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Q14117

- DPYS_HUMAN

UniProt

Q14117 - DPYS_HUMAN

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Protein

Dihydropyrimidinase

Gene

DPYS

Organism
Homo sapiens (Human)
Status
Reviewed - 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.

Cofactori

Binds 2 zinc ions per subunit.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi67 – 671Zinc 1
Metal bindingi69 – 691Zinc 1
Metal bindingi159 – 1591Zinc 1; via carbamate group
Metal bindingi159 – 1591Zinc 2; via carbamate group
Binding sitei164 – 1641SubstrateBy similarity
Metal bindingi192 – 1921Zinc 2
Metal bindingi248 – 2481Zinc 2
Metal bindingi326 – 3261Zinc 1
Binding sitei347 – 3471Substrate; via carbonyl oxygenBy similarity

GO - Molecular functioni

  1. amino acid binding Source: Ensembl
  2. dihydropyrimidinase activity Source: UniProtKB
  3. thymine binding Source: Ensembl
  4. uracil binding Source: Ensembl
  5. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. beta-alanine metabolic process Source: Ensembl
  2. nucleobase-containing small molecule metabolic process Source: Reactome
  3. protein homotetramerization Source: UniProtKB
  4. pyrimidine nucleobase catabolic process Source: UniProtKB
  5. pyrimidine nucleobase metabolic process Source: Reactome
  6. pyrimidine nucleoside catabolic process Source: Reactome
  7. small molecule metabolic process Source: Reactome
  8. thymine catabolic process Source: UniProtKB
  9. uracil catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_1023. Pyrimidine catabolism.

Protein family/group databases

MEROPSiM38.973.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydropyrimidinase (EC:3.5.2.2)
Short name:
DHP
Short name:
DHPase
Alternative name(s):
Dihydropyrimidine amidohydrolase
Hydantoinase
Gene namesi
Name:DPYS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:3013. DPYS.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: UniProtKB
  2. extracellular vesicular exosome Source: UniProt
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti68 – 681T → R in DHPD. 1 Publication
VAR_002267
Natural varianti334 – 3341Q → R in DHPD. 1 Publication
Corresponds to variant rs121964923 [ dbSNP | Ensembl ].
VAR_002268
Natural varianti360 – 3601W → R in DHPD. 1 Publication
Corresponds to variant rs121964924 [ dbSNP | Ensembl ].
VAR_002269
Natural varianti435 – 4351G → R in DHPD. 1 Publication
VAR_002270
Natural varianti490 – 4901R → T in DHPD. 1 Publication
VAR_002271

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi222748. phenotype.
Orphaneti38874. Dihydropyrimidinuria.
PharmGKBiPA146.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 519519DihydropyrimidinasePRO_0000165906Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei159 – 1591N6-carboxylysineBy similarity
Modified residuei256 – 2561N6-succinyllysineBy similarity

Post-translational modificationi

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

Proteomic databases

PaxDbiQ14117.
PRIDEiQ14117.

PTM databases

PhosphoSiteiQ14117.

Expressioni

Tissue specificityi

Liver and kidney.

Gene expression databases

BgeeiQ14117.
CleanExiHS_DPYS.
ExpressionAtlasiQ14117. baseline and differential.
GenevestigatoriQ14117.

Organism-specific databases

HPAiHPA024785.

Interactioni

Subunit structurei

Homotetramer.1 Publication

Protein-protein interaction databases

BioGridi108141. 2 interactions.
STRINGi9606.ENSP00000276651.

Structurei

Secondary structure

1
519
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 116
Beta strandi13 – 153
Beta strandi20 – 223
Beta strandi24 – 285
Beta strandi31 – 366
Beta strandi50 – 534
Beta strandi57 – 615
Beta strandi63 – 686
Beta strandi75 – 784
Helixi85 – 917
Turni92 – 943
Beta strandi95 – 1028
Helixi110 – 12112
Turni122 – 1243
Beta strandi126 – 13510
Helixi140 – 15112
Beta strandi157 – 1648
Turni165 – 1684
Helixi172 – 18514
Beta strandi188 – 1925
Helixi196 – 20813
Helixi215 – 2195
Helixi223 – 24018
Beta strandi244 – 2496
Helixi252 – 26312
Beta strandi268 – 2736
Helixi274 – 2785
Helixi282 – 2854
Helixi289 – 2935
Helixi307 – 31610
Helixi332 – 3354
Helixi336 – 3383
Helixi342 – 3443
Turni352 – 3543
Helixi355 – 3639
Turni364 – 3674
Helixi371 – 3788
Helixi380 – 3856
Turni389 – 3913
Beta strandi403 – 41311
Turni416 – 4183
Beta strandi420 – 4223
Turni427 – 4304
Beta strandi432 – 44211
Beta strandi445 – 4495
Helixi470 – 48213

