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Protein

2,4-dienoyl-CoA reductase

Gene

fadH

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

Functioni

Functions as an auxiliary enzyme in the beta-oxidation of unsaturated fatty acids with double bonds at even carbon positions. Catalyzes the NADPH-dependent reduction of the C4-C5 double bond of the acyl chain of 2,4-dienoyl-CoA to yield 2-trans-enoyl-CoA (PubMed:9346310, PubMed:6363415). Acts on both isomers, 2-trans,4-cis- and 2-trans,4-trans-decadienoyl-CoA, with almost equal efficiency (PubMed:6363415). Is not active with NADH instead of NADPH (PubMed:6363415). Does not show cis->trans isomerase activity (PubMed:10933894).3 Publications

Miscellaneous

The overall reaction mechanism can be divided into three stages: initially, reduction of FAD by NADPH, then electron transfer from FAD to FMN via the 4Fe-4S cluster, and finally reduction of substrate.1 Publication

Catalytic activityi

Trans-2,3-didehydroacyl-CoA + NADP+ = trans,trans-2,3,4,5-tetradehydroacyl-CoA + NADPH.3 Publications
(2E)-decenoyl-CoA + NADP+ = (2E,4E)-decadienoyl-CoA + NADPH.3 Publications
(2E)-decenoyl-CoA + NADP+ = (2E,4Z)-decadienoyl-CoA + NADPH.1 Publication

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Is non-competitively inhibited by NADH.1 Publication

Kineticsi

kcat is 16 sec(-1) for the NADPH-reduction of (2E,4E)-decadienoyl-CoA.1 Publication
  1. KM=50 µM for NADPH1 Publication
  2. KM=10.1 µM for NADPH1 Publication
  3. KM=2.3 µM for (2E,4E)-decadienoyl-CoA1 Publication
  4. KM=8.8 µM for (2E,4E)-decadienoyl-CoA1 Publication
  5. KM=4.1 µM for (2E,4Z)-decadienoyl-CoA1 Publication

    Pathwayi: fatty acid beta-oxidation

    This protein is involved in the pathway fatty acid beta-oxidation, which is part of Lipid metabolism.2 Publications
    View all proteins of this organism that are known to be involved in the pathway fatty acid beta-oxidation and in Lipid metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei59FMN; via amide nitrogenCombined sources1 Publication1
    Binding sitei101FMNCombined sources1 Publication1
    Active sitei167Proton donor2 Publications1
    Binding sitei176SubstrateCombined sources1 Publication1
    Binding sitei215FMNCombined sources1 Publication1
    Sitei253Important for catalytic activity, assists active site Tyr in protonation of C42 Publications1
    Binding sitei289FMN; via amide nitrogenCombined sources1 Publication1
    Metal bindingi335Iron-sulfur (4Fe-4S)Combined sources1 Publication1
    Metal bindingi338Iron-sulfur (4Fe-4S)Combined sources1 Publication1
    Binding sitei340FADCombined sources1 Publication1
    Binding sitei340NADPCombined sources1 Publication1
    Metal bindingi342Iron-sulfur (4Fe-4S)Combined sources1 Publication1
    Metal bindingi354Iron-sulfur (4Fe-4S)Combined sources1 Publication1
    Binding sitei385FAD; via amide nitrogenCombined sources1 Publication1
    Binding sitei404FADCombined sources1 Publication1
    Binding sitei412FADCombined sources1 Publication1
    Binding sitei422FADCombined sources1 Publication1
    Binding sitei449FAD; via amide nitrogen and carbonyl oxygenCombined sources1 Publication1
    Binding sitei567SubstrateCombined sources1 Publication1
    Binding sitei578SubstrateCombined sources1 Publication1
    Binding sitei649FAD; via amide nitrogenCombined sources1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi25 – 27FMNCombined sources1 Publication3
    Nucleotide bindingi311 – 312FMNCombined sources1 Publication2
    Nucleotide bindingi563 – 564NADPCombined sources1 Publication2
    Nucleotide bindingi654 – 656NADPCombined sources1 Publication3
    Nucleotide bindingi656 – 658FADCombined sources1 Publication3

