Dihydropyrimidinase - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot Q14117 (DPYS_HUMAN)

Last modified July 7, 2009. Version 83. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Dihydropyrimidinase
      Short name=DHPase
      Short name=DHP
    EC=3.5.2.2
Alternative name(s):
    Dihydropyrimidine amidohydrolase
    Hydantoinase

Gene names

Name:

DPYS

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	519 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyzes the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino isobutyrate.
Catalytic activity	5,6-dihydrouracil + H₂O = 3-ureidopropanoate.
Cofactor	Binds 2 zinc ions per subunit By similarity.
Subunit structure	Homotetramer Probable.
Tissue specificity	Liver and kidney.
Post-translational modification	Carbamylation allows a single lysine to coordinate two zinc ions By similarity.
Involvement in disease	Defects in DPYS are the cause of DHP deficiency [MIM:222748]. DHP deficiency is an autosomal recessive disorder characterized by dihydropyrimidinuria and associated with a variable clinical phenotype: epileptic or convulsive attacks, dysmorphic features and severe developmental delay, and congenital microvillous atrophy. Ref.2
Sequence similarities	Belongs to the DHOase family. Hydantoinase/dihydropyrimidinase subfamily.

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Ontologies

Keywords
Disease	Disease mutation
Ligand	Metal-binding Zinc
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	protein homotetramerization Inferred from sequence or structural similarity. Source: UniProtKB thymine catabolic process Inferred from sequence or structural similarity. Source: UniProtKB uracil catabolic process Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Ref.2 Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	dihydropyrimidinase activity Ref.2 Inferred from direct assay. Source: UniProtKB zinc ion binding Ref.2 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 519

519

Dihydropyrimidinase

PRO_0000165906

Sites

Metal binding

Zinc 1

Metal binding

Zinc 1

Metal binding

159

Zinc 1; via carbamate group

Metal binding

159

Zinc 2; via carbamate group

Metal binding

192

Zinc 2

Metal binding

248

Zinc 2

Metal binding

326

Zinc 1

Binding site

164

Substrate By similarity

Binding site

347

Substrate; via carbonyl oxygen By similarity

Amino acid modifications

Modified residue

159

N6-carboxylysine By similarity

Natural variations

Natural variant

T → R in DHP deficiency.

VAR_002267

Natural variant

334

Q → R in DHP deficiency.

VAR_002268

Natural variant

360

W → R in DHP deficiency.

VAR_002269

Natural variant

435

G → R in DHP deficiency.

VAR_002270

Natural variant

490

R → T in DHP deficiency.

VAR_002271

Secondary structure

519

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q14117-1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 882E33D7C49D6ECC
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FASTA

519

56,630

        10         20         30         40         50         60 
MAAPSRLLIR GGRVVNDDFS EVADVLVEDG VVRALGHDLL PPGGAPAGLR VLDAAGKLVL 

        70         80         90        100        110        120 
PGGIDTHTHM QFPFMGSRSI DDFHQGTKAA LSGGTTMIID FAIPQKGGSL IEAFETWRSW 

       130        140        150        160        170        180 
ADPKVCCDYS LHVAVTWWSD QVKEEMKILV QDKGVNSFKM FMAYKDLYMV TDLELYEAFS 

       190        200        210        220        230        240 
RCKEIGAIAQ VHAENGDLIA EGAKKMLALG ITGPEGHELC RPEAVEAEAT LRAITIASAV 

       250        260        270        280        290        300 
NCPLYIVHVM SKSAAKVIAD ARRDGKVVYG EPIAASLGTD GTHYWNKEWH HAAHHVMGPP 

       310        320        330        340        350        360 
LRPDPSTPDF LMNLLANDDL TTTGTDNCTF NTCQKALGKD DFTKIPNGVN GVEDRMSVIW 

       370        380        390        400        410        420 
EKGVHSGKMD ENRFVAVTST NAAKIFNLYP RKGRIAVGSD ADIVIWDPKG TRTISAKTHH 

       430        440        450        460        470        480 
QAVNFNIFEG MVCHGVPLVT ISRGKVVYEA GVFSVTAGDG KFIPRKPFAE YIYKRIKQRD 

       490        500        510 
RTCTPTPVER APYKGEVATL KSRVTKEDAT AGTRKQAHP

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution." Hamajima N., Matsuda K., Sakata S., Tamaki N., Sasaki M., Nonaka M. Gene 180:157-163(1996) [PubMed: 8973361] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Dihydropyrimidinase deficiency: structural organization, chromosomal localization, and mutation analysis of the human dihydropyrimidinase gene." Hamajima N., Kouwaki M., Vreken P., Matsuda K., Sumi S., Imaeda M., Ohba S., Kidouchi K., Nonaka M., Sasaki M., Tamaki N., Endo Y., de Abreu R., Rottevell J., van Kuilenburg A., van Gennip A., Togari H., Wada Y. Am. J. Hum. Genet. 63:717-726(1998) [PubMed: 9718352] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS DHP DEFICIENCY ARG-68; ARG-334; ARG-360; ARG-435 AND THR-490.
[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]. Tissue: Colon, Kidney and Stomach.
+	Additional computationally mapped references.

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Web resources

GeneReviews

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Cross-references

Sequence databases

D78011 mRNA. Translation: BAA11189.1.
AB004678 Genomic DNA. Translation: BAA33067.1.
BC034395 mRNA. Translation: AAH34395.1.

IPI

IPI00028910.

PIR

JC5315.

RefSeq

NP_001376.1.

UniGene

Hs.443161

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VR2	X-ray	2.80	A	1-519	[»]

ModBase

Search...

Protein family/group databases

MEROPS

M38.973.

Proteomic databases

PRIDE

Q14117.

Genome annotation databases

Ensembl

ENSG00000147647. Homo sapiens. [Contig view]

GeneID

1807.

KEGG

hsa:1807.

NMPDR

fig|9606.3.peg.30637.

UCSC

uc003yly.2. human.

Organism-specific databases

GeneCards

GC08M105460.

H-InvDB

HIX0007715.

HGNC

HGNC:3013. DPYS.

MIM

222748. gene+phenotype.

Orphanet

38874. Dihydropyrimidinuria.

PharmGKB

PA146.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q14117.

HOVERGEN

Q14117.

OMA

Q14117. YEAGVFS.

Enzyme and pathway databases

BRENDA

3.5.2.2. 247.

Reactome

REACT_1698. Metablism of nucleotides.

Gene expression databases

ArrayExpress

Q14117.

Bgee

Q14117.

CleanEx

HS_DPYS.

GermOnline

ENSG00000147647. Homo sapiens.

Family and domain databases

InterPro

IPR006680. Amidohydro_1.
IPR011778. D-hydantoinase.
[Graphical view]

Pfam

PF01979. Amidohydro_1. 1 hit.
[Graphical view]

ProDom

PD000518. DHOase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR02033. D-hydantoinase. 1 hit.

ProtoNet

Search...

Other Resources

NextBio

7365.

SOURCE

Search...

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Entry information

Entry name

DPYS_HUMAN

Accession

Primary (citable) accession number: Q14117

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	July 7, 2009
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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