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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.HMP:

Cofactori

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi67Zinc 1ND:1 Publication1
Metal bindingi69Zinc 1ND:1 Publication1
Metal bindingi159Zinc 1; via carbamate groupND:1 Publication1
Metal bindingi159Zinc 2; via carbamate groupND:1 Publication1
Binding sitei164SubstrateHMP:1
Metal bindingi192Zinc 2ND:1 Publication1
Metal bindingi248Zinc 2ND:1 Publication1
Metal bindingi326Zinc 1ND:1 Publication1
Binding sitei347Substrate; via carbonyl oxygenHMP:1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
LigandMetal-binding, Zinc

Enzyme and pathway databases

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

Protein family/group databases

MEROPSiM38.973.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydropyrimidinase (EC:3.5.2.2HMP:)
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

EuPathDBiHostDB:ENSG00000147647.12.
HGNCiHGNC:3013. DPYS.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs121964923Ensembl.1
Natural variantiVAR_002269360W → R in DPYSD. 1 PublicationCorresponds to variant dbSNP:rs121964924Ensembl.1
Natural variantiVAR_002270435G → R in DPYSD. 1 PublicationCorresponds to variant dbSNP:rs267606773Ensembl.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 residuei79PhosphoserineND:1
Modified residuei159N6-carboxylysineHMP:1
Modified residuei256N6-succinyllysineHMP:1

Post-translational modificationi

Carbamylation allows a single lysine to coordinate two zinc ions.HMP:

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.IKR:

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108141. 6 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 – 11ND:6
Beta strandi13 – 15ND:3
Beta strandi20 – 22ND:3
Beta strandi24 – 28ND:5
Beta strandi31 – 36ND:6
Beta strandi50 – 53ND:4
Beta strandi57 – 61ND:5
Beta strandi63 – 68ND:6
Beta strandi75 – 78ND:4
Helixi85 – 91ND:7
Turni92 – 94ND:3
Beta strandi95 – 102ND:8
Helixi110 – 121ND:12
Turni122 – 124ND:3
Beta strandi126 – 135ND:10
Helixi140 – 151ND:12
Beta strandi157 – 164ND:8
Turni165 – 168ND:4
Helixi172 – 185ND:14
Beta strandi188 – 192ND:5
Helixi196 – 208ND:13
Helixi215 – 219ND:5
Helixi223 – 240ND:18
Beta strandi244 – 249ND:6
Helixi252 – 263ND:12
Beta strandi268 – 273ND:6
Helixi274 – 278ND:5
Helixi282 – 285ND:4
Helixi289 – 293ND:5
Helixi307 – 316ND:10
Helixi332 – 335ND:4
Helixi336 – 338ND:3
Helixi342 – 344ND:3
Turni352 – 354ND:3
Helixi355 – 363ND:9
Turni364 – 367ND:4
Helixi371 – 378ND:8
Helixi380 – 385ND:6
Turni389 – 391ND:3
Beta strandi403 – 413ND:11
Turni416 – 418ND:3
Beta strandi420 – 422ND:3
Turni427 – 430ND:4
Beta strandi432 – 442ND:11
Beta strandi445 – 449ND:5
Helixi470 – 482ND:13

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.
OMAiIDPQVHF.
OrthoDBiEOG091G05F3.
PhylomeDBiQ14117.
TreeFamiTF314706.

Family and domain databases

CDDicd01314. D-HYD. 1 hit.
Gene3Di2.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR006680. Amidohydro-rel.
IPR011778. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
IPR032466. Metal_Hydrolase.
PfamiView protein in Pfam
PF01979. Amidohydro_1. 1 hit.
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 dbSNP:rs121964923Ensembl.1
Natural variantiVAR_002269360W → R in DPYSD. 1 PublicationCorresponds to variant dbSNP:rs121964924Ensembl.1
Natural variantiVAR_002270435G → R in DPYSD. 1 PublicationCorresponds to variant dbSNP:rs267606773Ensembl.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.

Similar proteinsi

Entry informationi

Entry nameiDPYS_HUMAN
AccessioniPrimary (citable) accession number: Q14117
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: October 25, 2017
This is version 160 of the entry and version 1 of the sequence. See 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