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Protein

Flavohemoprotein

Gene

hmp

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

Functioni

Is involved in NO detoxification in an aerobic process, termed nitric oxide dioxygenase (NOD) reaction that utilizes O2 and NAD(P)H to convert NO to nitrate, which protects the bacterium from various noxious nitrogen compounds. Therefore, plays a central role in the inducible response to nitrosative stress.
In the presence of oxygen and NADH, HMP has NADH oxidase activity, which leads to the generation of superoxide and H2O2, both in vitro and in vivo, and it has been suggested that HMP might act as an amplifier of superoxide stress. Under anaerobic conditions, HMP also exhibits nitric oxide reductase and FAD reductase activities. However, all these reactions are much lower than NOD activity.
Various electron acceptors are also reduced by HMP in vitro, including dihydropterine, ferrisiderophores, ferric citrate, cytochrome c, nitrite, S-nitrosoglutathione, and alkylhydroperoxides. However, it is unknown if these reactions are of any biological significance in vivo.

Catalytic activityi

2 nitric oxide + 2 O2 + NAD(P)H = 2 nitrate + NAD(P)+ + H+.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • FADNote: Binds 1 FAD per subunit.
  • heme bNote: Binds 1 heme b group per subunit.

Kineticsi

  1. KM=0.28 µM for NO1 Publication
  2. KM=90 µM for O21 Publication
  3. KM=1.8 µM for NADH1 Publication
  4. KM=19.6 µM for NADPH1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei29Involved in heme-bound ligand stabilization and O-O bond activation1
    Sitei84Influences the redox potential of the prosthetic heme and FAD groups1
    Metal bindingi85Iron (heme proximal ligand)1
    Active sitei95Charge relay system1 Publication1
    Active sitei135Charge relay system1 Publication1
    Binding sitei188FAD1
    Sitei388Influences the redox potential of the prosthetic heme and FAD groups1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi204 – 207FAD4
    Nucleotide bindingi268 – 273NADPBy similarity6
    Nucleotide bindingi389 – 392FAD4

    GO - Molecular functioni

    • FAD binding Source: EcoCyc
    • fatty acid binding Source: EcoCyc
    • heme binding Source: EcoCyc
    • hydroperoxide reductase activity Source: EcoCyc
    • metal ion binding Source: UniProtKB-KW
    • nitric oxide dioxygenase activity Source: EcoCyc
    • oxygen binding Source: InterPro
    • oxygen transporter activity Source: UniProtKB-HAMAP

    GO - Biological processi

    • cellular response to nitrosative stress Source: GO_Central
    • nitric oxide catabolic process Source: GO_Central
    • response to nitrosative stress Source: EcoCyc
    • response to toxic substance Source: UniProtKB-KW
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Detoxification, Oxygen transport, Transport

    Keywords - Ligandi

    FAD, Flavoprotein, Heme, Iron, Metal-binding, NAD, NADP

    Enzyme and pathway databases

    BioCyciEcoCyc:EG10456-MONOMER.
    ECOL316407:JW2536-MONOMER.
    MetaCyc:EG10456-MONOMER.
    BRENDAi1.14.12.17. 2026.
    SABIO-RKP24232.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Flavohemoprotein
    Alternative name(s):
    Flavohemoglobin
    HMP
    Hemoglobin-like protein
    Nitric oxide dioxygenase (EC:1.14.12.17)
    Short name:
    NO oxygenase
    Short name:
    NOD
    Gene namesi
    Name:hmp
    Synonyms:fsrB, hmpA
    Ordered Locus Names:b2552, JW2536
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10456. hmp.

    Subcellular locationi

    • Cytoplasm 1 Publication

    • Note: Has also been found to localize into the periplasm, but spectral analysis revealed that biochemically active HMP is exclusively found in the cytoplasmic fraction.

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi29Y → E or H: 15 to 35-fold reduction in NO dioxygenase activity. 1 Publication1
    Mutagenesisi29Y → F: 30-fold reduction in NO dioxygenase activity, and 80-fold increase in the O(2) dissociation rate constant. 1 Publication1

    Chemistry databases

    DrugBankiDB03147. Flavin adenine dinucleotide.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000524311 – 396FlavohemoproteinAdd BLAST396

    Proteomic databases

    EPDiP24232.
    PaxDbiP24232.
    PRIDEiP24232.

    Expressioni

    Inductioni

    By nitric oxyde NO (under aerobic conditions), nitrite, nitrate (under anaerobic conditions), nitroso compounds, and paraquat.3 Publications

    Interactioni

    Subunit structurei

    Monomer.

