RIR1_DICDI
ID RIR1_DICDI Reviewed; 870 AA.
AC Q54Q71;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Ribonucleoside-diphosphate reductase large subunit;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleotide reductase large subunit;
GN Name=rnrA; ORFNames=DDB_G0284071;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
CC -!- FUNCTION: Provides the precursors necessary for DNA synthesis.
CC Catalyzes the biosynthesis of deoxyribonucleotides from the
CC corresponding ribonucleotides (By similarity). {ECO:0000250}.
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. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC chain family. {ECO:0000305}.
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DR EMBL; AAFI02000063; EAL65376.1; -; Genomic_DNA.
DR RefSeq; XP_638726.1; XM_633634.1.
DR AlphaFoldDB; Q54Q71; -.
DR SMR; Q54Q71; -.
DR STRING; 44689.DDB0230075; -.
DR PaxDb; Q54Q71; -.
DR PRIDE; Q54Q71; -.
DR EnsemblProtists; EAL65376; EAL65376; DDB_G0284071.
DR GeneID; 8624396; -.
DR KEGG; ddi:DDB_G0284071; -.
DR dictyBase; DDB_G0284071; rnrA.
DR eggNOG; KOG1112; Eukaryota.
DR HOGENOM; CLU_000404_1_0_1; -.
DR InParanoid; Q54Q71; -.
DR OMA; RGSIQNI; -.
DR PhylomeDB; Q54Q71; -.
DR Reactome; R-DDI-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00326; -.
DR PRO; PR:Q54Q71; -.
DR Proteomes; UP000002195; Chromosome 4.
DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IDA:dictyBase.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; IDA:dictyBase.
DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; IDA:dictyBase.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-UniPathway.
DR GO; GO:0031288; P:sorocarp morphogenesis; IMP:dictyBase.
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.
PE 3: Inferred from homology;
KW Allosteric enzyme; ATP-binding; Cytoplasm; Deoxyribonucleotide synthesis;
KW Disulfide bond; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..870
FT /note="Ribonucleoside-diphosphate reductase large subunit"
FT /id="PRO_0000328498"
FT DOMAIN 16..110
FT /note="ATP-cone"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00492"
FT REGION 789..854
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 789..852
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 446
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 448
FT /note="Cysteine radical intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 450
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 20..21
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 26..32
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 71
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 75
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 235
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 244..246
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 261
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
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 281..282
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 446
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 450
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT BINDING 632..635
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /evidence="ECO:0000250|UniProtKB:P23921"
FT SITE 236
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 463
FT /note="Important for hydrogen atom transfer"
FT /evidence="ECO:0000250"
FT SITE 765
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 766
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 865
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 868
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT DISULFID 236..463
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 870 AA; 98019 MW; 41A13B6274074897 CRC64;
MISNSINVTP NKESKMYVVK RDGTKENVSF DKITSRISFL CEMEPKLNSD IVDPIEVAQK
VVSGVFPGVK TTELDNLAAE TAAYMSTRHP DYGILAARIS VSNLHKQTSK SFVETVKKQY
EFINPKSNLL APLVSKELYE IVMKHGERLE SVIDYYRDFD YDFFGFKTLE RSYLHRINGK
IVERPQHMLM RVSIGIHGED LESAINTYKR LSEKLFTHAT PTLFNAGTPS PQMSSCFLVQ
MKEDSIDGIY DTLKQCALIS KSAGGIGIAV HKIRAAQSYI RGTNGTSNGL VPMLRVFNDT
ARYVDQGGGK RKGAFAVYLE PWHADVFEFI DLKKNTGKEE MRARDLFYAL WVSDIFMERV
EQNGDWALFC PNEAPGLAET HSEEHRALYL KYEATPDLPR RVIKAQELWF AIMESQVETG
TPFILYKDAC NAKSNQKNLG TISSSNLCTE IIQYTSPDEI AVCNLASIAL PKFVRQKVGS
TDPKEKEFDH QFLFEITKLI TVNLNVIIDR NYYPVAEAKT SNLRHRPIGI GIQGLADVFI
KMRMPFDSVA AAKLNVEIAE TIYFAALTAS HELAIRDGTY ESFKGSPASK GILQFDMWNV
TPSSRWNWAE LKDNIVNKGG LRNSLLIAPM PTASTSQILG NNECFEPYTS NIYSRRVLAG
EFTIVNKQLL EDLMELGIWS PEMKNQIVAA RGSIQSIGGI PDDLKELYKT VWEIRQRTLI
DMAADRGAFI DQSQSFNVFI AEPTFAKLTS MHFYSWKKGL KTGMYYLRTR PAADAIQFTV
DPIVSQTPKP VENNINSTTP LKTPTKTPNS SNRISTSPTN NLTSPIRFNI TQQQQQQQQQ
QQQQNNNEDD LANYDGMTCR REEGCLVCGS
