DDX58_PIG
ID DDX58_PIG Reviewed; 940 AA.
AC Q9GLV6;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Antiviral innate immune response receptor RIG-I {ECO:0000250|UniProtKB:O95786};
DE AltName: Full=ATP-dependent RNA helicase DDX58 {ECO:0000250|UniProtKB:O95786};
DE EC=3.6.4.13 {ECO:0000250|UniProtKB:O95786};
DE AltName: Full=DEAD box protein 58;
DE AltName: Full=RHIV-1;
DE AltName: Full=RIG-I-like receptor 1;
DE Short=RLR-1;
DE AltName: Full=RNA helicase induced by virus;
DE AltName: Full=Retinoic acid-inducible gene 1 protein;
DE Short=RIG-1;
DE AltName: Full=Retinoic acid-inducible gene I protein;
DE Short=RIG-I;
GN Name=DDX58 {ECO:0000250|UniProtKB:O95786};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Peripheral blood;
RX PubMed=10799277; DOI=10.1006/mpat.1999.0349;
RA Zhang X., Wang C., Schook L.B., Hawken R.J., Rutherford M.S.;
RT "An RNA helicase, RHIV -1, induced by porcine reproductive and respiratory
RT syndrome virus (PRRSV) is mapped on porcine chromosome 10q13.";
RL Microb. Pathog. 28:267-278(2000).
CC -!- FUNCTION: Innate immune receptor that senses cytoplasmic viral nucleic
CC acids and activates a downstream signaling cascade leading to the
CC production of type I interferons and pro-inflammatory cytokines. Forms
CC a ribonucleoprotein complex with viral RNAs on which it
CC homooligomerizes to form filaments. The homooligomerization allows the
CC recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and
CC amplifies the RIG-I-mediated antiviral signaling in an RNA length-
CC dependent manner through ubiquitination-dependent and -independent
CC mechanisms. Upon activation, associates with mitochondria antiviral
CC signaling protein (MAVS/IPS1) that activates the IKK-related kinases
CC TBK1 and IKBKE which in turn phosphorylate the interferon regulatory
CC factors IRF3 and IRF7, activating transcription of antiviral
CC immunological genes including the IFN-alpha and IFN-beta interferons.
CC Ligands include: 5'-triphosphorylated ssRNA and dsRNA and short dsRNA
CC (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end
CC base pairing at the 5'-end of the RNA is very essential. Overhangs at
CC the non-triphosphorylated end of the dsRNA RNA have no major impact on
CC its activity. A 3'overhang at the 5'triphosphate end decreases and any
CC 5'overhang at the 5' triphosphate end abolishes its activity. Detects
CC both positive and negative strand RNA viruses including members of the
CC families Paramyxoviridae, Rhabdoviridae: vesicular stomatitis virus
CC (VSV) Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese
CC encephalitis virus (JEV). It also detects rotavirus and reovirus. Also
CC involved in antiviral signaling in response to viruses containing a
CC dsDNA genome. Detects dsRNA produced from non-self dsDNA by RNA
CC polymerase III. May play important roles in granulocyte production and
CC differentiation, bacterial phagocytosis and in the regulation of cell
CC migration. {ECO:0000250|UniProtKB:O95786}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC Evidence={ECO:0000250|UniProtKB:O95786};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000250|UniProtKB:O95786};
CC -!- SUBUNIT: Monomer; maintained as a monomer in an autoinhibited state.
CC Upon binding of viral RNAs and conformational shift, homooligomerizes
CC and forms filaments on these molecules. Interacts (via tandem CARD
CC domain) with MAVS/IPS1 promoting its filamentation. Interacts with
CC DHX58/LGP2, IKBKE, TBK1 and STING1. Interacts (via CARD domain) with
CC TRIM25 (via SPRY domain). Interacts (double-stranded RNA-bound
CC oligomeric form) with RNF135 (homodimer); involved in RNA length-
CC dependent activation of the RIG-I signaling pathway. Interacts with
CC CYLD. Interacts with NLRC5; blocks the interaction of MAVS/IPS1 to
CC DDX58. Interacts with SRC. Interacts with DDX60. Interacts with ZC3HAV1
CC (via zinc-fingers) in an RNA-dependent manner. Interacts (via tandem
CC CARD domain) with SEC14L1; the interaction is direct and impairs the
CC interaction of DDX58 with MAVS/IPS1. Interacts with VCP/p97;
CC interaction is direct and allows the recruitment of RNF125 and
CC subsequent ubiquitination and degradation. Interacts with NOP53; may
CC regulate DDX58 through USP15-mediated 'Lys-63'-linked deubiquitination.
CC Interacts with SIGLEC10, CBL and PTPN11; within a negative feedback
CC loop leading to DDX58 degradation. Interacts with LRRC25. Interacts
CC with ZCCHC3; leading to activation of DDX58/RIG-I. Interacts with
CC RNF123. Interacts with UBE2D3 and UBE2N; E2 ubiquitin ligases involved
CC in RNF135-mediated ubiquitination of DDX58 and activation of the RIG-I
CC signaling pathway. Interacts with IFIT3. Interacts with DDX3X.
