ID   RIR1_ARATH              Reviewed;         816 AA.
AC   Q9SJ20; O82573;
DT   21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 153.
DE   RecName: Full=Ribonucleoside-diphosphate reductase large subunit {ECO:0000303|PubMed:10542051};
DE            EC=1.17.4.1;
DE   AltName: Full=Protein DEFECTIVE IN POLLEN DNA DEGRADATION 2 {ECO:0000303|PubMed:22239102};
DE   AltName: Full=Ribonucleoside-diphosphate reductase R1 subunit {ECO:0000303|PubMed:10542051};
DE            Short=AtRNR1;
GN   Name=RNR1 {ECO:0000303|PubMed:10542051};
GN   Synonyms=DPD2 {ECO:0000303|PubMed:22239102};
GN   OrderedLocusNames=At2g21790 {ECO:0000312|Araport:AT2G21790};
GN   ORFNames=F7D8.11 {ECO:0000312|EMBL:AAD20398.1};
OS   Arabidopsis thaliana (Mouse-ear cress).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX   NCBI_TaxID=3702;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND ACTIVITY REGULATION.
RC   TISSUE=Callus;
RX   PubMed=10542051; DOI=10.1046/j.1432-1327.1999.00814.x;
RA   Sauge-Merle S., Falconet D., Fontecave M.;
RT   "An active ribonucleotide reductase from Arabidopsis thaliana cloning,
RT   expression and characterization of the large subunit.";
RL   Eur. J. Biochem. 266:62-69(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=cv. Columbia;
RX   PubMed=10617197; DOI=10.1038/45471;
RA   Lin X., Kaul S., Rounsley S.D., Shea T.P., Benito M.-I., Town C.D.,
RA   Fujii C.Y., Mason T.M., Bowman C.L., Barnstead M.E., Feldblyum T.V.,
RA   Buell C.R., Ketchum K.A., Lee J.J., Ronning C.M., Koo H.L., Moffat K.S.,
RA   Cronin L.A., Shen M., Pai G., Van Aken S., Umayam L., Tallon L.J.,
RA   Gill J.E., Adams M.D., Carrera A.J., Creasy T.H., Goodman H.M.,
RA   Somerville C.R., Copenhaver G.P., Preuss D., Nierman W.C., White O.,
RA   Eisen J.A., Salzberg S.L., Fraser C.M., Venter J.C.;
RT   "Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana.";
RL   Nature 402:761-768(1999).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=cv. Columbia;
RX   PubMed=27862469; DOI=10.1111/tpj.13415;
RA   Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA   Town C.D.;
RT   "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT   genome.";
RL   Plant J. 89:789-804(2017).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=cv. Columbia;
RX   PubMed=14593172; DOI=10.1126/science.1088305;
RA   Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA   Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA   Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA   Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA   Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA   Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA   Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA   Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA   Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA   Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA   Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA   Ecker J.R.;
RT   "Empirical analysis of transcriptional activity in the Arabidopsis
RT   genome.";
RL   Science 302:842-846(2003).
RN   [5]
RP   INDUCTION.
RX   PubMed=15075397; DOI=10.1105/tpc.018903;
RA   Culligan K., Tissier A., Britt A.;
RT   "ATR regulates a G2-phase cell-cycle checkpoint in Arabidopsis thaliana.";
RL   Plant Cell 16:1091-1104(2004).
RN   [6]
RP   FUNCTION, MUTAGENESIS OF PRO-274; GLY-290 AND GLY-718, DISRUPTION
RP   PHENOTYPE, AND TISSUE SPECIFICITY.
RX   PubMed=17346262; DOI=10.1111/j.1365-313x.2007.03035.x;
RA   Garton S., Knight H., Warren G.J., Knight M.R., Thorlby G.J.;
RT   "crinkled leaves 8--a mutation in the large subunit of ribonucleotide
RT   reductase--leads to defects in leaf development and chloroplast division in
RT   Arabidopsis thaliana.";
RL   Plant J. 50:118-127(2007).
RN   [7]
RP   FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-264.
RX   PubMed=22239102; DOI=10.1111/j.1365-313x.2012.04904.x;
RA   Tang L.Y., Matsushima R., Sakamoto W.;
RT   "Mutations defective in ribonucleotide reductase activity interfere with
RT   pollen plastid DNA degradation mediated by DPD1 exonuclease.";
RL   Plant J. 70:637-649(2012).
CC   -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC       Catalyzes the biosynthesis of deoxyribonucleotides from the
CC       corresponding ribonucleotides. R1 contains the binding sites for both
CC       substrates and allosteric effectors and carries out the actual
CC       reduction of the ribonucleotide. Ribonucleotide reductase (RNR) complex
CC       function is essential for efficient organellar DNA degradation in
CC       pollen. Involved in chloroplast division. {ECO:0000269|PubMed:10542051,
CC       ECO:0000269|PubMed:17346262, ECO:0000269|PubMed:22239102}.
