Q8TCD5 (NT5C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5'(3')-deoxyribonucleotidase, cytosolic type
EC=3.1.3.-

Alternative name(s):
Cytosolic 5',3'-pyrimidine nucleotidase
Deoxy-5'-nucleotidase 1
Short name=dNT-1

Gene names

Name:	NT5C
Synonyms:	DNT1, UMPH2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	201 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Dephosphorylates the 5' and 2'(3')-phosphates of deoxyribonucleotides, with a preference for dUMP and dTMP, intermediate activity towards dGMP, and low activity towards dCMP and dAMP.
Cofactor	Magnesium. Ref.8
Subunit structure	Homodimer. Ref.8
Subcellular location	Cytoplasm.
Tissue specificity	Detected in skeletal muscle, heart and pancreas. Ref.1
Sequence similarities	Belongs to the 5'(3')-deoxyribonucleotidase family.
Sequence caution	The sequence AAF36534.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Nucleotide metabolism
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Magnesium Metal-binding Nucleotide-binding
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	purine base metabolic process Traceable author statement. Source: Reactome purine nucleotide catabolic process Traceable author statement. Source: Reactome pyrimidine base metabolic process Traceable author statement. Source: Reactome pyrimidine deoxyribonucleotide catabolic process Inferred from direct assay Ref.1. Source: UniProtKB pyrimidine nucleoside catabolic process Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay Ref.1. Source: UniProtKB
Molecular function	5'-nucleotidase activity Inferred from experiment. Source: Reactome metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW pyrimidine nucleotide binding Inferred from direct assay Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8TCD5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8TCD5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     93-100: Missing.
     113-125: YRWVEQHLGPQFV → VWLPRPYSARGAA
     126-201: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 201

201

5'(3')-deoxyribonucleotidase, cytosolic type

PRO_0000164371

Sites

Active site

10

1

Nucleophile Probable

Active site

12

1

Proton donor Probable

Metal binding

10

1

Magnesium

Metal binding

12

1

Magnesium; via carbonyl oxygen

Metal binding

145

1

Magnesium

Binding site

18

1

Substrate

Binding site

44

1

Substrate

Binding site

65

1

Substrate By similarity

Binding site

99

1

Substrate Probable

Binding site

134

1

Substrate Probable

Amino acid modifications

Modified residue

182

1

Phosphoserine Ref.5 Ref.6

Natural variations

Alternative sequence

93 – 100

8

Missing in isoform 2.

VSP_008710

Alternative sequence

113 – 125

13

YRWVE…GPQFV → VWLPRPYSARGAA in isoform 2.

VSP_008711

Alternative sequence

126 – 201

76

Missing in isoform 2.

VSP_008712

Natural variant

68

1

P → L. Ref.3
Corresponds to variant rs11541956 [ dbSNP | Ensembl ].

VAR_048102

Secondary structure

1

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201

Helix Strand Turn

Details...

