FHP_CANAL
ID FHP_CANAL Reviewed; 398 AA.
AC Q59MV9; A0A1D8PTL9; Q59MX2;
DT 03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Flavohemoprotein;
DE EC=1.14.12.17;
DE AltName: Full=Flavohemoglobin;
DE AltName: Full=Hemoglobin-like protein;
DE AltName: Full=Nitric oxide dioxygenase;
DE Short=NO oxygenase;
DE Short=NOD;
GN Name=YHB1; OrderedLocusNames=CAALFM_CR07790CA;
GN ORFNames=CaO19.11192, CaO19.3707;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP INDUCTION.
RX PubMed=12388749; DOI=10.1091/mbc.e02-05-0272;
RA Nantel A., Dignard D., Bachewich C., Harcus D., Marcil A., Bouin A.P.,
RA Sensen C.W., Hogues H., van het Hoog M., Gordon P., Rigby T., Benoit F.,
RA Tessier D.C., Thomas D.Y., Whiteway M.;
RT "Transcription profiling of Candida albicans cells undergoing the yeast-to-
RT hyphal transition.";
RL Mol. Biol. Cell 13:3452-3465(2002).
RN [5]
RP FUNCTION, AND INDUCTION.
RX PubMed=15189992; DOI=10.1128/ec.3.3.715-723.2004;
RA Ullmann B.D., Myers H., Chiranand W., Lazzell A.L., Zhao Q., Vega L.A.,
RA Lopez-Ribot J.L., Gardner P.R., Gustin M.C.;
RT "Inducible defense mechanism against nitric oxide in Candida albicans.";
RL Eukaryot. Cell 3:715-723(2004).
RN [6]
RP INDUCTION.
RX PubMed=15470236; DOI=10.1128/ec.3.5.1076-1087.2004;
RA Lorenz M.C., Bender J.A., Fink G.R.;
RT "Transcriptional response of Candida albicans upon internalization by
RT macrophages.";
RL Eukaryot. Cell 3:1076-1087(2004).
RN [7]
RP INDUCTION.
RX PubMed=15387822; DOI=10.1111/j.1365-2958.2004.04214.x;
RA Lan C.Y., Rodarte G., Murillo L.A., Jones T., Davis R.W., Dungan J.,
RA Newport G., Agabian N.;
RT "Regulatory networks affected by iron availability in Candida albicans.";
RL Mol. Microbiol. 53:1451-1469(2004).
RN [8]
RP ACTIVITY REGULATION.
RX PubMed=15855504; DOI=10.1128/aac.49.5.1837-1843.2005;
RA Helmick R.A., Fletcher A.E., Gardner A.M., Gessner C.R., Hvitved A.N.,
RA Gustin M.C., Gardner P.R.;
RT "Imidazole antibiotics inhibit the nitric oxide dioxygenase function of
RT microbial flavohemoglobin.";
RL Antimicrob. Agents Chemother. 49:1837-1843(2005).
RN [9]
RP FUNCTION, AND INDUCTION.
RX PubMed=16030247; DOI=10.1091/mbc.e05-05-0435;
RA Hromatka B.S., Noble S.M., Johnson A.D.;
RT "Transcriptional response of Candida albicans to nitric oxide and the role
RT of the YHB1 gene in nitrosative stress and virulence.";
RL Mol. Biol. Cell 16:4814-4826(2005).
RN [10]
RP INDUCTION.
RX PubMed=17645752; DOI=10.1111/j.1462-5822.2007.01009.x;
RA Zakikhany K., Naglik J.R., Schmidt-Westhausen A., Holland G., Schaller M.,
RA Hube B.;
RT "In vivo transcript profiling of Candida albicans identifies a gene
RT essential for interepithelial dissemination.";
RL Cell. Microbiol. 9:2938-2954(2007).
RN [11]
RP FUNCTION, AND INDUCTION.
RX PubMed=18083829; DOI=10.1128/ec.00240-07;
RA Chiranand W., McLeod I., Zhou H., Lynn J.J., Vega L.A., Myers H.,
RA Yates J.R. III, Lorenz M.C., Gustin M.C.;
RT "CTA4 transcription factor mediates induction of nitrosative stress
RT response in Candida albicans.";
RL Eukaryot. Cell 7:268-278(2008).