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2VR2X-ray2.80A1-519[»]
ProteinModelPortaliQ14117.
SMRiQ14117. Positions 5-493.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14117.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0044.
GeneTreeiENSGT00760000119241.
HOGENOMiHOG000219145.
HOVERGENiHBG000806.
InParanoidiQ14117.
KOiK01464.
OMAiAVDYNIF.
OrthoDBiEOG7SJD48.
PhylomeDBiQ14117.
TreeFamiTF314706.

Family and domain databases

Gene3Di2.30.40.10. 2 hits.
InterProiIPR006680. Amidohydro_1.
IPR011778. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
[Graphical view]
PfamiPF01979. Amidohydro_1. 1 hit.
[Graphical view]
SUPFAMiSSF51338. SSF51338. 2 hits.
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti68 – 681T → R in DHPD. 1 Publication
VAR_002267
Natural varianti334 – 3341Q → R in DHPD. 1 Publication
Corresponds to variant rs121964923 [ dbSNP | Ensembl ].
VAR_002268
Natural varianti360 – 3601W → R in DHPD. 1 Publication
Corresponds to variant rs121964924 [ dbSNP | Ensembl ].
VAR_002269
Natural varianti435 – 4351G → R in DHPD. 1 Publication
VAR_002270
Natural varianti490 – 4901R → T in DHPD. 1 Publication
VAR_002271

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.4. human.

Polymorphism databases

DMDMi3122049.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D78011 mRNA. Translation: BAA11189.1 .
AB004678 Genomic DNA. Translation: BAA33067.1 .
BC034395 mRNA. Translation: AAH34395.1 .
CCDSi CCDS6302.1.
PIRi JC5315.
RefSeqi NP_001376.1. NM_001385.2.
UniGenei Hs.443161.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2VR2 X-ray 2.80 A 1-519 [» ]
ProteinModelPortali Q14117.
SMRi Q14117. Positions 5-493.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108141. 2 interactions.
STRINGi 9606.ENSP00000276651.

Protein family/group databases

MEROPSi M38.973.

PTM databases

PhosphoSitei Q14117.

Polymorphism databases

DMDMi 3122049.

Proteomic databases

PaxDbi Q14117.
PRIDEi Q14117.

Protocols and materials databases

DNASUi 1807.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000351513 ; ENSP00000276651 ; ENSG00000147647 .
GeneIDi 1807.
KEGGi hsa:1807.
UCSCi uc003yly.4. human.

Organism-specific databases

CTDi 1807.
GeneCardsi GC08M105391.
HGNCi HGNC:3013. DPYS.
HPAi HPA024785.
MIMi 222748. phenotype.
613326. gene.
neXtProti NX_Q14117.
Orphaneti 38874. Dihydropyrimidinuria.
PharmGKBi PA146.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0044.
GeneTreei ENSGT00760000119241.
HOGENOMi HOG000219145.
HOVERGENi HBG000806.
InParanoidi Q14117.
KOi K01464.
OMAi AVDYNIF.
OrthoDBi EOG7SJD48.
PhylomeDBi Q14117.
TreeFami TF314706.

Enzyme and pathway databases

Reactomei REACT_1023. Pyrimidine catabolism.

Miscellaneous databases

EvolutionaryTracei Q14117.
GeneWikii DPYS.
GenomeRNAii 1807.
NextBioi 7365.
PROi Q14117.
SOURCEi Search...

Gene expression databases

Bgeei Q14117.
CleanExi HS_DPYS.
ExpressionAtlasi Q14117. baseline and differential.
Genevestigatori Q14117.

Family and domain databases

Gene3Di 2.30.40.10. 2 hits.
InterProi IPR006680. Amidohydro_1.
IPR011778. Hydantoinase/dihydroPyrase.
IPR011059. Metal-dep_hydrolase_composite.
[Graphical view ]
Pfami PF01979. Amidohydro_1. 1 hit.
[Graphical view ]
SUPFAMi SSF51338. SSF51338. 2 hits.
TIGRFAMsi TIGR02033. D-hydantoinase. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

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: October 29, 2014
This is version 132 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

External Data

Dasty 3