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Q14117

- DPYS_HUMAN

UniProt

Q14117 - DPYS_HUMAN

Protein

Dihydropyrimidinase

Gene

DPYS

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 131 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    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

    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

    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

    ArrayExpressiQ14117.
    BgeeiQ14117.
    CleanExiHS_DPYS.
    GenevestigatoriQ14117.

    Organism-specific databases

    HPAiHPA024785.

    Interactioni

    Subunit structurei

    Homotetramer.1 Publication

    Protein-protein interaction databases

    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.
    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

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    MAAPSRLLIR GGRVVNDDFS EVADVLVEDG VVRALGHDLL PPGGAPAGLR    50
    VLDAAGKLVL PGGIDTHTHM QFPFMGSRSI DDFHQGTKAA LSGGTTMIID 100
    FAIPQKGGSL IEAFETWRSW ADPKVCCDYS LHVAVTWWSD QVKEEMKILV 150
    QDKGVNSFKM FMAYKDLYMV TDLELYEAFS RCKEIGAIAQ VHAENGDLIA 200
    EGAKKMLALG ITGPEGHELC RPEAVEAEAT LRAITIASAV NCPLYIVHVM 250
    SKSAAKVIAD ARRDGKVVYG EPIAASLGTD GTHYWNKEWH HAAHHVMGPP 300
    LRPDPSTPDF LMNLLANDDL TTTGTDNCTF NTCQKALGKD DFTKIPNGVN 350
    GVEDRMSVIW EKGVHSGKMD ENRFVAVTST NAAKIFNLYP RKGRIAVGSD 400
    ADIVIWDPKG TRTISAKTHH QAVNFNIFEG MVCHGVPLVT ISRGKVVYEA 450
    GVFSVTAGDG KFIPRKPFAE YIYKRIKQRD RTCTPTPVER APYKGEVATL 500
    KSRVTKEDAT AGTRKQAHP 519
    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

    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.
    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

    ArrayExpressi Q14117.
    Bgeei Q14117.
    CleanExi HS_DPYS.
    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

    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 1, 2014
    This is version 131 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