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Protein

Dihydropyrimidinase

Gene

DPYS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

5,6-dihydrouracil + H2O = 3-ureidopropanoate.By similarity

Cofactori

Zn2+1 PublicationNote: Binds 2 Zn2+ ions per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi67Zinc 1Combined sources1 Publication1
Metal bindingi69Zinc 1Combined sources1 Publication1
Metal bindingi159Zinc 1; via carbamate groupCombined sources1 Publication1
Metal bindingi159Zinc 2; via carbamate groupCombined sources1 Publication1
Binding sitei164SubstrateBy similarity1
Metal bindingi192Zinc 2Combined sources1 Publication1
Metal bindingi248Zinc 2Combined sources1 Publication1
Metal bindingi326Zinc 1Combined sources1 Publication1
Binding sitei347Substrate; via carbonyl oxygenBy similarity1

GO - Molecular functioni

  • amino acid binding Source: Ensembl
  • dihydropyrimidinase activity Source: UniProtKB
  • thymine binding Source: Ensembl
  • uracil binding Source: Ensembl
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS07460-MONOMER.
ZFISH:HS07460-MONOMER.
ReactomeiR-HSA-73621. Pyrimidine catabolism.

Protein family/group databases

MEROPSiM38.973.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydropyrimidinase (EC:3.5.2.2By similarity)
Short name:
DHP
Short name:
DHPase
Alternative name(s):
Dihydropyrimidine amidohydrolase
Hydantoinase
Gene namesi
Name:DPYS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:3013. DPYS.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Dihydropyrimidinase deficiency (DPYSD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder of pyrimidine metabolism characterized by dihydropyrimidinuria. It is associated with a variable clinical phenotype characterized by epileptic or convulsive attacks, dysmorphic features and severe developmental delay, and congenital microvillous atrophy. Most patients are, however, asymptomatic.
See also OMIM:222748
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00226768T → R in DPYSD. 1 Publication1
Natural variantiVAR_002268334Q → R in DPYSD. 1 PublicationCorresponds to variant rs121964923dbSNPEnsembl.1
Natural variantiVAR_002269360W → R in DPYSD. 1 PublicationCorresponds to variant rs121964924dbSNPEnsembl.1
Natural variantiVAR_002270435G → R in DPYSD. 1 PublicationCorresponds to variant rs267606773dbSNPEnsembl.1
Natural variantiVAR_002271490R → T in DPYSD. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1807.
MalaCardsiDPYS.
MIMi222748. phenotype.
OpenTargetsiENSG00000147647.
Orphaneti38874. Dihydropyrimidinuria.
PharmGKBiPA146.

Chemistry databases

ChEMBLiCHEMBL2465.

Polymorphism and mutation databases

BioMutaiDPYS.
DMDMi3122049.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001659061 – 519DihydropyrimidinaseAdd BLAST519

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei79PhosphoserineCombined sources1
Modified residuei159N6-carboxylysineBy similarity1
Modified residuei256N6-succinyllysineBy similarity1

Post-translational modificationi

Carbamylation allows a single lysine to coordinate two zinc ions.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ14117.
MaxQBiQ14117.
PaxDbiQ14117.
PeptideAtlasiQ14117.
PRIDEiQ14117.

PTM databases

iPTMnetiQ14117.
PhosphoSitePlusiQ14117.

Expressioni

Tissue specificityi

Liver and kidney.

Gene expression databases

BgeeiENSG00000147647.
CleanExiHS_DPYS.
ExpressionAtlasiQ14117. baseline and differential.
GenevisibleiQ14117. HS.

Organism-specific databases

HPAiHPA024785.

Interactioni

Subunit structurei

Homotetramer.1 Publication

Protein-protein interaction databases

BioGridi108141. 5 interactors.
IntActiQ14117. 1 interactor.
STRINGi9606.ENSP00000276651.