    Protein-protein interaction databases

    BioGridi4259200. 11 interactors.
    IntActiP24232. 4 interactors.
    STRINGi511145.b2552.

    Structurei

    Secondary structure

    1396
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi4 – 18Combined sources15
    Helixi21 – 35Combined sources15
    Helixi37 – 41Combined sources5
    Helixi52 – 65Combined sources14
    Helixi66 – 74Combined sources9
    Helixi75 – 87Combined sources13
    Helixi92 – 110Combined sources19
    Helixi114 – 144Combined sources31
    Beta strandi150 – 162Combined sources13
    Beta strandi164 – 174Combined sources11
    Beta strandi188 – 193Combined sources6
    Beta strandi202 – 207Combined sources6
    Beta strandi217 – 222Combined sources6
    Helixi228 – 235Combined sources8
    Beta strandi242 – 249Combined sources8
    Beta strandi262 – 267Combined sources6
    Helixi268 – 271Combined sources4
    Helixi272 – 283Combined sources12
    Beta strandi290 – 297Combined sources8
    Turni299 – 301Combined sources3
    Helixi305 – 313Combined sources9
    Beta strandi315 – 326Combined sources12
    Helixi329 – 334Combined sources6
    Beta strandi338 – 342Combined sources5
    Helixi345 – 347Combined sources3
    Beta strandi348 – 350Combined sources3
    Beta strandi358 – 363Combined sources6
    Helixi365 – 377Combined sources13
    Helixi382 – 384Combined sources3
    Beta strandi385 – 388Combined sources4
    Beta strandi390 – 392Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1GVHX-ray2.19A1-396[»]
    ProteinModelPortaliP24232.
    SMRiP24232.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP24232.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini150 – 255FAD-binding FR-typeAdd BLAST106

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni1 – 138GlobinAdd BLAST138
    Regioni147 – 396ReductaseAdd BLAST250
    Regioni259 – 396NAD or NADP-bindingAdd BLAST138

    Domaini

    Consists of two distinct domains; an N-terminal heme-containing oxygen-binding domain and a C-terminal reductase domain with binding sites for FAD and NAD(P)H.

    Sequence similaritiesi

    In the C-terminal section; belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.Curated
    Contains 1 FAD-binding FR-type domain.Curated

    Phylogenomic databases

    eggNOGiENOG4105CJJ. Bacteria.
    COG1017. LUCA.
    COG1018. LUCA.
    HOGENOMiHOG000238921.
    InParanoidiP24232.
    KOiK05916.
    OMAiDQYQIVG.
    PhylomeDBiP24232.

    Family and domain databases

    Gene3Di1.10.490.10. 1 hit.
    HAMAPiMF_01252. Hmp. 1 hit.
    InterProiIPR017927. Fd_Rdtase_FAD-bd.
    IPR000971. Globin.
    IPR009050. Globin-like.
    IPR012292. Globin/Proto.
    IPR023950. Hmp.
    IPR008333. OxRdtase_FAD-bd_dom.
    IPR001433. OxRdtase_FAD/NAD-bd.
    IPR001221. Phe_hydroxylase.
    IPR017938. Riboflavin_synthase-like_b-brl.
    [Graphical view]
    PfamiPF00970. FAD_binding_6. 1 hit.
    PF00042. Globin. 1 hit.
    PF00175. NAD_binding_1. 1 hit.
    [Graphical view]
    PRINTSiPR00410. PHEHYDRXLASE.
    SUPFAMiSSF46458. SSF46458. 1 hit.
    SSF63380. SSF63380. 1 hit.
    PROSITEiPS51384. FAD_FR. 1 hit.
    PS01033. GLOBIN. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P24232-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MLDAQTIATV KATIPLLVET GPKLTAHFYD RMFTHNPELK EIFNMSNQRN
    60 70 80 90 100
    GDQREALFNA IAAYASNIEN LPALLPAVEK IAQKHTSFQI KPEQYNIVGE
    110 120 130 140 150
    HLLATLDEMF SPGQEVLDAW GKAYGVLANV FINREAEIYN ENASKAGGWE
    160 170 180 190 200
    GTRDFRIVAK TPRSALITSF ELEPVDGGAV AEYRPGQYLG VWLKPEGFPH
    210 220 230 240 250
    QEIRQYSLTR KPDGKGYRIA VKREEGGQVS NWLHNHANVG DVVKLVAPAG
    260 270 280 290 300
    DFFMAVADDT PVTLISAGVG QTPMLAMLDT LAKAGHTAQV NWFHAAENGD
    310 320 330 340 350
    VHAFADEVKE LGQSLPRFTA HTWYRQPSEA DRAKGQFDSE GLMDLSKLEG
    360 370 380 390
    AFSDPTMQFY LCGPVGFMQF TAKQLVDLGV KQENIHYECF GPHKVL
    Length:396
    Mass (Da):43,868
    Last modified:March 1, 1992 - v1
    Checksum:i49961BDE1444BD6B
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X58872 Genomic DNA. Translation: CAA41682.1.
    U00096 Genomic DNA. Translation: AAC75605.1.
    AP009048 Genomic DNA. Translation: BAA16460.1.
    J01620 Genomic DNA. Translation: AAA23911.1.
    PIRiS15992.
    RefSeqiNP_417047.1. NC_000913.3.
    WP_000883122.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC75605; AAC75605; b2552.
    BAA16460; BAA16460; BAA16460.
    GeneIDi947018.
    KEGGiecj:JW2536.
    eco:b2552.
    PATRICi32120503. VBIEscCol129921_2654.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X58872 Genomic DNA. Translation: CAA41682.1.
    U00096 Genomic DNA. Translation: AAC75605.1.
    AP009048 Genomic DNA. Translation: BAA16460.1.
    J01620 Genomic DNA. Translation: AAA23911.1.
    PIRiS15992.
    RefSeqiNP_417047.1. NC_000913.3.
    WP_000883122.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1GVHX-ray2.19A1-396[»]
    ProteinModelPortaliP24232.
    SMRiP24232.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi4259200. 11 interactors.
    IntActiP24232. 4 interactors.
    STRINGi511145.b2552.

