HMP2_GIAIA
ID HMP2_GIAIA Reviewed; 457 AA.
AC E1F8H4;
DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 52.
DE RecName: Full=Flavohemoprotein-2;
DE AltName: Full=Flavohemoglobin-2;
DE Short=FlavoHb-2;
DE AltName: Full=Hemoglobin-like protein-2;
DE AltName: Full=Nitric oxide dioxygenase-2;
DE Short=NO oxygenase-2;
DE Short=NOD-2;
DE EC=1.14.12.17;
GN Name=hmpA-2; Synonyms=FLHb-2; ORFNames=GLP15_347;
OS Giardia intestinalis (strain P15) (Giardia lamblia).
OC Eukaryota; Metamonada; Diplomonadida; Hexamitidae; Giardiinae; Giardia.
OX NCBI_TaxID=658858;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=P15;
RX PubMed=20929575; DOI=10.1186/1471-2164-11-543;
RA Jerlstrom-Hultqvist J., Franzen O., Ankarklev J., Xu F., Nohynkova E.,
RA Andersson J.O., Svard S.G., Andersson B.;
RT "Genome analysis and comparative genomics of a Giardia intestinalis
RT assemblage E isolate.";
RL BMC Genomics 11:543-543(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 (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; ACVC01000235; EFO61241.1; -; Genomic_DNA.
DR AlphaFoldDB; E1F8H4; -.
DR SMR; E1F8H4; -.
DR STRING; 658858.E1F8H4; -.
DR EnsemblProtists; EFO61241; EFO61241; GLP15_347.
DR VEuPathDB; GiardiaDB:GLP15_347; -.
DR OMA; EICAAWG; -.
DR OrthoDB; 696109at2759; -.
DR Proteomes; UP000008974; 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:0062197; P:cellular response to chemical stress; IEA:UniProt.
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; 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 3: Inferred from homology;
KW Detoxification; FAD; Flavoprotein; Heme; Iron; Metal-binding; NAD; NADP;
KW Oxidoreductase; Oxygen transport; Transport.
FT CHAIN 1..457
FT /note="Flavohemoprotein-2"
FT /id="PRO_0000409356"
FT DOMAIN 171..278
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..159
FT /note="Globin"
FT /evidence="ECO:0000250"
FT REGION 168..456
FT /note="Reductase"
FT /evidence="ECO:0000250"
FT ACT_SITE 116
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 156
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT BINDING 106
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 210
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 227..230
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 449..452
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 105
FT /note="Influences the redox potential of the prosthetic
FT heme and FAD groups"
FT /evidence="ECO:0000250"
FT SITE 448
FT /note="Influences the redox potential of the prosthetic
FT heme and FAD groups"
FT /evidence="ECO:0000250"
SQ SEQUENCE 457 AA; 51416 MW; E62314501DDBFAD4 CRC64;
MALSEDTIKA VEATAGLIAA QGIEFTRAFY ERMLTKNEEL KDIFNLAHQR TLRQPKALLD
SLVAYALSIR RINELYELKG KDLPWTGHLA ELQGFFSVAE RVANKHTSVG IQPAQYQIVG
AHLLATIEDR VTKDKAVLAA WGKAYEFLAD LLIKREEEIY AETEGPEGGW RQTRTFRVEE
KTRVNEVICR FRLVPAKGGA SVVQHKPGQY LAIFVRNPEL FQHQQIRQYS IMSAPNSAYY
EIAVHKDGAG TVSRYLHDHV DTGDLLEVAP PYGDFFLRYL EAGEQTAADT QASSEFQMLQ
GRAVNFAAEK TAPIVLISGG IGQTPLLSML RFLAQKEGRE TARPIFWIHA AHDSRVRAFK
EEVDAIREAA LPSLRVVTFL SEVRATDREG EDYDFAGRIN LDRIPELARL EAGHANPHYF
FVGPTGFMTA VEEQLRARSV PDDRIHFEMF GPFKASH
