NT5M_HUMAN
ID NT5M_HUMAN Reviewed; 228 AA.
AC Q9NPB1;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=5'(3')-deoxyribonucleotidase, mitochondrial;
DE Short=5',3'-nucleotidase, mitochondrial;
DE EC=3.1.3.-;
DE AltName: Full=Deoxy-5'-nucleotidase 2;
DE Short=dNT-2;
DE Flags: Precursor;
GN Name=NT5M; Synonyms=DNT2;
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 [GENOMIC DNA / MRNA], FUNCTION, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Muscle;
RX PubMed=10899995; DOI=10.1073/pnas.97.15.8239;
RA Rampazzo C., Gallinaro L., Milanesi E., Frigimelica E., Reichard P.,
RA Bianchi V.;
RT "A deoxyribonucleotidase in mitochondria: involvement in regulation of dNTP
RT pools and possible link to genetic disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8239-8244(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
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 [3]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 34-227 IN COMPLEX WITH MAGNESIUM
RP AND A SUBSTRATE ANALOG.
RX PubMed=12352955; DOI=10.1038/nsb846;
RA Rinaldo-Matthis A., Rampazzo C., Reichard P., Bianchi V., Nordlund P.;
RT "Crystal structure of a human mitochondrial deoxyribonucleotidase.";
RL Nat. Struct. Biol. 9:779-787(2002).
CC -!- FUNCTION: Dephosphorylates specifically the 5' and 2'(3')-phosphates of
CC uracil and thymine deoxyribonucleotides, and so protects mitochondrial
CC DNA replication from excess dTTP. Has only marginal activity towards
CC dIMP and dGMP. {ECO:0000269|PubMed:10899995}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:12352955}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10899995}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, brain and skeletal
CC muscle. Detected at very low levels in kidney and pancreas.
CC {ECO:0000269|PubMed:10899995}.
CC -!- SIMILARITY: Belongs to the 5'(3')-deoxyribonucleotidase family.
CC {ECO:0000305}.
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DR EMBL; AJ277557; CAB99251.1; -; Genomic_DNA.
DR EMBL; AF210652; AAF87076.1; -; mRNA.
DR EMBL; BC035838; AAH35838.1; -; mRNA.
DR CCDS; CCDS32581.1; -.
DR RefSeq; NP_064586.1; NM_020201.3.
DR PDB; 1MH9; X-ray; 1.80 A; A=32-228.
DR PDB; 1Q91; X-ray; 1.60 A; A=32-228.
DR PDB; 1Q92; X-ray; 1.40 A; A=32-228.
DR PDB; 1Z4I; X-ray; 1.98 A; A=32-228.
DR PDB; 1Z4J; X-ray; 1.80 A; A=32-228.
DR PDB; 1Z4K; X-ray; 1.75 A; A=32-228.
DR PDB; 1Z4L; X-ray; 1.80 A; A=32-228.
DR PDB; 1Z4M; X-ray; 1.70 A; A=32-228.
DR PDB; 1Z4P; X-ray; 2.00 A; X=32-228.
DR PDB; 1Z4Q; X-ray; 2.05 A; A=32-228.
DR PDB; 2JAU; X-ray; 1.80 A; A=32-228.
DR PDB; 2JAW; X-ray; 1.95 A; A=32-228.
DR PDB; 4L6A; X-ray; 1.40 A; A=32-228.
DR PDB; 4L6C; X-ray; 1.80 A; A=32-228.
DR PDB; 4MUM; X-ray; 1.27 A; A=32-227.
DR PDB; 4MWO; X-ray; 1.67 A; A=32-227.
DR PDB; 4NFL; X-ray; 1.38 A; A=32-227.
DR PDB; 4YIK; X-ray; 1.48 A; A=32-227.
DR PDB; 6G22; X-ray; 1.85 A; A=32-228.
DR PDB; 6G2L; X-ray; 1.48 A; A=32-228.
DR PDB; 6G2M; X-ray; 1.37 A; A=32-228.
DR PDBsum; 1MH9; -.
DR PDBsum; 1Q91; -.
DR PDBsum; 1Q92; -.
DR PDBsum; 1Z4I; -.
DR PDBsum; 1Z4J; -.
DR PDBsum; 1Z4K; -.
DR PDBsum; 1Z4L; -.
DR PDBsum; 1Z4M; -.
DR PDBsum; 1Z4P; -.
DR PDBsum; 1Z4Q; -.
DR PDBsum; 2JAU; -.
DR PDBsum; 2JAW; -.
DR PDBsum; 4L6A; -.
DR PDBsum; 4L6C; -.
DR PDBsum; 4MUM; -.
DR PDBsum; 4MWO; -.
DR PDBsum; 4NFL; -.
DR PDBsum; 4YIK; -.
DR PDBsum; 6G22; -.
DR PDBsum; 6G2L; -.
DR PDBsum; 6G2M; -.
DR AlphaFoldDB; Q9NPB1; -.
DR SMR; Q9NPB1; -.
DR BioGRID; 121277; 8.
DR IntAct; Q9NPB1; 1.
DR STRING; 9606.ENSP00000373674; -.
DR ChEMBL; CHEMBL3751654; -.
DR DrugBank; DB04672; Cyclic 3',5'-thymidine monophosphate.
DR DrugBank; DB02217; Dpb-T.
DR DEPOD; NT5M; -.
DR iPTMnet; Q9NPB1; -.
DR PhosphoSitePlus; Q9NPB1; -.
DR BioMuta; NT5M; -.
