NT5C_HUMAN
ID NT5C_HUMAN Reviewed; 201 AA.
AC Q8TCD5; Q96HS6; Q9NP82;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=5'(3')-deoxyribonucleotidase, cytosolic type;
DE EC=3.1.3.-;
DE AltName: Full=Cytosolic 5',3'-pyrimidine nucleotidase;
DE AltName: Full=Deoxy-5'-nucleotidase 1;
DE Short=dNT-1;
GN Name=NT5C; Synonyms=DNT1, UMPH2;
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] (ISOFORM 1), PROTEIN SEQUENCE OF 52-66; 99-112;
RP 114-121 AND 125-146, AND TISSUE SPECIFICITY.
RX PubMed=10681516; DOI=10.1074/jbc.275.8.5409;
RA Rampazzo C., Johansson M., Gallinaro L., Ferraro P., Hellman U.,
RA Karlsson A., Reichard P., Bianchi V.;
RT "Mammalian 5'(3')-deoxyribonucleotidase, cDNA cloning, and overexpression
RT of the enzyme in Escherichia coli and mammalian cells.";
RL J. Biol. Chem. 275:5409-5415(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP LEU-68.
RC TISSUE=Brain, Eye, and Lung;
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 GENE STRUCTURE.
RX PubMed=12234672; DOI=10.1016/s0378-1119(02)00651-0;
RA Rampazzo C., Kost-Alimova M., Ruzzenente B., Dumanski J.P., Bianchi V.;
RT "Mouse cytosolic and mitochondrial deoxyribonucleotidases: cDNA cloning of
RT the mitochondrial enzyme, gene structures, chromosomal mapping and
RT comparison with the human orthologs.";
RL Gene 294:109-117(2002).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, 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 [10]
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 3-195 IN COMPLEX WITH MAGNESIUM
RP IONS AND THE SUBSTRATE ANALOG DEOXYURIDINE TETRAFLUOROALUMINATE, CATALYTIC
RP ACTIVITY, COFACTOR, AND SUBUNIT.
RX PubMed=17985935; DOI=10.1021/bi7014794;
RA Wallden K., Rinaldo-Matthis A., Ruzzenente B., Rampazzo C., Bianchi V.,
RA Nordlund P.;
RT "Crystal structures of human and murine deoxyribonucleotidases: insights
RT into recognition of substrates and nucleotide analogues.";
RL Biochemistry 46:13809-13818(2007).
CC -!- FUNCTION: Dephosphorylates the 5' and 2'(3')-phosphates of
CC deoxyribonucleotides, with a preference for dUMP and dTMP, intermediate
CC activity towards dGMP, and low activity towards dCMP and dAMP.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:17985935};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17985935}.
CC -!- INTERACTION:
CC Q8TCD5; Q8TCD5: NT5C; NbExp=6; IntAct=EBI-6137412, EBI-6137412;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TCD5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TCD5-2; Sequence=VSP_008710, VSP_008711, VSP_008712;
CC -!- TISSUE SPECIFICITY: Detected in skeletal muscle, heart and pancreas.
CC {ECO:0000269|PubMed:10681516}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the 5'(3')-deoxyribonucleotidase family.
CC {ECO:0000305}.
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DR EMBL; AF154829; AAF36534.2; -; mRNA.
DR EMBL; AK000419; BAA91151.1; -; mRNA.
DR EMBL; AC022211; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008183; AAH08183.1; -; mRNA.
DR EMBL; BC017454; AAH17454.1; -; mRNA.
DR EMBL; BC022334; AAH22334.1; -; mRNA.
DR EMBL; BK000192; DAA00070.1; -; Genomic_DNA.
DR CCDS; CCDS11715.1; -. [Q8TCD5-1]
DR RefSeq; NP_001239306.1; NM_001252377.1.
DR RefSeq; NP_055410.1; NM_014595.2. [Q8TCD5-1]
DR PDB; 2I7D; X-ray; 1.20 A; A/B=3-195.
DR PDB; 4L57; X-ray; 1.08 A; A/B=1-195.
DR PDB; 4YIH; X-ray; 1.82 A; A/B=1-195.
DR PDB; 6G2N; X-ray; 1.40 A; A/B=2-201.
DR PDBsum; 2I7D; -.
DR PDBsum; 4L57; -.
DR PDBsum; 4YIH; -.
DR PDBsum; 6G2N; -.
DR AlphaFoldDB; Q8TCD5; -.
DR BMRB; Q8TCD5; -.
DR SMR; Q8TCD5; -.
DR BioGRID; 119049; 58.
DR IntAct; Q8TCD5; 9.
DR STRING; 9606.ENSP00000245552; -.
DR ChEMBL; CHEMBL3751653; -.
DR DrugBank; DB00709; Lamivudine.
DR DEPOD; NT5C; -.
DR iPTMnet; Q8TCD5; -.
DR PhosphoSitePlus; Q8TCD5; -.
DR BioMuta; NT5C; -.
DR DMDM; 38258193; -.
DR OGP; Q8TCD5; -.
DR EPD; Q8TCD5; -.
DR jPOST; Q8TCD5; -.
DR MassIVE; Q8TCD5; -.
DR MaxQB; Q8TCD5; -.
DR PaxDb; Q8TCD5; -.
DR PeptideAtlas; Q8TCD5; -.
DR PRIDE; Q8TCD5; -.
DR ProteomicsDB; 74121; -. [Q8TCD5-1]
DR ProteomicsDB; 74122; -. [Q8TCD5-2]
DR Antibodypedia; 19500; 78 antibodies from 18 providers.
DR DNASU; 30833; -.
