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Protein

Dihydroorotase

Gene

pyrC

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the reversible cyclization of carbamoyl aspartate to dihydroorotate.UniRule annotation2 Publications

Catalytic activityi

(S)-dihydroorotate + H2O = N-carbamoyl-L-aspartate.UniRule annotation2 Publications

Cofactori

Zn2+UniRule annotation5 PublicationsNote: Binds 2 Zn2+ ions per subunit (PubMed:6142052, PubMed:11401542, PubMed:15826651). In vitro, can also use Co2+ or Cd2+ (PubMed:1671037, PubMed:15610022).5 Publications

Kineticsi

kcat is 127 sec(-1) with dihydroorotate as substrate and 195 sec(-1) with N-carbamoyl-DL-aspartate as substrate (PubMed:6142052). kcat is 100 sec(-1) with dihydroorotate as substrate and 160 sec(-1) with carbamoyl aspartate as substrate in the presence of Zn2+. kcat is 15 sec(-1) with dihydroorotate as substrate and 25 sec(-1) with carbamoyl aspartate as substrate in the presence of Co2+. kcat is 1.9 sec(-1) with dihydroorotate as substrate and 8.2 sec(-1) with carbamoyl aspartate as substrate in the presence of Cd2+ (PubMed:15610022).2 Publications
  1. KM=0.0756 mM for dihydroorotate1 Publication
  2. KM=0.080 mM for dihydroorotate (in the presence of Zn2+)1 Publication
  3. KM=0.70 mM for dihydroorotate (in the presence of Co2+)1 Publication
  4. KM=0.23 mM for dihydroorotate (in the presence of Cd2+)1 Publication
  5. KM=1.07 mM for N-carbamoyl-DL-aspartate1 Publication
  6. KM=1.70 mM for carbamoyl aspartate (in the presence of Zn2+)1 Publication
  7. KM=15 mM for carbamoyl aspartate (in the presence of Co2+)1 Publication
  8. KM=4.0 mM for carbamoyl aspartate (in the presence of Cd2+)1 Publication

    Pathwayi: UMP biosynthesis via de novo pathway

    This protein is involved in step 3 of the subpathway that synthesizes (S)-dihydroorotate from bicarbonate.UniRule annotationCurated
    Proteins known to be involved in the 3 steps of the subpathway in this organism are:
    1. Carbamoyl-phosphate synthase large chain (carB), Carbamoyl-phosphate synthase small chain (carA)
    2. Aspartate carbamoyltransferase catalytic subunit (pyrB)
    3. Dihydroorotase (pyrC)
    This subpathway is part of the pathway UMP biosynthesis via de novo pathway, which is itself part of Pyrimidine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes (S)-dihydroorotate from bicarbonate, the pathway UMP biosynthesis via de novo pathway and in Pyrimidine metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi17Zinc 1; via tele nitrogenUniRule annotationCombined sources2 Publications1
    Metal bindingi19Zinc 1; via tele nitrogenUniRule annotationCombined sources2 Publications1
    Binding sitei45SubstrateUniRule annotationCombined sources2 Publications1
    Metal bindingi103Zinc 1; via carbamate groupUniRule annotationCombined sources2 Publications1
    Metal bindingi103Zinc 2; via carbamate groupUniRule annotationCombined sources2 Publications1
    Metal bindingi140Zinc 2; via pros nitrogenUniRule annotationCombined sources2 Publications1
    Binding sitei140SubstrateUniRule annotationCombined sources1 Publication1
    Metal bindingi178Zinc 2; via tele nitrogenUniRule annotationCombined sources2 Publications1
    Binding sitei223Substrate; via amide nitrogen and carbonyl oxygenUniRule annotationCombined sources2 Publications1
    Active sitei251UniRule annotation1 Publication1
    Metal bindingi251Zinc 1UniRule annotationCombined sources2 Publications1
    Binding sitei255SubstrateUniRule annotationCombined sources2 Publications1
    Binding sitei267Substrate; via carbonyl oxygenUniRule annotationCombined sources2 Publications1