DR DMDM; 38258255; -.
DR jPOST; Q9NPB1; -.
DR MassIVE; Q9NPB1; -.
DR PaxDb; Q9NPB1; -.
DR PeptideAtlas; Q9NPB1; -.
DR PRIDE; Q9NPB1; -.
DR Antibodypedia; 25442; 94 antibodies from 20 providers.
DR DNASU; 56953; -.
DR Ensembl; ENST00000389022.9; ENSP00000373674.4; ENSG00000205309.14.
DR GeneID; 56953; -.
DR KEGG; hsa:56953; -.
DR MANE-Select; ENST00000389022.9; ENSP00000373674.4; NM_020201.4; NP_064586.1.
DR UCSC; uc002grf.4; human.
DR CTD; 56953; -.
DR DisGeNET; 56953; -.
DR GeneCards; NT5M; -.
DR HGNC; HGNC:15769; NT5M.
DR HPA; ENSG00000205309; Tissue enhanced (skeletal).
DR MIM; 605292; gene.
DR neXtProt; NX_Q9NPB1; -.
DR OpenTargets; ENSG00000205309; -.
DR PharmGKB; PA31805; -.
DR VEuPathDB; HostDB:ENSG00000205309; -.
DR eggNOG; ENOG502QPWJ; Eukaryota.
DR GeneTree; ENSGT00390000011596; -.
DR HOGENOM; CLU_100259_0_0_1; -.
DR OrthoDB; 1316201at2759; -.
DR PhylomeDB; Q9NPB1; -.
DR TreeFam; TF331117; -.
DR PathwayCommons; Q9NPB1; -.
DR Reactome; R-HSA-73621; Pyrimidine catabolism.
DR SABIO-RK; Q9NPB1; -.
DR SignaLink; Q9NPB1; -.
DR BioGRID-ORCS; 56953; 16 hits in 1080 CRISPR screens.
DR EvolutionaryTrace; Q9NPB1; -.
DR GenomeRNAi; 56953; -.
DR Pharos; Q9NPB1; Tchem.
DR PRO; PR:Q9NPB1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9NPB1; protein.
DR Bgee; ENSG00000205309; Expressed in monocyte and 99 other tissues.
DR ExpressionAtlas; Q9NPB1; baseline and differential.
DR Genevisible; Q9NPB1; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; TAS:ProtInc.
DR GO; GO:0008253; F:5'-nucleotidase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008252; F:nucleotidase activity; TAS:ProtInc.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; TAS:ProtInc.
DR GO; GO:0046079; P:dUMP catabolic process; IEA:Ensembl.
DR GO; GO:0009223; P:pyrimidine deoxyribonucleotide catabolic process; IBA:GO_Central.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR010708; 5'(3')-deoxyribonucleotidase.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR Pfam; PF06941; NT5C; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Magnesium; Metal-binding; Mitochondrion;
KW Nucleotide metabolism; Nucleotide-binding; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..31
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 32..228
FT /note="5'(3')-deoxyribonucleotidase, mitochondrial"
FT /id="PRO_0000000011"
FT ACT_SITE 41
FT /note="Nucleophile"
FT ACT_SITE 43
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT BINDING 41
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:12352955"
FT BINDING 43
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:12352955"
FT BINDING 43
FT /ligand="substrate"
FT BINDING 49
FT /ligand="substrate"
FT BINDING 75
FT /ligand="substrate"
FT BINDING 76
FT /ligand="substrate"
FT BINDING 77
FT /ligand="substrate"
FT BINDING 96
FT /ligand="substrate"
FT BINDING 130
FT /ligand="substrate"
FT BINDING 165
FT /ligand="substrate"
FT BINDING 176
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:12352955"
FT STRAND 36..40
FT /evidence="ECO:0007829|PDB:4MUM"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:4MUM"
FT HELIX 49..60
FT /evidence="ECO:0007829|PDB:4MUM"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:4MUM"
FT HELIX 77..84
FT /evidence="ECO:0007829|PDB:4MUM"
FT HELIX 88..96
FT /evidence="ECO:0007829|PDB:4MUM"
FT TURN 99..104
FT /evidence="ECO:0007829|PDB:4MUM"
FT HELIX 111..120
FT /evidence="ECO:0007829|PDB:4MUM"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:4MUM"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:6G2M"
FT HELIX 139..151
FT /evidence="ECO:0007829|PDB:4MUM"
FT HELIX 153..158
FT /evidence="ECO:0007829|PDB:4MUM"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:4MUM"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:4MUM"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:4MUM"
FT STRAND 188..194
FT /evidence="ECO:0007829|PDB:4MUM"
FT TURN 197..201
FT /evidence="ECO:0007829|PDB:4MUM"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:4MUM"
FT HELIX 218..223
FT /evidence="ECO:0007829|PDB:4MUM"
SQ SEQUENCE 228 AA; 25862 MW; 9AE6F57B16977F0F CRC64;
MIRLGGWCAR RLCSAAVPAG RRGAAGGLGL AGGRALRVLV DMDGVLADFE GGFLRKFRAR
FPDQPFIALE DRRGFWVSEQ YGRLRPGLSE KAISIWESKN FFFELEPLPG AVEAVKEMAS
LQNTDVFICT SPIKMFKYCP YEKYAWVEKY FGPDFLEQIV LTRDKTVVSA DLLIDDRPDI
TGAEPTPSWE HVLFTACHNQ HLQLQPPRRR LHSWADDWKA ILDSKRPC