Beta strand

5 – 9

5

Turn

27 – 29

3

Helix

38 – 40

3

Helix

46 – 53

8

Helix

57 – 65

9

Helix

81 – 88

8

Beta strand

93 – 99

7

Turn

106 – 108

3

Helix

112 – 119

8

Helix

125 – 127

3

Beta strand

128 – 130

3

Helix

134 – 136

3

Beta strand

141 – 147

7

Beta strand

157 – 163

7

Helix

166 – 168

3

Helix

187 – 192

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 31, 2003. Version 2. Checksum: C4C289BBDEC0FA89	FASTA	201	23,383
	10 20 30 40 50 60 MARSVRVLVD MDGVLADFEA GLLRGFRRRF PEEPHVPLEQ RRGFLAREQY RALRPDLADK 70 80 90 100 110 120 VASVYEAPGF FLDLEPIPGA LDAVREMNDL PDTQVFICTS PLLKYHHCVG EKYRWVEQHL 130 140 150 160 170 180 GPQFVERIIL TRDKTVVLGD LLIDDKDTVR GQEETPSWEH ILFTCCHNRH LVLPPTRRRL 190 200 LSWSDNWREI LDSKRGAAQR E
	Isoform 2 [UniParc]. Checksum: 014A63DE1B5347F6	FASTA	117	13,299
	10 20 30 40 50 60 MARSVRVLVD MDGVLADFEA GLLRGFRRRF PEEPHVPLEQ RRGFLAREQY RALRPDLADK 70 80 90 100 110 VASVYEAPGF FLDLEPIPGA LDAVREMNDL PDPLLKYHHC VGEKVWLPRP YSARGAA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mammalian 5'(3')-deoxyribonucleotidase, cDNA cloning, and overexpression of the enzyme in Escherichia coli and mammalian cells." Rampazzo C., Johansson M., Gallinaro L., Ferraro P., Hellman U., Karlsson A., Reichard P., Bianchi V. J. Biol. Chem. 275:5409-5415(2000) [PubMed: 10681516] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 52-66; 99-112; 114-121 AND 125-146, TISSUE SPECIFICITY.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT LEU-68. Tissue: Brain, Eye and Lung.
[4]	"Mouse cytosolic and mitochondrial deoxyribonucleotidases: cDNA cloning of the mitochondrial enzyme, gene structures, chromosomal mapping and comparison with the human orthologs." Rampazzo C., Kost-Alimova M., Ruzzenente B., Dumanski J.P., Bianchi V. Gene 294:109-117(2002) [PubMed: 12234672] [Abstract] Cited for: GENE STRUCTURE.
[5]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Crystal structures of human and murine deoxyribonucleotidases: insights into recognition of substrates and nucleotide analogues." Wallden K., Rinaldo-Matthis A., Ruzzenente B., Rampazzo C., Bianchi V., Nordlund P. Biochemistry 46:13809-13818(2007) [PubMed: 17985935] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 3-195 IN COMPLEX WITH MAGNESIUM IONS AND DEOXYURIDINE TETRAFLUOROALUMINATE, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF154829 mRNA. Translation: AAF36534.2. Different initiation.
AK000419 mRNA. Translation: BAA91151.1.
BC008183 mRNA. Translation: AAH08183.1.
BC017454 mRNA. Translation: AAH17454.1.
BC022334 mRNA. Translation: AAH22334.1.
BK000192 Genomic DNA. Translation: DAA00070.1.

IPI

IPI00005573.
IPI00386083.

RefSeq

NP_055410.1. NM_014595.2.

UniGene

Hs.67201.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I7D	X-ray	1.20	A/B	3-195	[»]

ProteinModelPortal

Q8TCD5.

SMR

Q8TCD5. Positions 3-195.

ModBase

Search...

Protein-protein interaction databases

STRING

Q8TCD5.

PTM databases

PhosphoSite

Q8TCD5.

Polymorphism databases

DMDM

38258193.

2D gel databases

OGP

Q8TCD5.

Proteomic databases

PeptideAtlas

Q8TCD5.

PRIDE

Q8TCD5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000245552; ENSP00000245552; ENSG00000125458.

GeneID

30833.

KEGG

hsa:30833.

UCSC

uc002jmx.1. human.

Organism-specific databases

CTD

30833.

GeneCards

GC17M073123.

H-InvDB

HIX0202406.

HGNC

HGNC:17144. NT5C.

HPA

HPA021581.
HPA023632.

MIM

191720. gene.

neXtProt

NX_Q8TCD5.

PharmGKB

PA31798.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12852.

GeneTree

ENSGT00390000011596.

HOGENOM

HBG353930.

HOVERGEN

HBG045599.

InParanoid

Q8TCD5.

OMA

DTIRGQE.

OrthoDB

EOG4DNF5C.

PhylomeDB

Q8TCD5.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q8TCD5.

Bgee

Q8TCD5.

CleanEx

HS_NT5C.

Genevestigator

Q8TCD5.

GermOnline

ENSG00000125458. Homo sapiens.

Family and domain databases

InterPro

IPR010708. 5'(3')-deoxyribonucleotidase.
IPR023214. HAD-like_dom.
[Graphical view]

Gene3D

G3DSA:3.40.50.1000. HAD-like_dom. 1 hit.

KO

K01081.

Pfam

PF06941. NT5C. 1 hit.
[Graphical view]

SUPFAM

SSF56784. HAD-like_dom. 1 hit.

ProtoNet

Search...

Other

NextBio

52940.

SOURCE

Search...

Entry information

Entry name

NT5C_HUMAN

Accession

Primary (citable) accession number: Q8TCD5
Secondary accession number(s): Q96HS6, Q9NP82

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2003
Last sequence update:	October 31, 2003
Last modified:	January 25, 2012
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.