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Protein

Flavohemoprotein

Gene

hmp

Organism
Cupriavidus necator (strain ATCC 17699 / H16 / DSM 428 / Stanier 337) (Ralstonia eutropha)
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, FHP 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 FHP might act as an amplifier of superoxide stress. Under anaerobic conditions, FHP also exhibits nitric oxide reductase and FAD reductase activities. However, all these reactions are much lower than NOD activity.

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:

Kineticsi

  1. KM=0.10 µM for NO
  2. KM=80 µM for O2
  3. KM=70 µM for NADH

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei29 – 291Involved in heme-bound ligand stabilization and O-O bond activation
    Sitei84 – 841Influences the redox potential of the prosthetic heme and FAD groups
    Metal bindingi85 – 851Iron (heme proximal ligand)
    Active sitei95 – 951Charge relay system
    Active sitei137 – 1371Charge relay system
    Binding sitei190 – 1901FAD
    Sitei394 – 3941Influences the redox potential of the prosthetic heme and FAD groups

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi206 – 2094FAD
    Nucleotide bindingi275 – 2806NADPBy similarity
    Nucleotide bindingi395 – 3984FAD

    GO - Molecular functioni

    GO - Biological processi

    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

    BioCyciCNEC381666:GJUJ-6476-MONOMER.
    BRENDAi1.14.12.17. 231.
    SABIO-RKP39662.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Flavohemoprotein
    Alternative name(s):
    FHP
    Flavohemoglobin
    Hemoglobin-like protein
    Nitric oxide dioxygenase (EC:1.14.12.17)
    Short name:
    NO oxygenase
    Short name:
    NOD
    Gene namesi
    Name:hmp
    Synonyms:fhp
    Ordered Locus Names:PHG200
    Encoded oniPlasmid megaplasmid pHG10 Publication
    OrganismiCupriavidus necator (strain ATCC 17699 / H16 / DSM 428 / Stanier 337) (Ralstonia eutropha)
    Taxonomic identifieri381666 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaBetaproteobacteriaBurkholderialesBurkholderiaceaeCupriavidus
    ProteomesiUP000008210 Componenti: Plasmid megaplasmid pHG1

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi60 – 601A → Y: Does not affect phospholipid-binding. 1 Publication
    Mutagenesisi98 – 981V → F: Blocks phospholipid-binding. 1 Publication

    Chemistry

    DrugBankiDB03147. Flavin adenine dinucleotide.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 403403FlavohemoproteinPRO_0000052441Add
    BLAST

    Expressioni

    Inductioni

    Under oxygen-limited conditions.1 Publication

    Interactioni

    Subunit structurei

    Monomer.

    Structurei

    Secondary structure

    1
    403
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi4 – 1916Combined sources
    Helixi21 – 3515Combined sources
    Helixi37 – 415Combined sources
    Helixi47 – 493Combined sources
    Helixi50 – 6718Combined sources
    Helixi71 – 8818Combined sources
    Helixi92 – 943Combined sources
    Helixi95 – 11016Combined sources
    Helixi111 – 1133Combined sources
    Helixi116 – 14530Combined sources
    Beta strandi155 – 16410Combined sources
    Beta strandi166 – 17611Combined sources
    Beta strandi190 – 1967Combined sources
    Turni198 – 2003Combined sources
    Beta strandi201 – 2099Combined sources
    Beta strandi219 – 2246Combined sources
    Beta strandi229 – 2313Combined sources
    Helixi235 – 2439Combined sources
    Beta strandi249 – 2524Combined sources
    Beta strandi269 – 2757Combined sources
    Helixi278 – 28811Combined sources
    Beta strandi290 – 2923Combined sources
    Beta strandi296 – 3038Combined sources
    Beta strandi305 – 3073Combined sources
    Helixi309 – 32012Combined sources
    Beta strandi324 – 3329Combined sources
    Turni339 – 3413Combined sources
    Beta strandi344 – 3485Combined sources
    Helixi351 – 3533Combined sources
    Helixi355 – 3584Combined sources
    Beta strandi364 – 3707Combined sources
    Helixi371 – 38313Combined sources
    Helixi388 – 3903Combined sources
    Beta strandi391 – 3933Combined sources
    Beta strandi396 – 3983Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CQXX-ray1.75A/B1-403[»]
    3OZUX-ray2.00A1-403[»]
    3OZVX-ray2.40A/B1-403[»]
    3OZWX-ray2.30A/B1-403[»]
    ProteinModelPortaliP39662.
    SMRiP39662. Positions 1-403.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP39662.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini152 – 262111FAD-binding FR-typeAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 140140GlobinAdd
    BLAST
    Regioni149 – 403255ReductaseAdd
    BLAST
    Regioni266 – 403138NAD or NADP-bindingAdd
    BLAST

    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

    eggNOGiCOG1018.
    HOGENOMiHOG000238921.
    KOiK05916.
    OMAiSAWAQAY.
    OrthoDBiEOG64V2BB.

    Family and domain databases

    Gene3Di1.10.490.10. 1 hit.
    HAMAPiMF_01252. Hmp.
    InterProiIPR017927. Fd_Rdtase_FAD-bd.
    IPR000971. Globin.
    IPR009050. Globin-like.
    IPR012292. Globin_dom.
    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.

