VP3_ROTSH
ID VP3_ROTSH Reviewed; 835 AA.
AC A2T3S5;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 23-FEB-2022, entry version 56.
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, ECO:0000269|PubMed:23878220};
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, ECO:0000269|PubMed:10603323};
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, ECO:0000269|PubMed:10603323};
OS Rotavirus A (isolate RVA/Monkey/South Africa/SA11-H96/1958/G3P5B[2]) (RV-A)
OS (Simian Agent 11 (isolate SI/South Africa/H96/58)).
OC Viruses; Riboviria; Orthornavirae; Duplornaviricota; Resentoviricetes;
OC Reovirales; Reoviridae; Sedoreovirinae; Rotavirus; Rotavirus A.
OX NCBI_TaxID=450149;
OH NCBI_TaxID=60710; Chlorocebus pygerythrus (Vervet monkey) (Cercopithecus pygerythrus).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=17059839; DOI=10.1016/j.virol.2006.09.024;
RA Small C., Barro M., Brown T.L., Patton J.T.;
RT "Genome heterogeneity of SA11 rotavirus due to reassortment with 'O'
RT agent.";
RL Virology 359:415-424(2007).
RN [2]
RP INTERACTION WITH VP2.
RX PubMed=9420216; DOI=10.1128/jvi.72.1.201-208.1998;
RA Zeng C.Q.-Y., Estes M.K., Charpilienne A., Cohen J.;
RT "The N terminus of rotavirus VP2 is necessary for encapsidation of VP1 and
RT VP3.";
RL J. Virol. 72:201-208(1998).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10603323; DOI=10.1006/viro.1999.0029;
RA Chen D., Luongo C.L., Nibert M.L., Patton J.T.;
RT "Rotavirus open cores catalyze 5'-capping and methylation of exogenous RNA:
RT evidence that VP3 is a methyltransferase.";
RL Virology 265:120-130(1999).
RN [4]
RP FUNCTION, DOMAIN, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-718 AND HIS-797,
RP AND ACTIVE SITE.
RX PubMed=23878220; DOI=10.1073/pnas.1306917110;
RA Zhang R., Jha B.K., Ogden K.M., Dong B., Zhao L., Elliott R., Patton J.T.,
RA Silverman R.H., Weiss S.R.;
RT "Homologous 2',5'-phosphodiesterases from disparate RNA viruses antagonize
RT antiviral innate immunity.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:13114-13119(2013).
RN [5]
RP DOMAIN.
RX PubMed=24899176; DOI=10.1128/jvi.00923-14;
RA Ogden K.M., Snyder M.J., Dennis A.F., Patton J.T.;
RT "Predicted structure and domain organization of rotavirus capping enzyme
RT and innate immune antagonist VP3.";
RL J. Virol. 88:9072-9085(2014).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.39 ANGSTROMS) OF 696-835, AND DOMAIN.
RX PubMed=25758703; DOI=10.1002/prot.24794;
RA Brandmann T., Jinek M.;
RT "Crystal structure of the C-terminal 2',5'-phosphodiesterase domain of
RT group A rotavirus protein VP3.";
RL Proteins 83:997-1002(2015).
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, ECO:0000305|PubMed:10603323}.
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 ECO:0000269|PubMed:23878220}.
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 ECO:0000269|PubMed:10603323};
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, ECO:0000269|PubMed:10603323};
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 ECO:0000269|PubMed:23878220};
CC -!- SUBUNIT: Interacts with VP1 (By similarity). Interacts with VP2
CC (PubMed:9420216). {ECO:0000255|HAMAP-Rule:MF_04128,
CC ECO:0000269|PubMed:9420216}.
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, ECO:0000269|PubMed:23878220,
CC ECO:0000269|PubMed:24899176, ECO:0000269|PubMed:25758703}.
CC -!- SIMILARITY: Belongs to the rotavirus VP3 family. {ECO:0000255|HAMAP-
CC Rule:MF_04128}.
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DR EMBL; DQ838645; ABG75824.1; -; Genomic_RNA.
DR RefSeq; YP_002302228.1; NC_011508.2.
DR PDB; 5AF2; X-ray; 1.39 A; A/B/C/D=696-835.
DR PDBsum; 5AF2; -.
DR SMR; A2T3S5; -.
DR GeneID; 7011370; -.
DR KEGG; vg:7011370; -.
DR Proteomes; UP000001119; Genome.
DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-UniRule.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0004484; F:mRNA guanylyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0106005; P:RNA 5'-cap (guanine-N7)-methylation; IDA:UniProtKB.
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; IPR039573; NS2A-like.
DR InterPro; IPR011181; VP3_Rotav.
DR Pfam; PF05213; Corona_NS2A; 1.
DR Pfam; PF06929; Rotavirus_VP3; 1.
DR PIRSF; PIRSF004015; LigT_rotavirus; 1.
DR PROSITE; PS51589; SAM_MT56_VP3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 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; Reference proteome; RNA-binding;
KW S-adenosyl-L-methionine; Transferase; Viral immunoevasion; Virion.
