ID VP3_ROTEL Reviewed; 835 AA. AC Q6WNV7; DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 24-JAN-2024, entry version 45. DE RecName: Full=Protein VP3 {ECO:0000255|HAMAP-Rule:MF_04128}; DE Includes: DE RecName: Full=2',5'-phosphodiesterase {ECO:0000255|HAMAP-Rule:MF_04128}; DE EC=3.1.4.- {ECO:0000255|HAMAP-Rule:MF_04128}; DE Includes: DE RecName: Full=mRNA guanylyltransferase {ECO:0000255|HAMAP-Rule:MF_04128}; DE EC=2.7.7.50 {ECO:0000255|HAMAP-Rule:MF_04128}; DE Includes: DE RecName: Full=mRNA (guanine-N(7))-methyltransferase {ECO:0000255|HAMAP-Rule:MF_04128}; DE EC=2.1.1.56 {ECO:0000255|HAMAP-Rule:MF_04128}; OS Rotavirus A (isolate RVA/Equine/United Kingdom/L338/1988/G13P12[18]) OS (RV-A). OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes; OC Reovirales; Sedoreoviridae; Rotavirus; Rotavirus A. OX NCBI_TaxID=36441; OH NCBI_TaxID=9796; Equus caballus (Horse). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=15039535; DOI=10.1099/vir.0.19629-0; RA Cook J.P., McCrae M.A.; RT "Sequence analysis of the guanylyltransferase (VP3) of group A RT rotaviruses."; RL J. Gen. Virol. 85:929-932(2004). CC -!- FUNCTION: Multifunctional enzyme involved in mRNA capping. Catalyzes CC the formation of the 5' cap structure on the viral plus-strand CC transcripts. Specifically binds to GTP and displays guanylyltransferase CC and methyltransferase activities. Has affinity for ssRNA but not for CC dsRNA. Capping activity is non-specific and caps RNAs that initiate CC with either a G or an A residue. Together with VP1 polymerase, forms a CC VP1-VP3 complex positioned near the channels situated at each of the CC five-fold vertices of the core. Following infection, the outermost CC layer of the virus is lost, leaving a double-layered particle (DLP) CC made up of the core and VP6 shell. VP1 then catalyzes the transcription CC of fully conservative plus-strand genomic RNAs that are capped by VP3 CC and extruded through the DLP's channels into the cytoplasm where they CC function as mRNAs for translation of viral proteins. DLPs probably have CC an RNA triphosphatase activity as well, whereas open cores do not. CC {ECO:0000255|HAMAP-Rule:MF_04128}. CC -!- FUNCTION: Counteracts the host innate immune response thanks to its CC phosphodiesterase that degrades the 5'-triphosphorylated, 2'-5' linked CC adenylate oligomers produced by the host cell IFN-inducible 2',5'- CC oligoadenylate synthetase (OAS). The host RNaseL is therefore not CC activated. {ECO:0000255|HAMAP-Rule:MF_04128}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end diphospho-ribonucleoside in mRNA + GTP + H(+) = a 5'- CC end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA + diphosphate; CC Xref=Rhea:RHEA:67012, Rhea:RHEA-COMP:17165, Rhea:RHEA-COMP:17166, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:167616, ChEBI:CHEBI:167617; EC=2.7.7.50; CC Evidence={ECO:0000255|HAMAP-Rule:MF_04128}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA + CC S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'- CC triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L- CC homocysteine; Xref=Rhea:RHEA:67008, Rhea:RHEA-COMP:17166, Rhea:RHEA- CC COMP:17167, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, CC ChEBI:CHEBI:167617; EC=2.1.1.56; Evidence={ECO:0000255|HAMAP- CC Rule:MF_04128}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5'-triphosphoadenylyl-(2'->5')-adenylyl-(2'->5')-adenosine + 2 CC H2O = 2 AMP + ATP + 2 H(+); Xref=Rhea:RHEA:45964, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:67143, CC ChEBI:CHEBI:456215; Evidence={ECO:0000255|HAMAP-Rule:MF_04128}; CC -!- SUBUNIT: Interacts with VP1. Interacts with VP2. {ECO:0000255|HAMAP- CC Rule:MF_04128}. CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04128}. CC Note=Attached inside the inner capsid as a minor component. There are CC about 11 to 12 copies per virion. {ECO:0000255|HAMAP-Rule:MF_04128}. CC -!