RIR1_SCHPO
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 03-AUG-2022, entry version 172.
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 -!- PATHWAY: Genetic information processing; DNA replication.
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}.
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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; 28.
DR IntAct; P36602; 1.
DR STRING; 4896.SPAC1F7.05.1; -.
DR iPTMnet; P36602; -.
DR MaxQB; P36602; -.
DR PaxDb; P36602; -.
DR PRIDE; P36602; -.
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; RGSIQNI; -.
DR PhylomeDB; P36602; -.
DR Reactome; R-SPO-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00326; -.
DR PRO; PR:P36602; -.
DR Proteomes; UP000002485; Chromosome I.
DR ExpressionAtlas; P36602; differential.
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; ISM:PomBase.
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:UniProtKB-UniPathway.
DR GO; GO:0006235; P:dTTP biosynthetic process; IMP:PomBase.
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..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