CC Interacts with RTN3 (By similarity). Interacts with ARL16; this
CC interaction is GTP-dependent and induced upon viral infection; this
CC interaction suppresses the RNA sensing activity of DDX58 (By
CC similarity). {ECO:0000250|UniProtKB:O95786,
CC ECO:0000250|UniProtKB:Q6Q899}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell projection, ruffle
CC membrane {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Cell
CC junction, tight junction {ECO:0000250}. Note=Colocalized with TRIM25 at
CC cytoplasmic perinuclear bodies. Associated with the actin cytoskeleton
CC at membrane ruffles. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC spleen, liver, intestine and heart. Up-regulated in tracheobronchial
CC lymph node and tonsils during porcine reproductive and respiratory
CC syndrome virus (PRRSV) infection. {ECO:0000269|PubMed:10799277}.
CC -!- DOMAIN: The RLR CTR domain controls homooligomerization and interaction
CC with MAVS/IPS1. In the absence of viral infection, the protein is
CC maintained as a monomer in an autoinhibited state with the CARD domains
CC masked through intramolecular interactions with the RLR CTR domain.
CC Upon binding to viral RNA and ubiquitination by RNF135, a
CC conformational change releases the autoinhibition promoting further
CC homooligomerization, interaction of the CARD domains with the adapter
CC protein MAVS/IPS1 and activation of the downstream RIG-I signaling
CC pathway. {ECO:0000250|UniProtKB:O95786}.
CC -!- DOMAIN: The helicase domain is responsible for dsRNA recognition.
CC {ECO:0000250|UniProtKB:O95786}.
CC -!- DOMAIN: The 2 CARD domains are responsible for interaction with and
CC signaling through MAVS/IPS1 and for association with the actin
CC cytoskeleton. {ECO:0000250|UniProtKB:O95786}.
CC -!- DOMAIN: The second CARD domain is the primary site for 'Lys-63'-linked
CC ubiquitination. {ECO:0000250|UniProtKB:O95786}.
CC -!- PTM: Phosphorylated in resting cells and dephosphorylated in RNA virus-
CC infected cells. Phosphorylation at Thr-773 results in inhibition of its
CC activity while dephosphorylation at these sites results in its
CC activation. {ECO:0000250|UniProtKB:O95786}.
CC -!- PTM: ISGylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-
CC beta stimulation. ISGylation negatively regulates its function in
CC antiviral signaling response. {ECO:0000250|UniProtKB:O95786}.
CC -!- PTM: Sumoylated, probably by MUL1; inhibiting its polyubiquitination.
CC {ECO:0000250|UniProtKB:O95786}.
CC -!- PTM: Ubiquitinated. 'Lys-63' ubiquitination by RNF135, which occurs
CC after RNA-binding and homodimerization, releases the autoinhibition of
CC the CARD domains by the RLR CTR domain, an essential step in the
CC activation of the RIG-I signaling pathway. Also ubiquitinated by TRIM4.
CC Also undergoes 'Lys-48' ubiquitination by RNF125 that leads to
CC proteasomal degradation. 'Lys-48' ubiquitination follows viral
CC infection and is enhanced by 'Lys-63'-linked ubiquitination of the CARD
CC domains that promotes interaction with VCP/p97 and subsequent
CC recruitment of RNF125 (By similarity). Within a negative feedback loop
CC involving SIGLEC10 and PTPN11, 'Lys-48' ubiquitination at Lys-815 by
CC CBL also elicits the proteasomal degradation of DDX58 (By similarity).
CC Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-
CC linked ubiquitin chains. Also probably deubiquitinated by USP17L2/USP17
CC that cleaves 'Lys-48'- and 'Lys-63'-linked ubiquitin chains and
CC positively regulates the receptor (By similarity). Ubiquitinated by
CC TRIM40 via 'Lys-48'-linked ubiquitination; leading to proteasomal
CC degradation (By similarity). Deubiquitinated by USP27X that cleaves
CC 'Lys-63'-linked ubiquitin chains and inhibits the innate immune
CC receptor activity (By similarity). {ECO:0000250|UniProtKB:O95786,
CC ECO:0000250|UniProtKB:Q6Q899}.
CC -!- SIMILARITY: Belongs to the helicase family. RLR subfamily.
CC {ECO:0000305}.
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DR EMBL; AF181119; AAG09428.1; -; mRNA.
DR AlphaFoldDB; Q9GLV6; -.
DR SMR; Q9GLV6; -.
DR IntAct; Q9GLV6; 1.
DR STRING; 9823.ENSSSCP00000023307; -.
DR PaxDb; Q9GLV6; -.
DR PeptideAtlas; Q9GLV6; -.
DR PRIDE; Q9GLV6; -.
DR eggNOG; KOG0354; Eukaryota.