Structurei

Secondary structure

1519
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 11Combined sources6
Beta strandi13 – 15Combined sources3
Beta strandi20 – 22Combined sources3
Beta strandi24 – 28Combined sources5
Beta strandi31 – 36Combined sources6
Beta strandi50 – 53Combined sources4
Beta strandi57 – 61Combined sources5
Beta strandi63 – 68Combined sources6
Beta strandi75 – 78Combined sources4
Helixi85 – 91Combined sources7
Turni92 – 94Combined sources3
Beta strandi95 – 102Combined sources8
Helixi110 – 121Combined sources12
Turni122 – 124Combined sources3
Beta strandi126 – 135Combined sources10
Helixi140 – 151Combined sources12
Beta strandi157 – 164Combined sources8
Turni165 – 168Combined sources4
Helixi172 – 185Combined sources14
Beta strandi188 – 192Combined sources5
Helixi196 – 208Combined sources13
Helixi215 – 219Combined sources5
Helixi223 – 240Combined sources18
Beta strandi244 – 249Combined sources6
Helixi252 – 263Combined sources12
Beta strandi268 – 273Combined sources6
Helixi274 – 278Combined sources5
Helixi282 – 285Combined sources4
Helixi289 – 293Combined sources5
Helixi307 – 316Combined sources10
Helixi332 – 335Combined sources4
Helixi336 – 338Combined sources3
Helixi342 – 344Combined sources3
Turni352 – 354Combined sources3
Helixi355 – 363Combined sources9
Turni364 – 367Combined sources4
Helixi371 – 378Combined sources8
Helixi380 – 385Combined sources6
Turni389 – 391Combined sources3
Beta strandi403 – 413Combined sources11
Turni416 – 418Combined sources3
Beta strandi420 – 422Combined sources3
Turni427 – 430Combined sources4
Beta strandi432 – 442Combined sources11
Beta strandi445 – 449Combined sources5
Helixi470 – 482Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2VR2X-ray2.80A1-519[»]
ProteinModelPortaliQ14117.
SMRiQ14117.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14117.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2584. Eukaryota.
COG0044. LUCA.
GeneTreeiENSGT00760000119241.
HOGENOMiHOG000219145.
HOVERGENiHBG000806.
InParanoidiQ14117.
KOiK01464.
OMAiFHMAVTW.
OrthoDBiEOG091G05F3.
PhylomeDBiQ14117.
TreeFamiTF314706.

Family and domain databases

CDDicd01314. D-HYD. 1 hit.
Gene3Di2.30.40.10. 2 hits.
InterProiIPR006680. Amidohydro-rel.
IPR030633. Dihydropyrimidinase.
IPR011778. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
IPR032466. Metal_Hydrolase.
[Graphical view]
PANTHERiPTHR11647:SF50. PTHR11647:SF50. 1 hit.
PfamiPF01979. Amidohydro_1. 1 hit.
[Graphical view]
SUPFAMiSSF51338. SSF51338. 2 hits.
SSF51556. SSF51556. 1 hit.
TIGRFAMsiTIGR02033. D-hydantoinase. 1 hit.

Sequencei

Sequence statusi: Complete.

Q14117-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAPSRLLIR GGRVVNDDFS EVADVLVEDG VVRALGHDLL PPGGAPAGLR
60 70 80 90 100
VLDAAGKLVL PGGIDTHTHM QFPFMGSRSI DDFHQGTKAA LSGGTTMIID
110 120 130 140 150
FAIPQKGGSL IEAFETWRSW ADPKVCCDYS LHVAVTWWSD QVKEEMKILV
160 170 180 190 200
QDKGVNSFKM FMAYKDLYMV TDLELYEAFS RCKEIGAIAQ VHAENGDLIA
210 220 230 240 250
EGAKKMLALG ITGPEGHELC RPEAVEAEAT LRAITIASAV NCPLYIVHVM
260 270 280 290 300
SKSAAKVIAD ARRDGKVVYG EPIAASLGTD GTHYWNKEWH HAAHHVMGPP
310 320 330 340 350
LRPDPSTPDF LMNLLANDDL TTTGTDNCTF NTCQKALGKD DFTKIPNGVN
360 370 380 390 400
GVEDRMSVIW EKGVHSGKMD ENRFVAVTST NAAKIFNLYP RKGRIAVGSD
410 420 430 440 450
ADIVIWDPKG TRTISAKTHH QAVNFNIFEG MVCHGVPLVT ISRGKVVYEA
460 470 480 490 500
GVFSVTAGDG KFIPRKPFAE YIYKRIKQRD RTCTPTPVER APYKGEVATL
510
KSRVTKEDAT AGTRKQAHP
Length:519
Mass (Da):56,630
Last modified:November 1, 1996 - v1
Checksum:i882E33D7C49D6ECC
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00226768T → R in DPYSD. 1 Publication1
Natural variantiVAR_002268334Q → R in DPYSD. 1 PublicationCorresponds to variant rs121964923dbSNPEnsembl.1
Natural variantiVAR_002269360W → R in DPYSD. 1 PublicationCorresponds to variant rs121964924dbSNPEnsembl.1
Natural variantiVAR_002270435G → R in DPYSD. 1 PublicationCorresponds to variant rs267606773dbSNPEnsembl.1
Natural variantiVAR_002271490R → T in DPYSD. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D78011 mRNA. Translation: BAA11189.1.
AB004678 Genomic DNA. Translation: BAA33067.1.
BC034395 mRNA. Translation: AAH34395.1.
CCDSiCCDS6302.1.
PIRiJC5315.
RefSeqiNP_001376.1. NM_001385.2.
UniGeneiHs.443161.

