Descriptions

Retinoic-acid-inducible gene-I (RIG-I; also called DDX58) is a cytosolic viral RNA receptor that interacts with MAVS to induce type I interferon-mediated host protective innate immunity against viral infection. The amino-terminal caspase recruitment domains (CARDs) of RIG-I undergo robust ubiquitination induced by TRIM25 that is involved in cell proliferation and antiviral activity in mammalian cells. In resting cells, RIG-I RD (a C-terminal repressor domain) represses its CARDs signaling. After viral infection, RIG-I RD recognizes 5’-triphosphate double-stranded RNA (dsRNA), which results in a conformational change in the RIG-I protein.

Autoinhibitory domains (AIDs)

Target domain

1-186 (CARD domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

3 structures for Q6Q899

Entry ID Method Resolution Chain Position Source
3TBK X-ray 214 A A 240-794 PDB
6BZH X-ray 250 A A/B/C/D/E 2-189 PDB
AF-Q6Q899-F1 Predicted AlphaFoldDB

19 variants for Q6Q899

Variant ID(s) Position Change Description Diseaes Association Provenance
rs215492009 14 D>N No Ensembl
rs226816483 113 E>G No Ensembl
rs259889292 126 E>D No Ensembl
rs247265874 133 N>D No Ensembl
rs27761369 215 Q>R No Ensembl
rs231647867 229 P>L No Ensembl
rs215417447 244 P>A No Ensembl
rs27761375 288 C>R No Ensembl
rs27761379 323 A>S No Ensembl
rs248026553 359 G>R No Ensembl
rs245694118 439 V>E No Ensembl
rs27761412 573 H>R No Ensembl
rs27761413 585 R>Q No Ensembl
rs223868832 670 R>Q No Ensembl
rs223697977 786 V>L No Ensembl
rs864301026 796 H>Q No Ensembl
rs227507964 829 T>M No Ensembl
rs261430342 834 V>I No Ensembl
rs264395665 905 R>W No Ensembl

No associated diseases with Q6Q899

7 regional properties for Q6Q899

Type Name Position InterPro Accession
domain CARD domain 1087 - 1170 IPR001315
repeat Leucine-rich repeat 687 - 709 IPR001611
domain NACHT nucleoside triphosphatase 131 - 440 IPR007111
domain FIIND domain 794 - 1077 IPR025307
domain CARD8/ASC/NALP1, CARD domain 1087 - 1167 IPR033516
domain NOD2, winged helix domain 370 - 424 IPR041075
domain NACHT, LRR and PYD domains-containing protein, helical domain HD2 426 - 537 IPR041267

Functions

Description
EC Number 3.6.4.13 Acting on ATP; involved in cellular and subcellular movement
Subcellular Localization
  • Cytoplasm
  • Cell projection, ruffle membrane
  • Cytoplasm, cytoskeleton
  • Cell junction, tight junction
  • Colocalized with TRIM25 at cytoplasmic perinuclear bodies
  • Associated with the actin cytoskeleton at membrane ruffles
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

7 GO annotations of cellular component

Name Definition
actin cytoskeleton The part of the cytoskeleton (the internal framework of a cell) composed of actin and associated proteins. Includes actin cytoskeleton-associated complexes.
bicellular tight junction An occluding cell-cell junction that is composed of a branching network of sealing strands that completely encircles the apical end of each cell in an epithelial sheet; the outer leaflets of the two interacting plasma membranes are seen to be tightly apposed where sealing strands are present. Each sealing strand is composed of a long row of transmembrane adhesion proteins embedded in each of the two interacting plasma membranes.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
ribonucleoprotein complex A macromolecular complex that contains both RNA and protein molecules.
ruffle membrane The portion of the plasma membrane surrounding a ruffle.

9 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
ATP hydrolysis activity Catalysis of the reaction: ATP + H2O = ADP + H+ phosphate. ATP hydrolysis is used in some reactions as an energy source, for example to catalyze a reaction or drive transport against a concentration gradient.
double-stranded DNA binding Binding to double-stranded DNA.
double-stranded RNA binding Binding to double-stranded RNA.
identical protein binding Binding to an identical protein or proteins.
RNA helicase activity Unwinding of an RNA helix, driven by ATP hydrolysis.
single-stranded RNA binding Binding to single-stranded RNA.
ubiquitin protein ligase binding Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.
zinc ion binding Binding to a zinc ion (Zn).

