RIR1_HHV2H
ID RIR1_HHV2H Reviewed; 1142 AA.
AC P89462;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 119.
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}; OrderedLocusNames=UL39;
OS Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus 2).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10315;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=9499055; DOI=10.1128/jvi.72.3.2010-2021.1998;
RA Dolan A., Jamieson F.E., Cunningham C., Barnett B.C., McGeoch D.J.;
RT "The genome sequence of herpes simplex virus type 2.";
RL J. Virol. 72:2010-2021(1998).
RN [2]
RP SUBCELLULAR LOCATION.
RX PubMed=7618272; DOI=10.1006/viro.1995.1351;
RA Hunter J.C., Smith C.C., Bose D., Kulka M., Broderick R., Aurelian L.;
RT "Intracellular internalization and signaling pathways triggered by the
RT large subunit of HSV-2 ribonucleotide reductase (ICP10).";
RL Virology 210:345-360(1995).
RN [3]
RP FUNCTION.
RX PubMed=11773417; DOI=10.1128/jvi.76.3.1435-1449.2002;
RA Perkins D., Pereira E.F., Gober M., Yarowsky P.J., Aurelian L.;
RT "The herpes simplex virus type 2 R1 protein kinase (ICP10 PK) blocks
RT apoptosis in hippocampal neurons, involving activation of the MEK/MAPK
RT survival pathway.";
RL J. Virol. 76:1435-1449(2002).
RN [4]
RP ALPHA-CRYSTALLIN DOMAIN.
RX PubMed=12804778; DOI=10.1016/s0014-5793(03)00547-7;
RA Chabaud S., Lambert H., Sasseville A.M., Lavoie H., Guilbault C.,
RA Massie B., Landry J., Langelier Y.;
RT "The R1 subunit of herpes simplex virus ribonucleotide reductase has
RT chaperone-like activity similar to Hsp27.";
RL FEBS Lett. 545:213-218(2003).
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).
RN [6]
RP FUNCTION, AND INTERACTION WITH HOST RIPK1; RIPK3 AND CASP8.
RX PubMed=25674983; DOI=10.1016/j.chom.2015.01.003;
RA Guo H., Omoto S., Harris P.A., Finger J.N., Bertin J., Gough P.J.,
RA Kaiser W.J., Mocarski E.S.;
RT "Herpes simplex virus suppresses necroptosis in human cells.";
RL Cell Host Microbe 17:243-251(2015).
CC -!- FUNCTION: Ribonucleoside-diphosphate reductase holoenzyme that provides
CC the precursors necessary for viral DNA synthesis. Allows virus growth
CC in non-dividing cells, as well as reactivation from latency in infected
CC hosts. Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides (By similarity). The N-terminal region
CC confers antiapoptotic activity in differentiated cells such as neurons
CC and is important for viral reactivation to increase neural
CC survivability (PubMed:11773417). Prevents host necroptosis by targeting
CC host RIPK1 and RIPK3, thereby hampering the formation of necroptotic
CC RIPK1-RIPK3 complexes (PubMed:25674983). May form hetero-amyloid
CC structures with host proteins RIPK3 or ZBP1, thereby preventing
CC RIPK3- and ZBP1-mediated necroptosis (By similarity). In addition,
CC inhibits extrinsic apoptosis by targeting host CASP8 (PubMed:25674983).
CC {ECO:0000250|UniProtKB:P08543, ECO:0000255|HAMAP-Rule:MF_04026,
CC ECO:0000269|PubMed:11773417, ECO:0000269|PubMed:25674983}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-disulfide + a 2'-deoxyribonucleoside 5'-
CC diphosphate + H2O = [thioredoxin]-dithiol + a ribonucleoside 5'-
CC diphosphate; 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 -!- PATHWAY: Genetic information processing; DNA replication.
CC {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 (By
CC similarity). May self-assemble (via RIP homotypic interaction
CC motif/RHIM) into homomeric fibrillar amyloid structures (By
CC similarity). Interacts (via RHIM) with human RIPK1 (via RHIM)
CC (PubMed:25674983). Interacts (via RHIM) with human RIPK3 (via RHIM)
CC (PubMed:25674983). May interact (via RHIM) with human ZBP1 (via RHIM)
CC (By similarity). Interacts (via C-terminus) with host CASP8
CC (PubMed:25674983). {ECO:0000250|UniProtKB:P08543, ECO:0000255|HAMAP-
CC Rule:MF_04026, ECO:0000269|PubMed:25674983}.
CC -!- SUBCELLULAR LOCATION: Host cell membrane {ECO:0000269|PubMed:7618272}.
CC Host endosome membrane {ECO:0000269|PubMed:7618272}. Note=Associates
CC with the host cytoskeleton. {ECO:0000305}.
CC -!- DOMAIN: Contains an alpha-crystallin domain homologous to small heat-
CC shock proteins.
CC -!- DOMAIN: The RIP homotypic interaction motif/RHIM may drive self-
CC assembly into homomeric amyloid structures and mediates interaction
CC with the RHIM motif of host proteins RIPK3 and ZBP1 to form heteromeric
CC amyloid structures. {ECO:0000250|UniProtKB:P08543}.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC chain family. {ECO:0000255|HAMAP-Rule:MF_04026}.
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DR EMBL; Z86099; CAB06725.1; -; Genomic_DNA.
DR PIR; A05247; A05247.
DR RefSeq; YP_009137191.1; NC_001798.2.