    GO - Molecular functioni

    • 2,4-dienoyl-CoA reductase (NADPH) activity Source: EcoCyc
    • 4 iron, 4 sulfur cluster binding Source: EcoCyc
    • FAD binding Source: EcoCyc
    • FMN binding Source: EcoCyc
    • metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    • fatty acid beta-oxidation, unsaturated, even number, reductase/isomerase pathway Source: EcoCyc

    Keywordsi

    Molecular functionOxidoreductase
    Ligand4Fe-4S, FAD, Flavoprotein, FMN, Iron, Iron-sulfur, Metal-binding, NADP

    Enzyme and pathway databases

    BioCyciEcoCyc:DIENOYLCOAREDUCT-MONOMER.
    MetaCyc:DIENOYLCOAREDUCT-MONOMER.
    BRENDAi1.3.1.34. 2026.
    UniPathwayiUPA00659.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    2,4-dienoyl-CoA reductase2 Publications (EC:1.3.1.343 Publications)
    Short name:
    DCR1 Publication
    Alternative name(s):
    2,4-dienoyl-coenzyme A reductase [NADPH]1 Publication
    Gene namesi
    Name:fadH1 Publication
    Synonyms:ygjL
    Ordered Locus Names:b3081, JW3052
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG12723. fadH.

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi165E → A: Exhibits 1.3% of wild-type activity. 1 Publication1
    Mutagenesisi165E → Q: Loss of enzyme activity; when associated with Ala-167. 1 Publication1
    Mutagenesisi167Y → F: Forms 3-enoyl-CoA as the product of the reaction instead of 2-enoyl-CoA, at a rate which is 26% of wild-type. 2-fold increase in substrate affinity. Loss of enzyme activity; when associated with Gln-165. 1 Publication1
    Mutagenesisi253H → A: 1000-fold reduction in enzyme activity. Forms both 3-enoyl-CoA and 2-enoyl-CoA as products of the reaction. 1 Publication1
    Mutagenesisi253H → F: Loss of enzyme activity. 1 Publication1
    Mutagenesisi338C → A: 1000-fold reduction in enzyme activity. Highly affects iron-sulfur cluster binding. 1 Publication1

    Chemistry databases

    DrugBankiDB03461. 2'-Monophosphoadenosine 5'-Diphosphoribose.
    DB03698. 5-Mercaptoethanol-2-Decenoyl-Coenzyme A.
    DB03147. Flavin adenine dinucleotide.
    DB03247. Riboflavin Monophosphate.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00001944822 – 6722,4-dienoyl-CoA reductaseAdd BLAST671

    Proteomic databases

    PaxDbiP42593.
    PRIDEiP42593.

    Expressioni

    Inductioni

    Induced when cells are grown on oleate as sole carbon source. Repressed by glucose.1 Publication

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi4261984. 13 interactors.
    DIPiDIP-9562N.
    IntActiP42593. 10 interactors.
    STRINGi511145.b3081.

