MCE_VACCW
ID MCE_VACCW Reviewed; 333 AA.
AC P07617;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1988, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Cap-specific mRNA (nucleoside-2'-O-)-methyltransferase;
DE EC=2.1.1.57;
DE AltName: Full=Poly(A) polymerase regulatory subunit;
DE AltName: Full=Poly(A) polymerase small subunit;
DE Short=PAP-S;
DE AltName: Full=VP39;
GN Name=PAPS; OrderedLocusNames=VACWR095; ORFNames=J3R;
OS Vaccinia virus (strain Western Reserve) (VACV) (Vaccinia virus (strain
OS WR)).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus; Vaccinia virus.
OX NCBI_TaxID=10254;
OH NCBI_TaxID=9913; Bos taurus (Bovine).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2987815; DOI=10.1093/nar/13.3.985;
RA Plucienniczak A., Schroeder E., Zettlmeissl G., Streeck R.E.;
RT "Nucleotide sequence of a cluster of early and late genes in a conserved
RT segment of the vaccinia virus genome.";
RL Nucleic Acids Res. 13:985-998(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Esposito J.J., Frace A.M., Sammons S.A., Olsen-Rasmussen M., Osborne J.,
RA Wohlhueter R.;
RT "Sequencing of the coding region of Vaccinia-WR to an average 9-fold
RT redundancy and an error rate of 0.16/10kb.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 196-205; 210-219 AND 247-256, AND FUNCTION.
RX PubMed=1313572; DOI=10.1073/pnas.89.7.2897;
RA Schnierle B.S., Gershon P.D., Moss B.;
RT "Cap-specific mRNA (nucleoside-O2'-)-methyltransferase and poly(A)
RT polymerase stimulatory activities of vaccinia virus are mediated by a
RT single protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:2897-2901(1992).
RN [4]
RP FUNCTION, AND INTERACTION WITH VP55/E1.
RX PubMed=1670500; DOI=10.1016/0092-8674(91)90048-4;
RA Gershon P.D., Ahn B.-Y., Garfield M., Moss B.;
RT "Poly(A) polymerase and a dissociable polyadenylation stimulatory factor
RT encoded by vaccinia virus.";
RL Cell 66:1269-1278(1991).
RN [5]
RP INTERACTION WITH H4 AND NPH-I/D11.
RX PubMed=11162828; DOI=10.1006/viro.2000.0749;
RA Mohamed M.R., Latner D.R., Condit R.C., Niles E.G.;
RT "Interaction between the J3R subunit of vaccinia virus poly(A) polymerase
RT and the H4L subunit of the viral RNA polymerase.";
RL Virology 280:143-152(2001).
RN [6]
RP RNA-BINDING.
RX PubMed=12079779; DOI=10.1016/s1074-5521(02)00163-1;
RA Oguro A., Johnson L., Gershon P.D.;
RT "Path of an RNA ligand around the surface of the vaccinia VP39 subunit of
RT its cognate VP39-VP55 protein heterodimer.";
RL Chem. Biol. 9:679-690(2002).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF HIS-56; ILE-58; GLY-96 AND LYS-175.
RX PubMed=12359447; DOI=10.1006/viro.2002.1538;
RA Latner D.R., Thompson J.M., Gershon P.D., Storrs C., Condit R.C.;
RT "The positive transcription elongation factor activity of the vaccinia
RT virus J3 protein is independent from its (nucleoside-2'-O-)
RT methyltransferase and poly(A) polymerase stimulatory functions.";
RL Virology 301:64-80(2002).
RN [8]
RP ACTIVE SITE.
RX PubMed=15134442; DOI=10.1021/bi0359980;
RA Li C., Xia Y., Gao X., Gershon P.D.;
RT "Mechanism of RNA 2'-O-methylation: evidence that the catalytic lysine acts
RT to steer rather than deprotonate the target nucleophile.";
RL Biochemistry 43:5680-5687(2004).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE.
RX PubMed=8612277; DOI=10.1016/s0092-8674(00)81101-0;
RA Hodel A.E., Gershon P.D., Shi X., Quiocho F.A.;
RT "The 1.85 A structure of vaccinia protein VP39: a bifunctional enzyme that
RT participates in the modification of both mRNA ends.";
RL Cell 85:247-256(1996).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS.