    GO - Molecular functioni

    • dihydroorotase activity Source: EcoCyc
    • zinc ion binding Source: EcoCyc

    GO - Biological processi

    Keywordsi

    Molecular functionHydrolase
    Biological processPyrimidine biosynthesis
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    BioCyciEcoCyc:DIHYDROOROT-MONOMER.
    MetaCyc:DIHYDROOROT-MONOMER.
    BRENDAi3.5.2.3. 2026.
    SABIO-RKiP05020.
    UniPathwayiUPA00070; UER00117.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DihydroorotaseUniRule annotation (EC:3.5.2.3UniRule annotation2 Publications)
    Short name:
    DHOaseUniRule annotation
    Gene namesi
    Name:pyrC1 PublicationUniRule annotation
    Ordered Locus Names:b1062, JW1049
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10806. pyrC.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: EcoCyc

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi21R → K: 9-fold decrease in catalytic efficiency with carbamoyl aspartate as substrate. 1 Publication1
    Mutagenesisi21R → M or Q: Lack of activity. 1 Publication1
    Mutagenesisi45N → A: Lack of activity. 1 Publication1
    Mutagenesisi251D → A, H or N: Lack of activity. 1 Publication1
    Mutagenesisi251D → E: 24-fold decrease in catalytic efficiency with carbamoyl aspartate as substrate. 1 Publication1
    Mutagenesisi251D → S: 3500-fold decrease in catalytic efficiency with carbamoyl aspartate as substrate. 1 Publication1
    Mutagenesisi255H → N: Lack of activity. 1 Publication1

    Chemistry databases

    DrugBankiDB02129. Dihydroorotic Acid.
    DB03801. Lysine Nz-Carboxylic Acid.
    DB04252. N-Carbamoyl-L-Aspartate.
    DB02262. Orotic Acid.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00001472052 – 348DihydroorotaseAdd BLAST347

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei103N6-carboxylysineUniRule annotationCombined sources2 Publications1

    Proteomic databases

    PaxDbiP05020.
    PRIDEiP05020.

    Expressioni

    Inductioni

    Induced by pyrimidine limitation.1 Publication

    Interactioni

    Subunit structurei

    Homodimer.UniRule annotation3 Publications

    Protein-protein interaction databases

    BioGridi4261761. 17 interactors.
    DIPiDIP-10624N.
    IntActiP05020. 6 interactors.
    STRINGi316385.ECDH10B_1133.

    Chemistry databases

    BindingDBiP05020.

    Structurei

    Secondary structure

    1348
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi7 – 11Combined sources5
    Beta strandi15 – 18Combined sources4
    Helixi23 – 34Combined sources12
    Beta strandi38 – 42Combined sources5
    Helixi53 – 65Combined sources13
    Beta strandi74 – 80Combined sources7
    Helixi87 – 95Combined sources9
    Beta strandi98 – 104Combined sources7
    Turni113 – 115Combined sources3
    Helixi120 – 123Combined sources4
    Helixi124 – 133Combined sources10
    Beta strandi137 – 139Combined sources3
    Helixi150 – 152Combined sources3
    Helixi153 – 160Combined sources8
    Helixi162 – 168Combined sources7
    Turni169 – 171Combined sources3
    Beta strandi174 – 176Combined sources3
    Helixi182 – 189Combined sources8
    Beta strandi195 – 199Combined sources5
    Helixi201 – 205Combined sources5
    Helixi208 – 212Combined sources5
    Helixi218 – 220Combined sources3
    Helixi229 – 240Combined sources12
    Beta strandi246 – 248Combined sources3
    Helixi257 – 260Combined sources4
    Beta strandi261 – 265Combined sources5
    Turni272 – 274Combined sources3
    Helixi275 – 285Combined sources11
    Helixi289 – 291Combined sources3
    Helixi292 – 297Combined sources6
    Helixi299 – 304Combined sources6
    Beta strandi312 – 316Combined sources5
    Beta strandi329 – 333Combined sources5
    Turni336 – 339Combined sources4
    Beta strandi341 – 343Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1J79X-ray1.70A/B2-348[»]
    1XGEX-ray1.90A/B2-348[»]
    2E25X-ray2.70A2-348[»]
    2EG6X-ray1.70A/B2-348[»]
    2EG7X-ray2.00A/B2-348[»]
    2EG8X-ray2.20A/B2-348[»]
    2Z24X-ray1.90A/B2-348[»]
    2Z25X-ray1.87A/B2-348[»]
    2Z26X-ray1.29A/B2-348[»]
    2Z27X-ray1.87A/B2-348[»]
    2Z28X-ray1.87A/B2-348[»]
    2Z29X-ray1.90A/B2-348[»]
    2Z2AX-ray1.87A/B2-348[»]
    2Z2BX-ray1.85A2-348[»]
    ProteinModelPortaliP05020.
    SMRiP05020.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP05020.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni19 – 21Substrate bindingUniRule annotationCombined sources2 Publications3

    Domaini

    There is an asymmetry between active sites in the dimer, with dihydroorotate bound to the active site of subunit A and N-carbamoyl-L-aspartate bound to the active site of subunit B.1 Publication

    Sequence similaritiesi

    Belongs to the metallo-dependent hydrolases superfamily. DHOase family. Class II DHOase subfamily.UniRule annotationCurated

    Phylogenomic databases

    eggNOGiENOG4105EKE. Bacteria.
    COG0418. LUCA.
    HOGENOMiHOG000256259.
    InParanoidiP05020.
    KOiK01465.
    PhylomeDBiP05020.

    Family and domain databases

    CDDicd01294. DHOase. 1 hit.
    HAMAPiMF_00219. PyrC_classII. 1 hit.
    InterProiView protein in InterPro
    IPR006680. Amidohydro-rel.
    IPR004721. DHOdimr.
    IPR002195. Dihydroorotase_CS.
    IPR032466. Metal_Hydrolase.
    PANTHERiPTHR43137:SF1. PTHR43137:SF1. 1 hit.
    PfamiView protein in Pfam
    PF01979. Amidohydro_1. 1 hit.
    PIRSFiPIRSF001237. DHOdimr. 1 hit.
    SFLDiSFLDF00074. dihydroorotase3. 1 hit.
    SUPFAMiSSF51556. SSF51556. 1 hit.
    TIGRFAMsiTIGR00856. pyrC_dimer. 1 hit.
    PROSITEiView protein in PROSITE
    PS00482. DIHYDROOROTASE_1. 1 hit.
    PS00483. DIHYDROOROTASE_2. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P05020-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MTAPSQVLKI RRPDDWHLHL RDGDMLKTVV PYTSEIYGRA IVMPNLAPPV
    60 70 80 90 100
    TTVEAAVAYR QRILDAVPAG HDFTPLMTCY LTDSLDPNEL ERGFNEGVFT
    110 120 130 140 150
    AAKLYPANAT TNSSHGVTSI DAIMPVLERM EKIGMPLLVH GEVTHADIDI
    160 170 180 190 200
    FDREARFIES VMEPLRQRLT ALKVVFEHIT TKDAADYVRD GNERLAATIT
    210 220 230 240 250
    PQHLMFNRNH MLVGGVRPHL YCLPILKRNI HQQALRELVA SGFNRVFLGT
    260 270 280 290 300
    DSAPHARHRK ESSCGCAGCF NAPTALGSYA TVFEEMNALQ HFEAFCSVNG
    310 320 330 340
    PQFYGLPVND TFIELVREEQ QVAESIALTD DTLVPFLAGE TVRWSVKQ
    Length:348
    Mass (Da):38,827
    Last modified:January 23, 2007 - v2
    Checksum:i179B35324204A111
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X04469 Genomic DNA. Translation: CAA28157.1.
    M16752 Genomic DNA. Translation: AAA24482.1.
    U00096 Genomic DNA. Translation: AAC74146.1.
    AP009048 Genomic DNA. Translation: BAA35870.1.
    D31709 Genomic DNA. Translation: BAA06514.1.
    PIRiA25008. DEECOO.
    RefSeqiNP_415580.1. NC_000913.3.
    WP_000126534.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC74146; AAC74146; b1062.
    BAA35870; BAA35870; BAA35870.
    GeneIDi945787.
    KEGGiecj:JW1049.
    eco:b1062.
    PATRICifig|1411691.4.peg.1206.

    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.

    Entry informationi

    Entry nameiPYRC_ECOLI
    AccessioniPrimary (citable) accession number: P05020
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: January 23, 2007
    Last modified: July 5, 2017
    This is version 162 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families