DNPH1_RAT
ID DNPH1_RAT Reviewed; 163 AA.
AC O35820;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=2'-deoxynucleoside 5'-phosphate N-hydrolase 1 {ECO:0000255|HAMAP-Rule:MF_03036};
DE EC=3.2.2.- {ECO:0000255|HAMAP-Rule:MF_03036, ECO:0000269|PubMed:17234634, ECO:0000269|PubMed:19822152, ECO:0000269|PubMed:24260472, ECO:0000269|PubMed:25108359};
DE AltName: Full=Deoxyribonucleoside 5'-monophosphate N-glycosidase;
DE AltName: Full=c-Myc-responsive protein Rcl {ECO:0000255|HAMAP-Rule:MF_03036};
GN Name=Dnph1; Synonyms=Rcl;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INDUCTION.
RC TISSUE=Liver;
RX PubMed=9271375; DOI=10.1128/mcb.17.9.4967;
RA Lewis B.C., Shim H., Li Q., Wu C.S., Lee L.A., Maity A., Dang C.V.;
RT "Identification of putative c-Myc-responsive genes: characterization of
RT rcl, a novel growth-related gene.";
RL Mol. Cell. Biol. 17:4967-4978(1997).
RN [2]
RP MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, HOMODIMERIZATION, SUBUNIT, CLEAVAGE OF
RP INITIATOR METHIONINE, AND MUTAGENESIS OF GLU-93.
RX PubMed=17234634; DOI=10.1074/jbc.m610648200;
RA Ghiorghi Y.K., Zeller K.I., Dang C.V., Kaminski P.A.;
RT "The c-Myc target gene Rcl (C6orf108) encodes a novel enzyme,
RT deoxynucleoside 5'-monophosphate N-glycosidase.";
RL J. Biol. Chem. 282:8150-8156(2007).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4]
RP STRUCTURE BY NMR IN COMPLEX WITH GMP, MUTAGENESIS OF TYR-13 AND GLU-93, AND
RP SUBUNIT.
RX PubMed=19720067; DOI=10.1016/j.jmb.2009.08.054;
RA Doddapaneni K., Mahler B., Pavlovicz R., Haushalter A., Yuan C., Wu Z.;
RT "Solution structure of RCL, a novel 2'-deoxyribonucleoside 5'-monophosphate
RT N-glycosidase.";
RL J. Mol. Biol. 394:423-434(2009).
RN [5]
RP STRUCTURE BY NMR OF 11-151 IN COMPLEX WITH THE SUBSTRATE GMP, SUBUNIT,
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=19822152; DOI=10.1016/j.jmb.2009.10.004;
RA Yang Y., Padilla A., Zhang C., Labesse G., Kaminski P.A.;
RT "Structural characterization of the mammalian deoxynucleotide N-hydrolase
RT Rcl and its stabilizing interactions with two inhibitors.";
RL J. Mol. Biol. 394:435-447(2009).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 11-151 IN COMPLEX WITH SUBSTRATE
RP ANALOGS.
RX PubMed=23385460; DOI=10.1107/s0907444912045039;
RA Padilla A., Amiable C., Pochet S., Kaminski P.A., Labesse G.;
RT "Structure of the oncoprotein Rcl bound to three nucleotide analogues.";
RL Acta Crystallogr. D 69:247-255(2013).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.69 ANGSTROMS) OF 11-151 IN COMPLEX WITH SUBSTRATE
RP ANALOGS, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24260472; DOI=10.1371/journal.pone.0080755;
RA Amiable C., Pochet S., Padilla A., Labesse G., Kaminski P.A.;
RT "N (6)-substituted AMPs inhibit mammalian deoxynucleotide N-hydrolase
RT DNPH1.";
RL PLoS ONE 8:E80755-E80755(2013).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 11-151 IN COMPLEX WITH THE
RP SUBSTRATE ANALOG
RP 6-(NAPHTHALEN-2-YL)-9-(5-O-PHOSPHONO-BETA-D-RIBOFURANOSYL)-9H-PURINE,
RP CATALYTIC ACTIVITY, FUNCTION, AND SUBUNIT.
RX PubMed=25108359; DOI=10.1016/j.ejmech.2014.07.110;
RA Amiable C., Paoletti J., Haouz A., Padilla A., Labesse G., Kaminski P.A.,
RA Pochet S.;
RT "6-(Hetero)Arylpurine nucleotides as inhibitors of the oncogenic target
RT DNPH1: Synthesis, structural studies and cytotoxic activities.";
RL Eur. J. Med. Chem. 85C:418-437(2014).