RX PubMed=9145102; DOI=10.1038/nsb0597-350;
RA Hodel A.E., Gershon P.D., Shi X., Wang S.-M., Quiocho F.A.;
RT "Specific protein recognition of an mRNA cap through its alkylated base.";
RL Nat. Struct. Biol. 4:350-354(1997).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYLHOMOCYSTEINE AND SUBSTRATE ANALOG.
RX PubMed=9660928; DOI=10.1016/s1097-2765(00)80044-1;
RA Hodel A.E., Gershon P.D., Quiocho F.A.;
RT "Structural basis for sequence-nonspecific recognition of 5'-capped mRNA by
RT a cap-modifying enzyme.";
RL Mol. Cell 1:443-447(1998).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-307 IN COMPLEXES WITH SUBSTRATE
RP ANALOGS.
RX PubMed=10377383; DOI=10.1073/pnas.96.13.7149;
RA Hu G., Gershon P.D., Hodel A.E., Quiocho F.A.;
RT "mRNA cap recognition: dominant role of enhanced stacking interactions
RT between methylated bases and protein aromatic side chains.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:7149-7154(1999).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 1-307 IN COMPLEX WITH SUBSTRATES.
RX PubMed=12056899; DOI=10.1021/bi0201926;
RA Hu G., Oguro A., Li C., Gershon P.D., Quiocho F.A.;
RT "The 'cap-binding slot' of an mRNA cap-binding protein: quantitative
RT effects of aromatic side chain choice in the double-stacking sandwich with
RT cap.";
RL Biochemistry 41:7677-7687(2002).
CC -!- FUNCTION: Displays methyltransferase, positive regulation of the
CC poly(A) polymerase and transcription elongation activities. Involved in
CC the modification of both mRNA ends and in intermediate and late gene
CC positive transcription elongation. At the mRNAs 5' end, methylates the
CC ribose 2' OH group of the first transcribed nucleotide, thereby
CC producing a 2'-O-methylpurine cap. At the 3' end, functions as a
CC processivity factor which stimulates the activity of the viral poly(A)
CC polymerase VP55 that creates mRNA's poly(A) tail. In the presence of
CC VP39, VP55 does not dissociate from the RNA allowing tail elongation to
CC around 250 adenylates. {ECO:0000269|PubMed:12359447,
CC ECO:0000269|PubMed:1313572, ECO:0000269|PubMed:1670500}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside
CC in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167,
CC Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609;
CC EC=2.1.1.57;
CC -!- SUBUNIT: Methyltransferase activity: Monomer, poly(A) polymerase
CC activity: Heterodimer composed of a catalytic component, VP55, and a
CC processivity factor, VP39. Interacts with Rap94 and NPH-I; these
CC interactions might help linking transcription to capping and
CC polyadenylation. {ECO:0000269|PubMed:11162828,
CC ECO:0000269|PubMed:12056899, ECO:0000269|PubMed:1670500,
CC ECO:0000269|PubMed:8612277, ECO:0000269|PubMed:9145102,
CC ECO:0000269|PubMed:9660928}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000305}. Note=Localizes to the
CC virion core. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Poxvirus/kinetoplastid 2'-O-MTase family.
CC {ECO:0000255|PROSITE-ProRule:PRU00944}.
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DR EMBL; X01978; CAA26017.1; -; Genomic_DNA.
DR EMBL; AY243312; AAO89374.1; -; Genomic_DNA.
DR PIR; H23092; QQVZF9.
DR RefSeq; YP_232977.1; NC_006998.1.
DR PDB; 1AV6; X-ray; 2.80 A; A=3-297.
DR PDB; 1B42; X-ray; 2.20 A; A=1-297.
DR PDB; 1BKY; X-ray; 2.00 A; A=1-307.
DR PDB; 1EAM; X-ray; 2.00 A; A=1-307.
DR PDB; 1EQA; X-ray; 2.20 A; A=1-297.
DR PDB; 1JSZ; X-ray; 1.93 A; A=1-307.
DR PDB; 1JTE; X-ray; 2.00 A; A=1-307.
DR PDB; 1JTF; X-ray; 2.60 A; A=1-307.
DR PDB; 1P39; X-ray; 2.00 A; A=1-307.
DR PDB; 1V39; X-ray; 1.80 A; A=1-307.
