ID   RIR1_SCHPO              Reviewed;         811 AA.
AC   P36602;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 2.
DT   27-MAR-2024, entry version 180.
DE   RecName: Full=Ribonucleoside-diphosphate reductase large chain;
DE            EC=1.17.4.1;
DE   AltName: Full=Ribonucleotide reductase;
GN   Name=cdc22; ORFNames=SPAC1F7.05;
OS   Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC   Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC   Schizosaccharomyces.
OX   NCBI_TaxID=284812;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=972 / ATCC 24843;
RX   PubMed=8479429; DOI=10.1007/bf00279553;
RA   Fernandez-Sarabia M.J., McInerny C., Harris P., Gordon C., Fantes P.;
RT   "The cell cycle genes cdc22+ and suc22+ of the fission yeast
RT   Schizosaccharomyces pombe encode the large and small subunits of
RT   ribonucleotide reductase.";
RL   Mol. Gen. Genet. 238:241-251(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=972 / ATCC 24843;
RX   PubMed=11859360; DOI=10.1038/nature724;
RA   Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA   Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA   Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA   Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA   Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA   Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA   Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA   Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA   O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA   Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA   Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA   Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA   Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA   Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA   Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA   Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA   Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA   Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA   Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA   Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA   del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA   Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA   Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA   Nurse P.;
RT   "The genome sequence of Schizosaccharomyces pombe.";
RL   Nature 415:871-880(2002).
RN   [3]
RP   INTERACTION WITH SPD1.
RX   PubMed=8887552; DOI=10.1002/j.1460-2075.1996.tb00838.x;
RA   Woollard A., Basi G., Nurse P.;
RT   "A novel S phase inhibitor in fission yeast.";
RL   EMBO J. 15:4603-4612(1996).
RN   [4]
RP   FUNCTION, AND INTERACTION WITH CDC22.
RX   PubMed=16317005; DOI=10.1074/jbc.m511716200;
RA   Hakansson P., Dahl L., Chilkova O., Domkin V., Thelander L.;
RT   "The Schizosaccharomyces pombe replication inhibitor Spd1 regulates
RT   ribonucleotide reductase activity and dNTPs by binding to the large Cdc22
RT   subunit.";
RL   J. Biol. Chem. 281:1778-1783(2006).
CC   -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC       Catalyzes the biosynthesis of deoxyribonucleotides from the
CC       corresponding ribonucleotides. {ECO:0000269|PubMed:16317005}.
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: Heterodimer of a large and a small subunit. Interacts with
CC       SPD1. {ECO:0000269|PubMed:16317005, ECO:0000269|PubMed:8887552}.
CC   -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC       chain family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; X65116; CAA46232.1; -; Genomic_DNA.
DR   EMBL; CU329670; CAA91952.1; -; Genomic_DNA.
DR   PIR; S34807; S34807.
DR   PIR; S62577; S62577.
DR   RefSeq; NP_594491.1; NM_001019920.2.
DR   AlphaFoldDB; P36602; -.
DR   SMR; P36602; -.
DR   BioGRID; 278191; 30.
DR   IntAct; P36602; 1.
DR   STRING; 284812.P36602; -.
DR   iPTMnet; P36602; -.
DR   MaxQB; P36602; -.
DR   PaxDb; 4896-SPAC1F7-05-1; -.
DR   EnsemblFungi; SPAC1F7.05.1; SPAC1F7.05.1:pep; SPAC1F7.05.
DR   GeneID; 2541695; -.
DR   KEGG; spo:SPAC1F7.05; -.
DR   PomBase; SPAC1F7.05; cdc22.
DR   VEuPathDB; FungiDB:SPAC1F7.05; -.
DR   eggNOG; KOG1112; Eukaryota.
DR   HOGENOM; CLU_000404_1_2_1; -.
DR   InParanoid; P36602; -.
DR   OMA; QMSSCYL; -.
DR   PhylomeDB; P36602; -.
DR   PRO; PR:P36602; -.
DR   Proteomes; UP000002485; Chromosome I.
DR   GO; GO:0005737; C:cytoplasm; HDA:PomBase.
DR   GO; GO:0005829; C:cytosol; HDA:PomBase.
DR   GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IPI:PomBase.
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:0046704; P:CDP metabolic process; IDA:PomBase.
DR   GO; GO:0006240; P:dCDP biosynthetic process; IDA:PomBase.
DR   GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0006260; P:DNA replication; IEA:InterPro.
DR   GO; GO:0006235; P:dTTP biosynthetic process; IMP:PomBase.
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.
PE   1: Evidence at protein level;
KW   Allosteric enzyme; ATP-binding; Deoxyribonucleotide synthesis;
KW   Disulfide bond; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT   CHAIN           1..811
FT                   /note="Ribonucleoside-diphosphate reductase large chain"
FT                   /id="PRO_0000187201"
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         603..606
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            736
FT                   /note="Important for electron transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            737
FT                   /note="Important for electron transfer"
FT                   /evidence="ECO:0000250"
FT   SITE            806
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000250"
FT   SITE            809
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000250"
FT   DISULFID        218..444
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        251
FT                   /note="N -> Y (in Ref. 1; CAA46232)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        327
FT                   /note="E -> Q (in Ref. 1; CAA46232)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        425
FT                   /note="C -> S (in Ref. 1; CAA46232)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        560..561
FT                   /note="AS -> CI (in Ref. 1; CAA46232)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        583
FT                   /note="L -> F (in Ref. 1; CAA46232)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   811 AA;  91999 MW;  6650E0EE4C2E8DF6 CRC64;
     MFVYKRDGRQ EKVAFDKITA RVSRLCYGLD SDHVDPVEIT QKVISGVYPG VTTIELDNLA
     AETAATMTTK HPDYAILAAR IAVSNLHKQT EKVFSTVVQQ LHDYVNPKTD KPAPMISDKI
     YDIVMKHKDE LDSAIIYDRD FTYNFFGFKT LERSYLLRID GKVAERPQHM IMRVAVGIHG
     EDIEAAIETY NLMSQRYFTH ASPTLFNAGT PRPQLSSCFL VTMKDDSIEG IYDTLKMCAM
     ISKTAGGIGI NIHNIRATGS YIAGTNGTSN GIVPMIRVYN NTARYVDQGG NKRPGAFAAY
     LEPWHADVMD FLELRKTHGN EDFRAREMFY ALWIPDLFMQ RVERNEQWTF FCPNEAPGLA
     DVWGDEFVAL YEKYEKENRG RRSLPAQKVW YAILQSQVET GNPFMLYKDS CNRKSNQKNV
     GTIRCSNLCT EIVEYSSPDE VAVCNLASVA LPTFIKDGKY NFQKLHDVVK VVTRNLNKII
     DVNYYPVPEA RRSNMRHRPV GLGVQGLADA FFALRLPFES AGAKKLNIQI FETIYHAALE
     ASCEIAQVEG TYESYEGSPA SQGILQYDMW NVNPTDLWDW AELKEKIAKH GIRNSLLVAP
     MPTASTSQIL GFNECFEPYT SNMYQRRVLS GEFQIVNPWL LKDLVERDLW NEDMKNKLVM
     LDGSIQAIPE IPQDLKDLYK TVWEISQKTV IDYAADRGPF IDQSQSLNIH LKDPSYGKIT
     SMHFYGWKKG LKTGMYYLRT MAASAAIKFT VDPVALRARN EESNEENKKP VIKNGKAEIS
     AEPTKEEIDI YNEKVLACSI KNPEACEMCS A
//