FHBA_DICDI
ID FHBA_DICDI Reviewed; 397 AA.
AC Q9UAG7; Q54D74;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Flavohemoprotein A;
DE EC=1.14.12.17;
DE AltName: Full=DdFHa;
DE AltName: Full=Flavohemoglobin A;
DE AltName: Full=Hemoglobin-like protein A;
DE AltName: Full=Nitric oxide dioxygenase A;
DE Short=NO oxygenase A;
DE Short=NOD A;
GN Name=fhbA; ORFNames=DDB_G0292378;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND INDUCTION.
RC STRAIN=AX3-1;
RX PubMed=10791894; DOI=10.1247/csf.25.47;
RA Iijima M., Shimizu H., Tanaka Y., Urushihara H.;
RT "Identification and characterization of two flavohemoglobin genes in
RT Dictyostelium discoideum.";
RL Cell Struct. Funct. 25:47-55(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
CC -!- FUNCTION: Is involved in NO detoxification in an aerobic process,
CC termed nitric oxide dioxygenase (NOD) reaction that utilizes O(2) and
CC NAD(P)H to convert NO to nitrate, which protects the cell from various
CC noxious nitrogen compounds. Therefore, plays a central role in the
CC inducible response to nitrosative stress.
CC {ECO:0000269|PubMed:10791894}.
CC -!- FUNCTION: In the presence of oxygen and NADH, it has NADH oxidase
CC activity, which leads to the generation of superoxide and H(2)O(2).
CC Under anaerobic conditions, it also exhibits nitric oxide reductase and
CC FAD reductase activities. However, all these reactions are much lower
CC than NOD activity (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADPH + 2 nitric oxide + 2 O2 = H(+) + NADP(+) + 2 nitrate;
CC Xref=Rhea:RHEA:19465, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16480, ChEBI:CHEBI:17632, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.14.12.17;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADH + 2 nitric oxide + 2 O2 = H(+) + NAD(+) + 2 nitrate;
CC Xref=Rhea:RHEA:19469, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16480, ChEBI:CHEBI:17632, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.14.12.17;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC Note=Binds 1 FAD per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000250};
CC Note=Binds 1 heme b group per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Accumulates in macrocysts.
CC {ECO:0000269|PubMed:10791894}.
CC -!- INDUCTION: By submerged conditions, in growing cells.
CC {ECO:0000269|PubMed:10791894}.
CC -!- DOMAIN: Consists of two distinct domains; a N-terminal heme-containing
CC oxygen-binding domain and a C-terminal reductase domain with binding
CC sites for FAD and NAD(P)H.
CC -!- SIMILARITY: Belongs to the globin family. Two-domain flavohemoproteins
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00238}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the flavoprotein
CC pyridine nucleotide cytochrome reductase family. {ECO:0000305}.
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DR EMBL; AB025583; BAA83810.1; -; mRNA.
DR EMBL; AAFI02000190; EAL61168.1; -; Genomic_DNA.
DR RefSeq; XP_629622.1; XM_629620.1.
DR AlphaFoldDB; Q9UAG7; -.
DR SMR; Q9UAG7; -.
DR STRING; 44689.DDB0191099; -.
DR PaxDb; Q9UAG7; -.
DR EnsemblProtists; EAL61168; EAL61168; DDB_G0292378.
DR GeneID; 8628685; -.
DR KEGG; ddi:DDB_G0292378; -.
DR dictyBase; DDB_G0292378; fhbA.
DR eggNOG; KOG3378; Eukaryota.
DR HOGENOM; CLU_003827_12_0_1; -.
DR InParanoid; Q9UAG7; -.
DR OMA; ADIHYEV; -.
DR PhylomeDB; Q9UAG7; -.
DR PRO; PR:Q9UAG7; -.
DR Proteomes; UP000002195; Chromosome 6.
DR GO; GO:0045335; C:phagocytic vesicle; HDA:dictyBase.
DR GO; GO:0071949; F:FAD binding; IBA:GO_Central.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008941; F:nitric oxide dioxygenase activity; IBA:GO_Central.
DR GO; GO:0019825; F:oxygen binding; IEA:InterPro.
DR GO; GO:0005344; F:oxygen carrier activity; IEA:UniProtKB-KW.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IMP:dictyBase.
DR GO; GO:0071500; P:cellular response to nitrosative stress; IGI:dictyBase.
DR GO; GO:0046210; P:nitric oxide catabolic process; IBA:GO_Central.
DR GO; GO:0009636; P:response to toxic substance; IEA:UniProtKB-KW.
DR Gene3D; 1.10.490.10; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR008333; Cbr1-like_FAD-bd_dom.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR000971; Globin.
DR InterPro; IPR009050; Globin-like_sf.
DR InterPro; IPR012292; Globin/Proto.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR Pfam; PF00970; FAD_binding_6; 1.
DR Pfam; PF00042; Globin; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR PRINTS; PR00371; FPNCR.
DR SUPFAM; SSF46458; SSF46458; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS01033; GLOBIN; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Detoxification; FAD; Flavoprotein; Heme; Iron; Metal-binding;
KW NAD; NADP; Oxidoreductase; Oxygen transport; Reference proteome; Transport.
FT CHAIN 1..397
FT /note="Flavohemoprotein A"
FT /id="PRO_0000327849"
FT DOMAIN 151..266
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..141
FT /note="Globin"
FT /evidence="ECO:0000250"
FT REGION 150..397
FT /note="Reductase"
FT /evidence="ECO:0000250"
FT ACT_SITE 94
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 136
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT BINDING 84
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="proximal binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00238"
FT BINDING 189
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 208..211
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 279..284
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 390..393
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT SITE 30
FT /note="Involved in heme-bound ligand stabilization and O-O
FT bond activation"
FT /evidence="ECO:0000250"
FT SITE 83
FT /note="Influences the redox potential of the prosthetic
FT heme and FAD groups"
FT /evidence="ECO:0000250"
FT SITE 389
FT /note="Influences the redox potential of the prosthetic
FT heme and FAD groups"
FT /evidence="ECO:0000250"
SQ SEQUENCE 397 AA; 43925 MW; 9641037821908183 CRC64;
MSLSQQSISI IKATVPVLQV HGVNITTTFY RNMFKANPQL LNIFNHSNQR EGKQQNALAN
TVLQAAIHID KLNELNLAPI VHKHVALGVL PEHYPIVGTN LLGAIKEVLQ DAATDEILGA
WGEAYGVIAQ AFIDAEAALY KVTEEQIGGW RDTREFIVDR KVEESSNIIS FYFKPADGKP
IATYIPGQYI TIKVPLTLEN GEQRTHIRHY SLSDTPSEQY YRISVKKEDA LKKSDPNGVV
SNHLHANVKV GDKVLLSPPA GDYVVDQLSS NPILLVSGGV GITPLLSMAK ATLAKQPERE
VTFVHSSKNK QYQPFANELS QLEKSNKVKV STVHSETDGQ ITKDKLEKFI NPSQIKDTKV
FICGPVSFMS AINKQLIELG YPKENISYEI FGPLTNV
