ID   RIR1_EBVB9              Reviewed;         826 AA.
AC   P03190; Q777G1;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   02-SEP-2026, entry version 122.
DE   RecName: Full=Ribonucleoside-diphosphate reductase large subunit {ECO:0000255|HAMAP-Rule:MF_04026};
DE            Short=R1 {ECO:0000255|HAMAP-Rule:MF_04026};
DE            EC=1.17.4.1 {ECO:0000255|HAMAP-Rule:MF_04026};
DE   AltName: Full=Ribonucleotide reductase large subunit {ECO:0000255|HAMAP-Rule:MF_04026};
GN   Name=RIR1 {ECO:0000255|HAMAP-Rule:MF_04026}; ORFNames=BORF2;
OS   Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Gammaherpesvirinae; Lymphocryptovirus;
OC   Lymphocryptovirus humangamma4; Epstein-Barr virus.
OX   NCBI_TaxID=10377;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=6087149; DOI=10.1038/310207a0;
RA   Baer R., Bankier A.T., Biggin M.D., Deininger P.L., Farrell P.J.,
RA   Gibson T.J., Hatfull G., Hudson G.S., Satchwell S.C., Seguin C.,
RA   Tuffnell P.S., Barrell B.G.;
RT   "DNA sequence and expression of the B95-8 Epstein-Barr virus genome.";
RL   Nature 310:207-211(1984).
RN   [2]
RP   GENOME REANNOTATION.
RX   PubMed=12771413; DOI=10.1099/vir.0.19054-0;
RA   de Jesus O., Smith P.R., Spender L.C., Elgueta Karstegl C., Niller H.H.,
RA   Huang D., Farrell P.J.;
RT   "Updated Epstein-Barr virus (EBV) DNA sequence and analysis of a promoter
RT   for the BART (CST, BARF0) RNAs of EBV.";
RL   Virology 84:1443-1450(2003).
RN   [3]
RP   IDENTIFICATION OF PROTEIN.
RX   PubMed=6330697; DOI=10.1093/nar/12.12.5087;
RA   Gibson T.J., Stockwell P., Ginsburg M., Barrell B.G.;
RT   "Homology between two EBV early genes and HSV ribonucleotide reductase and
RT   38K genes.";
RL   Nucleic Acids Res. 12:5087-5099(1984).
RN   [4]
RP   SUBCELLULAR LOCATION.
RX   PubMed=15534216; DOI=10.1073/pnas.0407320101;
RA   Johannsen E., Luftig M., Chase M.R., Weicksel S., Cahir-McFarland E.,
RA   Illanes D., Sarracino D., Kieff E.;
RT   "Proteins of purified Epstein-Barr virus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:16286-16291(2004).
RN   [5]
RP   REVIEW.
RX   PubMed=18990579; DOI=10.1016/j.tibs.2008.09.008;
RA   Lembo D., Brune W.;
RT   "Tinkering with a viral ribonucleotide reductase.";
RL   Trends Biochem. Sci. 34:25-32(2009).
CC   -!- FUNCTION: Ribonucleoside-diphosphate reductase holoenzyme provides the
CC       precursors necessary for viral DNA synthesis. Allows virus growth in
CC       non-dividing cells, as well as reactivation from latency in infected
CC       hosts. Catalyzes the biosynthesis of deoxyribonucleotides from the
CC       corresponding ribonucleotides. {ECO:0000255|HAMAP-Rule:MF_04026}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 2'-deoxyribonucleoside 5'-diphosphate + [thioredoxin]-
CC         disulfide + H2O = a ribonucleoside 5'-diphosphate + [thioredoxin]-
CC         dithiol; Xref=Rhea:RHEA:23252, Rhea:RHEA-COMP:10698, Rhea:RHEA-
CC         COMP:10700, ChEBI:CHEBI:15377, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC         ChEBI:CHEBI:57930, ChEBI:CHEBI:73316; EC=1.17.4.1;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_04026};
CC   -!- SUBUNIT: Heterotetramer composed of a homodimer of the large subunit
CC       (R1) and a homodimer of the small subunit (R2). Larger multisubunit
CC       protein complex are also active, composed of (R1)n(R2)n.
CC       {ECO:0000255|HAMAP-Rule:MF_04026}.
CC   -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC       chain family. {ECO:0000255|HAMAP-Rule:MF_04026}.
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DR   EMBL; V01555; CAA24842.1; -; Genomic_DNA.
DR   EMBL; AJ507799; CAD53405.1; -; Genomic_DNA.
DR   PIR; A03753; QQBE11.
DR   RefSeq; YP_401655.1; NC_007605.1.
DR   PDB; 7RW6; EM; 2.55 A; A/C=1-826.
DR   AlphaFoldDB; P03190; -.
DR   EMDB; EMD-24709; -.
DR   SMR; P03190; -.
DR   IntAct; P03190; 2.
DR   MINT; P03190; -.
DR   DNASU; 3783725; -.
DR   GeneID; 3783725; -.
DR   KEGG; vg:3783725; -.
DR   Proteomes; UP000153037; Segment.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IEA:UniProtKB-UniRule.
DR   GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IEA:InterPro.
DR   GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR   GO; GO:0019046; P:release from viral latency; IEA:UniProtKB-KW.