- DOMAIN: Contains a bipartite N7-methyltransferase domain, a 2'-O- CC methyltransferase domain and a GTase/RTPase domain. The C-terminus CC contains a phosphodiesterase domain that degrades the 5'- CC triphosphorylated, 2'-5' linked adenylate oligomers produced by the CC host cell in response to IFN stimulation. {ECO:0000255|HAMAP- CC Rule:MF_04128}. CC -!- SIMILARITY: Belongs to the rotavirus VP3 family. {ECO:0000255|HAMAP- CC Rule:MF_04128}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY277922; AAQ21049.1; -; Genomic_RNA. DR SMR; Q6WNV7; -. DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-UniRule. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-UniRule. DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW. DR GO; GO:0004482; F:mRNA 5'-cap (guanine-N7-)-methyltransferase activity; IEA:UniProtKB-UniRule. DR GO; GO:0004484; F:mRNA guanylyltransferase activity; IEA:UniProtKB-UniRule. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-UniRule. DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW. DR CDD; cd20757; capping_2-OMTase_Rotavirus; 1. DR HAMAP; MF_04124; Rota_VP3; 1. DR HAMAP; MF_04128; Rota_VP3_A; 1. DR InterPro; IPR011181; VP3_Rotav. DR Pfam; PF06929; Rotavirus_VP3; 1. DR PIRSF; PIRSF004015; LigT_rotavirus; 1. DR PROSITE; PS51589; SAM_MT56_VP3; 1. PE 3: Inferred from homology; KW GTP-binding; Host-virus interaction; Hydrolase; KW Inhibition of host innate immune response by virus; Methyltransferase; KW mRNA capping; mRNA processing; Multifunctional enzyme; Nucleotide-binding; KW Nucleotidyltransferase; RNA-binding; S-adenosyl-L-methionine; Transferase; KW Viral immunoevasion; Virion. FT CHAIN 1..835 FT /note="Protein VP3" FT /id="PRO_0000368066" FT REGION 171..245 FT /note="N7-methyltransferase activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128" FT REGION 246..428 FT /note="2'-O-methyltransferase activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128" FT REGION 429..555 FT /note="N7-methyltransferase activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128" FT REGION 556..692 FT /note="GTase/RTPase activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128" FT REGION 693..835 FT /note="2'-5'-phosphodiesterase activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128" FT ACT_SITE 718 FT /note="For 2'-5'-phosphodiesterase activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128" FT ACT_SITE 720 FT /note="For 2'-5'-phosphodiesterase activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128" FT ACT_SITE 797 FT /note="For 2'-5'-phosphodiesterase activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128" FT ACT_SITE 799 FT /note="For 2'-5'-phosphodiesterase activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128" SQ SEQUENCE 835 AA; 98047 MW; D7B1FC83AF2FA14F CRC64; MKVLALRHSV TQVYADTQTY LHDDMKDDYE NAFLISNLTV HNILYLNYSL KTLEILNKSG IAAVEVQGIE ELLALIRCNF TYDYLNNVVF LHDYSYYTNN EIRTDQHWIT KTDIENYLLP GWKLTYVGYN GKSTRGHYNF SFTCQNAATD DDIIIEYIYS NELDFQNFML SKIKERMTTA LPIARLSNRV FRDKLFQSLS LNNDKIVNVG PRNESMFTFL KFPSIKQFSD GPYLVKDTIK LKQERWLGKR VSQFDIGQYK NMLNVITTIY YYYNLYAEKP IVYMLGSAPS YWIYDIKQYS EFVFETWDPL DTPYSNMHHK ELFFEKDTIK LKDNSILYID IRTDRGDIDW KEWRKIVKEQ TLSNLNIAYK YLSTGKSKVC CVKMTAMDIE LPISAKLLHH PTTEIRSEFY MIVDLSDFKN IKRFVPKGVL YSFINNITTE NVFIQHPFKL RKMKNEYIVA LYALSNDFNN RENVIKLINE QEKSLITVRL NNTFKDEPKI GFKNIYDWTF LPTDFNTRNS IITSYDGCIG MFGLSISLSS KPTGNNHIFI LNGTDKYEMI DQFANHMGIS RRSHQIRFSE SATSYSGYIF RDLSNNNFNL IGTNVENSVS GHVYNAIIYF RYNYSFDLKR WIHLHSVDKV KIEGGRYYEH APIELIYACR SAKEFAKMQD DLTTLRYANE IERYINKVYS IVYADDPNYF IGIKFVSIPY KYDVKVPHLT FGVLHISDNM IPDVISILNQ MKVELFKMNI TTSYTYMLSD GIHVANVSGV LLTYFKIYNV FYKKQITFGQ SRMFIPHITL SFKTNKTIRI NITKLKIESI YLRKIKGETV FAMTE //