ID RIR1_HUMAN Reviewed; 792 AA. AC P23921; Q9UNN2; DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-1992, sequence version 1. DT 27-MAR-2024, entry version 220. 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; Synonyms=RR1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Bone marrow; RX PubMed=1840662; DOI=10.1093/nar/19.13.3741; RA Parker N.J., Begley C.G., Fox R.M.; RT "Human M1 subunit of ribonucleotide reductase: cDNA sequence and expression RT in stimulated lymphocytes."; RL Nucleic Acids Res. 19:3741-3741(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Mammary carcinoma; RX PubMed=1627826; DOI=10.3109/10425179209020807; RA Pavloff N., Rivard D., Masson S., Shen S.-H., Mes-Masson A.-M.; RT "Sequence analysis of the large and small subunits of human ribonucleotide RT reductase."; RL DNA Seq. 2:227-234(1992). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9933563; DOI=10.1006/geno.1998.5659; RA Bepler G., O'Briant K.C., Kim Y.-C., Schreiber G., Pitterle D.M.; RT "A 1.4-Mb high-resolution physical map and contig of chromosome segment RT 11p15.5 and genes in the LOH11A metastasis suppressor region."; RL Genomics 55:164-175(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6. RC TISSUE=Placenta; RX PubMed=8188248; DOI=10.1006/geno.1994.1017; RA Parker N.J., Begley C.G., Fox R.M.; RT "Human R1 subunit of ribonucleotide reductase (RRM1): 5' flanking region of RT the gene."; RL Genomics 19:91-96(1994). RN [6] RP ACTIVITY REGULATION. RX PubMed=1867633; DOI=10.1016/0006-2952(91)90033-2; RA Harrington J.A., Spector T.; RT "Human ribonucleotide reductase. Activation and inhibition by analogs of RT ATP."; RL Biochem. Pharmacol. 42:759-763(1991). RN [7] RP INTERACTION WITH RRM2B. RX PubMed=12615712; RA Xue L., Zhou B., Liu X., Qiu W., Jin Z., Yen Y.; RT "Wild-type p53 regulates human ribonucleotide reductase by protein-protein RT interaction with p53R2 as well as hRRM2 subunits."; RL Cancer Res. 63:980-986(2003). RN [8] RP CATALYTIC ACTIVITY, SUBUNIT, AND ACTIVITY REGULATION. RX PubMed=16376858; DOI=10.1016/j.bbrc.2005.12.019; RA Qiu W., Zhou B., Darwish D., Shao J., Yen Y.; RT "Characterization of enzymatic properties of human ribonucleotide reductase RT holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits."; RL Biochem. Biophys. Res. Commun. 340:428-434(2006). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-17 AND LYS-376, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-751, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP ACTIVITY REGULATION, MUTAGENESIS OF ASP-57, AND INTERACTION WITH AHCYL1. RX PubMed=25237103; DOI=10.1126/science.1251550; RA Arnaoutov A., Dasso M.; RT "Enzyme regulation. IRBIT is a novel regulator of ribonucleotide reductase RT in higher eukaryotes."; RL Science 345:1512-1515(2014). RN [13] {ECO:0007744|PDB:2WGH, ECO:0007744|PDB:3HNC, ECO:0007744|PDB:3HND, ECO:0007744|PDB:3HNE, ECO:0007744|PDB:3HNF} RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 75-742 IN COMPLEX WITH ALLOSTERIC RP EFFECTORS ATP; DATP; DTTP; SUBSTRATE GDP AND MAGNESIUM IONS. RX PubMed=21336276; DOI=10.1038/nsmb.2007; RA Fairman J.W., Wijerathna S.R., Ahmad M.F., Xu H., Nakano R., Jha S., RA Prendergast J., Welin R.M., Flodin S., Roos A., Nordlund P., Li Z., RA Walz T., Dealwis C.G.; RT "Structural basis for allosteric regulation of human ribonucleotide RT reductase by nucleotide-induced oligomerization."; RL Nat. Struct. Mol. Biol. 18:316-322(2011). 