DR PDB; 1VP3; X-ray; 1.90 A; A=1-333.
DR PDB; 1VP9; X-ray; 1.95 A; A=1-307.
DR PDB; 1VPT; X-ray; 1.80 A; A=1-333.
DR PDB; 2GA9; X-ray; 2.30 A; A=1-297.
DR PDB; 2GAF; X-ray; 2.40 A; A=1-297.
DR PDB; 2VP3; X-ray; 1.95 A; A=1-307.
DR PDB; 3ER8; X-ray; 3.18 A; A/B=1-297.
DR PDB; 3ER9; X-ray; 2.06 A; A=1-297.
DR PDB; 3ERC; X-ray; 3.21 A; A/B=1-297.
DR PDB; 3MAG; X-ray; 1.80 A; A=1-307.
DR PDB; 3MCT; X-ray; 2.00 A; A=1-297.
DR PDB; 4DCG; X-ray; 1.80 A; A=1-307.
DR PDBsum; 1AV6; -.
DR PDBsum; 1B42; -.
DR PDBsum; 1BKY; -.
DR PDBsum; 1EAM; -.
DR PDBsum; 1EQA; -.
DR PDBsum; 1JSZ; -.
DR PDBsum; 1JTE; -.
DR PDBsum; 1JTF; -.
DR PDBsum; 1P39; -.
DR PDBsum; 1V39; -.
DR PDBsum; 1VP3; -.
DR PDBsum; 1VP9; -.
DR PDBsum; 1VPT; -.
DR PDBsum; 2GA9; -.
DR PDBsum; 2GAF; -.
DR PDBsum; 2VP3; -.
DR PDBsum; 3ER8; -.
DR PDBsum; 3ER9; -.
DR PDBsum; 3ERC; -.
DR PDBsum; 3MAG; -.
DR PDBsum; 3MCT; -.
DR PDBsum; 4DCG; -.
DR SMR; P07617; -.
DR DIP; DIP-48310N; -.
DR IntAct; P07617; 1.
DR DrugBank; DB04314; 1-Methylcytosine.
DR DrugBank; DB04103; 3-Methylcytosine.
DR DrugBank; DB03164; 6-amino-1-methyl-7H-purin-1-ium.
DR DrugBank; DB01978; 7,9-Dimethylguanine.
DR DrugBank; DB03358; 7-Methyl-7,8-dihydroguanosine 5'-(tetrahydrogen triphosphate).
DR DrugBank; DB01960; 7-methyl-7,8-dihydroguanosine-5'-diphosphate.
DR DrugBank; DB03493; 7-Methylguanosine.
DR DrugBank; DB01752; S-adenosyl-L-homocysteine.
DR DNASU; 3707551; -.
DR GeneID; 3707551; -.
DR KEGG; vg:3707551; -.
DR BRENDA; 2.1.1.57; 6591.
DR EvolutionaryTrace; P07617; -.
DR Proteomes; UP000000344; Genome.
DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003746; F:translation elongation factor activity; IEA:UniProtKB-KW.
DR GO; GO:0006370; P:7-methylguanosine mRNA capping; IEA:UniProtKB-KW.
DR GO; GO:0031440; P:regulation of mRNA 3'-end processing; IEA:InterPro.
DR CDD; cd20756; capping_2-OMTase_Poxviridae; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR000176; mRNA_MeTrfase-like.
DR InterPro; IPR025804; Pox/kineto_cap_MeTfrase.
DR InterPro; IPR030375; Poxvir_cap_MeTfrase.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF01358; PARP_regulatory; 1.
DR PIRSF; PIRSF003726; PolA_polym_reg_poxV; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51612; SAM_MT_2O_PK; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Elongation factor;
KW Methyltransferase; mRNA capping; mRNA processing; Protein biosynthesis;
KW Reference proteome; RNA-binding; S-adenosyl-L-methionine; Transcription;
KW Transferase; Virion.
