HMP_GIAIC
ID HMP_GIAIC Reviewed; 458 AA.
AC E2RTZ4; A8BWC7; Q86QZ2;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=Flavohemoprotein;
DE AltName: Full=Flavohemoglobin;
DE Short=FlavoHb;
DE AltName: Full=Hemoglobin-like protein;
DE AltName: Full=Nitric oxide dioxygenase;
DE Short=NO oxygenase;
DE Short=NOD;
DE EC=1.14.12.17;
GN Name=hmpA; Synonyms=FLHb; ORFNames=GL50803_15009;
OS Giardia intestinalis (strain ATCC 50803 / WB clone C6) (Giardia lamblia).
OC Eukaryota; Metamonada; Diplomonadida; Hexamitidae; Giardiinae; Giardia.
OX NCBI_TaxID=184922;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 50803 / WB clone C6;
RX PubMed=12546782; DOI=10.1016/s0960-9822(03)00003-4;
RA Andersson J.O., Sjogren A.M., Davis L.A., Embley T.M., Roger A.J.;
RT "Phylogenetic analyses of diplomonad genes reveal frequent lateral gene
RT transfers affecting eukaryotes.";
RL Curr. Biol. 13:94-104(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 50803 / WB clone C6;
RX PubMed=17901334; DOI=10.1126/science.1143837;
RA Morrison H.G., McArthur A.G., Gillin F.D., Aley S.B., Adam R.D.,
RA Olsen G.J., Best A.A., Cande W.Z., Chen F., Cipriano M.J., Davids B.J.,
RA Dawson S.C., Elmendorf H.G., Hehl A.B., Holder M.E., Huse S.M., Kim U.U.,
RA Lasek-Nesselquist E., Manning G., Nigam A., Nixon J.E.J., Palm D.,
RA Passamaneck N.E., Prabhu A., Reich C.I., Reiner D.S., Samuelson J.,
RA Svard S.G., Sogin M.L.;
RT "Genomic minimalism in the early diverging intestinal parasite Giardia
RT lamblia.";
RL Science 317:1921-1926(2007).
RN [3]
RP FUNCTION, HEME-BINDING, SUBUNIT, AND COFACTOR.
RX PubMed=20655876; DOI=10.1016/j.bbrc.2010.07.073;
RA Rafferty S., Luu B., March R.E., Yee J.;
RT "Giardia lamblia encodes a functional flavohemoglobin.";
RL Biochem. Biophys. Res. Commun. 399:347-351(2010).
RN [4]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND INDUCTION.
RX PubMed=20691663; DOI=10.1016/j.bbrc.2010.07.137;
RA Mastronicola D., Testa F., Forte E., Bordi E., Pucillo L.P., Sarti P.,
RA Giuffre A.;
RT "Flavohemoglobin and nitric oxide detoxification in the human protozoan
RT parasite Giardia intestinalis.";
RL Biochem. Biophys. Res. Commun. 399:654-658(2010).
CC -!- FUNCTION: Flavohemoprotein involved in nitric oxide (NO) detoxification
CC in an aerobic process, termed nitric oxide dioxygenase (NOD) reaction
CC that utilizes O(2) and NAD(P)H to convert NO to nitrate, which protects
CC the protozoan parasite from various noxious nitrogen compounds.
CC Therefore, plays a central role in the inducible response to
CC nitrosative stress. May also be involved in O(2) detoxification.
CC {ECO:0000269|PubMed:20655876, ECO:0000269|PubMed:20691663}.
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=heme b; Xref=ChEBI:CHEBI:60344;
CC Note=Binds 1 heme b group.;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Note=Binds 1 FAD.;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=22 uM for O(2) {ECO:0000269|PubMed:20691663};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:20655876}.
CC -!- INDUCTION: Expressed at very low levels in untreated trophozoites of
CC the parasite. Expression is markedly stimulated in nitrite-supplemented
CC medium. Induction by nitrite is probably mediated by NO, likely
CC generated upon reduction of nitrite. Also induced in cells grown in the
CC presence of the NO-donors 3,3-bis(aminoethyl)-1-hydroxy-2-oxo-1-
CC triazene (DETA-NONOate), and S-nitrosoglutathione (GSNO).
CC {ECO:0000269|PubMed:20691663}.
CC -!- DOMAIN: Consists of two distinct domains; an 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY132357; AAM94640.1; -; Genomic_DNA.
DR EMBL; AACB02000055; EDO76804.1; -; Genomic_DNA.
DR RefSeq; XP_001704478.1; XM_001704426.1.
DR AlphaFoldDB; E2RTZ4; -.
DR SMR; E2RTZ4; -.
DR STRING; 5741.EDO76804; -.
DR PRIDE; E2RTZ4; -.
DR EnsemblProtists; EDO76804; EDO76804; GL50803_15009.
DR GeneID; 5697339; -.
DR KEGG; gla:GL50803_0015009; -.
DR VEuPathDB; GiardiaDB:GL50803_15009; -.
DR HOGENOM; CLU_003827_12_0_1; -.
DR InParanoid; E2RTZ4; -.
DR OMA; ADIHYEV; -.
DR OrthoDB; 696109at2759; -.
DR SABIO-RK; E2RTZ4; -.
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:0071500; P:cellular response to nitrosative stress; IBA:GO_Central.
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; -; 2.
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; IPR017938; Riboflavin_synthase-like_b-brl.
DR PANTHER; PTHR43396:SF3; PTHR43396:SF3; 1.
DR Pfam; PF00970; FAD_binding_6; 1.
DR Pfam; PF00175; NAD_binding_1; 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 Detoxification; FAD; Flavoprotein; Heme; Iron; Metal-binding; NAD; NADP;
KW Oxidoreductase; Oxygen transport; Transport.
FT CHAIN 1..458
FT /note="Flavohemoprotein"
FT /id="PRO_0000409354"
FT DOMAIN 172..279
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..160
FT /note="Globin"
FT /evidence="ECO:0000250"
FT REGION 169..457
FT /note="Reductase"
FT /evidence="ECO:0000250"
FT ACT_SITE 117
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 157
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT BINDING 107
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 211
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 228..231
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 321..326
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 450..453
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 106
FT /note="Influences the redox potential of the prosthetic
FT heme and FAD groups"
FT /evidence="ECO:0000250"
FT SITE 449
FT /note="Influences the redox potential of the prosthetic
FT heme and FAD groups"
FT /evidence="ECO:0000250"
SQ SEQUENCE 458 AA; 52003 MW; 1A55B5C1CD2A38CB CRC64;
MTLSEDTLRA VEATAGLIAA QGIEFTRAFY ERMLTKNEEL KNIFNLAHQR TLRQPKALLD
SLVAYALNIR RINELYELKG KGLPVPPEHW AELQGFFSAA ERVANKHTSF GIQPAQYQIV
GAHLLATIED RITKDKDILA EWAKAYQFLA DLFIKREEEI YAATEGCKGG WRQTRTFRVE
EKTRVNEIIC KFRLVPAEEG AGVVEHRPGQ YLAIFVRSPE HFQHQQIRQY SIISAPNSAY
YEIAVHRDEK GTVSRYLHDY VSTGDLLEVA PPYGDFFLRY LEADEQAPAD TQASQEFQML
QSGAINFAAE KTMPIVLISG GIGQTPLLSM LRFLAQKEGK ETARPIFWIH AAHNSRVRAF
KEEVDAIRET ALPSLRVVTF LSEVRATDRE GEDYDFAGRI NLDRISELTK LEADNANPHY
FFVGPTGFMT AVEEQLKTKS VPNSRIHFEM FGPFKASH