    Structurei

    Secondary structure

    1672
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Turni4 – 7Combined sources4
    Beta strandi16 – 23Combined sources8
    Helixi36 – 49Combined sources14
    Beta strandi53 – 64Combined sources12
    Helixi78 – 80Combined sources3
    Helixi81 – 93Combined sources13
    Beta strandi98 – 102Combined sources5
    Helixi106 – 108Combined sources3
    Beta strandi109 – 111Combined sources3
    Beta strandi115 – 119Combined sources5
    Helixi134 – 153Combined sources20
    Beta strandi157 – 163Combined sources7
    Helixi168 – 173Combined sources6
    Turni175 – 177Combined sources3
    Beta strandi185 – 187Combined sources3
    Helixi188 – 206Combined sources19
    Beta strandi208 – 219Combined sources12
    Helixi228 – 241Combined sources14
    Beta strandi244 – 250Combined sources7
    Beta strandi259 – 261Combined sources3
    Turni266 – 269Combined sources4
    Helixi270 – 276Combined sources7
    Beta strandi284 – 286Combined sources3
    Helixi293 – 301Combined sources9
    Beta strandi306 – 311Combined sources6
    Helixi313 – 316Combined sources4
    Helixi320 – 325Combined sources6
    Helixi329 – 331Combined sources3
    Turni340 – 342Combined sources3
    Helixi343 – 347Combined sources5
    Turni358 – 361Combined sources4
    Turni363 – 365Combined sources3
    Beta strandi376 – 380Combined sources5
    Helixi384 – 394Combined sources11
    Turni395 – 397Combined sources3
    Beta strandi399 – 409Combined sources11
    Helixi413 – 416Combined sources4
    Helixi425 – 439Combined sources15
    Beta strandi442 – 446Combined sources5
    Beta strandi451 – 454Combined sources4
    Beta strandi457 – 462Combined sources6
    Beta strandi466 – 468Combined sources3
    Turni475 – 477Combined sources3
    Beta strandi481 – 483Combined sources3
    Helixi484 – 488Combined sources5
    Beta strandi496 – 501Combined sources6
    Helixi504 – 514Combined sources11
    Helixi521 – 523Combined sources3
    Helixi525 – 531Combined sources7
    Helixi541 – 543Combined sources3
    Beta strandi555 – 561Combined sources7
    Turni568 – 571Combined sources4
    Turni574 – 576Combined sources3
    Helixi577 – 586Combined sources10
    Beta strandi590 – 592Combined sources3
    Beta strandi596 – 601Combined sources6
    Beta strandi604 – 609Combined sources6
    Beta strandi612 – 616Combined sources5
    Beta strandi619 – 623Combined sources5
    Beta strandi627 – 629Combined sources3
    Helixi634 – 638Combined sources5
    Turni639 – 641Combined sources3
    Beta strandi644 – 646Combined sources3
    Helixi648 – 650Combined sources3
    Helixi658 – 671Combined sources14

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1PS9X-ray2.20A2-672[»]
    ProteinModelPortaliP42593.
    SMRiP42593.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP42593.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni253 – 256Substrate bindingCombined sources1 Publication4

    Domaini

    Is composed of three domains: an N-terminal TIM barrel (residues 1-368) which binds FMN, the 4Fe-4S cluster, and the substrate; a flavodoxin-like fold (residues 369-467 and 626-671) which binds FAD; and an NADP(H)-binding domain (residues 468-625).1 Publication

    Sequence similaritiesi

    In the N-terminal section; belongs to the NADH:flavin oxidoreductase/NADH oxidase family.Curated

    Phylogenomic databases

    eggNOGiENOG4105CCY. Bacteria.
    COG0446. LUCA.
    COG1902. LUCA.
    HOGENOMiHOG000237760.
    InParanoidiP42593.
    KOiK00219.
    PhylomeDBiP42593.

    Family and domain databases

    Gene3Di3.20.20.70. 1 hit.
    3.50.50.60. 2 hits.
    InterProiView protein in InterPro
    IPR013785. Aldolase_TIM.
    IPR023753. FAD/NAD-binding_dom.
    IPR001155. OxRdtase_FMN_N.
    PfamiView protein in Pfam
    PF00724. Oxidored_FMN. 1 hit.
    PF07992. Pyr_redox_2. 1 hit.
    SUPFAMiSSF51905. SSF51905. 1 hit.

    Sequencei

    Sequence statusi: Complete.

