RIR1_DANRE
ID RIR1_DANRE Reviewed; 794 AA.
AC P79732;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Ribonucleoside-diphosphate reductase large subunit;
DE EC=1.17.4.1;
DE AltName: Full=Ribonucleoside-diphosphate reductase subunit M1;
DE AltName: Full=Ribonucleotide reductase large subunit;
DE AltName: Full=Ribonucleotide reductase protein R1 class I;
GN Name=rrm1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8983196;
RA Mathews C.Z., Sjoeberg B.-M., Karlsson M.;
RT "Cloning and sequencing of cDNAs encoding ribonucleotide reductase from
RT zebrafish Danio rerio.";
RL Mol. Mar. Biol. Biotechnol. 5:284-287(1996).
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 M1 subunit. The type of nucleotide bound at
CC the specificity site determines substrate preference. It seems probable
CC that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction
CC and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP
CC binding to the activity site (By similarity). {ECO:0000250}.
CC -!- PATHWAY: Genetic information processing; DNA replication.
CC -!- SUBUNIT: Heterodimer of a large and a small subunit.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC chain family. {ECO:0000305}.
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DR EMBL; U57964; AAB37102.1; -; mRNA.
DR AlphaFoldDB; P79732; -.
DR SMR; P79732; -.
DR STRING; 7955.ENSDARP00000010800; -.
DR PaxDb; P79732; -.
DR ZFIN; ZDB-GENE-990415-247; rrm1.
DR eggNOG; KOG1112; Eukaryota.
DR InParanoid; P79732; -.
DR PhylomeDB; P79732; -.
DR Reactome; R-DRE-499943; Interconversion of nucleotide di- and triphosphates.
DR UniPathway; UPA00326; -.
DR PRO; PR:P79732; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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 2: Evidence at transcript level;
KW Allosteric enzyme; ATP-binding; Cytoplasm; Deoxyribonucleotide synthesis;
KW Disulfide bond; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..794
FT /note="Ribonucleoside-diphosphate reductase large subunit"
FT /id="PRO_0000187192"
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 604..607
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 737
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 738
FT /note="Important for electron transfer"
FT /evidence="ECO:0000250"
FT SITE 789
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT SITE 792
FT /note="Interacts with thioredoxin/glutaredoxin"
FT /evidence="ECO:0000250"
FT DISULFID 218..444
FT /note="Redox-active"
FT /evidence="ECO:0000250"
SQ SEQUENCE 794 AA; 89816 MW; 128355C073B3908C CRC64;
MHVIKRDGGQ EGVMFDKITS RIQKLCYGLN SDFVDPTQIT MKVIQGLYSG VTTVELDTLA
AETAATSTTK HPDYAILAAR IAVSNLHKET KKVFSEVMED LYNYVNPLNS RHSPMISKET
LDIVLANKDR LNSAIIYDRD FSYNFFGFKT LERSYLLKIN GKVAERPQHM LMRVSVGIHK
EDIAAAIETY NLLSEKWFTH ASPTLFNAGT NRPQLSSCFL LAMKDDSIEG IYDTLKQCAL
ISKSAGGIGV AVSCIRATGR YIAGTNGNSN GLVPMLRVNN NTARYVDQGG NKRPGAFAMY
LEPWHFDIFD FLELKKNTGK EEQRARDLFY ALWIPDLFMK RVETNGDWSL MCPNDCPGLD
ECWGEEFEKL YAKYEQEGRA KRVVKAQQLW YAIIESQTET GTPYMLYKDA CNRKSNRQNL
GTIKCSNLCT EIVEYTSADE VAVCNLASIA LNMYVTSERT FDFQKLASVT KVIVKNLNKI
IDINYYPVKE AENSNKRHRP IGIGVQGLAD AFILMRFPFE STEAQLLNTQ IFETIYYAAL
ESSCELAAEY GPYQTYAGCP VSKGILQYDM WEKTPTDLWD WAALKEKIAN DGVRNSLLLA
PMPTASTAQI LGNNESIEPY TSNIYHRRVL SGEFQIVNPH LLKDLTERGL WNEEMKNQII
AQNGSIQTIP AIPDDLKELY KTVWEISQKT ILKMAADRGA YIDQSQSLNI HIAEPNYGKL
TSMHFYGWKQ GLKTGMYYLR TKPGANPIQF TLNKEKLKET QKTTSSEDEE TKERNKAAMV
CSLENRHECL MCGS