DR   Gene3D; 3.20.70.20; -; 1.
DR   HAMAP; MF_04026; HSV_RIR1; 1.
DR   InterPro; IPR034717; HSV_RIR1.
DR   InterPro; IPR013346; NrdE_NrdA_C.
DR   InterPro; IPR000788; RNR_lg_C.
DR   InterPro; IPR013509; RNR_lsu_N.
DR   InterPro; IPR039718; Rrm1.
DR   NCBIfam; TIGR02506; NrdE_NrdA; 1.
DR   PANTHER; PTHR11573; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE LARGE CHAIN; 1.
DR   PANTHER; PTHR11573:SF6; RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE LARGE SUBUNIT; 1.
DR   Pfam; PF02867; Ribonuc_red_lgC; 1.
DR   Pfam; PF00317; Ribonuc_red_lgN; 1.
DR   PRINTS; PR01183; RIBORDTASEM1.
DR   SUPFAM; SSF51998; PFL-like glycyl radical enzymes; 1.
DR   PROSITE; PS00089; RIBORED_LARGE; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Disulfide bond; DNA replication; Early protein;
KW   Nucleotide-binding; Oxidoreductase; Reference proteome; Viral latency;
KW   Viral reactivation from latency.
FT   CHAIN           1..826
FT                   /note="Ribonucleoside-diphosphate reductase large subunit"
FT                   /id="PRO_0000187234"
FT   REGION          747..769
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        749..758
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        387
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   ACT_SITE        389
FT                   /note="Cysteine radical intermediate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   ACT_SITE        391
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   BINDING         171
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   BINDING         186..187
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   BINDING         217
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   BINDING         387..391
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   BINDING         594..598
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   SITE            187
FT                   /note="Important for hydrogen atom transfer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   SITE            403
FT                   /note="Important for hydrogen atom transfer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   SITE            725
FT                   /note="Important for electron transfer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   SITE            726
FT                   /note="Important for electron transfer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   SITE            822
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   SITE            825
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   DISULFID        187..403
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT   HELIX           8..20
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   TURN            21..25
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           27..40
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           49..55
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           57..60
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           64..68
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           70..82
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           84..90
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           94..99
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           100..104
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           116..134
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           137..144
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           151..163
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          166..169
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           171..175
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          176..179
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          187..190
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           209..212
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          214..221
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          256..260
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           267..271
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          285..291
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           293..300
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   TURN            312..314
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   TURN            316..320
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           324..335
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           345..358
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          362..366
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           367..372
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          374..376
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          379..381
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          397..399
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          401..409
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           410..413
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           432..435
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           458..477
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           481..486
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          488..494
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           496..502
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           510..538
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           549..552
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          560..562
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           563..565
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           571..582
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           598..602
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           657..660
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           663..665
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   TURN            668..670
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           673..683
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           684..686
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          695..697
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   TURN            699..705
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   HELIX           707..717
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          721..725
FT                   /evidence="ECO:0007829|PDB:7RW6"
FT   STRAND          727..729
FT                   /evidence="ECO:0007829|PDB:7RW6"
SQ   SEQUENCE   826 AA;  93031 MW;  6E5C25623D371EF1 CRC64;
     MATTSHVEHE LLSKLIDELK VKANSDPEAD VLAGRLLHRL KAESVTHTVA EYLEVFSDKF
     YDEEFFQMHR DELETRVSAF AQSPAYERIV SSGYLSALRY YDTYLYVGRS GKQESVQHFY
     MRLAGFCAST TCLYAGLRAA LQRARPEIES DMEVFDYYFE HLTSQTVCCS TPFMRFAGVE
     NSTLASCILT TPDLSSEWDV TQALYRHLGR YLFQRAGVGV GVTGAGQDGK HISLLMRMIN
     SHVEYHNYGC KRPVSVAAYM EPWHSQIFKF LETKLPENHE RCPGIFTGLF VPELFFKLFR
     DTPWSDWYLF DPKDAGDLER LYGEEFEREY YRLVTAGKFC GRVSIKSLMF SIVNCAVKAG
     SPFILLKEAC NAHFWRDLQG EAMNAANLCA EVLQPSRKSV ATCNLANICL PRCLVNAPLA
     VRAQRADTQG DELLLALPRL SVTLPGEGAV GDGFSLARLR DATQCATFVV ACSILQGSPT
     YDSRDMASMG LGVQGLADVF ADLGWQYTDP PSRSLNKEIF EHMYFTALCT SSLIGLHTRK
     IFPGFKQSKY AGGWFHWHDW AGTDLSIPRE IWSRLSERIV RDGLFNSQFI ALMPTSGCAQ
     VTGCSDAFYP FYANASTKVT NKEEALRPNR SFWRHVRLDD REALNLVGGR VSCLPEALRQ
     RYLRFQTAFD YNQEDLIQMS RDRAPFVDQS QSHSLFLREE DAARASTLAN LLVRSYELGL
     KTIMYYCRIE KAADLGVMEC KASAALSVPR EEQNERSPAE QMPPRPMEPA QVAGPVDIMS
     KGPGEGPGGW CVPGGLEVCY KYRQLFSEDD LLETDGFTER ACESCQ
//