DR Ensembl; ENST00000245552.7; ENSP00000245552.2; ENSG00000125458.7. [Q8TCD5-1]
DR Ensembl; ENST00000580758.5; ENSP00000462123.1; ENSG00000125458.7. [Q8TCD5-2]
DR GeneID; 30833; -.
DR KEGG; hsa:30833; -.
DR MANE-Select; ENST00000245552.7; ENSP00000245552.2; NM_014595.3; NP_055410.1.
DR UCSC; uc060jte.1; human. [Q8TCD5-1]
DR CTD; 30833; -.
DR DisGeNET; 30833; -.
DR GeneCards; NT5C; -.
DR HGNC; HGNC:17144; NT5C.
DR HPA; ENSG00000125458; Low tissue specificity.
DR MIM; 191720; gene.
DR neXtProt; NX_Q8TCD5; -.
DR OpenTargets; ENSG00000125458; -.
DR PharmGKB; PA31798; -.
DR VEuPathDB; HostDB:ENSG00000125458; -.
DR eggNOG; ENOG502QZUW; Eukaryota.
DR GeneTree; ENSGT00390000011596; -.
DR HOGENOM; CLU_2095990_0_0_1; -.
DR OMA; GPKFVER; -.
DR PhylomeDB; Q8TCD5; -.
DR TreeFam; TF331117; -.
DR PathwayCommons; Q8TCD5; -.
DR Reactome; R-HSA-73621; Pyrimidine catabolism.
DR Reactome; R-HSA-74259; Purine catabolism.
DR SABIO-RK; Q8TCD5; -.
DR SignaLink; Q8TCD5; -.
DR BioGRID-ORCS; 30833; 25 hits in 1085 CRISPR screens.
DR ChiTaRS; NT5C; human.
DR EvolutionaryTrace; Q8TCD5; -.
DR GeneWiki; NT5C; -.
DR GenomeRNAi; 30833; -.
DR Pharos; Q8TCD5; Tbio.
DR PRO; PR:Q8TCD5; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8TCD5; protein.
DR Bgee; ENSG00000125458; Expressed in mucosa of transverse colon and 147 other tissues.
DR ExpressionAtlas; Q8TCD5; baseline and differential.
DR Genevisible; Q8TCD5; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008253; F:5'-nucleotidase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050483; F:IMP 5'-nucleotidase activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008252; F:nucleotidase activity; IDA:UniProtKB.
DR GO; GO:0019103; F:pyrimidine nucleotide binding; IDA:UniProtKB.
DR GO; GO:0000255; P:allantoin metabolic process; IEA:Ensembl.
DR GO; GO:0006249; P:dCMP catabolic process; IEA:Ensembl.
DR GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR GO; GO:0046055; P:dGMP catabolic process; IEA:Ensembl.
DR GO; GO:0046074; P:dTMP catabolic process; IEA:Ensembl.
DR GO; GO:0046079; P:dUMP catabolic process; IEA:Ensembl.
DR GO; GO:0006204; P:IMP catabolic process; IEA:Ensembl.
DR GO; GO:0009223; P:pyrimidine deoxyribonucleotide catabolic process; IDA:UniProtKB.
DR GO; GO:0046050; P:UMP catabolic process; IEA:Ensembl.
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; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Magnesium; Metal-binding; Nucleotide metabolism;
KW Nucleotide-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..201
FT /note="5'(3')-deoxyribonucleotidase, cytosolic type"
FT /id="PRO_0000164371"
FT ACT_SITE 10
FT /note="Nucleophile"
FT /evidence="ECO:0000305"
FT ACT_SITE 12
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT BINDING 10
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 12
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 18
FT /ligand="substrate"
FT BINDING 44
FT /ligand="substrate"
FT BINDING 65
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 99
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 134
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 145
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 93..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008710"
FT VAR_SEQ 113..125
FT /note="YRWVEQHLGPQFV -> VWLPRPYSARGAA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008711"
FT VAR_SEQ 126..201
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008712"
FT VARIANT 68
FT /note="P -> L (in dbSNP:rs11541956)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_048102"
FT STRAND 5..9
FT /evidence="ECO:0007829|PDB:4L57"
FT TURN 13..15
FT /evidence="ECO:0007829|PDB:4L57"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:4L57"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:4L57"
FT HELIX 46..53
FT /evidence="ECO:0007829|PDB:4L57"
FT HELIX 57..65
FT /evidence="ECO:0007829|PDB:4L57"
FT TURN 68..73
FT /evidence="ECO:0007829|PDB:4L57"
FT HELIX 80..89
FT /evidence="ECO:0007829|PDB:4L57"
FT STRAND 93..99
FT /evidence="ECO:0007829|PDB:4L57"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:4L57"
FT HELIX 109..120
FT /evidence="ECO:0007829|PDB:4L57"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:4L57"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:4L57"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:4L57"
FT STRAND 140..147
FT /evidence="ECO:0007829|PDB:4L57"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:4L57"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:4L57"
FT STRAND 177..180
FT /evidence="ECO:0007829|PDB:6G2N"
FT HELIX 187..192
FT /evidence="ECO:0007829|PDB:4L57"
SQ SEQUENCE 201 AA; 23383 MW; C4C289BBDEC0FA89 CRC64;
MARSVRVLVD MDGVLADFEA GLLRGFRRRF PEEPHVPLEQ RRGFLAREQY RALRPDLADK
VASVYEAPGF FLDLEPIPGA LDAVREMNDL PDTQVFICTS PLLKYHHCVG EKYRWVEQHL
GPQFVERIIL TRDKTVVLGD LLIDDKDTVR GQEETPSWEH ILFTCCHNRH LVLPPTRRRL
LSWSDNWREI LDSKRGAAQR E
