Reviewed, UniProtKB/Swiss-Prot P33316 (DUT_HUMAN)

Names and origin

Protein names

Recommended name:
    Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial
      Short name=dUTPase
    EC=3.6.1.23
Alternative name(s):
    dUTP pyrophosphatase

Gene names

Name:

DUT

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	252 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.
Catalytic activity	dUTP + H2O = dUMP + diphosphate.
Cofactor	Magnesium.
Enzyme regulation	Phosphorylation is necessary for activity.
Pathway	Pyrimidine metabolism; dUMP biosynthesis; dUMP from dCTP (dUTP route): step 2/2.
Subcellular location	Isoform 1: Mitochondrion. Isoform 2: Nucleus.
Tissue specificity	Found in a variety of tissues.
Post-translational modification	Phosphorylation in mature T-cells occur in a cell cycle-dependent manner.
Sequence similarities	Belongs to the dUTPase family.

Ontologies

Keywords
Biological process	Nucleotide metabolism
Cellular component	Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	Magnesium
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	DNA replication Ref.9 Traceable author statement. Source: ProtInc dUTP metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Ref.1 Inferred from Experiment. Source: Reactome mitochondrion Ref.1 Traceable author statement. Source: ProtInc nucleus Ref.1 Traceable author statement. Source: ProtInc
Molecular function	dUTP diphosphatase activity Ref.1 Inferred from Experiment. Source: Reactome magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P33316-1)

Also known as: DUT-M;

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: P33316-2)

Also known as: DUT-N;

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: MTPLCPRPAL...KAGGSPAPGP → MPCSE

Note: Major isoform.

Isoform 3 (identifier: P33316-3)

The sequence of this isoform differs from the canonical sequence as follows:
     29-47: TAEGRSRGTLRARPAPRPP → ARQRAEAAVLSGPGPPLGR

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 69

69

Mitochondrion

Chain

70 – 252

183

Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial

PRO_0000007392

Amino acid modifications

Modified residue

99

1

Phosphoserine Ref.12

Natural variations

Alternative sequence

1 – 93

93

MTPLC…PAPGP → MPCSE in isoform 2.

VSP_001324

Alternative sequence

29 – 47

19

TAEGR…APRPP → ARQRAEAAVLSGPGPPLGR in isoform 3.

VSP_035458

Natural variant

100

1

P → S Ref.6

VAR_022314

Secondary structure

1

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252

Helix Strand Turn

Details...

Beta strand

113 – 120

8

Beta strand

134 – 139

6

Beta strand

144 – 146

3

Beta strand

150 – 155

6

Beta strand

158 – 161

4

Beta strand

166 – 171

6

Helix

174 – 180

7

Beta strand

182 – 185

4

Beta strand

198 – 203

6

Beta strand

205 – 207

3

Beta strand

209 – 211

3

Beta strand

216 – 225

10

Beta strand

229 – 232

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (DUT-M) [UniParc]. Last modified July 15, 1998. Version 3. Checksum: 9D3E69031D2FECC7	FASTA	252	26,706
	10 20 30 40 50 60 MTPLCPRPAL CYHFLTSLLR SAMQNARGTA EGRSRGTLRA RPAPRPPAAQ HGIPRPLSSA 70 80 90 100 110 120 GRLSQGCRGA STVGAAGWKG ELPKAGGSPA PGPETPAISP SKRARPAEVG GMQLRFARLS 130 140 150 160 170 180 EHATAPTRGS ARAAGYDLYS AYDYTIPPME KAVVKTDIQI ALPSGCYGRV APRSGLAAKH 190 200 210 220 230 240 FIDVGAGVID EDYRGNVGVV LFNFGKEKFE VKKGDRIAQL ICERIFYPEI EEVQALDDTE 250 RGSGGFGSTG KN
	Isoform 2 (DUT-N). Checksum: E75BC583BF8C7245	FASTA	164	17,748
	10 20 30 40 50 60 MPCSEETPAI SPSKRARPAE VGGMQLRFAR LSEHATAPTR GSARAAGYDL YSAYDYTIPP 70 80 90 100 110 120 MEKAVVKTDI QIALPSGCYG RVAPRSGLAA KHFIDVGAGV IDEDYRGNVG VVLFNFGKEK 130 140 150 160 FEVKKGDRIA QLICERIFYP EIEEVQALDD TERGSGGFGS TGKN
	Isoform 3. Checksum: 8E2EBC9ED5B0FAD2	FASTA	252	26,563
	10 20 30 40 50 60 MTPLCPRPAL CYHFLTSLLR SAMQNARGAR QRAEAAVLSG PGPPLGRAAQ HGIPRPLSSA 70 80 90 100 110 120 GRLSQGCRGA STVGAAGWKG ELPKAGGSPA PGPETPAISP SKRARPAEVG GMQLRFARLS 130 140 150 160 170 180 EHATAPTRGS ARAAGYDLYS AYDYTIPPME KAVVKTDIQI ALPSGCYGRV APRSGLAAKH 190 200 210 220 230 240 FIDVGAGVID EDYRGNVGVV LFNFGKEKFE VKKGDRIAQL ICERIFYPEI EEVQALDDTE 250 RGSGGFGSTG KN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of distinct nuclear and mitochondrial forms of human deoxyuridine triphosphate nucleotidohydrolase." Ladner R.D., McNulty D.E., Carr S.A., Roberts G.D., Caradonna S.J. J. Biol. Chem. 271:7745-7751(1996) [PubMed: 8631816] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PARTIAL PROTEIN SEQUENCE. Tissue: T-cell.
[2]	"Assignment of the human dUTPase gene (DUT) to chromosome 15q15-q21. 1 by fluorescence in situ hybridization." Cohen D., Heng H.H.Q., Shi X.-M., McIntosh E.M., Tsui L.-C., Pearlman R.E. Genomics 40:213-215(1997) [PubMed: 9070952] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	"Human genomic nuclear and mitochondria dUTPase gene." Pearlman R.E. Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
[4]	"The human dUTPase gene encodes both nuclear and mitochondrial isoforms: differential expression of the isoforms and characterization of a cDNA encoding the mitochondrial species." Ladner R.D., Caradonna S.J. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[5]	"Unknown transcriptional variant of nuclear dUTPase in human osteosarcoma." Chano T., Okabe H., Baldini N., Lapucci C., Scotlandi K., Serra M., Saeki Y. Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[6]	NIEHS SNPs program Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-100.
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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 2 AND 3). Tissue: Brain, Eye and Urinary bladder.
[9]	"Human dUTP pyrophosphatase: cDNA sequence and potential biological importance of the enzyme." McIntosh E.M., Ager D.D., Gadsden M.H., Haynes R.H. Proc. Natl. Acad. Sci. U.S.A. 89:8020-8024(1992) [PubMed: 1325640] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 112-252.
[10]	Erratum McIntosh E.M., Ager D.D., Gadsden M.H., Haynes R.H. Proc. Natl. Acad. Sci. U.S.A. 90:4328-4328(1993)
[11]	"Maturation stage and proliferation-dependent expression of dUTPase in human T cells." Strahler J.R., Zhu X.-X., Wang Y.K., Hora N., Andrews P.C., Roseman N.A., Neel J.V., Turka L., Hanash S.M. Proc. Natl. Acad. Sci. U.S.A. 90:4991-4995(1993) [PubMed: 8389461] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 112-252, PARTIAL PROTEIN SEQUENCE, PHOSPHORYLATION. Tissue: Lymphocyte.
[12]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and active sites formed by three separate subunits." Mol C.D., Harris J.M., McIntosh E.M., Tainer J.A. Structure 4:1077-1092(1996) [PubMed: 8805593] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 112-252.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

