HMP_GIAIB
ID HMP_GIAIB Reviewed; 458 AA.
AC C6LR75;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 1.
DT 03-AUG-2022, entry version 61.
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=GL50581_1257;
OS Giardia intestinalis (strain ATCC 50581 / GS clone H7) (Giardia lamblia).
OC Eukaryota; Metamonada; Diplomonadida; Hexamitidae; Giardiinae; Giardia.
OX NCBI_TaxID=598745;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 50581 / GS clone H7;
RX PubMed=19696920; DOI=10.1371/journal.ppat.1000560;
RA Franzen O., Jerlstrom-Hultqvist J., Castro E., Sherwood E., Ankarklev J.,
RA Reiner D.S., Palm D., Andersson J.O., Andersson B., Svard S.G.;
RT "Draft genome sequencing of giardia intestinalis assemblage B isolate GS:
RT is human giardiasis caused by two different species?";
RL PLoS Pathog. 5:E1000560-E1000560(2009).
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 (By
CC 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=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000250};
CC Note=Binds 1 heme b group. {ECO:0000250};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC Note=Binds 1 FAD. {ECO:0000250};
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
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}.
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DR EMBL; ACGJ01001771; EET01482.1; -; Genomic_DNA.
DR AlphaFoldDB; C6LR75; -.
DR SMR; C6LR75; -.
DR EnsemblProtists; EET01482; EET01482; GL50581_1257.
DR VEuPathDB; GiardiaDB:GL50581_1257; -.
DR OMA; ADIHYEV; -.
DR OrthoDB; 696109at2759; -.
DR Proteomes; UP000002488; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
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; IEA:UniProtKB-EC.
DR GO; GO:0019825; F:oxygen binding; IEA:InterPro.
DR GO; GO:0005344; F:oxygen carrier activity; IEA:UniProtKB-KW.
DR GO; GO:0051409; P:response to nitrosative stress; IEA:InterPro.
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; 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; 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 3: Inferred from homology;
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_0000409357"
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 320..325
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; 51330 MW; 2092C576945DFBAE CRC64;
MPLSEDTIKA VEATADLVAA QGLDFTRAFY ERMLTRNEEL KDVFNLSHQR DLRQPKALLD
SLVAYARSIR KINELHELQE QGLPVPAERL AELQGFFAVA ERIAHKHASV GIQPAQYQIV
GAHLLATIEE RVTADKAILA AWSKAYDFLA HLFVRREEEI YTETESSEGG WRQTRSFRVE
EKAQITERIF RFRLVPAEKG TAVALHKPGQ YLAVFVRDPR LSPHRQIRQY SITSAPNHTY
YEIAVHRDKQ ATVSGYLHDH VAVGDLLKLA PPYGDFFLEY REPGGQAADG QPSPEPLALH
GGAVNFAAER MTPIVLISGG IGQTPLLSIL RFLAEKEGQA AIRPIFWIHA AHDSRARAFK
AEVDAIKVTD LPGLRTTTFL SEVDETMDKK GEDYDFAGRI SLDRVPGLAE LEADGANPHY
FFVGPAGFMV AVEQQLKAWS VPEDRIHFEM FGPFKPLQ