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   -!- ACTIVITY REGULATION: Under complex allosteric control mediated by
CC       deoxynucleoside triphosphates and ATP binding to separate specificity
CC       and activation sites on the large subunit. The type of nucleotide bound
CC       at the specificity site determines substrate preference. It seems
CC       probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP
CC       reduction and dTTP favors GDP reduction. Stimulated by ATP and
CC       inhibited by dATP binding to the activity site (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Heterotetramer of two large/R1 and two small/R2 subunits. A
CC       radical transfer pathway may occur between 'Tyr-125' of protein R2 and
CC       R1. {ECO:0000269|PubMed:10542051}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22239102}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in actively growing tissues such
CC       as young leaves, shoot apices, inflorescences and carpels. Very low
CC       expression in cotyledons, adult and cauline leaves and senescent
CC       leaves. {ECO:0000269|PubMed:17346262}.
CC   -!- INDUCTION: Basal expression regulated by ATR/RAD3. Can be induced by
CC       another pathway when dNTPs levels are low.
CC       {ECO:0000269|PubMed:15075397}.
CC   -!- PTM: Contains a disulfide bonds (Probable). Binding of the substrate
CC       occurs primarily when the active-site cysteines are reduced.
CC       {ECO:0000305}.
CC   -!- DISRUPTION PHENOTYPE: Lethal when homozygous. RNAi-mediated knockdown
CC       causes severe developmental defects in seedlings failing to develop
CC       beyond the four-leaf stage. {ECO:0000269|PubMed:17346262}.
CC   -!- MISCELLANEOUS: Two distinct regulatory sites have been defined: one
CC       controls substrate specificity and the other regulates the overall
CC       catalytic activity. A substrate-binding catalytic site, located on R1,
CC       is formed only in the presence of the second subunit R2.
CC   -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC       chain family. {ECO:0000305}.
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DR   EMBL; AF092841; AAC61773.1; -; mRNA.
DR   EMBL; AC007019; AAD20398.1; -; Genomic_DNA.
DR   EMBL; CP002685; AEC07222.1; -; Genomic_DNA.
DR   EMBL; AY035080; AAK59585.1; -; mRNA.
DR   EMBL; BT008573; AAP40400.1; -; mRNA.
DR   PIR; B84605; B84605.
DR   PIR; T51813; T51813.
DR   RefSeq; NP_179770.1; NM_127748.4.
DR   AlphaFoldDB; Q9SJ20; -.
DR   SMR; Q9SJ20; -.
DR   STRING; 3702.Q9SJ20; -.
DR   iPTMnet; Q9SJ20; -.
DR   PaxDb; 3702-AT2G21790-1; -.
DR   ProteomicsDB; 226841; -.
DR   EnsemblPlants; AT2G21790.1; AT2G21790.1; AT2G21790.
DR   GeneID; 816715; -.
DR   Gramene; AT2G21790.1; AT2G21790.1; AT2G21790.
DR   KEGG; ath:AT2G21790; -.
DR   Araport; AT2G21790; -.
DR   TAIR; AT2G21790; RNR1.
DR   eggNOG; KOG1112; Eukaryota.
DR   HOGENOM; CLU_000404_1_0_1; -.
DR   InParanoid; Q9SJ20; -.
DR   OMA; YIVYRDQ; -.
DR   OrthoDB; 5472715at2759; -.
DR   PhylomeDB; Q9SJ20; -.
DR   BioCyc; ARA:AT2G21790-MONOMER; -.
DR   BioCyc; MetaCyc:AT2G21790-MONOMER; -.
DR   PRO; PR:Q9SJ20; -.
DR   Proteomes; UP000006548; Chromosome 2.
DR   ExpressionAtlas; Q9SJ20; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; ISS:UniProtKB.
DR   GO; GO:0009202; P:deoxyribonucleoside triphosphate biosynthetic process; IMP:TAIR.
DR   GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0006260; P:DNA replication; IMP:TAIR.
DR   CDD; cd01679; RNR_I; 1.
DR   Gene3D; 3.20.70.20; -; 1.
DR   InterPro; IPR005144; ATP-cone_dom.
DR   InterPro; IPR013346; NrdE_NrdA_C.
DR   InterPro; IPR000788; RNR_lg_C.
DR   InterPro; IPR013509; RNR_lsu_N.
DR   InterPro; IPR008926; RNR_R1-su_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; PF03477; ATP-cone; 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   SUPFAM; SSF48168; R1 subunit of ribonucleotide reductase, N-terminal domain; 1.
DR   PROSITE; PS51161; ATP_CONE; 1.
DR   PROSITE; PS00089; RIBORED_LARGE; 1.
DR   Genevisible; Q9SJ20; AT.
