[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. PubMed=8125952 [NCBI, ExPASy, EBI, Israel, Japan] Cramm R., Siddiqui R.A., Friedrich B.; "Primary sequence and evidence for a physiological function of the flavohemoprotein of Alcaligenes eutrophus."; J. Biol. Chem. 269:7349-7354(1994).
[2]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. DOI=10.1016/S0022-2836(03)00894-5; PubMed=12948488 [NCBI, ExPASy, EBI, Israel, Japan] Schwartz E., Henne A., Cramm R., Eitinger T., Friedrich B., Gottschalk G.; "Complete nucleotide sequence of pHG1: a Ralstonia eutropha H16 megaplasmid encoding key enzymes of H(2)-based lithoautotrophy and anaerobiosis."; J. Mol. Biol. 332:369-383(2003).
[3]	PARTIAL PROTEIN SEQUENCE. PubMed=1594608 [NCBI, ExPASy, EBI, Israel, Japan] Zhu H., Riggs A.F.; "Yeast flavohemoglobin is an ancient protein related to globins and a reductase family."; Proc. Natl. Acad. Sci. U.S.A. 89:5015-5019(1992).
[4]	COFACTOR, INDUCTION, AND SPECTRAL PROPERTIES. DOI=10.1016/0005-2795(79)90422-7; PubMed=218634 [NCBI, ExPASy, EBI, Israel, Japan] Probst I., Wolf G., Schlegel H.G.; "An oxygen-binding flavohemoprotein from Alcaligenes eutrophus."; Biochim. Biophys. Acta 576:471-478(1979).
[5]	ENZYME ACTIVITY. DOI=10.1074/jbc.M004141200; PubMed=10922365 [NCBI, ExPASy, EBI, Israel, Japan] Gardner P.R., Gardner A.M., Martin L.A., Dou Y., Li T., Olson J.S., Zhu H., Riggs A.F.; "Nitric-oxide dioxygenase activity and function of flavohemoglobins. Sensitivity to nitric oxide and carbon monoxide inhibition."; J. Biol. Chem. 275:31581-31587(2000).
[6]	X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS). PubMed=8557026 [NCBI, ExPASy, EBI, Israel, Japan] Ermler U., Siddiqui R.A., Cramm R., Friedrich B.; "Crystal structure of the flavohemoglobin from Alcaligenes eutrophus at 1.75-A resolution."; EMBO J. 14:6067-6077(1995).
[7]	X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF NATIVE PROTEIN AND MUTANT V98F, PHOSPHOLIPID BINDING, AND MUTAGENESIS OF ALA-60 AND VAL-98. PubMed=10336624 [NCBI, ExPASy, EBI, Israel, Japan] Ollesch G., Kaunzinger A., Juchelka D., Schubert-Zsilavecz M., Ermler U.; "Phospholipid bound to the flavohemoprotein from Alcaligenes eutrophus."; Eur. J. Biochem. 262:396-405(1999).

Comments

FUNCTION: Is involved in NO detoxification in an aerobic process, termed nitric oxide dioxygenase (NOD) reaction that utilizes O(2) 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.
FUNCTION: In the presence of oxygen and NADH, FHP has NADH oxidase activity, which leads to the generation of superoxide and H(2)O(2), 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 ACTIVITY: 2 NO + 2 O₂ + NAD(P)H = 2 NO₃^- + NAD(P)⁺.
COFACTOR: Binds 1 FAD per subunit.
COFACTOR: Binds 1 heme B group per subunit.
BIOPHYSICOCHEMICAL PROPERTIES:

Kinetic parameters: K_M=0.10 µM for NO;
K_M=80 µM for O₂;
K_M=70 µM for NADH;
SUBUNIT: Monomer.
SUBCELLULAR LOCATION: Cytoplasm.
INDUCTION: Under oxygen-limited conditions.
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.
MISCELLANEOUS: No protein-heme interactions have been detected at the distal side of the heme molecule.
MISCELLANEOUS: FHP is able to bind phospholipids with high affinity.
SIMILARITY: Belongs to the globin family. Two-domain flavohemoproteins subfamily.
SIMILARITY: In the C-terminal section; belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
SIMILARITY: Contains 1 FAD-binding FR-type domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

X74334; CAA52381.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY305378; AAP85952.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

A53396; A53396.

RefSeq

NP_942838.1; -.

3D structure databases

PDB

1CQX; X-ray; 1.75 A; A/B=1-403.

[ExPASy / RCSB / EBI]

PDBsum

1CQX; -.

