RIR1_DROME
ID RIR1_DROME Reviewed; 812 AA.
AC P48591; Q9UB08; Q9VKZ3;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Ribonucleoside-diphosphate reductase large subunit;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleoside-diphosphate reductase subunit M1;
DE AltName: Full=Ribonucleotide reductase large subunit;
GN Name=RnrL; ORFNames=CG5371;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA Harvey D.A.;
RT "A Drosophila complementary DNA resource.";
RL Science 287:2222-2224(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 164-343.
RC STRAIN=Oregon-R;
RX PubMed=8050359; DOI=10.1242/dev.120.6.1503;
RA Duronio R.J., O'Farrell P.H.;
RT "Developmental control of a G1-S transcriptional program in Drosophila.";
RL Development 120:1503-1515(1994).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-778; SER-782 AND TYR-786, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides.
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 M1 subunit. The type of nucleotide bound at
CC the specificity site determines substrate preference. It seems probable
CC that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction
CC and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP
CC binding to the activity site (By similarity). {ECO:0000250}.
CC -!- PATHWAY: Genetic information processing; DNA replication.
CC -!- SUBUNIT: Heterodimer of a large and a small subunit.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC chain family. {ECO:0000305}.
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DR EMBL; AE014134; AAF52913.2; -; Genomic_DNA.
DR EMBL; AF132143; AAD33590.1; -; mRNA.
DR EMBL; AY119149; AAM51009.1; -; mRNA.
DR EMBL; U09369; AAA56995.1; -; Genomic_DNA.
DR RefSeq; NP_477027.1; NM_057679.5.
DR AlphaFoldDB; P48591; -.
DR SMR; P48591; -.
DR BioGRID; 60477; 5.
DR DIP; DIP-19582N; -.
DR STRING; 7227.FBpp0079648; -.
DR iPTMnet; P48591; -.
DR PaxDb; P48591; -.
DR PRIDE; P48591; -.
DR EnsemblMetazoa; FBtr0080059; FBpp0079648; FBgn0011703.
DR GeneID; 34392; -.
DR KEGG; dme:Dmel_CG5371; -.
DR CTD; 34392; -.
DR FlyBase; FBgn0011703; RnrL.
DR VEuPathDB; VectorBase:FBgn0011703; -.
DR eggNOG; KOG1112; Eukaryota.
DR GeneTree; ENSGT00910000144246; -.
DR HOGENOM; CLU_000404_1_0_1; -.
DR InParanoid; P48591; -.
DR OMA; RGSIQNI; -.
DR OrthoDB; 156716at2759; -.
DR PhylomeDB; P48591; -.
DR Reactome; R-DME-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00326; -.
DR BioGRID-ORCS; 34392; 2 hits in 3 CRISPR screens.
DR GenomeRNAi; 34392; -.
DR PRO; PR:P48591; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0011703; Expressed in secondary oocyte and 45 other tissues.
DR Genevisible; P48591; DM.
DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; ISS:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:FlyBase.
DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniPathway.
DR GO; GO:0042246; P:tissue regeneration; IMP:FlyBase.
DR InterPro; IPR005144; ATP-cone_dom.
DR InterPro; IPR013346; NrdE_NrdA.
DR InterPro; IPR000788; RNR_lg_C.
DR InterPro; IPR013509; RNR_lsu_N.
DR InterPro; IPR008926; RNR_R1-su_N.
DR InterPro; IPR039718; Rrm1.
DR PANTHER; PTHR11573; PTHR11573; 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; SSF48168; SSF48168; 1.
DR TIGRFAMs; TIGR02506; NrdE_NrdA; 1.
DR PROSITE; PS51161; ATP_CONE; 1.
DR PROSITE; PS00089; RIBORED_LARGE; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Deoxyribonucleotide synthesis;
KW Disulfide bond; Nucleotide-binding; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..812
FT /note="Ribonucleoside-diphosphate reductase large subunit"
FT /id="PRO_0000187193"
FT DOMAIN 12..103
FT /note="ATP-cone"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
FT ACT_SITE 438
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 440
FT /note="Cysteine radical intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 442
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 16..17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 22..28
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 64
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 68
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 213
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 228
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 237..239
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 254
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 267
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 274..275
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 438
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 442
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 615..618
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT SITE 229
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 455
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 748
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 749
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 807
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 810
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT MOD_RES 778
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 782
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 786
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT DISULFID 229..455
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 812 AA; 91978 MW; 6E4FC608AC04A5FD CRC64;
MLKNKSMKTS KLYVIKRDGR QEEVHFDKIT SRIQKLCYNL NMDFVDPVTI TLQVINGLYC
GVTTQELDNL AAEIAAGLTC NHPDYAILAA RIAVSNLHKE TKKAFSDVFE DLYNHVNKET
NQKVPLVSEF HYNVVKKNAT RLNSSIIYDR DFGYNYFGFK TLERSYLLKR NGKIAERPQH
MLMRVAIGIH GEDIDAAVET YNLLSERYFT HASPTLFAAA TNRPQLSSCF LLTMTADSIE
GIFKSVEQCA MISKSAGGIG LNVHCIRAKG TSICGTNGTS NGLVPMLRVF NNVARYVDQG
GGKRPGAFAI YLEPWHSDVF EFLELKKNTG KEENRARDLF YALWIPDLFM KRVEANGDWS
LMCPHKCPGL HDVWGDEFEK LYEKYEQEGR ANRTVKAQSL WFAIIEAQVE TGNPYMLFKD
ACNRKSNQQN VGTIKCSNLC TEIVEYSAPD EIAVCNLASI ALNMFVTPEK TYDFKKLKEV
TKIVTKNLNK IIDINYYPLP EARKSNLRHR PVGIGIQGFA DALILMRFPY ESEEAGLLNQ
QIFETIYYGA LEASCELAQT EGPYETYEGS PVSKGILQYD MWDKVPTNLW DWQKLKESIR
MHGVRNSLLV APMPTASTAQ IMGNNESFEP YTTNIYTRRV LSGEFQVVNH HLLRDLTELD
LWDDDMKNQI ISSRGSIQNI ETIPPKVRDL YKTVWEISVK STIKMAADRG AFIDQSQSFN
IHVAEPNYGK LTSIHFYSWK AGLKTGMYYL RTKPAANAIQ FTVNKKQGAV SMNGQNGTAE
GSPQKYEEDR ERKMADMVCS LENKDACMSC GS
