | 1 | D → A: No cleavage and no acceleration of DNA degradation. Ref.5 | |||||||||||||||||||||||||||||||||||
| Mutagenesis | 444 | 1 | E → A: No acceleration of DNA degradation, no binding to ATP, and no helicase activity. Ref.5 | |||||||||||||||||||||||||||||||||||
| Sequence conflict | 439 | 1 | L → F in AAG54076. Ref.2 | |||||||||||||||||||||||||||||||||||
| Sequence conflict | 475 | 1 | N → H in BAB71141. Ref.4 | |||||||||||||||||||||||||||||||||||
| Sequence conflict | 592 | 1 | E → K in AAG34368. Ref.1 | |||||||||||||||||||||||||||||||||||
| Sequence conflict | 598 | 1 | R → S in AAG54076. Ref.2 | |||||||||||||||||||||||||||||||||||
| Sequence conflict | 609 | 1 | E → K in AAG54076. Ref.2 | |||||||||||||||||||||||||||||||||||
| Sequence conflict | 782 | 1 | K → R in BAB71141. Ref.4 | |||||||||||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||||||||||
| Helix | 293 – 299 | 7 | ||||||||||||||||||||||||||||||||||||
| Helix | 310 – 320 | 11 | ||||||||||||||||||||||||||||||||||||
| Beta strand | 325 – 328 | 4 | ||||||||||||||||||||||||||||||||||||
| Helix | 332 – 352 | 21 | ||||||||||||||||||||||||||||||||||||
| Beta strand | 359 – 365 | 7 | ||||||||||||||||||||||||||||||||||||
| Helix | 366 – 375 | 10 | ||||||||||||||||||||||||||||||||||||
| Helix | 377 – 381 | 5 | ||||||||||||||||||||||||||||||||||||
| Turn | 382 – 384 | 3 | ||||||||||||||||||||||||||||||||||||
| Beta strand | 387 – 389 | 3 | ||||||||||||||||||||||||||||||||||||
| Helix | 400 – 406 | 7 | ||||||||||||||||||||||||||||||||||||
| Beta strand | 408 – 413 | 6 | ||||||||||||||||||||||||||||||||||||
| Helix | 414 – 422 | 9 | ||||||||||||||||||||||||||||||||||||
| Helix | 434 – 436 | 3 | ||||||||||||||||||||||||||||||||||||
| Beta strand | 438 – 442 | 5 | ||||||||||||||||||||||||||||||||||||
| Helix | 454 – 473 | 20 | ||||||||||||||||||||||||||||||||||||
| Beta strand | 483 – 488 | 6 | ||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [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: 11805321] [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: 14645903] [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: 15489334] [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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [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: 12015121] [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: 15563593] [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: 16127453] [Abstract] Cited for: INTERACTION WITH MAVS. |
| [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: 16177806] [Abstract] Cited for: INTERACTION WITH MAVS. |
| [10] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [11] | "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: 16699517] [Abstract] Cited for: VARIANT THR-946, ASSOCIATION WITH INSULIN-DEPENDENT DIABETES MELLITUS 19. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | |||||||||||||||||||||||||
| IPI | IPI00005577. IPI00556546. | ||||||||||||||||||||||||
| RefSeq | NP_071451.2. | ||||||||||||||||||||||||
| UniGene | Hs.163173 | ||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||
| |||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||
| PhosphoSite | Q9BYX4. | ||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||
| Ensembl | ENSG00000115267. Homo sapiens. [Contig view] | ||||||||||||||||||||||||
| GeneID | 64135. | ||||||||||||||||||||||||
| KEGG | hsa:64135. | ||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||
| GeneCards | GC02M162831. | ||||||||||||||||||||||||
| H-InvDB | HIX0002549. | ||||||||||||||||||||||||
| HGNC | HGNC:18873. IFIH1. | ||||||||||||||||||||||||
| HPA | HPA002656. | ||||||||||||||||||||||||
| MIM | 606951. gene. 610155. phenotype. | ||||||||||||||||||||||||
| PharmGKB | PA134889215. | ||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||
| HOGENOM | Q9BYX4. | ||||||||||||||||||||||||
| HOVERGEN | Q9BYX4. | ||||||||||||||||||||||||
| OMA | Q9BYX4. ENEKFAE. | ||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||
| ArrayExpress | Q9BYX4. | ||||||||||||||||||||||||
| Bgee | Q9BYX4. | ||||||||||||||||||||||||
| CleanEx | HS_IFIH1. | ||||||||||||||||||||||||
| GermOnline | ENSG00000115267. Homo sapiens. | ||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||
| InterPro | IPR001315. CARD. IPR014001. DEAD-like_N. IPR001650. DNA/RNA_helicase_C. IPR014021. Helicase_SF1/SF2_ATP-bd. IPR006935. Restrct_endonuc_I_R/III_Res. [Graphical view] | ||||||||||||||||||||||||
| Pfam | PF00619. CARD. 1 hit. PF00271. Helicase_C. 1 hit. PF04851. ResIII. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| SMART | SM00487. DEXDc. 1 hit. SM00490. HELICc. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| PROSITE | PS50209. CARD. False negative. PS51192. HELICASE_ATP_BIND_1. 1 hit. PS51194. HELICASE_CTER. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||
| NextBio | 66034. | ||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||
Entry information
| Entry name | IFIH1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9BYX4 Secondary accession number(s): Q2NKL6 Q9H3G6 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