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 Evidence={ECO:0000269|PubMed:16376858}; 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. {ECO:0000269|PubMed:16376858, CC ECO:0000269|PubMed:1867633, ECO:0000269|PubMed:25237103}. CC -!- SUBUNIT: Heterodimer of a large and a small subunit. Heterodimer with CC small subunit RRM2 or RRM2B. The heterodimer with RRM2 has higher CC catalytic activity than the heterodimer with RRM2B. Interacts with CC AHCYL1 which inhibits its activity. {ECO:0000269|PubMed:16376858, CC ECO:0000269|PubMed:21336276, ECO:0000269|PubMed:25237103}. CC -!- INTERACTION: CC P23921; P23921: RRM1; NbExp=5; IntAct=EBI-717006, EBI-717006; CC P23921; P31350: RRM2; NbExp=6; IntAct=EBI-717006, EBI-2339245; CC P23921; Q8N720: ZNF655; NbExp=3; IntAct=EBI-717006, EBI-625509; CC -!- SUBCELLULAR LOCATION: Cytoplasm. 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. CC -!- MISCELLANEOUS: The level of the enzyme activity is closely correlated CC with the growth rate of a cell and appears to vary with the cell cycle. CC -!- SIMILARITY: Belongs to the ribonucleoside diphosphate reductase large CC chain family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ribonucleotide reductase entry; CC URL="https://en.wikipedia.org/wiki/Ribonucleotide_reductase"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42174/RRM1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X59543; CAA42118.1; -; mRNA. DR EMBL; X59617; CAA42180.1; -; mRNA. DR EMBL; AF107045; AAD37491.1; -; Genomic_DNA. DR EMBL; BC006498; AAH06498.1; -; mRNA. DR EMBL; L10342; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS7750.1; -. DR PIR; S16680; S16680. DR RefSeq; NP_001024.1; NM_001033.4. DR RefSeq; NP_001304993.1; NM_001318064.1. DR RefSeq; NP_001304994.1; NM_001318065.1. DR PDB; 2WGH; X-ray; 2.30 A; A/B=75-742. DR PDB; 3HNC; X-ray; 2.41 A; A/B=1-792. DR PDB; 3HND; X-ray; 3.21 A; A/B=1-792. DR PDB; 3HNE; X-ray; 3.11 A; A/B=1-792. DR PDB; 3HNF; X-ray; 3.16 A; A/B=1-792. DR PDB; 4X3V; X-ray; 3.70 A; A/B=1-792. DR PDB; 5D1Y; X-ray; 9.01 A; A/B=1-792. DR PDB; 5TUS; X-ray; 2.66 A; A/B=1-792. DR PDB; 6AUI; EM; 3.30 A; A/B/C/D/E/F=1-792. DR PDB; 6L3R; X-ray; 2.00 A; A/E=75-742. DR PDB; 6L7L; X-ray; 2.17 A; A/E=75-742. DR PDB; 6LKM; X-ray; 2.55 A; A/B=75-742. DR PDBsum; 2WGH; -. DR PDBsum; 3HNC; -. DR PDBsum; 3HND; -. DR PDBsum; 3HNE; -. DR PDBsum; 3HNF; -. DR PDBsum; 4X3V; -. DR PDBsum; 5D1Y; -. DR PDBsum; 5TUS; -. DR PDBsum; 6AUI; -. DR PDBsum; 6L3R; -. DR PDBsum; 6L7L; -. DR PDBsum; 6LKM; -. DR AlphaFoldDB; P23921; -. DR EMDB; EMD-7006; -. DR SMR; P23921; -. DR BioGRID; 112154; 141. DR ComplexPortal; CPX-2194; Ribonucleoside-diphosphate reductase RR1 complex, RRM2 variant. DR ComplexPortal; CPX-369; Ribonucleoside-diphosphate reductase RR1 complex, RRM2B variant. DR DIP; DIP-24233N; -. DR IntAct; P23921; 30. DR MINT; P23921; -. DR STRING; 9606.ENSP00000300738; -. DR BindingDB; P23921; -. DR ChEMBL; CHEMBL1830; -. DR DrugBank; DB00242; Cladribine. DR DrugBank; DB00631; Clofarabine. DR DrugBank; DB01073; Fludarabine. DR DrugBank; DB05420; Gallium maltolate. DR DrugBank; DB00441; Gemcitabine. DR DrugBank; DB01005; Hydroxyurea. DR DrugBank; DB05003; Imexon. DR DrugBank; DB06433; Tezacitabine. DR DrugCentral; P23921; -. DR GuidetoPHARMACOLOGY; 2630; -. DR GlyCosmos; P23921; 4 sites, 1 glycan. DR GlyGen; P23921; 6 sites, 1 O-linked glycan (6 sites). DR iPTMnet; P23921; -. DR MetOSite; P23921; -. DR PhosphoSitePlus; P23921; -. DR SwissPalm; P23921; -. DR BioMuta; RRM1; -. DR DMDM; 132608; -. DR EPD; P23921; -. DR jPOST; P23921; -. DR MassIVE; P23921; -. DR