Genome annotation databases

EnsembliENST00000351513; ENSP00000276651; ENSG00000147647.
GeneIDi1807.
KEGGihsa:1807.
UCSCiuc003yly.5. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D78011 mRNA. Translation: BAA11189.1.
AB004678 Genomic DNA. Translation: BAA33067.1.
BC034395 mRNA. Translation: AAH34395.1.
CCDSiCCDS6302.1.
PIRiJC5315.
RefSeqiNP_001376.1. NM_001385.2.
UniGeneiHs.443161.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2VR2X-ray2.80A1-519[»]
ProteinModelPortaliQ14117.
SMRiQ14117.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108141. 5 interactors.
IntActiQ14117. 1 interactor.
STRINGi9606.ENSP00000276651.

Chemistry databases

ChEMBLiCHEMBL2465.

Protein family/group databases

MEROPSiM38.973.

PTM databases

iPTMnetiQ14117.
PhosphoSitePlusiQ14117.

Polymorphism and mutation databases

BioMutaiDPYS.
DMDMi3122049.

Proteomic databases

EPDiQ14117.
MaxQBiQ14117.
PaxDbiQ14117.
PeptideAtlasiQ14117.
PRIDEiQ14117.

Protocols and materials databases

DNASUi1807.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000351513; ENSP00000276651; ENSG00000147647.
GeneIDi1807.
KEGGihsa:1807.
UCSCiuc003yly.5. human.

Organism-specific databases

CTDi1807.
DisGeNETi1807.
GeneCardsiDPYS.
HGNCiHGNC:3013. DPYS.
HPAiHPA024785.
MalaCardsiDPYS.
MIMi222748. phenotype.
613326. gene.
neXtProtiNX_Q14117.
OpenTargetsiENSG00000147647.
Orphaneti38874. Dihydropyrimidinuria.
PharmGKBiPA146.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2584. Eukaryota.
COG0044. LUCA.
GeneTreeiENSGT00760000119241.
HOGENOMiHOG000219145.
HOVERGENiHBG000806.
InParanoidiQ14117.
KOiK01464.
OMAiFHMAVTW.
OrthoDBiEOG091G05F3.
PhylomeDBiQ14117.
TreeFamiTF314706.

Enzyme and pathway databases

BioCyciMetaCyc:HS07460-MONOMER.
ZFISH:HS07460-MONOMER.
ReactomeiR-HSA-73621. Pyrimidine catabolism.

Miscellaneous databases

EvolutionaryTraceiQ14117.
GeneWikiiDPYS.
GenomeRNAii1807.
PROiQ14117.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147647.
CleanExiHS_DPYS.
ExpressionAtlasiQ14117. baseline and differential.
GenevisibleiQ14117. HS.

Family and domain databases

CDDicd01314. D-HYD. 1 hit.
Gene3Di2.30.40.10. 2 hits.
InterProiIPR006680. Amidohydro-rel.
IPR030633. Dihydropyrimidinase.
IPR011778. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
IPR032466. Metal_Hydrolase.
[Graphical view]
PANTHERiPTHR11647:SF50. PTHR11647:SF50. 1 hit.
PfamiPF01979. Amidohydro_1. 1 hit.
[Graphical view]
SUPFAMiSSF51338. SSF51338. 2 hits.
SSF51556. SSF51556. 1 hit.
TIGRFAMsiTIGR02033. D-hydantoinase. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiDPYS_HUMAN
AccessioniPrimary (citable) accession number: Q14117
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.