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

    P42593-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSYPSLFAPL DLGFTTLKNR VLMGSMHTGL EEYPDGAERL AAFYAERARH
    60 70 80 90 100
    GVALIVSGGI APDLTGVGME GGAMLNDASQ IPHHRTITEA VHQEGGKIAL
    110 120 130 140 150
    QILHTGRYSY QPHLVAPSAL QAPINRFVPH ELSHEEILQL IDNFARCAQL
    160 170 180 190 200
    AREAGYDGVE VMGSEGYLIN EFLTLRTNQR SDQWGGDYRN RMRFAVEVVR
    210 220 230 240 250
    AVRERVGNDF IIIYRLSMLD LVEDGGTFAE TVELAQAIEA AGATIINTGI
    260 270 280 290 300
    GWHEARIPTI ATPVPRGAFS WVTRKLKGHV SLPLVTTNRI NDPQVADDIL
    310 320 330 340 350
    SRGDADMVSM ARPFLADAEL LSKAQSGRAD EINTCIGCNQ ACLDQIFVGK
    360 370 380 390 400
    VTSCLVNPRA CHETKMPILP AVQKKNLAVV GAGPAGLAFA INAAARGHQV
    410 420 430 440 450
    TLFDAHSEIG GQFNIAKQIP GKEEFYETLR YYRRMIEVTG VTLKLNHTVT
    460 470 480 490 500
    ADQLQAFDET ILASGIVPRT PPIDGIDHPK VLSYLDVLRD KAPVGNKVAI
    510 520 530 540 550
    IGCGGIGFDT AMYLSQPGES TSQNIAGFCN EWGIDSSLQQ AGGLSPQGMQ
    560 570 580 590 600
    IPRSPRQIVM LQRKASKPGQ GLGKTTGWIH RTTLLSRGVK MIPGVSYQKI
    610 620 630 640 650
    DDDGLHVVIN GETQVLAVDN VVICAGQEPN RALAQPLIDS GKTVHLIGGC
    660 670
    DVAMELDARR AIAQGTRLAL EI
    Length:672
    Mass (Da):72,678
    Last modified:January 23, 2007 - v3
    Checksum:iB26C7CAAACE760C3
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U93405 Genomic DNA. Translation: AAB82738.1.
    U18997 Genomic DNA. Translation: AAA57882.1.
    U00096 Genomic DNA. Translation: AAC76116.1.
    AP009048 Genomic DNA. Translation: BAE77131.1.
    PIRiF65096.
    RefSeqiNP_417552.1. NC_000913.3.
    WP_000121433.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC76116; AAC76116; b3081.
    BAE77131; BAE77131; BAE77131.
    GeneIDi947594.
    KEGGiecj:JW3052.
    eco:b3081.
    PATRICifig|511145.12.peg.3176.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U93405 Genomic DNA. Translation: AAB82738.1.
    U18997 Genomic DNA. Translation: AAA57882.1.
    U00096 Genomic DNA. Translation: AAC76116.1.
    AP009048 Genomic DNA. Translation: BAE77131.1.
    PIRiF65096.
    RefSeqiNP_417552.1. NC_000913.3.
    WP_000121433.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1PS9X-ray2.20A2-672[»]
    ProteinModelPortaliP42593.
    SMRiP42593.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi4261984. 13 interactors.
    DIPiDIP-9562N.
    IntActiP42593. 10 interactors.
    STRINGi511145.b3081.

    Chemistry databases

    DrugBankiDB03461. 2'-Monophosphoadenosine 5'-Diphosphoribose.
    DB03698. 5-Mercaptoethanol-2-Decenoyl-Coenzyme A.
    DB03147. Flavin adenine dinucleotide.
    DB03247. Riboflavin Monophosphate.

    Proteomic databases

    PaxDbiP42593.
    PRIDEiP42593.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC76116; AAC76116; b3081.
    BAE77131; BAE77131; BAE77131.
    GeneIDi947594.
    KEGGiecj:JW3052.
    eco:b3081.
    PATRICifig|511145.12.peg.3176.

    Organism-specific databases

    EchoBASEiEB2582.
    EcoGeneiEG12723. fadH.

    Phylogenomic databases

    eggNOGiENOG4105CCY. Bacteria.
    COG0446. LUCA.
    COG1902. LUCA.
    HOGENOMiHOG000237760.
    InParanoidiP42593.
    KOiK00219.
    PhylomeDBiP42593.

    Enzyme and pathway databases

    UniPathwayiUPA00659.
    BioCyciEcoCyc:DIENOYLCOAREDUCT-MONOMER.
    MetaCyc:DIENOYLCOAREDUCT-MONOMER.
    BRENDAi1.3.1.34. 2026.

    Miscellaneous databases

    EvolutionaryTraceiP42593.
    PROiPR:P42593.

    Family and domain databases

    Gene3Di3.20.20.70. 1 hit.
    3.50.50.60. 2 hits.
    InterProiView protein in InterPro
    IPR013785. Aldolase_TIM.
    IPR023753. FAD/NAD-binding_dom.
    IPR001155. OxRdtase_FMN_N.
    PfamiView protein in Pfam
    PF00724. Oxidored_FMN. 1 hit.
    PF07992. Pyr_redox_2. 1 hit.
    SUPFAMiSSF51905. SSF51905. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiFADH_ECOLI
    AccessioniPrimary (citable) accession number: P42593
    Secondary accession number(s): Q2M9C5
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: January 23, 2007
    Last modified: June 7, 2017
    This is version 153 of the entry and version 3 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

    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.