RN [12]
RP INDUCTION.
RX PubMed=18625733; DOI=10.1128/iai.00588-07;
RA Marcil A., Gadoury C., Ash J., Zhang J., Nantel A., Whiteway M.;
RT "Analysis of PRA1 and its relationship to Candida albicans- macrophage
RT interactions.";
RL Infect. Immun. 76:4345-4358(2008).
RN [13]
RP FUNCTION.
RX PubMed=19897505; DOI=10.1093/jac/dkp407;
RA Arana D.M., Nombela C., Pla J.;
RT "Fluconazole at subinhibitory concentrations induces the oxidative- and
RT nitrosative-responsive genes TRR1, GRE2 and YHB1, and enhances the
RT resistance of Candida albicans to phagocytes.";
RL J. Antimicrob. Chemother. 65:54-62(2010).
RN [14]
RP INDUCTION.
RX PubMed=21131439; DOI=10.1128/ec.00158-10;
RA Hsu P.C., Yang C.Y., Lan C.Y.;
RT "Candida albicans Hap43 is a repressor induced under low-iron conditions
RT and is essential for iron-responsive transcriptional regulation and
RT virulence.";
RL Eukaryot. Cell 10:207-225(2011).
RN [15]
RP FUNCTION, AND INDUCTION.
RX PubMed=22952822; DOI=10.1371/journal.pone.0043956;
RA Sellam A., Tebbji F., Whiteway M., Nantel A.;
RT "A novel role for the transcription factor Cwt1p as a negative regulator of
RT nitrosative stress in Candida albicans.";
RL PLoS ONE 7:E43956-E43956(2012).
RN [16]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23285201; DOI=10.1371/journal.pone.0052850;
RA Miramon P., Dunker C., Windecker H., Bohovych I.M., Brown A.J., Kurzai O.,
RA Hube B.;
RT "Cellular responses of Candida albicans to phagocytosis and the
RT extracellular activities of neutrophils are critical to counteract
RT carbohydrate starvation, oxidative and nitrosative stress.";
RL PLoS ONE 7:E52850-E52850(2012).
CC -!- FUNCTION: Nitric oxide dioxygenase involved in NO detoxification in an
CC aerobic process, termed nitric oxide dioxygenase (NOD) reaction that
CC utilizes O(2) and NAD(P)H to convert NO to nitrate, which protects the
CC fungus from various noxious nitrogen compounds. Therefore, plays a
CC central role in the inducible response to nitrosative stress. Plays a
CC role in virulence since nitric oxide is generated by macrophages of the
CC host immune system. {ECO:0000269|PubMed:15189992,
CC ECO:0000269|PubMed:16030247, ECO:0000269|PubMed:18083829,
CC ECO:0000269|PubMed:19897505, ECO:0000269|PubMed:22952822,
CC ECO:0000269|PubMed:23285201}.
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;
CC Note=Binds 1 FAD per subunit.;
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Note=Binds 1 heme b group per subunit.;
CC -!- ACTIVITY REGULATION: Inhibited by imidazoles.
CC {ECO:0000269|PubMed:15855504}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- INDUCTION: Expression is under the control of the CDA4 transcription
CC factor. Induced by nitric oxide, high-iron conditions, during
CC transition to filamentous growth, by contact with host macrophages, and
CC during oral infection. Expression is repressed by HAP43 and CWT1.
CC {ECO:0000269|PubMed:12388749, ECO:0000269|PubMed:15189992,
CC ECO:0000269|PubMed:15387822, ECO:0000269|PubMed:15470236,
CC ECO:0000269|PubMed:16030247, ECO:0000269|PubMed:17645752,
CC ECO:0000269|PubMed:18083829, ECO:0000269|PubMed:18625733,
CC ECO:0000269|PubMed:21131439, ECO:0000269|PubMed:22952822,
CC ECO:0000269|PubMed:23285201}.
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. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Leads to increased susceptibility to neutrophils.