ModBase

P39662.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-KW).
GO:0009055;	Molecular function: electron carrier activity (inferred from electronic annotation from InterPro).
GO:0020037;	Molecular function: heme binding (inferred from electronic annotation from InterPro).
GO:0005506;	Molecular function: iron ion binding (inferred from electronic annotation from InterPro).
GO:0008941;	Molecular function: nitric oxide dioxygenase activity (inferred from electronic annotation from HAMAP).
GO:0019825;	Molecular function: oxygen binding (inferred from electronic annotation from InterPro).
GO:0005344;	Molecular function: oxygen transporter activity (inferred from electronic annotation from HAMAP).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0015671;	Biological process: oxygen transport (inferred from electronic annotation from HAMAP).
GO:0009636;	Biological process: response to toxin (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

HAMAP

MF_01252; -; 1.
PBIL [Tree]

InterPro

IPR001709; FPN_cyt_redctse.
IPR012292; Globin.
IPR000971; Globin_subset.
IPR008333; OxRdtase_FAD-bd.
IPR001433; OxRdtase_FAD/NAD_bd.
IPR001221; Phe_hydroxylase.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.490.10; Globin_related; 1.

Pfam

PF00970; FAD_binding_6; 1.
PF00042; Globin; 1.
PF00175; NAD_binding_1; 1.
Pfam graphical view of domain structure.

PRINTS

PR00371; FPNCR.
PR00410; PHEHYDRXLASE.

PROSITE

PS51384; FAD_FR; 1.
PS01033; GLOBIN; 1.
PROSITE graphical view of domain structure (profiles).

ProtoNet

P39662.

Genome annotation databases

GeneID

2656642; -.

GenomeReviews

AY305378_GR; PHG200.

KEGG

reh:PHG200; -.

Phylogenomic databases

HOGENOM

P39662; -.

Genome annotation databases

CMR

P39662; PHG200.

Other

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Complete proteome; Cytoplasm; Detoxification; Direct protein sequencing; FAD; Flavoprotein; Heme; Iron; Metal-binding; NAD; NADP; Oxidoreductase; Oxygen transport; Plasmid; Transport.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 403`	`403`	`Flavohemoprotein.`	`PRO_0000052441`
`DOMAIN`	`152 262`	`111`	`FAD-binding FR-type.`
`NP_BIND`	`206 209`	`4`	`FAD.`
`NP_BIND`	`275 280`	`6`	`NADP (By similarity).`
`NP_BIND`	`395 398`	`4`	`FAD.`
`REGION`	`1 140`	`140`	`Globin.`
`REGION`	`149 403`	`255`	`Reductase.`
`REGION`	`266 403`	`138`	`NAD or NADP-binding.`
`ACT_SITE`	`95 95`		`Charge relay system.`
`ACT_SITE`	`137 137`		`Charge relay system.`
`METAL`	`85 85`		`Iron (heme proximal ligand).`
`BINDING`	`190 190`		`FAD.`
`SITE`	`29 29`	`1`	`Involved in heme-bound ligand stabilization and O-O bond activation.`
`SITE`	`84 84`	`1`	`Influences the redox potential of the prosthetic heme and FAD groups.`
`SITE`	`394 394`	`1`	`Influences the redox potential of the prosthetic heme and FAD groups.`
`MUTAGEN`	`60 60`		`A->Y: Does not affect phospholipid-binding.`
`MUTAGEN`	`98 98`		`V->F: Blocks phospholipid-binding.`
`CONFLICT`	`218 218`		`S -> T (in Ref. 1; CAA52381).`
`HELIX`	`4 19`	`16`
`HELIX`	`21 35`	`15`
`HELIX`	`37 41`	`5`
`HELIX`	`50 67`	`18`
`HELIX`	`71 88`	`18`
`HELIX`	`92 94`	`3`
`HELIX`	`95 110`	`16`
`HELIX`	`111 113`	`3`
`HELIX`	`116 145`	`30`
`STRAND`	`155 164`	`10`
`STRAND`	`166 176`	`11`
`STRAND`	`190 196`	`7`
`TURN`	`198 200`	`3`
`STRAND`	`201 209`	`9`
`STRAND`	`219 224`	`6`
`HELIX`	`235 243`	`9`
`STRAND`	`249 252`	`4`
`STRAND`	`269 275`	`7`
`HELIX`	`278 288`	`11`
`STRAND`	`296 303`	`8`
`STRAND`	`305 307`	`3`
`HELIX`	`309 320`	`12`
`STRAND`	`324 332`	`9`
`TURN`	`339 341`	`3`
`STRAND`	`344 348`	`5`
`HELIX`	`351 353`	`3`
`HELIX`	`355 358`	`4`
`STRAND`	`364 370`	`7`
`HELIX`	`371 383`	`13`
`HELIX`	`388 390`	`3`
`STRAND`	`391 393`	`3`

Sequence information

Length: 403 AA [This is the length of the unprocessed precursor]

Molecular weight: 44782 Da [This is the MW of the unprocessed precursor]

CRC64: 2E3ED365087F5EA0 [This is a checksum on the sequence]

        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

P39662 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools