FHP_YEAST
ID FHP_YEAST Reviewed; 399 AA.
AC P39676; D6VV14; Q6B1W6; Q9C1R6;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 201.
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; Synonyms=YHB; OrderedLocusNames=YGR234W; ORFNames=G8572;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], PROTEIN SEQUENCE OF 1-31, AND
RP VARIANTS GLU-153; ASP-345 AND VAL-365.
RC STRAIN=DBY939, and JM43;
RX PubMed=1594608; DOI=10.1073/pnas.89.11.5015;
RA Zhu H., Riggs A.F.;
RT "Yeast flavohemoglobin is an ancient protein related to globins and a
RT reductase family.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:5015-5019(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8701610;
RX DOI=10.1002/(sici)1097-0061(19960330)12:4<385::aid-yea910>3.0.co;2-g;
RA van der Aart Q.J.M., Kleine K., Steensma H.Y.;
RT "Sequence analysis of the 43 kb CRM1-YLM9-PET54-DIE2-SMI1-PHO81-YHB4-PFK1
RT region from the right arm of Saccharomyces cerevisiae chromosome VII.";
RL Yeast 12:385-390(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169869;
RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL Nature 387:81-84(1997).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36.
RC STRAIN=T73;
RA Perez-Ortin J.E.;
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP REGULATION OF EXPRESSION.
RX PubMed=7896850; DOI=10.1074/jbc.270.12.6991;
RA Crawford M.J., Sherman D.R., Goldberg D.E.;
RT "Regulation of Saccharomyces cerevisiae flavohemoglobin gene expression.";
RL J. Biol. Chem. 270:6991-6996(1995).
RN [8]
RP ROLE IN OXIDATIVE STRESS.
RX PubMed=8810268; DOI=10.1074/jbc.271.41.25131;
RA Buisson N., Labbe-Bois R.;
RT "Function and expression of flavohemoglobin in Saccharomyces cerevisiae.
RT Evidence for a role in the oxidative stress response.";
RL J. Biol. Chem. 271:25131-25138(1996).
RN [9]
RP ROLE IN OXIDATIVE STRESS.
RX PubMed=9545281; DOI=10.1074/jbc.273.16.9527;
RA Buisson N., Labbe-Bois R.;
RT "Flavohemoglobin expression and function in Saccharomyces cerevisiae. No
RT relationship with respiration and complex response to oxidative stress.";
RL J. Biol. Chem. 273:9527-9533(1998).
RN [10]
RP ENZYME ACTIVITY.
RX PubMed=10922365; DOI=10.1074/jbc.m004141200;
RA Gardner P.R., Gardner A.M., Martin L.A., Dou Y., Li T., Olson J.S., Zhu H.,
RA Riggs A.F.;
RT "Nitric-oxide dioxygenase activity and function of flavohemoglobins.
RT Sensitivity to nitric oxide and carbon monoxide inhibition.";
RL J. Biol. Chem. 275:31581-31587(2000).
RN [11]
RP ROLE IN NITRIC OXIDE DETOXIFICATION.
RX PubMed=10758168; DOI=10.1073/pnas.090083597;
RA Liu L., Zeng M., Hausladen A., Heitman J., Stamler J.S.;
RT "Protection from nitrosative stress by yeast flavohemoglobin.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:4672-4676(2000).
RN [12]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-22, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
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 fungus from
CC various noxious nitrogen compounds. Therefore, plays a central role in
CC the inducible response to nitrosative stress.
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.
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 Evidence={ECO:0000269|PubMed:10922365};
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 Evidence={ECO:0000269|PubMed:10922365};
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 -!- INTERACTION:
CC P39676; Q07540: YFH1; NbExp=2; IntAct=EBI-6905, EBI-2206814;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
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 -!- MISCELLANEOUS: Present with 13000 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
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; L07070; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; L07071; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X87941; CAA61184.1; -; Genomic_DNA.
DR EMBL; Z73019; CAA97262.1; -; Genomic_DNA.
DR EMBL; AY692964; AAT92983.1; -; Genomic_DNA.
DR EMBL; AF239759; AAK15081.1; -; Genomic_DNA.
DR EMBL; BK006941; DAA08325.1; -; Genomic_DNA.
DR PIR; S57699; S57699.