MaxQB; P23921; -. DR PaxDb; 9606-ENSP00000300738; -. DR PeptideAtlas; P23921; -. DR ProteomicsDB; 54166; -. DR Pumba; P23921; -. DR Antibodypedia; 10853; 767 antibodies from 38 providers. DR DNASU; 6240; -. DR Ensembl; ENST00000300738.10; ENSP00000300738.5; ENSG00000167325.15. DR GeneID; 6240; -. DR KEGG; hsa:6240; -. DR MANE-Select; ENST00000300738.10; ENSP00000300738.5; NM_001033.5; NP_001024.1. DR UCSC; uc001lyw.5; human. DR AGR; HGNC:10451; -. DR CTD; 6240; -. DR DisGeNET; 6240; -. DR GeneCards; RRM1; -. DR HGNC; HGNC:10451; RRM1. DR HPA; ENSG00000167325; Low tissue specificity. DR MIM; 180410; gene. DR neXtProt; NX_P23921; -. DR OpenTargets; ENSG00000167325; -. DR PharmGKB; PA298; -. DR VEuPathDB; HostDB:ENSG00000167325; -. DR eggNOG; KOG1112; Eukaryota. DR GeneTree; ENSGT00910000144246; -. DR HOGENOM; CLU_000404_1_0_1; -. DR InParanoid; P23921; -. DR OMA; QMSSCYL; -. DR OrthoDB; 5472715at2759; -. DR PhylomeDB; P23921; -. DR TreeFam; TF300578; -. DR BioCyc; MetaCyc:HS09541-MONOMER; -. DR BRENDA; 1.17.4.1; 2681. DR PathwayCommons; P23921; -. DR Reactome; R-HSA-499943; Interconversion of nucleotide di- and triphosphates. DR SignaLink; P23921; -. DR SIGNOR; P23921; -. DR BioGRID-ORCS; 6240; 845 hits in 1174 CRISPR screens. DR ChiTaRS; RRM1; human. DR EvolutionaryTrace; P23921; -. DR GeneWiki; RRM1; -. DR GenomeRNAi; 6240; -. DR Pharos; P23921; Tclin. DR PRO; PR:P23921; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P23921; Protein. DR Bgee; ENSG00000167325; Expressed in ventricular zone and 217 other cell types or tissues. DR ExpressionAtlas; P23921; baseline and differential. DR GO; GO:0042995; C:cell projection; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IEA:GOC. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005635; C:nuclear envelope; IEA:Ensembl. DR GO; GO:0005971; C:ribonucleoside-diphosphate reductase complex; IPI:ComplexPortal. DR GO; GO:0005524; F:ATP binding; IBA:GO_Central. DR GO; GO:0097718; F:disordered domain specific binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0061731; F:ribonucleoside-diphosphate reductase activity; IMP:CACAO. DR GO; GO:0004748; F:ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor; ISS:UniProtKB. DR GO; GO:0009265; P:2'-deoxyribonucleotide biosynthetic process; IDA:ComplexPortal. DR GO; GO:0021846; P:cell proliferation in forebrain; IEA:Ensembl. DR GO; GO:0009263; P:deoxyribonucleotide biosynthetic process; ISS:UniProtKB. DR GO; GO:0006281; P:DNA repair; IDA:ComplexPortal. DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; NAS:ComplexPortal. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0006264; P:mitochondrial DNA replication; IMP:ComplexPortal. DR GO; GO:0070318; P:positive regulation of G0 to G1 transition; IDA:ComplexPortal. DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IDA:ComplexPortal. DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IDA:ComplexPortal. DR GO; GO:0051290; P:protein heterotetramerization; IEA:Ensembl. DR GO; GO:0006206; P:pyrimidine nucleobase metabolic process; IEA:Ensembl. DR GO; GO:0010212; P:response to ionizing radiation; IEA:Ensembl. DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl. DR GO; GO:0009185; P:ribonucleoside diphosphate metabolic process; IDA:ComplexPortal. 