ID   RIR1_PONAB              Reviewed;         792 AA.
AC   Q5R919;
DT   12-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   27-MAR-2024, entry version 81.
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;
GN   Name=RRM1;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Heart;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 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, the dATP inhibition is mediated by AHCYL1
CC       which stabilizes dATP in the site (By similarity).
CC       {ECO:0000250|UniProtKB:P23921}.
CC   -!- SUBUNIT: Heterodimer of a large and a small subunit. Interacts with
CC       RRM2B. Interacts with AHCYL1 which inhibits its activity (By
CC       similarity). {ECO:0000250|UniProtKB:P23921}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- MISCELLANEOUS: Two distinct regulatory sites have been defined: the
CC       specificity site, which controls substrate specificity, and the
CC       activity site which regulates overall catalytic activity. A substrate-
CC       binding catalytic site, located on M1, is formed only in the presence
CC       of the second subunit M2 (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large
CC       chain family. {ECO:0000305}.
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DR   EMBL; CR859577; CAH91741.1; -; mRNA.
DR   RefSeq; NP_001126012.1; NM_001132540.2.
DR   AlphaFoldDB; Q5R919; -.
DR   SMR; Q5R919; -.
DR   STRING; 9601.ENSPPYP00000004146; -.
DR   GeneID; 100172956; -.
DR   KEGG; pon:100172956; -.
DR   CTD; 6240; -.
DR   eggNOG; KOG1112; Eukaryota.
DR   InParanoid; Q5R919; -.
DR   OrthoDB; 5472715at2759; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:InterPro.
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   2: Evidence at transcript level;
KW   Acetylation; Allosteric enzyme; ATP-binding; Cytoplasm;
KW   Deoxyribonucleotide synthesis; Disulfide bond; Nucleotide-binding;
KW   Oxidoreductase; Phosphoprotein; Reference proteome.
FT   CHAIN           1..792
FT                   /note="Ribonucleoside-diphosphate reductase large subunit"
FT                   /id="PRO_0000290352"
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         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            787
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000250"
FT   SITE            790
FT                   /note="Interacts with thioredoxin/glutaredoxin"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         17
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   MOD_RES         376
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   MOD_RES         751
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P23921"
FT   DISULFID        218..444
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   792 AA;  90027 MW;  93AC48CB6CEEC044 CRC64;
     MHVIKRDGRQ ERVMFDKITS RIQKLCYGLN MDFVDPAQIT MKVIQGLYSG VTTVELDTLA
     AETAATLTTK HPDYAILAAR IAVSNLHKEA KKVFSDVMED LYNYINPHNG KHSPMVAKST
     LDIVLANKDR LNSAIIYDRD FSYNYFGFKT LERSYLLKIN GKVAERPQHM LMRVSVGIHK
     EDIDAAIETY NLLSERWFTH ASPTLFNAGT NRPQLSSCFL LSMKDDSIEG IYDTLKQCAL
     ISKSAGGIGV AVSCIRATGS YIAGTNGNSN GLVPMLRVYN NTARYVDQGG NKRPGAFAIY
     LEPWHLDIFE FLDLKKNTGK EEQRARDLFF ALWIPDLFMK RVETNQDWSL MCPNECPGLD
     EVWGEEFEKL YASYEKQGRV RKVVKAQQLW YAIIESQTET GTPYMLYKDS CNRKSNQQNL
     GTIKCSSLCT EIVEYTSKDE VAVCNLASLA LNMYVTSEHT YDFKKLAEVT KVVVRNLNKI
     IDINYYPVPE ACLSNKRHRP IGIGVQGLAD AFILMRYPFE SAEAQLLNKQ IFETIYYGAL
     EASCDLAKEQ GPYETYEGSP VSKGILQYDM WNVTPTDLWD WKLLKEKIAK YGIRNSLLIA
     PMPTASTAQI LGNNESIEPY TSNIYTRRVL SGEFQIVNPH LLKDLTERGL WHEEMKNQII
     ACNGSIQSIP EIPDDLKQLY KTVWEISQKT VLKMAAERGA FIDQSQSLNI HIAEPNYGKL
     TSMHFYGWKQ GLKTGMYYLR TRPAANPIQF TLNKEKLKDK EKVSKEEEEK ERNTAAMVCS
     LENRDECLMC GS
//