FT CHAIN 1..333
FT /note="Cap-specific mRNA (nucleoside-2'-O-)-
FT methyltransferase"
FT /id="PRO_0000099112"
FT REGION 169..333
FT /note="Binding to Rap94"
FT REGION 169..249
FT /note="Binding to NPH-I"
FT REGION 305..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 311..325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 175
FT /note="For methyltransferase activity"
FT /evidence="ECO:0000305|PubMed:15134442"
FT BINDING 22
FT /ligand="mRNA"
FT /ligand_id="ChEBI:CHEBI:33699"
FT /ligand_part="mRNA cap"
FT BINDING 39
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00944,
FT ECO:0000269|PubMed:8612277"
FT BINDING 66
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00944,
FT ECO:0000269|PubMed:8612277"
FT BINDING 68
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00944,
FT ECO:0000269|PubMed:8612277"
FT BINDING 72
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00944,
FT ECO:0000269|PubMed:8612277"
FT BINDING 95
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00944,
FT ECO:0000269|PubMed:8612277"
FT BINDING 97
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00944,
FT ECO:0000269|PubMed:8612277"
FT BINDING 116
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00944,
FT ECO:0000269|PubMed:8612277"
FT BINDING 138
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00944,
FT ECO:0000269|PubMed:8612277"
FT BINDING 177..180
FT /ligand="mRNA"
FT /ligand_id="ChEBI:CHEBI:33699"
FT /ligand_part="mRNA cap"
FT BINDING 182
FT /ligand="mRNA"
FT /ligand_id="ChEBI:CHEBI:33699"
FT /ligand_part="mRNA cap"
FT BINDING 205..207
FT /ligand="mRNA"
FT /ligand_id="ChEBI:CHEBI:33699"
FT /ligand_part="mRNA cap"
FT BINDING 233
FT /ligand="mRNA"
FT /ligand_id="ChEBI:CHEBI:33699"
FT /ligand_part="mRNA cap"
FT MUTAGEN 56
FT /note="H->R: Complete loss of poly(A) polymerase
FT stimulatory activity; when associated with S-58."
FT /evidence="ECO:0000269|PubMed:12359447"
FT MUTAGEN 58
FT /note="I->S: Complete loss of poly(A) polymerase
FT stimulatory activity; when associated with R-56."
FT /evidence="ECO:0000269|PubMed:12359447"
FT MUTAGEN 96
FT /note="G->D: Complete loss of elongation factor activity."
FT /evidence="ECO:0000269|PubMed:12359447"
FT MUTAGEN 175
FT /note="K->R: Complete loss of methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:12359447"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:1V39"
FT HELIX 24..28
FT /evidence="ECO:0007829|PDB:1V39"
FT HELIX 37..55
FT /evidence="ECO:0007829|PDB:1V39"
FT TURN 58..61
FT /evidence="ECO:0007829|PDB:3ERC"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:1V39"
FT HELIX 73..84
FT /evidence="ECO:0007829|PDB:1V39"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:1V39"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:1V39"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:1V39"
FT HELIX 118..128
FT /evidence="ECO:0007829|PDB:1V39"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:1V39"
FT HELIX 150..167
FT /evidence="ECO:0007829|PDB:1V39"
FT STRAND 170..176
FT /evidence="ECO:0007829|PDB:1V39"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:1V39"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:1V39"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:1V39"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:1V39"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:1AV6"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:1V39"
FT HELIX 226..241
FT /evidence="ECO:0007829|PDB:1V39"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:1V39"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:3ER8"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:3ERC"
FT HELIX 258..267
FT /evidence="ECO:0007829|PDB:1V39"
FT HELIX 279..294
FT /evidence="ECO:0007829|PDB:1V39"
SQ SEQUENCE 333 AA; 38888 MW; 55A299DA4AAE1AD4 CRC64;
MDVVSLDKPF MYFEEIDNEL DYEPESANEV AKKLPYQGQL KLLLGELFFL SKLQRHGILD
GATVVYIGSA PGTHIRYLRD HFYNLGVIIK WMLIDGRHHD PILNGLRDVT LVTRFVDEEY
LRSIKKQLHP SKIILISDVR SKRGGNEPST ADLLSNYALQ NVMISILNPV ASSLKWRCPF
PDQWIKDFYI PHGNKMLQPF APSYSAEMRL LSIYTGENMR LTRVTKSDAV NYEKKMYYLN
KIVRNKVVVN FDYPNQEYDY FHMYFMLRTV YCNKTFPTTK AKVLFLQQSI FRFLNIPTTS
TEKVSHEPIQ RKISSKNSMS KNRNSKRSVR SNK