FT CHAIN 1..835
FT /note="Protein VP3"
FT /id="PRO_0000367814"
FT REGION 171..245
FT /note="N7-methyltransferase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128,
FT ECO:0000269|PubMed:24899176"
FT REGION 246..428
FT /note="2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128,
FT ECO:0000269|PubMed:24899176"
FT REGION 429..555
FT /note="N7-methyltransferase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128,
FT ECO:0000269|PubMed:24899176"
FT REGION 556..693
FT /note="GTase/RTPase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128,
FT ECO:0000269|PubMed:24899176"
FT REGION 693..835
FT /note="2'-5'-phosphodiesterase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128,
FT ECO:0000269|PubMed:23878220"
FT ACT_SITE 718
FT /note="For 2'-5'-phosphodiesterase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128,
FT ECO:0000269|PubMed:23878220, ECO:0000305|PubMed:25758703"
FT ACT_SITE 720
FT /note="For 2'-5'-phosphodiesterase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128,
FT ECO:0000305|PubMed:25758703"
FT ACT_SITE 797
FT /note="For 2'-5'-phosphodiesterase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128,
FT ECO:0000269|PubMed:23878220, ECO:0000305|PubMed:25758703"
FT ACT_SITE 799
FT /note="For 2'-5'-phosphodiesterase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04128,
FT ECO:0000305|PubMed:25758703"
FT MUTAGEN 718
FT /note="H->A: Complete loss of 2'-5'-phosphodiesterase
FT activity; when associated with A-797."
FT /evidence="ECO:0000269|PubMed:23878220"
FT MUTAGEN 797
FT /note="H->A: Complete loss of 2'-5'-phosphodiesterase
FT activity; when associated with A-718."
FT /evidence="ECO:0000269|PubMed:23878220"
FT STRAND 699..706
FT /evidence="ECO:0007829|PDB:5AF2"
FT STRAND 714..716
FT /evidence="ECO:0007829|PDB:5AF2"
FT STRAND 718..725
FT /evidence="ECO:0007829|PDB:5AF2"
FT HELIX 728..730
FT /evidence="ECO:0007829|PDB:5AF2"
FT HELIX 731..740
FT /evidence="ECO:0007829|PDB:5AF2"
FT HELIX 742..746
FT /evidence="ECO:0007829|PDB:5AF2"
FT STRAND 751..759
FT /evidence="ECO:0007829|PDB:5AF2"
FT STRAND 762..766
FT /evidence="ECO:0007829|PDB:5AF2"
FT HELIX 771..783
FT /evidence="ECO:0007829|PDB:5AF2"
FT STRAND 787..792
FT /evidence="ECO:0007829|PDB:5AF2"
FT STRAND 797..803
FT /evidence="ECO:0007829|PDB:5AF2"
FT STRAND 809..814
FT /evidence="ECO:0007829|PDB:5AF2"
FT STRAND 817..824
FT /evidence="ECO:0007829|PDB:5AF2"
FT STRAND 829..833
FT /evidence="ECO:0007829|PDB:5AF2"
SQ SEQUENCE 835 AA; 98069 MW; B761FCA189B7FBB5 CRC64;
MKVLALRHSV AQVYADTQVY VHDDTKDSYE NAFLISNLTT HNILYLNYSI KTLEILNKSG
IAAIALQSLE ELFTLIRCNF TYDYELDIIY LHDYSYYTNN EIRTDQHWIT KTNIEEYLLP
GWKLTYVGYN GSETRGHYNF SFKCQNAATD DDLIIEYIYS EALDFQNFML KKIKERMTTS
LPIARLSNRV FRDKLFPSLL KEHKNVVNVG PRNESMFTFL NYPTIKQFSN GAYLVKDTIK
LKQERWLGKR ISQFDIGQYK NMLNVLTAIY YYYNLYKSKP IIYMIGSAPS YWIYDVRHYS
DFFFETWDPL DTPYSSIHHK ELFFINDVKK LKDNSILYID IRTDRGNADW KKWRKTVEEQ
TINNLDIAYE YLRTGKAKVC CVKMTAMDLE LPISAKLLHH PTTEIRSEFY LLLDTWDLTN
IRRFIPKGVL YSFINNIITE NVFIQQPFKV KVLNDSYIVA LYALSNDFNN RSEVIKLINN
QKQSLITVRI NNTFKDEPKV GFKNIYDWTF LPTDFDTKEA IITSYDGCLG LFGLSISLAS
KPTGNNHLFI LSGTDKYYKL DQFANHTSIS RRSHQIRFSE SATSYSGYIF RDLSNNNFNL
IGTNIENSVS GHVYNALIYY RYNYSFDLKR WIYLHSIDKV DIEGGKYYEL APIELIYACR
SAKEFATLQD DLTVLRYSNE IENYINTVYS ITYADDPNYF IGIQFRNIPY KYDVKIPHLT
FGVLHISDNM VPDVIDILKI MKNELFKMDI TTSYTYMLSD GIYVANVSGV LSTYFKIYNV
FYKNQITFGQ SRMFIPHITL SFNNMRTVRI ETTKLQIKSI YLRKIKGDTV FDMVE
