RIR1_CAEEL
ID RIR1_CAEEL Reviewed; 788 AA.
AC Q03604;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Ribonucleoside-diphosphate reductase large subunit;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleotide reductase large subunit;
GN Name=rnr-1; ORFNames=T23G5.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=7906398; DOI=10.1038/368032a0;
RA Wilson R., Ainscough R., Anderson K., Baynes C., Berks M., Bonfield J.,
RA Burton J., Connell M., Copsey T., Cooper J., Coulson A., Craxton M.,
RA Dear S., Du Z., Durbin R., Favello A., Fraser A., Fulton L., Gardner A.,
RA Green P., Hawkins T., Hillier L., Jier M., Johnston L., Jones M.,
RA Kershaw J., Kirsten J., Laisster N., Latreille P., Lightning J., Lloyd C.,
RA Mortimore B., O'Callaghan M., Parsons J., Percy C., Rifken L., Roopra A.,
RA Saunders D., Shownkeen R., Sims M., Smaldon N., Smith A., Smith M.,
RA Sonnhammer E., Staden R., Sulston J., Thierry-Mieg J., Thomas K.,
RA Vaudin M., Vaughan K., Waterston R., Watson A., Weinstock L.,
RA Wilkinson-Sproat J., Wohldman P.;
RT "2.2 Mb of contiguous nucleotide sequence from chromosome III of C.
RT elegans.";
RL Nature 368:32-38(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
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 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 -!- 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; Z19158; CAA79574.1; -; Genomic_DNA.
DR PIR; S28302; S28302.
DR RefSeq; NP_499039.1; NM_066638.4.
DR AlphaFoldDB; Q03604; -.
DR SMR; Q03604; -.
DR BioGRID; 41500; 26.
DR DIP; DIP-26889N; -.
DR IntAct; Q03604; 3.
DR STRING; 6239.T23G5.1.1; -.
DR iPTMnet; Q03604; -.
DR EPD; Q03604; -.
DR PaxDb; Q03604; -.
DR PeptideAtlas; Q03604; -.
DR EnsemblMetazoa; T23G5.1.1; T23G5.1.1; WBGene00004391.
DR EnsemblMetazoa; T23G5.1.2; T23G5.1.2; WBGene00004391.
DR GeneID; 176301; -.
DR UCSC; T23G5.1.2; c. elegans.
DR CTD; 176301; -.
DR WormBase; T23G5.1; CE00331; WBGene00004391; rnr-1.
DR eggNOG; KOG1112; Eukaryota.
DR GeneTree; ENSGT00910000144246; -.
DR HOGENOM; CLU_000404_1_2_1; -.
DR InParanoid; Q03604; -.
DR OMA; RGSIQNI; -.
DR OrthoDB; 156716at2759; -.
DR PhylomeDB; Q03604; -.
DR Reactome; R-CEL-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00326; -.
DR PRO; PR:Q03604; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00004391; Expressed in germ line (C elegans) and 4 other tissues.
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:0009263; P:deoxyribonucleotide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniPathway.
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 3: Inferred from homology;
KW Allosteric enzyme; ATP-binding; Deoxyribonucleotide synthesis;
KW Disulfide bond; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..788
FT /note="Ribonucleoside-diphosphate reductase large subunit"
FT /id="PRO_0000187194"
FT DOMAIN 7..98
FT /note="ATP-cone"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
FT ACT_SITE 433
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 435
FT /note="Cysteine radical intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 437
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 11..12
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 17..23
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 59
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 208
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 223
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 232..234
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 249
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 262
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 269..270
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 433
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 437
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 610..613
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT SITE 224
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 450
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 743
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 744
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 783
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 786
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT DISULFID 224..450
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 788 AA; 88970 MW; B1AF398B173407D4 CRC64;
MQRYNSTYVV KRDGRKEDVH FDKITSRIQK LSYGLNMDFV DPVAVAIKVI SGLYKGVTTV
ELDNLAAETA ASMTTQHPEY ALLAARIAVS NLHKKTNKVF SEVMKTLHEF HHPHTGKHAP
MISDETWAII EKNADKLNSA IVYDRDYSYT YFGFKTLERS YLLKINKEIV ERPQQMLMRV
SIGIHGDDIT SAIETYNLMS ERYMTHASPT LFNSGTCRPQ MSSCFLLTMS EDSILGIYDT
LKQCALISKS AGGIGLNVHK IRATGSVIAG TNGTSNGLIP MLRVYNNTAR YVDQGGNKRP
GAFAIYLEPW HADIFEFVSL RKNTGPEEER ARDLFLALWI PDLFMKRVEK DQEWSLMCPC
ECPGLDDCWG EEFEALYAKY EAEGRVRKTV KARKLWEHIV SNQIETGLPY ITYKDAANRK
SNQQNLGTIK CSNLCTEIIE YSAPDEIAVC NLASIALNRY VTPEKKFDFV KLAEVTKVIT
RNLNKIIDVN YYPVEEARNS NMRHRPIGLG VQGLADCFML MRYPFTSAEA RDLNKRIFET
IYYAALEASC ELAELNGPYS TYEGSPVSKG QLQFDMWGVT PTDQCDWATL RKKIAKHGIR
NSLLMAPMPT ASTAQILGNN ESIEPYTSNI YSRRVLSGDF QIVNPHMLKD LVERGLWTDE
MKNRLIANNG SIQNIDGIPS DIKELYRTVW EISQKDIIEM AADRGAYIDQ SQSLNIHMAK
PSYAGITSMH FYGWKKGLKT GMYYLRTKPA VNAVQFTVDK NALKTNQQAE TPATVAESQD
EGCLMCSG