DR SMR; P89462; -.
DR BioGRID; 1677930; 1.
DR IntAct; P89462; 2.
DR PRIDE; P89462; -.
DR GeneID; 1487325; -.
DR KEGG; vg:1487325; -.
DR UniPathway; UPA00326; -.
DR Proteomes; UP000001874; Genome.
DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
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:0006260; P:DNA replication; IEA:UniProtKB-UniRule.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IMP:AgBase.
DR GO; GO:0019046; P:release from viral latency; IEA:UniProtKB-KW.
DR GO; GO:0039650; P:suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process; IEA:UniProtKB-KW.
DR HAMAP; MF_04026; HSV_RIR1; 1.
DR InterPro; IPR034717; HSV_RIR1.
DR InterPro; IPR013346; NrdE_NrdA.
DR InterPro; IPR000788; RNR_lg_C.
DR InterPro; IPR013509; RNR_lsu_N.
DR InterPro; IPR039718; Rrm1.
DR PANTHER; PTHR11573; PTHR11573; 1.
DR Pfam; PF02867; Ribonuc_red_lgC; 1.
DR Pfam; PF00317; Ribonuc_red_lgN; 1.
DR PRINTS; PR01183; RIBORDTASEM1.
DR TIGRFAMs; TIGR02506; NrdE_NrdA; 1.
DR PROSITE; PS00089; RIBORED_LARGE; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Disulfide bond; DNA replication; Early protein;
KW Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW Inhibition of host caspases by virus; Membrane;
KW Modulation of host cell apoptosis by virus; Nucleotide-binding;
KW Oxidoreductase; Reference proteome; Viral latency;
KW Viral reactivation from latency.
FT CHAIN 1..1142
FT /note="Ribonucleoside-diphosphate reductase large subunit"
FT /id="PRO_0000385162"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..322
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 294..400
FT /note="alpha-crystallin domain"
FT MOTIF 55..75
FT /note="RIP homotypic interaction motif (RHIM)"
FT /evidence="ECO:0000250|UniProtKB:P08543"
FT COMPBIAS 118..136
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 144..161
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 189..203
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 796
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT ACT_SITE 798
FT /note="Cysteine radical intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT ACT_SITE 800
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT BINDING 571
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT BINDING 586..587
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT BINDING 617
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT BINDING 796..800
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT BINDING 973..977
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 587
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 813
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 1116
FT /note="Important for electron transfer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 1117
FT /note="Important for electron transfer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 1137
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 1140
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT DISULFID 587..813
FT /note="Redox-active"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
SQ SEQUENCE 1142 AA; 124923 MW; 5A46D3985338BB21 CRC64;
MANRPAASAL AGARSPSERQ EPREPEVAPP GGDHVFCRKV SGVMVLSSDP PGPAAYRISD
SSFVQCGSNC SMIIDGDVAR GHLRDLEGAT STGAFVAISN VAAGGDGRTA VVALGGTSGP
SATTSVGTQT SGEFLHGNPR TPEPQGPQAV PPPPPPPFPW GHECCARRDA RGGAEKDVGA
AESWSDGPSS DSETEDSDSS DEDTGSETLS RSSSIWAAGA TDDDDSDSDS RSDDSVQPDV
VVRRRWSDGP APVAFPKPRR PGDSPGNPGL GAGTGPGSAT DPRASADSDS AAHAAAPQAD
VAPVLDSQPT VGTDPGYPVP LELTPENAEA VARFLGDAVD REPALMLEYF CRCAREESKR
VPPRTFGSAP RLTEDDFGLL NYALAEMRRL CLDLPPVPPN AYTPYHLREY ATRLVNGFKP
LVRRSARLYR ILGVLVHLRI RTREASFEEW MRSKEVDLDF GLTERLREHE AQLMILAQAL
NPYDCLIHST PNTLVERGLQ SALKYEEFYL KRFGGHYMES VFQMYTRIAG FLACRATRGM
RHIALGRQGS WWEMFKFFFH RLYDHQIVPS TPAMLNLGTR NYYTSSCYLV NPQATTNQAT
LRAITGNVSA ILARNGGIGL CMQAFNDASP GTASIMPALK VLDSLVAAHN KQSTRPTGAC
VYLEPWHSDV RAVLRMKGVL AGEEAQRCDN IFSALWMPDL FFKRLIRHLD GEKNVTWSLF
DRDTSMSLAD FHGEEFEKLY EHLEAMGFGE TIPIQDLAYA IVRSAATTGS PFIMFKDAVN
RHYIYDTQGA AIAGSNLCTE IVHPASKRSS GVCNLGSVNL ARCVSRQTFD FGRLRDAVQA
CVLMVNIMID STLQPTPQCT RGNDNLRSMG IGMQGLHTAC LKMGLDLESA EFRDLNTHIA
EVMLLAAMKT SNALCVRGAR PFSHFKRSMY RAGRFHWERF SNASPRYEGE WEMLRQSMMK
HGLRNSQFIA LMPTAASAQI SDVSEGFAPL FTNLFSKVTR DGETLRPNTL LLKELERTFG
GKRLLDAMDG LEAKQWSVAQ ALPCLDPAHP LRRFKTAFDY DQELLIDLCA DRAPYVDHSQ
SMTLYVTEKA DGTLPASTLV RLLVHAYKRG LKTGMYYCKV RKATNSGVFA GDDNIVCTSC
AL
