ID A0A2K5V3D8_MACFA Unreviewed; 1153 AA.
AC A0A2K5V3D8;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 02-JUN-2021, sequence version 2.
DT 24-JAN-2024, entry version 31.
DE RecName: Full=Nitric oxide synthase {ECO:0000256|PIRNR:PIRNR000333};
DE EC=1.14.13.39 {ECO:0000256|PIRNR:PIRNR000333};
GN Name=NOS2 {ECO:0000313|Ensembl:ENSMFAP00000019245.2};
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541 {ECO:0000313|Ensembl:ENSMFAP00000019245.2, ECO:0000313|Proteomes:UP000233100};
RN [1] {ECO:0000313|Ensembl:ENSMFAP00000019245.2, ECO:0000313|Proteomes:UP000233100}
RP NUCLEOTIDE SEQUENCE.
RA Warren W., Wilson R.K.;
RL Submitted (MAR-2013) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSMFAP00000019245.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2023) to UniProtKB.
CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with
CC diverse functions. {ECO:0000256|PIRNR:PIRNR000333}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + 2 L-arginine + 3 NADPH + 4 O2 = 4 H2O + 2 L-citrulline
CC + 3 NADP(+) + 2 nitric oxide; Xref=Rhea:RHEA:19897,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16480, ChEBI:CHEBI:32682, ChEBI:CHEBI:57743,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.39;
CC Evidence={ECO:0000256|ARBA:ARBA00035595};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19898;
CC Evidence={ECO:0000256|ARBA:ARBA00035595};
CC -!- COFACTOR:
CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin;
CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000256|ARBA:ARBA00001950};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000256|PIRNR:PIRNR000333};
CC Note=Binds 1 FAD. {ECO:0000256|PIRNR:PIRNR000333};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000256|PIRNR:PIRNR000333};
CC Note=Binds 1 FMN. {ECO:0000256|PIRNR:PIRNR000333};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000256|ARBA:ARBA00001970,
CC ECO:0000256|PIRNR:PIRNR000333};
CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000256|ARBA:ARBA00006267,
CC ECO:0000256|PIRNR:PIRNR000333}.
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DR AlphaFoldDB; A0A2K5V3D8; -.
DR Ensembl; ENSMFAT00000069793.2; ENSMFAP00000019245.2; ENSMFAG00000032615.2.
DR VEuPathDB; HostDB:ENSMFAG00000032615; -.
DR GeneTree; ENSGT00940000159752; -.
DR OrthoDB; 276396at2759; -.
DR Proteomes; UP000233100; Chromosome 16.
DR Bgee; ENSMFAG00000032615; Expressed in colon.
DR GO; GO:0030863; C:cortical cytoskeleton; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005777; C:peroxisome; IEA:Ensembl.
DR GO; GO:0034618; F:arginine binding; IEA:Ensembl.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:Ensembl.
DR GO; GO:0010181; F:FMN binding; IEA:Ensembl.
DR GO; GO:0020037; F:heme binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0004517; F:nitric-oxide synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0034617; F:tetrahydrobiopterin binding; IEA:Ensembl.
DR GO; GO:0006527; P:arginine catabolic process; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071346; P:cellular response to type II interferon; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0042742; P:defense response to bacterium; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IEA:Ensembl.
DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; IEA:Ensembl.
DR GO; GO:0032310; P:prostaglandin secretion; IEA:Ensembl.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; IEA:Ensembl.
DR GO; GO:0050796; P:regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0006801; P:superoxide metabolic process; IEA:Ensembl.
DR CDD; cd00795; NOS_oxygenase_euk; 1.
DR Gene3D; 3.40.50.360; -; 2.
DR Gene3D; 6.10.250.410; -; 1.
DR Gene3D; 3.90.440.10; Nitric Oxide Synthase;Heme Domain;Chain A domain 2; 1.
DR Gene3D; 3.40.50.80; Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module; 1.
DR Gene3D; 2.40.30.10; Translation factors; 1.
DR InterPro; IPR003097; CysJ-like_FAD-binding.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR001094; Flavdoxin-like.
DR InterPro; IPR008254; Flavodoxin/NO_synth.
DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR023173; NADPH_Cyt_P450_Rdtase_alpha.
DR InterPro; IPR044943; NOS_dom_1.
DR InterPro; IPR044940; NOS_dom_2.
DR InterPro; IPR044944; NOS_dom_3.
DR InterPro; IPR012144; NOS_euk.
DR InterPro; IPR004030; NOS_N.
DR InterPro; IPR036119; NOS_N_sf.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR PANTHER; PTHR43410; NITRIC OXIDE SYNTHASE OXYGENASE; 1.
DR PANTHER; PTHR43410:SF1; NITRIC OXIDE SYNTHASE OXYGENASE; 1.
DR Pfam; PF00667; FAD_binding_1; 1.
DR Pfam; PF00258; Flavodoxin_1; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR Pfam; PF02898; NO_synthase; 1.
DR PIRSF; PIRSF000333; NOS; 2.
DR PRINTS; PR00369; FLAVODOXIN.
DR PRINTS; PR00371; FPNCR.
DR SUPFAM; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 1.
DR SUPFAM; SSF52218; Flavoproteins; 1.
DR SUPFAM; SSF56512; Nitric oxide (NO) synthase oxygenase domain; 1.
DR SUPFAM; SSF63380; Riboflavin synthase domain-like; 1.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
DR PROSITE; PS60001; NOS; 1.
PE 3: Inferred from homology;
KW Calmodulin-binding {ECO:0000256|ARBA:ARBA00022860,
KW ECO:0000256|PIRNR:PIRNR000333};
KW FAD {ECO:0000256|ARBA:ARBA00022827, ECO:0000256|PIRNR:PIRNR000333};
KW Flavoprotein {ECO:0000256|ARBA:ARBA00022630};
KW FMN {ECO:0000256|ARBA:ARBA00022643, ECO:0000256|PIRNR:PIRNR000333};
KW Heme {ECO:0000256|ARBA:ARBA00022617, ECO:0000256|PIRNR:PIRNR000333};
KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|PIRNR:PIRNR000333};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRNR:PIRNR000333};
KW NADP {ECO:0000256|ARBA:ARBA00022857, ECO:0000256|PIRNR:PIRNR000333};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW ECO:0000256|PIRNR:PIRNR000333};
KW Reference proteome {ECO:0000313|Proteomes:UP000233100}.
FT DOMAIN 539..677
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000259|PROSITE:PS50902"
FT DOMAIN 730..970
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000259|PROSITE:PS51384"
FT REGION 50..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 200
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000256|PIRSR:PIRSR000333-1"
SQ SEQUENCE 1153 AA; 130884 MW; 90DF36081F04435E CRC64;
MACPWKFLFK TKFHQYTMTG GKDINNNMEK AACATPSLVT QDDLQYHSLS KQQNESPQPL
VGTGKKSPES LVKPDATPLS SPRHVRIKNW GSGMTFQDTL HHKAKGILTC RSKSCLGSIM
TPKSLTRGPR DKPTPPDELL PQAIEFVNQY YGSFKEAKIE EHLARVEAVT KEIETTGTYQ
LTGDELIFAT KQAWRNAPRC IGRIQWSNLQ VFDARNCSTA REMFEHICRH VRYSTNNGNI
RSAITVFPQR SDGKHDFRVW NAQLIRYAGY QMPDGSIRGD PANVEFTQLC IDLGWKPKYG
RFDVVPLVLQ ADGRDPELFE IPPDLVLEVA MEHPKYEWFR ELELKWYALP AVANMLLEVG
GLEFPGCPFN GWYMGTEIGV RDFCDVQRYN ILEEVGRRMG LETHKLASLW KDQAVVEINI
AVLHSFQKQN VTIMDHHSAA ESFMKYMQNE YRSRGGCPAD WIWLVPPMSG SITPVFHQEM
LNYVLSPFYY YQVEAWKTHV WQDEKRRPKR REIPLKVLVK AVLFACMLMR KTMASRVRVT
ILFATETGKS EALAWDLGAL FSCAFNPKVV CMDKYSLSCL EEERLLLVVT STFGNGDCPG
NGEKLKKSLF MLKELTNKFR YAVFGLGSSM YPRFCAFAHD IDQKLSHLGA SQLTPMGEGD
ELSGQEDAFR SWAVQTFKAA CETFDVRGKQ HIQIPKLYTS SVTWDPHHYR LVQDSQPLDL
SKALSNVHAK NVFTMRLKSR QNLQSLTSSR ATILVELSCE DGQGLNYLPG EHLGVCPGNQ
PALVQGILER VVDGPAPHQT VRLEALDESG SYWVSDKRLP PCSLSQALTY FLDITTPPTQ
LLLQKLAQMA TEATERQRLE ALCQPSEYSK WKFTNSPTFL EVLEEFPSLR VSAGFLLSQL
PILKPRFYSI SSSRDHTPTE IHLTVAVVTY HTQDGQGPLH HGVCSTWLNS LKPRDPVPCF
IRNARGFHLP EDPSHPCILV GPGTGIAPFR SFWQQRLHDS QHKGVRGGRM TLVFGCRRPD
EDHIYQKEML EMAQKGVLHA VHTAYSRLPG KPKVYVQDIL RQQLASEVLR VLHEEPGHLY
VCGDVRMAWD VAHTLKQLVA AKLNLNEEQV EDYFFQLKSQ KRYHEDIFGV VFPYEAKKDG
AAAQPRSLEM SAL
//