PE   1: Evidence at protein level;
KW   Allosteric enzyme; ATP-binding; Cytoplasm; Deoxyribonucleotide synthesis;
KW   Disulfide bond; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT   CHAIN           1..816
FT                   /note="Ribonucleoside-diphosphate reductase large subunit"
FT                   /id="PRO_0000187195"
FT   DOMAIN          1..92
FT                   /note="ATP-cone"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
FT   ACT_SITE        427
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        429
FT                   /note="Cysteine radical intermediate"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        431
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         5..6
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         11..17
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         53
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         57
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /ligand_note="allosteric activator"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         202
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         217
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         226..228
FT                   /ligand="dTTP"
FT                   /ligand_id="ChEBI:CHEBI:37568"
FT                   /ligand_note="allosteric effector that controls substrate
FT                   specificity"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         243
FT                   /ligand="dTTP"
FT                   /ligand_id="ChEBI:CHEBI:37568"
FT                   /ligand_note="allosteric effector that controls substrate
FT                   specificity"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         256
FT                   /ligand="dTTP"
FT                   /ligand_id="ChEBI:CHEBI:37568"
FT                   /ligand_note="allosteric effector that controls substrate
FT                   specificity"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         263..264
FT                   /ligand="dTTP"
FT                   /ligand_id="ChEBI:CHEBI:37568"
FT                   /ligand_note="allosteric effector that controls substrate
FT                   specificity"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         427
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         431
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   BINDING         623..626
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   SITE            218
FT                   /note="Important for hydrogen atom transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            444
FT                   /note="Important for hydrogen atom transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            756
FT                   /note="Important for electron transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            757
FT                   /note="Important for electron transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            811
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000250"
FT   SITE            814
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000250"
FT   DISULFID        218..444
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         264
FT                   /note="G->D: In dpd2; loss of pollen plastid DNA
FT                   degradation."
FT                   /evidence="ECO:0000269|PubMed:22239102"
FT   MUTAGEN         274
FT                   /note="P->L: In cls8-3; moderate pale leaf phenotype."
FT                   /evidence="ECO:0000269|PubMed:17346262"
FT   MUTAGEN         290
FT                   /note="G->R: In cls8-2; reduced growth with bleached areas
FT                   and crinckled leaves."
FT                   /evidence="ECO:0000269|PubMed:17346262"
FT   MUTAGEN         718
FT                   /note="G->E: In cls8-1; crinckled phenotype."
FT                   /evidence="ECO:0000269|PubMed:17346262"
FT   CONFLICT        37
FT                   /note="V -> I (in Ref. 1; AAC61773)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        233
FT                   /note="E -> G (in Ref. 1; AAC61773)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   816 AA;  91816 MW;  A6769E2F210488EA CRC64;
     MYVVKRDGRQ ETVHFDKITA RLKKLSYGLS SDHCDPVLVA QKVCAGVYKG VTTSQLDELA
     AETAAAMTCN HPDYASLAAR IAVSNLHKNT KKSFSETIKD MFYHVNDRSG LKSPLIADDV
     FEIIMQNAAR LDSEIIYDRD FEYDYFGFKT LERSYLLKVQ GTVVERPQHM LMRVAVGIHK
     DDIDSVIQTY HLMSQRWFTH ASPTLFNAGT PRPQLSSCFL VCMKDDSIEG IYETLKECAV
     ISKSAGGIGV SVHNIRATGS YIRGTNGTSN GIVPMLRVFN DTARYVDQGG GKRKGAFAVY
     LEPWHADVYE FLELRKNHGK EEHRARDLFY ALWLPDLFME RVQNNGQWSL FCPNEAPGLA
     DCWGAEFETL YTKYEREGKA KKVVQAQQLW YEILTSQVET GTPYMLFKDS CNRKSNQQNL
     GTIKSSNLCT EIIEYTSPTE TAVCNLASIA LPRFVREKGV PLDSHPPKLA GSLDSKNRYF
     DFEKLAEVTA TVTVNLNKII DVNYYPVETA KTSNMRHRPI GIGVQGLADA FILLGMPFDS
     PEAQQLNKDI FETIYYHALK ASTELAARLG PYETYAGSPV SKGILQPDMW NVIPSDRWDW
     AVLRDMISKN GVRNSLLVAP MPTASTSQIL GNNECFEPYT SNIYSRRVLS GEFVVVNKHL
     LHDLTDMGLW TPTLKNKLIN ENGSIVNVAE IPDDLKAIYR TVWEIKQRTV VDMAADRGCY
     IDQSQSLNIH MDKPNFAKLT SLHFYTWKKG LKTGMYYLRS RAAADAIKFT VDTAMLKEKP
     SVAEGDKEVE EEDNETKLAQ MVCSLTNPEE CLACGS
//