DR InParanoid; Q9GLV6; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0015629; C:actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005923; C:bicellular tight junction; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
DR GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0003724; F:RNA helicase activity; ISS:UniProtKB.
DR GO; GO:0003727; F:single-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0140374; P:antiviral innate immune response; ISS:UniProtKB.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISS:UniProtKB.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0002735; P:positive regulation of myeloid dendritic cell cytokine production; ISS:UniProtKB.
DR GO; GO:0060760; P:positive regulation of response to cytokine stimulus; ISS:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0043330; P:response to exogenous dsRNA; ISS:UniProtKB.
DR GO; GO:0009615; P:response to virus; IBA:GO_Central.
DR GO; GO:0039529; P:RIG-I signaling pathway; ISS:UniProtKB.
DR CDD; cd08817; CARD_RIG-I_r2; 1.
DR Gene3D; 1.10.533.10; -; 2.
DR Gene3D; 2.170.150.30; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR031964; CARD_dom.
DR InterPro; IPR042145; CARD_RIG-I_r2.
DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041204; RIG-I_C.
DR InterPro; IPR038557; RLR_C_sf.
DR InterPro; IPR021673; RLR_CTR.
DR Pfam; PF16739; CARD_2; 2.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF18119; RIG-I_C; 1.
DR Pfam; PF11648; RIG-I_C-RD; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS51789; RLR_CTR; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Antiviral defense; ATP-binding; Cell junction; Cell membrane;
KW Cell projection; Cytoplasm; Cytoskeleton; Helicase; Hydrolase; Immunity;
KW Innate immunity; Isopeptide bond; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW RNA-binding; Tight junction; Ubl conjugation; Zinc.
FT CHAIN 1..940
FT /note="Antiviral innate immune response receptor RIG-I"
FT /id="PRO_0000144095"
FT DOMAIN 1..87
FT /note="CARD 1"
FT DOMAIN 92..172
FT /note="CARD 2"
FT DOMAIN 249..428
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 613..779
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 795..928
FT /note="RLR CTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT REGION 219..928
FT /note="Interaction with ZC3HAV1"
FT /evidence="ECO:0000250"
FT REGION 738..928
FT /note="Mediates interaction with RNF135"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT MOTIF 370..373
FT /note="DECH box"
FT BINDING 262..269
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 813
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 816
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 867
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT BINDING 872
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01125"
FT MOD_RES 773
FT /note="Phosphothreonine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT MOD_RES 861
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 48
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 96
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 154
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 164
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 172
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 190
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95786"
FT CROSSLNK 815
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q6Q899"
SQ SEQUENCE 940 AA; 107584 MW; 118CA910B0AF7821 CRC64;
MTAEQRRNLH AFGDYVRKTL DPTFILSYMA PWFRDDEVQH IQAEKNNKGP TEAASLFLQF
LLELQEEGWF RGFLDALNQA GYCGLCEAIE SWDFQKIEKL EEYRSLLRRL QPEFKTTINP
KDILPEIAEC LISQECEEIL QICSSKGLMA GAEKMVECLL RSDKENWPKT LKLALEKEES
RFSELWMVDK GAEDVKMKDL EDDEMKTCDV QIFYKEEPEN QNLSQNSCSS SAPHTYSPLK
PRKYQLELAL PAQNGKNTII CAPTGCGKTF VSLLICEHHL KKFPRGRKGK VVFFAIQLPV
YEQQKSVFSK HFERLGYKVA GISGATSDTV CVEQIVENSD IIILTPQILV NCLTNGTIPS
LSVFTLMIFD ECHNTSKQHP YNVIMFSYLD RKLGGSSDSL PQVIGLTASV GVGDAKNKAE
ATEYICKLCA SLDTSVIATV RDNLEELEEV VYKPQKFFRK VELRTTDRFK CIISQLMMEI
ESLAKSIFEE LGTITLGGLF QIQNSNFGTQ KYEQWIVKVQ KECAVFQMPD KDKESRICKA
LFSYMSHLRI YNDALIINEH ARMKDALDYL KDFFRNIRAA GFDEIEQDLT QRFEEKLQEL
ESISIDPSNE NPKLRDLCFI LQEEYHLNPE TRTILFVKTR ALVDALKKWI KENPKLSFLK
PSILTGRGKT NQNIGMTLPA QKCVLDTFRT DKDNKILITT SVADEGIDIA QCNLVILYEY
VGNVIKMIQT RGRGRARGSK CFLLTANADL IDKEKMNMYK EEMMNGAILI LQTWDEAVFK
EKIHQIQIRE KIIRDNQGKP EPVPDKKTKK LLCKKCKAFA CYTADIRMVE KCHFTVVGDA
FRERFVSKLH PKPKSFGNIE KRAKIYCARP DCSHDWGIYV RYKAFEMPFI KIESFVVEDI
ATGVQTVHAK WKDFNFEKLS FDAAEMAGGA QDLGLQGMGN