CC -!- FUNCTION: Catalyzes the cleavage of the N-glycosidic bond of
CC deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate
CC and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates
CC containing purine bases are preferred to those containing pyrimidine
CC bases. {ECO:0000255|HAMAP-Rule:MF_03036, ECO:0000269|PubMed:17234634,
CC ECO:0000269|PubMed:19822152, ECO:0000269|PubMed:24260472,
CC ECO:0000269|PubMed:25108359}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a pyrimidine 2'-deoxyribonucleoside 5'-phosphate + H2O = 2-
CC deoxy-D-ribose 5-phosphate + a pyrimidine nucleobase;
CC Xref=Rhea:RHEA:57852, ChEBI:CHEBI:15377, ChEBI:CHEBI:26432,
CC ChEBI:CHEBI:62877, ChEBI:CHEBI:142209; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03036, ECO:0000269|PubMed:17234634,
CC ECO:0000269|PubMed:19822152, ECO:0000269|PubMed:24260472,
CC ECO:0000269|PubMed:25108359};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a purine 2'-deoxyribonucleoside 5'-phosphate + H2O = 2-deoxy-
CC D-ribose 5-phosphate + a purine nucleobase; Xref=Rhea:RHEA:51132,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:26386, ChEBI:CHEBI:62877,
CC ChEBI:CHEBI:142198; Evidence={ECO:0000255|HAMAP-Rule:MF_03036,
CC ECO:0000269|PubMed:17234634, ECO:0000269|PubMed:19822152,
CC ECO:0000269|PubMed:24260472, ECO:0000269|PubMed:25108359};
CC -!- ACTIVITY REGULATION: Inhibited by zinc ions. Competitive inhibition of
CC dGMP hydrolysis by GMP and 6-methylthio-GMP.
CC {ECO:0000269|PubMed:17234634}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=48 uM for dGMP {ECO:0000269|PubMed:17234634};
CC KM=250 uM for dAMP {ECO:0000269|PubMed:17234634};
CC KM=450 uM for dIMP {ECO:0000269|PubMed:17234634};
CC KM=4 mM for dCMP {ECO:0000269|PubMed:17234634};
CC KM=15.6 mM for dUMP {ECO:0000269|PubMed:17234634};
CC Vmax=0.09 umol/min/mg enzyme toward dGMP
CC {ECO:0000269|PubMed:17234634};
CC pH dependence:
CC Optimum pH is 6.0 with dGMP or dCMP as substrate.
CC {ECO:0000269|PubMed:17234634};
CC -!- SUBUNIT: Monomer and homodimer. {ECO:0000255|HAMAP-Rule:MF_03036,
CC ECO:0000269|PubMed:17234634, ECO:0000269|PubMed:19720067,
CC ECO:0000269|PubMed:19822152, ECO:0000269|PubMed:25108359}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03036}.
CC Nucleus {ECO:0000255|HAMAP-Rule:MF_03036, ECO:0000269|PubMed:9271375}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, kidney, liver and
CC spleen. Weakly expressed in lung and skeletal muscle.
CC {ECO:0000269|PubMed:9271375}.
CC -!- INDUCTION: Up-regulated in response to c-Myc and by partial
CC hepatectomy. {ECO:0000269|PubMed:9271375}.
CC -!- MASS SPECTROMETRY: Mass=17649.54; Mass_error=0.92; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:17234634};
CC -!- SIMILARITY: Belongs to the 2'-deoxynucleoside 5'-phosphate N-hydrolase
CC 1 family. {ECO:0000255|HAMAP-Rule:MF_03036}.
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DR EMBL; U82591; AAB95314.1; -; mRNA.
DR RefSeq; NP_598209.1; NM_133525.1.
DR PDB; 2KHZ; NMR; -; A/B=1-163.
DR PDB; 2KLH; NMR; -; A/B=11-151.
DR PDB; 4FYH; X-ray; 2.44 A; A/B/C/D=11-151.
DR PDB; 4FYI; X-ray; 1.96 A; A/B/C/D=11-151.
DR PDB; 4FYK; X-ray; 1.79 A; A/B/C/D=11-151.
DR PDB; 4KXL; X-ray; 1.69 A; A/B/C/D=11-151.
DR PDB; 4KXM; X-ray; 2.24 A; A/B/C/D=11-151.
DR PDB; 4KXN; X-ray; 1.90 A; A/B/C/D=11-151.
DR PDB; 4P5D; X-ray; 2.11 A; A/C=11-151.
DR PDBsum; 2KHZ; -.
DR PDBsum; 2KLH; -.
DR PDBsum; 4FYH; -.
DR PDBsum; 4FYI; -.
DR PDBsum; 4FYK; -.
DR PDBsum; 4KXL; -.
DR PDBsum; 4KXM; -.
DR PDBsum; 4KXN; -.
DR PDBsum; 4P5D; -.
DR AlphaFoldDB; O35820; -.
DR BMRB; O35820; -.
DR SMR; O35820; -.
DR STRING; 10116.ENSRNOP00000024815; -.
DR BindingDB; O35820; -.
DR ChEMBL; CHEMBL3329079; -.
DR DrugCentral; O35820; -.
DR iPTMnet; O35820; -.
DR PhosphoSitePlus; O35820; -.
DR jPOST; O35820; -.
DR PaxDb; O35820; -.
DR PRIDE; O35820; -.