    P39662-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MLTQKTKDIV KATAPVLAEH GYDIIKCFYQ RMFEAHPELK NVFNMAHQEQ
    60 70 80 90 100
    GQQQQALARA VYAYAENIED PNSLMAVLKN IANKHASLGV KPEQYPIVGE
    110 120 130 140 150
    HLLAAIKEVL GNAATDDIIS AWAQAYGNLA DVLMGMESEL YERSAEQPGG
    160 170 180 190 200
    WKGWRTFVIR EKRPESDVIT SFILEPADGG PVVNFEPGQY TSVAIDVPAL
    210 220 230 240 250
    GLQQIRQYSL SDMPNGRSYR ISVKREGGGP QPPGYVSNLL HDHVNVGDQV
    260 270 280 290 300
    KLAAPYGSFH IDVDAKTPIV LISGGVGLTP MVSMLKVALQ APPRQVVFVH
    310 320 330 340 350
    GARNSAVHAM RDRLREAAKT YENLDLFVFY DQPLPEDVQG RDYDYPGLVD
    360 370 380 390 400
    VKQIEKSILL PDADYYICGP IPFMRMQHDA LKNLGIHEAR IHYEVFGPDL

    FAE
    Length:403
    Mass (Da):44,782
    Last modified:January 23, 2007 - v2
    Checksum:i2E3ED365087F5EA0
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti218 – 2181S → T in CAA52381 (PubMed:8125952).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X74334 Genomic DNA. Translation: CAA52381.1.
    AY305378 Genomic DNA. Translation: AAP85952.1.
    PIRiA53396.
    RefSeqiNP_942838.1. NC_005241.1.
    WP_011154115.1. NC_005241.1.

    Genome annotation databases

    EnsemblBacteriaiAAP85952; AAP85952; PHG200.
    GeneIDi2656642.
    KEGGireh:PHG200.
    PATRICi35228958. VBIRalEut6770_0150.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X74334 Genomic DNA. Translation: CAA52381.1.
    AY305378 Genomic DNA. Translation: AAP85952.1.
    PIRiA53396.
    RefSeqiNP_942838.1. NC_005241.1.
    WP_011154115.1. NC_005241.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CQXX-ray1.75A/B1-403[»]
    3OZUX-ray2.00A1-403[»]
    3OZVX-ray2.40A/B1-403[»]
    3OZWX-ray2.30A/B1-403[»]
    ProteinModelPortaliP39662.
    SMRiP39662. Positions 1-403.
    ModBaseiSearch...
    MobiDBiSearch...

    Chemistry

    DrugBankiDB03147. Flavin adenine dinucleotide.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAP85952; AAP85952; PHG200.
    GeneIDi2656642.
    KEGGireh:PHG200.
    PATRICi35228958. VBIRalEut6770_0150.

    Phylogenomic databases

    eggNOGiCOG1018.
    HOGENOMiHOG000238921.
    KOiK05916.
    OMAiSAWAQAY.
    OrthoDBiEOG64V2BB.

    Enzyme and pathway databases

    BioCyciCNEC381666:GJUJ-6476-MONOMER.
    BRENDAi1.14.12.17. 231.
    SABIO-RKP39662.

    Miscellaneous databases

    EvolutionaryTraceiP39662.

    Family and domain databases

    Gene3Di1.10.490.10. 1 hit.
    HAMAPiMF_01252. Hmp.
    InterProiIPR017927. Fd_Rdtase_FAD-bd.
    IPR000971. Globin.
    IPR009050. Globin-like.
    IPR012292. Globin_dom.
    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...

    Publicationsi

    « Hide 'large scale' publications
    1. "Primary sequence and evidence for a physiological function of the flavohemoprotein of Alcaligenes eutrophus."
      Cramm R., Siddiqui R.A., Friedrich B.
      J. Biol. Chem. 269:7349-7354(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Complete nucleotide sequence of pHG1: a Ralstonia eutropha H16 megaplasmid encoding key enzymes of H(2)-based lithoautotrophy and anaerobiosis."
      Schwartz E., Henne A., Cramm R., Eitinger T., Friedrich B., Gottschalk G.
      J. Mol. Biol. 332:369-383(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 17699 / H16 / DSM 428 / Stanier 337.
    3. "Yeast flavohemoglobin is an ancient protein related to globins and a reductase family."
      Zhu H., Riggs A.F.
      Proc. Natl. Acad. Sci. U.S.A. 89:5015-5019(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL PROTEIN SEQUENCE.
    4. "An oxygen-binding flavohemoprotein from Alcaligenes eutrophus."
      Probst I., Wolf G., Schlegel H.G.
      Biochim. Biophys. Acta 576:471-478(1979) [PubMed] [Europe PMC] [Abstract]
      Cited for: COFACTOR, INDUCTION, SPECTRAL PROPERTIES.
    5. "Nitric-oxide dioxygenase activity and function of flavohemoglobins. Sensitivity to nitric oxide and carbon monoxide inhibition."
      Gardner P.R., Gardner A.M., Martin L.A., Dou Y., Li T., Olson J.S., Zhu H., Riggs A.F.
      J. Biol. Chem. 275:31581-31587(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME ACTIVITY.
    6. "Crystal structure of the flavohemoglobin from Alcaligenes eutrophus at 1.75-A resolution."
      Ermler U., Siddiqui R.A., Cramm R., Friedrich B.
      EMBO J. 14:6067-6077(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS).
    7. "Phospholipid bound to the flavohemoprotein from Alcaligenes eutrophus."
      Ollesch G., Kaunzinger A., Juchelka D., Schubert-Zsilavecz M., Ermler U.
      Eur. J. Biochem. 262:396-405(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF NATIVE PROTEIN AND MUTANT V98F, PHOSPHOLIPID BINDING, MUTAGENESIS OF ALA-60 AND VAL-98.

    Entry informationi

    Entry nameiHMP_CUPNH
    AccessioniPrimary (citable) accession number: P39662
    Secondary accession number(s): Q7WXD4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: January 23, 2007
    Last modified: June 24, 2015
    This is version 133 of the entry and version 2 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.
    FHP is able to bind phospholipids with high affinity.

    Keywords - Technical termi

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

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    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 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.