DR RefSeq; NP_011750.1; NM_001181363.1.
DR AlphaFoldDB; P39676; -.
DR SMR; P39676; -.
DR BioGRID; 33486; 142.
DR DIP; DIP-1355N; -.
DR IntAct; P39676; 46.
DR MINT; P39676; -.
DR STRING; 4932.YGR234W; -.
DR iPTMnet; P39676; -.
DR MaxQB; P39676; -.
DR PaxDb; P39676; -.
DR PRIDE; P39676; -.
DR TopDownProteomics; P39676; -.
DR EnsemblFungi; YGR234W_mRNA; YGR234W; YGR234W.
DR GeneID; 853149; -.
DR KEGG; sce:YGR234W; -.
DR SGD; S000003466; YHB1.
DR VEuPathDB; FungiDB:YGR234W; -.
DR eggNOG; KOG3378; Eukaryota.
DR GeneTree; ENSGT01000000220046; -.
DR HOGENOM; CLU_003827_12_0_1; -.
DR InParanoid; P39676; -.
DR OMA; ADIHYEV; -.
DR BioCyc; YEAST:G3O-30912-MON; -.
DR SABIO-RK; P39676; -.
DR PRO; PR:P39676; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P39676; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0010494; C:cytoplasmic stress granule; HDA:SGD.
DR GO; GO:0005829; C:cytosol; IDA:SGD.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
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:0016966; F:nitric oxide reductase activity; IMP:SGD.
DR GO; GO:0019825; F:oxygen binding; IEA:InterPro.
DR GO; GO:0071218; P:cellular response to misfolded protein; IMP:SGD.
DR GO; GO:0071500; P:cellular response to nitrosative stress; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:SGD.
DR GO; GO:1902170; P:cellular response to reactive nitrogen species; IMP:SGD.
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; 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; 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 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 1: Evidence at protein level;
KW Cytoplasm; Detoxification; Direct protein sequencing; FAD; Flavoprotein;
KW Heme; Iron; Metal-binding; NAD; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..399
FT /note="Flavohemoprotein"
FT /id="PRO_0000052458"
FT DOMAIN 147..264
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..138
FT /note="Globin"
FT REGION 146..399
FT /note="Reductase"
FT ACT_SITE 95
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 137
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT BINDING 85
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 207..210
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 281..286
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 389..392
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT SITE 29
FT /note="Involved in heme-bound ligand stabilization and O-O
FT bond activation"
FT /evidence="ECO:0000250"
FT SITE 84
FT /note="Influences the redox potential of the prosthetic
FT heme and FAD groups"
FT /evidence="ECO:0000250"
FT SITE 388
FT /note="Influences the redox potential of the prosthetic
FT heme and FAD groups"
FT /evidence="ECO:0000250"
FT MOD_RES 22
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT VARIANT 153
FT /note="D -> E (in strain: JM43)"
FT /evidence="ECO:0000269|PubMed:1594608"
FT VARIANT 345
FT /note="N -> D (in strain: JM43)"
FT /evidence="ECO:0000269|PubMed:1594608"
FT VARIANT 365
FT /note="L -> V (in strain: JM43)"
FT /evidence="ECO:0000269|PubMed:1594608"
SQ SEQUENCE 399 AA; 44646 MW; 8AF1DE3280220D56 CRC64;
MLAEKTRSII KATVPVLEQQ GTVITRTFYK NMLTEHTELL NIFNRTNQKV GAQPNALATT
VLAAAKNIDD LSVLMDHVKQ IGHKHRALQI KPEHYPIVGE YLLKAIKEVL GDAATPEIIN
AWGEAYQAIA DIFITVEKKM YEEALWPGWK PFDITAKEYV ASDIVEFTVK PKFGSGIELE
SLPITPGQYI TVNTHPIRQE NQYDALRHYS LCSASTKNGL RFAVKMEAAR ENFPAGLVSE
YLHKDAKVGD EIKLSAPAGD FAINKELIHQ NEVPLVLLSS GVGVTPLLAM LEEQVKCNPN
RPIYWIQSSY DEKTQAFKKH VDELLAECAN VDKIIVHTDT EPLINAAFLK EKSPAHADVY
TCGSLAFMQA MIGHLKELEH RDDMIHYEPF GPKMSTVQV