DR Ensembl; ENSRNOT00000024815; ENSRNOP00000024815; ENSRNOG00000018397.
DR GeneID; 171047; -.
DR KEGG; rno:171047; -.
DR UCSC; RGD:620382; rat.
DR CTD; 10591; -.
DR RGD; 620382; Dnph1.
DR eggNOG; ENOG502S2J2; Eukaryota.
DR GeneTree; ENSGT00390000001216; -.
DR HOGENOM; CLU_100069_0_0_1; -.
DR InParanoid; O35820; -.
DR OMA; MHIYFCG; -.
DR OrthoDB; 1533988at2759; -.
DR PhylomeDB; O35820; -.
DR TreeFam; TF329719; -.
DR Reactome; R-RNO-74259; Purine catabolism.
DR EvolutionaryTrace; O35820; -.
DR PRO; PR:O35820; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000018397; Expressed in pancreas and 19 other tissues.
DR Genevisible; O35820; RN.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0070694; F:deoxyribonucleoside 5'-monophosphate N-glycosidase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0000255; P:allantoin metabolic process; IDA:MGI.
DR GO; GO:0009159; P:deoxyribonucleoside monophosphate catabolic process; IDA:UniProtKB.
DR GO; GO:0046055; P:dGMP catabolic process; IDA:MGI.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR GO; GO:0009116; P:nucleoside metabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
DR HAMAP; MF_03036; Nuc_phosphate_hydrolase; 1.
DR InterPro; IPR028607; DNPH1.
DR InterPro; IPR007710; Nucleoside_deoxyribTrfase.
DR Pfam; PF05014; Nuc_deoxyrib_tr; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Glycosidase; Hydrolase;
KW Nucleotide metabolism; Nucleus; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O43598, ECO:0000255|HAMAP-
FT Rule:MF_03036, ECO:0000269|PubMed:17234634"
FT CHAIN 2..163
FT /note="2'-deoxynucleoside 5'-phosphate N-hydrolase 1"
FT /id="PRO_0000097202"
FT BINDING 13..19
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:19720067,
FT ECO:0000269|PubMed:19822152, ECO:0000269|PubMed:23385460,
FT ECO:0000269|PubMed:24260472, ECO:0000269|PubMed:25108359"
FT BINDING 28
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:19822152"
FT BINDING 45
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:19822152,
FT ECO:0000269|PubMed:24260472"
FT BINDING 93
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:19720067,
FT ECO:0000269|PubMed:19822152, ECO:0000269|PubMed:23385460,
FT ECO:0000269|PubMed:24260472, ECO:0000269|PubMed:25108359"
FT BINDING 117..119
FT /ligand="substrate"
FT /ligand_note="ligand shared between homodimeric partners"
FT /evidence="ECO:0000269|PubMed:19720067,
FT ECO:0000269|PubMed:19822152, ECO:0000269|PubMed:23385460,
FT ECO:0000269|PubMed:24260472, ECO:0000269|PubMed:25108359"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O43598"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43598"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43598"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43598"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 127
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43598"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43598"
FT MUTAGEN 13
FT /note="Y->A: 100-fold decrease binding affinity for GMP as
FT substrate."
FT /evidence="ECO:0000269|PubMed:19720067"
FT MUTAGEN 93
FT /note="E->A: 100-fold increase in Km and 170-fold decrease
FT in catalytic efficiency for dGMP as substrate."
FT /evidence="ECO:0000269|PubMed:17234634,
FT ECO:0000269|PubMed:19720067"
FT STRAND 11..15
FT /evidence="ECO:0007829|PDB:4KXL"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:2KLH"
FT HELIX 25..35
FT /evidence="ECO:0007829|PDB:4KXL"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:4KXL"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:4KXL"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:4KXL"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:2KHZ"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4KXL"
FT HELIX 62..75
FT /evidence="ECO:0007829|PDB:4KXL"
FT STRAND 77..82
FT /evidence="ECO:0007829|PDB:4KXL"
FT HELIX 88..100
FT /evidence="ECO:0007829|PDB:4KXL"
FT STRAND 104..108
FT /evidence="ECO:0007829|PDB:4KXL"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:4KXL"
FT HELIX 118..121
FT /evidence="ECO:0007829|PDB:4KXL"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:4KXL"
FT STRAND 129..133
FT /evidence="ECO:0007829|PDB:4KXL"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:4P5D"
FT HELIX 139..150
FT /evidence="ECO:0007829|PDB:4KXL"
SQ SEQUENCE 163 AA; 17781 MW; C670D4213F96D883 CRC64;
MAASGEQAPC SVYFCGSIRG GREDQALYAR IVSRLRRYGK VLTEHVADAE LEPLGEEAAG
GDQFIHEQDL NWLQQADVVV AEVTQPSLGV GYELGRAVAL GKPILCLFRP QSGRVLSAMI
RGAADGSRFQ VWDYAEGEVE TMLDRYFEAY LPQKTASSSH PSA
