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Q14117 (DPYS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dihydropyrimidinase

Short name=DHP
Short name=DHPase
EC=3.5.2.2
Alternative name(s):
Dihydropyrimidine amidohydrolase
Hydantoinase
Gene names
Name:DPYS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length519 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze 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. Ref.4

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

Dihydropyrimidinase deficiency (DHPD) [MIM:222748]: A disorder characterized by dihydropyrimidinuria and associated with a variable clinical phenotype characterized by epileptic or convulsive attacks, dysmorphic features and severe developmental delay, and congenital microvillous atrophy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2

Sequence similarities

Belongs to the DHOase family. Hydantoinase/dihydropyrimidinase subfamily.

Ontologies

Keywords
   DiseaseDisease mutation
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbeta-alanine metabolic process

Inferred from electronic annotation. Source: Ensembl

nucleobase-containing small molecule metabolic process

Traceable author statement. Source: Reactome

protein homotetramerization

Inferred from sequence or structural similarity. Source: UniProtKB

pyrimidine nucleobase catabolic process

Inferred from direct assay Ref.2. Source: UniProtKB

pyrimidine nucleobase metabolic process

Traceable author statement. Source: Reactome

pyrimidine nucleoside catabolic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

thymine catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

uracil catabolic process

Inferred from direct assay PubMed 10410956. Source: UniProtKB

   Cellular_componentcytosol

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

   Molecular_functionamino acid binding

Inferred from electronic annotation. Source: Ensembl

dihydropyrimidinase activity

Inferred from direct assay PubMed 10410956Ref.2. Source: UniProtKB

thymine binding

Inferred from electronic annotation. Source: Ensembl

uracil binding

Inferred from electronic annotation. Source: Ensembl

zinc ion binding

Non-traceable author statement Ref.2. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 519519Dihydropyrimidinase
PRO_0000165906

Sites

Metal binding671Zinc 1
Metal binding691Zinc 1
Metal binding1591Zinc 1; via carbamate group
Metal binding1591Zinc 2; via carbamate group
Metal binding1921Zinc 2
Metal binding2481Zinc 2
Metal binding3261Zinc 1
Binding site1641Substrate By similarity
Binding site3471Substrate; via carbonyl oxygen By similarity

Amino acid modifications

Modified residue1591N6-carboxylysine By similarity
Modified residue2561N6-succinyllysine By similarity

Natural variations

Natural variant681T → R in DHPD. Ref.2
VAR_002267
Natural variant3341Q → R in DHPD. Ref.2
Corresponds to variant rs121964923 [ dbSNP | Ensembl ].
VAR_002268
Natural variant3601W → R in DHPD. Ref.2
Corresponds to variant rs121964924 [ dbSNP | Ensembl ].
VAR_002269
Natural variant4351G → R in DHPD. Ref.2
VAR_002270
Natural variant4901R → T in DHPD. Ref.2
VAR_002271

Secondary structure

..................................................................................... 519
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q14117 [UniParc].

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

FASTA51956,630
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS DHPD 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon, Kidney and Stomach.
[4]"The crystal structure of human dihydropyrimidinase."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH ZINC IONS, COFACTOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D78011 mRNA. Translation: BAA11189.1.
AB004678 Genomic DNA. Translation: BAA33067.1.
BC034395 mRNA. Translation: AAH34395.1.
CCDSCCDS6302.1.
PIRJC5315.
RefSeqNP_001376.1. NM_001385.2.
UniGeneHs.443161.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2VR2X-ray2.80A1-519[»]
ProteinModelPortalQ14117.
SMRQ14117. Positions 5-493.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000276651.

Protein family/group databases

MEROPSM38.973.

PTM databases

PhosphoSiteQ14117.

Polymorphism databases

DMDM3122049.

Proteomic databases

PaxDbQ14117.
PRIDEQ14117.

Protocols and materials databases

DNASU1807.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000351513; ENSP00000276651; ENSG00000147647.
GeneID1807.
KEGGhsa:1807.
UCSCuc003yly.4. human.

Organism-specific databases

CTD1807.
GeneCardsGC08M105391.
HGNCHGNC:3013. DPYS.
HPAHPA024785.
MIM222748. phenotype.
613326. gene.
neXtProtNX_Q14117.
Orphanet38874. Dihydropyrimidinuria.
PharmGKBPA146.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0044.
HOGENOMHOG000219145.
HOVERGENHBG000806.
InParanoidQ14117.
KOK01464.
OMAAVDYNIF.
OrthoDBEOG7SJD48.
PhylomeDBQ14117.
TreeFamTF314706.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ14117.
BgeeQ14117.
CleanExHS_DPYS.
GenevestigatorQ14117.

Family and domain databases

Gene3D2.30.40.10. 2 hits.
InterProIPR006680. Amidohydro_1.
IPR011778. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
[Graphical view]
PfamPF01979. Amidohydro_1. 1 hit.
[Graphical view]
SUPFAMSSF51338. SSF51338. 2 hits.
TIGRFAMsTIGR02033. D-hydantoinase. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ14117.
GeneWikiDPYS.
GenomeRNAi1807.
NextBio7365.
PROQ14117.
SOURCESearch...

Entry information

Entry nameDPYS_HUMAN
AccessionPrimary (citable) accession number: Q14117
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM