RIR1_PONAB
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 03-AUG-2022, entry version 75.
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 -!- PATHWAY: Genetic information processing; DNA replication.
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; 156716at2759; -.
DR UniPathway; UPA00326; -.
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: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 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
