RIR1_HHV23
ID RIR1_HHV23 Reviewed; 1144 AA.
AC P09853;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 105.
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};
OS Human herpesvirus 2 (strain 333) (HHV-2) (Human herpes simplex virus 2).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10313;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2419588; DOI=10.1128/jvi.57.3.802-808.1986;
RA Swain M.A., Galloway D.A.;
RT "Herpes simplex virus specifies two subunits of ribonucleotide reductase
RT encoded by 3'-coterminal transcripts.";
RL J. Virol. 57:802-808(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 981-1144.
RX PubMed=6321759; DOI=10.1128/jvi.49.3.724-730.1984;
RA Galloway D.A., Swain M.A.;
RT "Organization of the left-hand end of the herpes simplex virus type 2 BglII
RT N fragment.";
RL J. Virol. 49:724-730(1984).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1036-1144.
RX PubMed=6315408; DOI=10.1002/j.1460-2075.1983.tb01684.x;
RA McLauchlan J., Clements J.B.;
RT "DNA sequence homology between two co-linear loci on the HSV genome which
RT have different transforming abilities.";
RL EMBO J. 2:1953-1961(1983).
RN [4]
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 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. Prevents host necroptosis by targeting host RIPK1 and
CC RIPK3, thereby hampering the formation of necroptotic RIPK1-RIPK3
CC complexes (By similarity). May form hetero-amyloid structures with host
CC proteins RIPK3 or ZBP1, thereby preventing RIPK3- and ZBP1-mediated
CC necroptosis (By similarity). In addition, inhibits extrinsic apoptosis
CC by targeting host CASP8 (By similarity). {ECO:0000250|UniProtKB:P08543,
CC ECO:0000250|UniProtKB:P89462, ECO:0000255|HAMAP-Rule:MF_04026}.
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 Interacts (via RHIM) with human RIPK3 (via RHIM) (By similarity). May
CC interact (via RHIM) with human ZBP1 (via RHIM) (By similarity).
CC Interacts (via C-terminus) with host CASP8 (By similarity).
CC {ECO:0000250|UniProtKB:P08543, ECO:0000250|UniProtKB:P89462,
CC ECO:0000255|HAMAP-Rule:MF_04026}.
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; M12700; AAA45806.1; -; Genomic_DNA.
DR EMBL; X00048; CAA24929.1; -; Genomic_DNA.
DR SMR; P09853; -.
DR UniPathway; UPA00326; -.
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: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 3: Inferred from homology;
KW ATP-binding; Disulfide bond; DNA replication; Early protein;
KW Host-virus interaction; Inhibition of host caspases by virus;
KW Modulation of host cell apoptosis by virus; Nucleotide-binding;
KW Oxidoreductase; Viral latency; Viral reactivation from latency.
FT CHAIN 1..1144
FT /note="Ribonucleoside-diphosphate reductase large subunit"
FT /id="PRO_0000187237"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 COMPBIAS 204..221
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 798
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT ACT_SITE 800
FT /note="Cysteine radical intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT ACT_SITE 802
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT BINDING 573
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT BINDING 588..589
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT BINDING 619
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT BINDING 798..802
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT BINDING 975..979
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 589
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 815
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 1118
FT /note="Important for electron transfer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 1119
FT /note="Important for electron transfer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 1139
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT SITE 1142
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
FT DISULFID 589..815
FT /note="Redox-active"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04026"
SQ SEQUENCE 1144 AA; 125093 MW; 4771481C3103FC78 CRC64;
MANRPAASAL AGARSPSERQ EPREPEVAPP GGDHVFCRKV SGVMVLSSDP PGPAAYRISD
SSFVQCGSNC SMIIDGDVAR GHLRDLEGAT STGAFVAISN VAAGGDGRTA VVALGGTSGP
SATTSVGTQT SGEFLHGNPR TPEPQGPQAV PPPPPPPFPW GHECCARRDA RGGAEKDVGA
AESWSDGPSS DSETEDSDSS DEDTGSGSET LSRSSSIWAA GATDDDDSDS DSRSDDSVQP
DVVVRRRWSD GPAPVAFPKP RRPGDSPGNP GLGAGTGPGS ATDPRASADS DSAAHAAAPQ
ADVAPVLDSQ PTVGTDPGYP VPLELTPENA EAVARFLGDA VDREPALMLE YFCRCAREES
KRVPPRTFGS APRLTEDDFG LLNYALAEMR RLCLDLPPVP PNAYTPYHLR EYATRLVNGF
KPLVRRSARL YRILGILVHL RIRTREASFE EWMRSKEVDL DFGLTERLRE HEAQLMILAQ
ALNPYDCLIH STPNTLVERG LQSALKYEEF YLKRFGGHYM ESVFQMYTRI AGFLACRATR
GMRHIALGRQ GSWWEMFKFF FHRLYDHQIV PSTPAMLNLG TRNYYTSSCY LVNPQATTNQ
ATLRAITGNV SAILARNGGI GLCMQAFNDA SPGTASIMPA LKVLDSLVAA HNKQSTRPTG
ACVYLEPWHS DVRAVLRMKG VLAGEEAQRC DNIFSALWMP DLFFKRLIRH LDGEKNVTWS
LFDRDTSMSL ADFHGEEFEK LYEHLEAMGF GETIPIQDLA YAIVRSAATT GSPFIMFKDA
VNRHYIYDTQ GAAIAGSNLC TEIVHPSSKR SSGVCNLGSV NLARCVSRRT FDFGMLRDAV
QACVLMVNIM IDSTLQPTPQ CARGHDNLRS MGIGMQGLHT ACLKMGLDLE SAEFRDLNTH
IAEVMLLAAM KTSNALCVRG ARPFSHFKRS MYRAGRFHWE RFSNASPRYE GEWEMLRQSM
MKHGLRNSQF IALMPTAASA QISDVSEGFA PLFTNLFSKV TRDGETLRPN TLLLKELERT
FGGKRLLDAM DGLEAKQWSV AQALPCLDPA HPLRRFKTAF DYDQELLIDL CADRAPYVDH
SQSMTLYVTE KADGTLPAST LVRLLVHAYK RGLKTGMYYC KVRKATNSGV FAGDDNIVCT
SCAL