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. DR Genevisible; P23921; HS. PE 1: Evidence at protein level; KW 3D-structure; 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_0000187190" 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:0007744|PDB:3HNE" FT BINDING 11..17 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="allosteric activator" FT /evidence="ECO:0007744|PDB:3HNE" FT BINDING 53 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="allosteric activator" FT /evidence="ECO:0007744|PDB:3HNE" FT BINDING 57 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /ligand_note="allosteric activator" FT /evidence="ECO:0007744|PDB:3HNE" FT BINDING 202 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0007744|PDB:3HND" FT BINDING 217 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0007744|PDB:3HND" 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:0007744|PDB:3HNE" 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:0007744|PDB:3HNE" 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:0007744|PDB:3HNE" 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:0007744|PDB:3HNE" FT BINDING 427 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0007744|PDB:3HND" FT BINDING 431 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0007744|PDB:3HND" FT BINDING 604..607 FT /ligand="GDP" FT /ligand_id="ChEBI:CHEBI:58189" FT /evidence="ECO:0007744|PDB:3HND" 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:0007744|PubMed:19608861" FT MOD_RES 376 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 751 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT DISULFID 218..444 FT /note="Redox-active" FT /evidence="ECO:0000250" FT VARIANT 590 FT /note="K -> Q (in dbSNP:rs2228123)" FT /id="VAR_052052" FT VARIANT 778 FT /note="V -> A (in dbSNP:rs2229196)" FT /id="VAR_052053" FT MUTAGEN 57 FT /note="D->N: Severely decreases interaction with AHCYL1 in FT the presence of dATP." FT /evidence="ECO:0000269|PubMed:25237103" FT CONFLICT 6 FT /note="R -> Q (in Ref. 3; AAD37491)" FT /evidence="ECO:0000305" FT STRAND 2..4 FT /evidence="ECO:0007829|PDB:3HNC" FT TURN 6..8 FT /evidence="ECO:0007829|PDB:6AUI" FT STRAND 10..12 FT /evidence="ECO:0007829|PDB:3HNC" FT HELIX 15..23 FT /evidence="ECO:0007829|PDB:3HNC" FT HELIX 24..26 FT /evidence="ECO:0007829|PDB:6AUI" FT TURN 31..33 FT /evidence="ECO:0007829|PDB:3HNC" FT HELIX 36..44 FT /evidence="ECO:0007829|PDB:3HNC" FT STRAND 48..50 FT /evidence="ECO:0007829|PDB:3HND" FT HELIX 53..66 FT /evidence="ECO:0007829|PDB:3HNC" FT HELIX 67..69 FT /evidence="ECO:0007829|PDB:3HNC" FT HELIX 76..88 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 94..103 FT /evidence="ECO:0007829|PDB:6L3R" FT TURN 107..109 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 118..126 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 128..134 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 137..142 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 145..154 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 158..163 FT /evidence="ECO:0007829|PDB:3HNF" FT HELIX 167..179 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 183..194 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 197..200 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 202..207 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 210..212 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 218..222 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 228..243 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 247..251 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 258..261 FT /evidence="ECO:0007829|PDB:3HNE" FT TURN 263..266 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 268..270 FT /evidence="ECO:0007829|PDB:3HNE" FT HELIX 272..285 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 286..288 FT /evidence="ECO:0007829|PDB:6AUI" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:6LKM" FT STRAND 297..301 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 308..311 FT /evidence="ECO:0007829|PDB:6L3R" FT TURN 312..315 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 317..319 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 321..323 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 328..334 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 336..343 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 347..351 FT /evidence="ECO:0007829|PDB:6L3R" FT TURN 353..355 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 359..361 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 364..376 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 381..385 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 386..400 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 404..407 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 408..413 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 418..420 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 428..430 FT /evidence="ECO:0007829|PDB:3HNC" FT STRAND 442..444 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 446..450 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 451..454 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 459..461 FT /evidence="ECO:0007829|PDB:3HND" FT HELIX 463..483 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 489..498 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 502..506 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 508..514 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 519..521 FT /evidence="ECO:0007829|PDB:6LKM" FT HELIX 522..550 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 554..556 FT /evidence="ECO:0007829|PDB:3HNE" FT HELIX 561..563 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 567..570 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 577..579 FT /evidence="ECO:0007829|PDB:2WGH" FT HELIX 581..591 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 605..611 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 615..618 FT /evidence="ECO:0007829|PDB:6AUI" FT STRAND 623..625 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 632..637 FT /evidence="ECO:0007829|PDB:3HNC" FT HELIX 639..647 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 655..661 FT /evidence="ECO:0007829|PDB:6L3R" FT TURN 662..664 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 666..668 FT /evidence="ECO:0007829|PDB:6AUI" FT STRAND 670..672 FT /evidence="ECO:0007829|PDB:6L7L" FT HELIX 674..679 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 683..685 FT /evidence="ECO:0007829|PDB:6L3R" FT HELIX 688..699 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 709..711 FT /evidence="ECO:0007829|PDB:6AUI" FT HELIX 717..729 FT /evidence="ECO:0007829|PDB:6L3R" FT STRAND 733..737 FT /evidence="ECO:0007829|PDB:6L3R" SQ SEQUENCE 792 AA; 90070 MW; 4470A76C61E8F86A CRC64; MHVIKRDGRQ ERVMFDKITS RIQKLCYGLN MDFVDPAQIT MKVIQGLYSG VTTVELDTLA AETAATLTTK HPDYAILAAR IAVSNLHKET 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 GTIKCSNLCT EIVEYTSKDE VAVCNLASLA LNMYVTSEHT YDFKKLAEVT KVVVRNLNKI IDINYYPVPE ACLSNKRHRP IGIGVQGLAD AFILMRYPFE SAEAQLLNKQ IFETIYYGAL EASCDLAKEQ GPYETYEGSP VSKGILQYDM WNVTPTDLWD WKVLKEKIAK YGIRNSLLIA PMPTASTAQI LGNNESIEPY TSNIYTRRVL SGEFQIVNPH LLKDLTERGL WHEEMKNQII ACNGSIQSIP EIPDDLKQLY KTVWEISQKT VLKMAAERGA FIDQSQSLNI HIAEPNYGKL TSMHFYGWKQ GLKTGMYYLR TRPAANPIQF TLNKEKLKDK EKVSKEEEEK ERNTAAMVCS LENRDECLMC GS //