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P39662 (HMP_CUPNH) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Flavohemoprotein
Alternative name(s):
FHP
Flavohemoglobin
Hemoglobin-like protein
Nitric oxide dioxygenase
Short name=NO oxygenase
Short name=NOD
EC=1.14.12.17
Gene names
Name:hmp
Synonyms:fhp
Ordered Locus Names:PHG200
Encoded onPlasmid megaplasmid pHG1
OrganismCupriavidus necator (strain ATCC 17699 / H16 / DSM 428 / Stanier 337) (Ralstonia eutropha) [Complete proteome] [HAMAP]
Taxonomic identifier381666 [NCBI]
Taxonomic lineageBacteria › Proteobacteria › Betaproteobacteria › Burkholderiales › Burkholderiaceae › Cupriavidus ›

Protein attributes

Sequence length403 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. HAMAP-Rule MF_01252

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. HAMAP-Rule MF_01252

Catalytic activity

2 NO + 2 O2 + NAD(P)H = 2 NO3- + NAD(P)+. Ref.5

Cofactor

Binds 1 FAD per subunit. Ref.4

Binds 1 heme B group per subunit. Ref.4

Subunit structure

Monomer.

Subcellular location

Cytoplasm HAMAP-Rule MF_01252.

Induction

Under oxygen-limited conditions. Ref.4

Domain

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. HAMAP-Rule MF_01252

Miscellaneous

No protein-heme interactions have been detected at the distal side of the heme molecule. HAMAP-Rule MF_01252

FHP is able to bind phospholipids with high affinity. HAMAP-Rule MF_01252

Sequence similarities

Belongs to the globin family. Two-domain flavohemoproteins subfamily.

In the C-terminal section; belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.

Contains 1 FAD-binding FR-type domain.

Biophysicochemical properties

Kinetic parameters:

KM=0.10 µM for NO

KM=80 µM for O2

KM=70 µM for NADH

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 403403Flavohemoprotein HAMAP-Rule MF_01252
PRO_0000052441

Regions

Domain152 – 262111FAD-binding FR-type
Nucleotide binding206 – 2094FAD HAMAP-Rule MF_01252
Nucleotide binding275 – 2806NADP By similarity
Nucleotide binding395 – 3984FAD HAMAP-Rule MF_01252
Region1 – 140140Globin HAMAP-Rule MF_01252
Region149 – 403255Reductase HAMAP-Rule MF_01252
Region266 – 403138NAD or NADP-binding HAMAP-Rule MF_01252

Sites

Active site951Charge relay system
Active site1371Charge relay system
Metal binding851Iron (heme proximal ligand)
Binding site1901FAD
Site291Involved in heme-bound ligand stabilization and O-O bond activation
Site841Influences the redox potential of the prosthetic heme and FAD groups
Site3941Influences the redox potential of the prosthetic heme and FAD groups

Experimental info

Mutagenesis601A → Y: Does not affect phospholipid-binding. Ref.7
Mutagenesis981V → F: Blocks phospholipid-binding. Ref.7
Sequence conflict2181S → T in CAA52381. Ref.1

Secondary structure

1 ................................................................. 403
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P39662 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 2E3ED365087F5EA0

FASTA40344,782
        10         20         30         40         50         60 
MLTQKTKDIV KATAPVLAEH GYDIIKCFYQ RMFEAHPELK NVFNMAHQEQ GQQQQALARA 

        70         80         90        100        110        120 
VYAYAENIED PNSLMAVLKN IANKHASLGV KPEQYPIVGE HLLAAIKEVL GNAATDDIIS 

       130        140        150        160        170        180 
AWAQAYGNLA DVLMGMESEL YERSAEQPGG WKGWRTFVIR EKRPESDVIT SFILEPADGG 

       190        200        210        220        230        240 
PVVNFEPGQY TSVAIDVPAL GLQQIRQYSL SDMPNGRSYR ISVKREGGGP QPPGYVSNLL 

       250        260        270        280        290        300 
HDHVNVGDQV KLAAPYGSFH IDVDAKTPIV LISGGVGLTP MVSMLKVALQ APPRQVVFVH 

       310        320        330        340        350        360 
GARNSAVHAM RDRLREAAKT YENLDLFVFY DQPLPEDVQG RDYDYPGLVD VKQIEKSILL 

       370        380        390        400 
PDADYYICGP IPFMRMQHDA LKNLGIHEAR IHYEVFGPDL FAE

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		X74334 Genomic DNA. Translation: CAA52381.1.
AY305378 Genomic DNA. Translation: AAP85952.1.
PIRA53396.
RefSeqNP_942838.1. NC_005241.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CQXX-ray1.75A/B1-403[»]
3OZUX-ray2.00A1-403[»]
3OZVX-ray2.40A/B1-403[»]
3OZWX-ray2.30A/B1-403[»]
ProteinModelPortalP39662.
SMRP39662. Positions 1-403.
ModBaseSearch...

Protein-protein interaction databases

STRING381666.PHG200.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID2656642.
KEGGreh:PHG200.
PATRIC35228958. VBIRalEut6770_0150.

Organism-specific databases

CMRSearch...

Phylogenomic databases

eggNOGCOG1018.
HOGENOMHOG000238921.
KOK05916.
OMAYERLFEN.
ProtClustDBPRK13289.

Enzyme and pathway databases

BioCycCNEC381666:GJUJ-6476-MONOMER.

Family and domain databases

Gene3D1.10.490.10. 1 hit.
HAMAPMF_01252. Hmp.
InterProIPR017927. 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]
PfamPF00970. FAD_binding_6. 1 hit.
PF00042. Globin. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSPR00410. PHEHYDRXLASE.
SUPFAMSSF46458. Globin_like. 1 hit.
SSF63380. Riboflavin_synthase_like_b-brl. 1 hit.
PROSITEPS51384. FAD_FR. 1 hit.
PS01033. GLOBIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP39662.

Entry information

Entry nameHMP_CUPNH
AccessionPrimary (citable) accession number: P39662
Secondary accession number(s): Q7WXD4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: January 23, 2007
Last modified: May 1, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents