RIR1_NEUCR
ID RIR1_NEUCR Reviewed; 929 AA.
AC Q9UW15; Q7RXZ9; Q9P3G2;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 30-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Ribonucleoside-diphosphate reductase large chain;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleotide reductase large subunit;
GN Name=rnr-1; ORFNames=B2A19.30, NCU03539;
OS Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS FGSC 987).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX NCBI_TaxID=367110;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, ENZYME ACTIVITY, AND
RP MUTAGENESIS OF CYS-26; VAL-124 AND MET-125.
RC STRAIN=Oak Ridge;
RX PubMed=10660063; DOI=10.1007/pl00008645;
RA Smith M.L., Hubbard S.P., Jacobson D.J., Micali O.C., Glass N.L.;
RT "An osmotic-remedial, temperature-sensitive mutation in the allosteric
RT activity site of ribonucleotide reductase in Neurospora crassa.";
RL Mol. Gen. Genet. 262:1022-1035(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12655011; DOI=10.1093/nar/gkg293;
RA Mannhaupt G., Montrone C., Haase D., Mewes H.-W., Aign V., Hoheisel J.D.,
RA Fartmann B., Nyakatura G., Kempken F., Maier J., Schulte U.;
RT "What's in the genome of a filamentous fungus? Analysis of the Neurospora
RT genome sequence.";
RL Nucleic Acids Res. 31:1944-1954(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12712197; DOI=10.1038/nature01554;
RA Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT "The genome sequence of the filamentous fungus Neurospora crassa.";
RL Nature 422:859-868(2003).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides. {ECO:0000269|PubMed:10660063}.
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:0000269|PubMed:10660063};
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 -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC chain family. {ECO:0000305}.
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DR EMBL; AF171697; AAD49743.1; -; Genomic_DNA.
DR EMBL; AL390092; CAB98233.1; -; Genomic_DNA.
DR EMBL; CM002237; EAA27582.1; -; Genomic_DNA.
DR PIR; T43711; T43711.
DR RefSeq; XP_956818.1; XM_951725.3.
DR AlphaFoldDB; Q9UW15; -.
DR SMR; Q9UW15; -.
DR BioGRID; 1974838; 3.
DR STRING; 5141.EFNCRP00000002608; -.
DR EnsemblFungi; EAA27582; EAA27582; NCU03539.
DR GeneID; 3872956; -.
DR KEGG; ncr:NCU03539; -.
DR VEuPathDB; FungiDB:NCU03539; -.
DR HOGENOM; CLU_000404_1_2_1; -.
DR InParanoid; Q9UW15; -.
DR OMA; RGSIQNI; -.
DR UniPathway; UPA00326; -.
DR Proteomes; UP000001805; Chromosome 6, Linkage Group II.
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 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Deoxyribonucleotide synthesis;
KW Disulfide bond; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..929
FT /note="Ribonucleoside-diphosphate reductase large chain"
FT /id="PRO_0000187202"
FT DOMAIN 1..92
FT /note="ATP-cone"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
FT REGION 789..904
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 789..814
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 874..888
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 605..608
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 738
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 739
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 924
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 927
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT DISULFID 218..444
FT /note="Redox-active"
FT /evidence="ECO:0000250"
FT MUTAGEN 26
FT /note="C->Y: In un-24; temperature-sensitive mutant."
FT /evidence="ECO:0000269|PubMed:10660063"
FT MUTAGEN 124
FT /note="V->I: In un-24; temperature-sensitive mutant."
FT /evidence="ECO:0000269|PubMed:10660063"
FT MUTAGEN 125
FT /note="M->I: In un-24; temperature-sensitive mutant."
FT /evidence="ECO:0000269|PubMed:10660063"
FT CONFLICT 912
FT /note="A -> R (in Ref. 1; AAD49743)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 929 AA; 103804 MW; 68C47E8B21C047B8 CRC64;
MYVKKRDGRQ ERVQFDKITA RVSRLCYGLD MNHVDPVAIT QKVISGVYGG VTTAQLDDLA
AETAAYMTVT HPDYAILAAR IAVSNLHKQT KKQWSLVISE LYNYVNPRTG KHSPMIAKDV
YECVMRHKDE FDSAIVYDRD FNYQYFGFKT LERSYLLKLD GQIAERPQHM IMRVAVGIWG
DDVERVIETY NLMSLKTFTH ASPTLFNAGT PQPQLSSCFL VDMKEDSIEG IYDTLKTCAM
ISKMAGGIGL NIHRIRATGS YIAGTNGTSN GIVPMLRVFN NTARYVDQGG NKRPGAFAIY
LEPWHADVFE FLDLRKNHGK EEVRARDLFL ALWIPDLFMK RVEQNGQWTL MCPHECPGLA
DVYGDEFEAL YEKYEKEGKG RKTVKAQKLW YAILEAQTET GNPFMLYKDA CNRKSNQKNL
GTIRSSNLCT EIIEYSAPDE VAVCNLASLA LSAFIDYENA SYDFKKLHEV TQVVVRNLNK
IIDINHYPVK EAHNSNMRHR PIGVGVQGLA DAFLALRMPF DSDAASKLNI QIFETIYHAA
LTASCQLAKE QGPYATYEGS PVSQGILQYD MWNVTPTNLW DWTALKADIK KYGVRNSLLL
APMPTASTSQ ILGNNECFEP YTSNIYQRRV LAGEFQVVNP WLLRDLVEMG LWSDAMKNRI
IAEGGSIQNI QSIPNDIKAL YKTVWEISQR TIVKMAADRG AFIDQSQSLN IHMREPTMGK
ITSMHFAGWK MGLKTGMYYL RTQAAAQPIQ FTVDQEALRA TDDRVAPAHS GLKKRSPPAG
TYTSIVLREN TSGPRPYAQT GVSGTSTPIG TRDVPTPAST PPPTEVPETL VQSDNRPRPL
VSPAKSAGFK ADLPEPESPK ALATDPIVKT EDIGSPLLER KEGQNEDVDE DSQERDENIY
SNAPLSEQQV AACAWNPGAD PSSCEMCSG