U31930 mRNA. Translation: AAC50418.1.
U62891 mRNA. Translation: AAC51123.1.
AF018432 , AF018429, AF018430, AF018431 Genomic DNA. Translation: AAB71393.1.
AF018432 , AF018429, AF018430, AF018431 Genomic DNA. Translation: AAB71394.1.
U90223 mRNA. Translation: AAB94642.1.
U90224 Genomic DNA. Translation: AAB93866.1.
U90224 Genomic DNA. Translation: AAB93867.1.
AB049113 mRNA. Translation: BAB13724.1.
AY935242 Genomic DNA. Translation: AAX14045.1.
CH471082 Genomic DNA. Translation: EAW77350.1.
BC033645 mRNA. Translation: AAH33645.1.
BC070339 mRNA. Translation: AAH70339.1.
BC110377 mRNA. Translation: AAI10378.1.
M89913 mRNA. Translation: AAA58444.1.
L11877 mRNA. Translation: AAA36801.1.

IPI

IPI00013679.
IPI00375015.
IPI00749113.

PIR

A46256.
G02777.

RefSeq

NP_001020419.1.
NP_001939.1.

UniGene

Hs.527980

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Q5H	X-ray	2.00	A/B/C	112-252	[»]
1Q5U	X-ray	2.00	X/Y/Z	112-252	[»]
2HQU	X-ray	2.20	A/B/C	94-252	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P33316. 5 interactions.

PTM databases

PhosphoSite

P33316.

Proteomic databases

PeptideAtlas

P33316.

PRIDE

P33316.

Genome annotation databases

Ensembl

ENSG00000128951. Homo sapiens. [Contig view]

GeneID

1854.

KEGG

hsa:1854.

Organism-specific databases

GeneCards

GC15P046410.

H-InvDB

HIX0031255.

HGNC

HGNC:3078. DUT.

MIM

601266. gene.

PharmGKB

PA151.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P33316.

OMA

P33316. MQLRFAR.

Enzyme and pathway databases

BRENDA

3.6.1.23. 247.

Gene expression databases

ArrayExpress

P33316.

Bgee

P33316.

CleanEx

HS_DUT.

GermOnline

ENSG00000128951. Homo sapiens.

Family and domain databases

InterPro

IPR008180. DeoxyUTPase.
IPR008181. dUTP_pyrophosphatase_subfam_1.
[Graphical view]

Pfam

PF00692. dUTPase. 1 hit.
[Graphical view]

ProDom

PD004900. dCTP_deaminase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR00576. dut. 1 hit.

ProtoNet

Search...

Other Resources

NextBio

7591.

SOURCE

Search...

Entry information

Entry name

DUT_HUMAN

Accession

Primary (citable) accession number: P33316
Secondary accession number(s): O14785 , Q16708, Q16860, Q6NSA3, Q96Q81

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	July 15, 1998
Last modified:	June 16, 2009
This is version 99 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)