CC {ECO:0000269|PubMed:23285201}.
CC -!- SIMILARITY: Belongs to the globin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00238}.
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DR EMBL; CP017630; AOW31470.1; -; Genomic_DNA.
DR RefSeq; XP_711046.1; XM_705954.1.
DR AlphaFoldDB; Q59MV9; -.
DR SMR; Q59MV9; -.
DR BioGRID; 1230425; 2.
DR STRING; 237561.Q59MV9; -.
DR PRIDE; Q59MV9; -.
DR GeneID; 3647353; -.
DR KEGG; cal:CAALFM_CR07790CA; -.
DR CGD; CAL0000179202; YHB1.
DR VEuPathDB; FungiDB:CR_07790C_A; -.
DR eggNOG; KOG3378; Eukaryota.
DR HOGENOM; CLU_003827_12_0_1; -.
DR InParanoid; Q59MV9; -.
DR OMA; ADIHYEV; -.
DR OrthoDB; 696109at2759; -.
DR PHI-base; PHI:500; -.
DR PRO; PR:Q59MV9; -.
DR Proteomes; UP000000559; Chromosome R.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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; IMP:CGD.
DR GO; GO:0019825; F:oxygen binding; IEA:InterPro.
DR GO; GO:0071500; P:cellular response to nitrosative stress; IEP:CGD.
DR GO; GO:0030447; P:filamentous growth; IMP:CGD.
DR GO; GO:0044182; P:filamentous growth of a population of unicellular organisms; IMP:CGD.
DR GO; GO:0046210; P:nitric oxide catabolic process; IMP:CGD.
DR GO; GO:0009636; P:response to toxic substance; IMP:CGD.
DR GO; GO:0052163; P:symbiont defense to host-produced nitric oxide; IMP:CGD.
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; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR000971; Globin.
DR InterPro; IPR009050; Globin-like_sf.
DR InterPro; IPR012292; Globin/Proto.
DR InterPro; IPR023950; Hmp.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR000951; Ph_dOase_redase.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR PANTHER; PTHR43396:SF3; PTHR43396:SF3; 1.
DR Pfam; PF00970; FAD_binding_6; 1.
DR Pfam; PF00042; Globin; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR PRINTS; PR00409; PHDIOXRDTASE.
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; Reference proteome; Virulence.
FT CHAIN 1..398
FT /note="Flavohemoprotein"
FT /id="PRO_0000422070"
FT DOMAIN 156..263
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..147
FT /note="Globin"
FT /evidence="ECO:0000250"
FT REGION 155..398
FT /note="Reductase"
FT /evidence="ECO:0000250"
FT ACT_SITE 103
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 146
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT BINDING 93
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 196
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 212..215
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 276..281
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 395..398
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT SITE 37
FT /note="Involved in heme-bound ligand stabilization and O-O
FT bond activation"
FT /evidence="ECO:0000250"
FT SITE 92
FT /note="Influences the redox potential of the prosthetic
FT heme and FAD groups"
FT /evidence="ECO:0000250"
SQ SEQUENCE 398 AA; 45819 MW; 3E3827CC14DF04BA CRC64;
MTVEYETKQL TPAQIKIILD TVPILEEAGE TLTQKFYQRM IGNYDEVKPF FNTTDQKLLR
QPKILAFALL NYAKNIEDLT PLTDFVKQIV VKHIGLQVLP EHYPIVGTCL IQTMVELLPP
EIANKDFLEA WTIAYGNLAK LLIDLEAAEY AKQPWRWFKD FKVTRIVQEC KDVKSVYFTP
VDKDLLPLPK PERGQYLCFR WKLPGEEFEI SREYSVSEFP KENEYRISVR HVPGGKISGY
IHNNLKVGDI LKVAPPAGNF VYDPATDKEL IFVAGGIGIT PLLSMIERAL EEGKNVKLLY
SNRSAETRAF GNLFKEYKSK FGDKFQAIEY FSEDNNTDDK IVIDKAFNRK LTTDDLDFIA
PEHDVYLVGP REFMKDIKEH LGKKNVPVKL EYFGPYDP