    Chemistry databases

    DrugBankiDB03147. Flavin adenine dinucleotide.

    Proteomic databases

    EPDiP24232.
    PaxDbiP24232.
    PRIDEiP24232.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC75605; AAC75605; b2552.
    BAA16460; BAA16460; BAA16460.
    GeneIDi947018.
    KEGGiecj:JW2536.
    eco:b2552.
    PATRICi32120503. VBIEscCol129921_2654.

    Organism-specific databases

    EchoBASEiEB0451.
    EcoGeneiEG10456. hmp.

    Phylogenomic databases

    eggNOGiENOG4105CJJ. Bacteria.
    COG1017. LUCA.
    COG1018. LUCA.
    HOGENOMiHOG000238921.
    InParanoidiP24232.
    KOiK05916.
    OMAiDQYQIVG.
    PhylomeDBiP24232.

    Enzyme and pathway databases

    BioCyciEcoCyc:EG10456-MONOMER.
    ECOL316407:JW2536-MONOMER.
    MetaCyc:EG10456-MONOMER.
    BRENDAi1.14.12.17. 2026.
    SABIO-RKP24232.

    Miscellaneous databases

    EvolutionaryTraceiP24232.
    PROiP24232.

    Family and domain databases

    Gene3Di1.10.490.10. 1 hit.
    HAMAPiMF_01252. Hmp. 1 hit.
    InterProiIPR017927. Fd_Rdtase_FAD-bd.
    IPR000971. Globin.
    IPR009050. Globin-like.
    IPR012292. Globin/Proto.
    IPR023950. Hmp.
    IPR008333. OxRdtase_FAD-bd_dom.
    IPR001433. OxRdtase_FAD/NAD-bd.
    IPR001221. Phe_hydroxylase.
    IPR017938. Riboflavin_synthase-like_b-brl.
    [Graphical view]
    PfamiPF00970. FAD_binding_6. 1 hit.
    PF00042. Globin. 1 hit.
    PF00175. NAD_binding_1. 1 hit.
    [Graphical view]
    PRINTSiPR00410. PHEHYDRXLASE.
    SUPFAMiSSF46458. SSF46458. 1 hit.
    SSF63380. SSF63380. 1 hit.
    PROSITEiPS51384. FAD_FR. 1 hit.
    PS01033. GLOBIN. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiHMP_ECOLI
    AccessioniPrimary (citable) accession number: P24232
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 1, 1992
    Last sequence update: March 1, 1992
    Last modified: November 30, 2016
    This is version 161 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    No protein-heme interactions have been detected at the distal side of the heme molecule.
    HMP is able to bind specifically unsaturated and/or cyclopropanated fatty acids with high affinity.

    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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. 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.