21 GO annotations of biological process

Name Definition
antiviral innate immune response A defense response against viruses mediated through an innate immune response. An innate immune response is mediated by germline encoded components that directly recognize components of potential pathogens.
cellular response to exogenous dsRNA Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an exogenous double-stranded RNA stimulus.
defense response to virus Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
detection of virus The series of events in which a stimulus from a virus is received and converted into a molecular signal.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
positive regulation of defense response to virus by host Any host process that results in the promotion of antiviral immune response mechanisms, thereby limiting viral replication.
positive regulation of DNA-binding transcription factor activity Any process that activates or increases the frequency, rate or extent of activity of a transcription factor, any factor involved in the initiation or regulation of transcription.
positive regulation of gene expression Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
positive regulation of granulocyte macrophage colony-stimulating factor production Any process that activates or increases the frequency, rate, or extent of granulocyte macrophage colony-stimulating factor production.
positive regulation of interferon-alpha production Any process that activates or increases the frequency, rate, or extent of interferon-alpha production.
positive regulation of interferon-beta production Any process that activates or increases the frequency, rate, or extent of interferon-beta production.
positive regulation of interleukin-6 production Any process that activates or increases the frequency, rate, or extent of interleukin-6 production.
positive regulation of interleukin-8 production Any process that activates or increases the frequency, rate, or extent of interleukin-8 production.
positive regulation of myeloid dendritic cell cytokine production Any process that activates or increases the frequency, rate, or extent of myeloid dendritic cell cytokine production.
positive regulation of response to cytokine stimulus Any process that increases the rate, frequency, or extent of a response to cytokine stimulus.
positive regulation of transcription by RNA polymerase II Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
positive regulation of tumor necrosis factor production Any process that activates or increases the frequency, rate or extent of tumor necrosis factor production.
regulation of cell migration Any process that modulates the frequency, rate or extent of cell migration.
response to exogenous dsRNA Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an exogenous double-stranded RNA stimulus.
response to virus Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a virus.
RIG-I signaling pathway The series of molecular signals initiated by the binding of viral RNA to a pattern recognition receptor (PRR) RIG-1 (also known as DDX58). RIG-I is a cytoplasmic receptor that detects RNA synthesized during viral replication and triggers a signaling pathway to protect the host against viral infection, for example by inducing the expression of antiviral cytokines.

8 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q96C10 DHX58 ATP-dependent RNA helicase DHX58 Homo sapiens (Human) PR
Q9BYX4 IFIH1 Interferon-induced helicase C domain-containing protein 1 Homo sapiens (Human) PR
O95786 RIGI Antiviral innate immune response receptor RIG-I Homo sapiens (Human) EV
Q9UPY3 DICER1 Endoribonuclease Dicer Homo sapiens (Human) EV
Q8R5F7 Ifih1 Interferon-induced helicase C domain-containing protein 1 Mus musculus (Mouse) PR
Q9GLV6 DDX58 Antiviral innate immune response receptor RIG-I Sus scrofa (Pig) SS
P34529 dcr-1 Endoribonuclease dcr-1 Caenorhabditis elegans PR
Q6TV19 dicer1 Endoribonuclease Dicer Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MTAEQRQNLQ AFRDYIKKIL DPTYILSYMS SWLEDEEVQY IQAEKNNKGP MEAASLFLQY
70 80 90 100 110 120
LLKLQSEGWF QAFLDALYHA GYCGLCEAIE SWDFQKIEKL EEHRLLLRRL EPEFKATVDP
130 140 150 160 170 180
NDILSELSEC LINQECEEIR QIRDTKGRMA GAEKMAECLI RSDKENWPKV LQLALEKDNS
190 200 210 220 230 240
KFSELWIVDK GFKRAESKAD EDDGAEASSI QIFIQEEPEC QNLSQNPGPP SEASSNNLHS
250 260 270 280 290 300
PLKPRNYQLE LALPAKKGKN TIICAPTGCG KTFVSLLICE HHLKKFPCGQ KGKVVFFANQ
310 320 330 340 350 360
IPVYEQQATV FSRYFERLGY NIASISGATS DSVSVQHIIE DNDIIILTPQ ILVNNLNNGA
370 380 390 400 410 420
IPSLSVFTLM IFDECHNTSK NHPYNQIMFR YLDHKLGESR DPLPQVVGLT ASVGVGDAKT
430 440 450 460 470 480
AEEAMQHICK LCAALDASVI ATVRDNVAEL EQVVYKPQKI SRKVASRTSN TFKCIISQLM
490 500 510 520 530 540
KETEKLAKDV SEELGKLFQI QNREFGTQKY EQWIVGVHKA CSVFQMADKE EESRVCKALF
550 560 570 580 590 600
LYTSHLRKYN DALIISEDAQ MTDALNYLKA FFHDVREAAF DETERELTRR FEEKLEELEK
610 620 630 640 650 660
VSRDPSNENP KLRDLYLVLQ EEYHLKPETK TILFVKTRAL VDALKKWIEE NPALSFLKPG
670 680 690 700 710 720
ILTGRGRTNR ATGMTLPAQK CVLEAFRASG DNNILIATSV ADEGIDIAEC NLVILYEYVG
730 740 750 760 770 780
NVIKMIQTRG RGRARDSKCF LLTSSADVIE KEKANMIKEK IMNESILRLQ TWDEMKFGKT
790 800 810 820 830 840
VHRIQVNEKL LRDSQHKPQP VPDKENKKLL CGKCKNFACY TADIRVVETS HYTVLGDAFK
850 860 870 880 890 900
ERFVCKPHPK PKIYDNFEKK AKIFCAKQNC SHDWGIFVRY KTFEIPVIKI ESFVVEDIVS
910 920
GVQNRHSKWK DFHFERIQFD PAEMSV