ID G1SGE1_RABIT Unreviewed; 1146 AA.
AC G1SGE1;
DT 19-OCT-2011, integrated into UniProtKB/TrEMBL.
DT 11-DEC-2019, sequence version 2.
DT 27-MAR-2024, entry version 84.
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:ENSOCUP00000001643.3};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986 {ECO:0000313|Ensembl:ENSOCUP00000001643.3, ECO:0000313|Proteomes:UP000001811};
RN [1] {ECO:0000313|Ensembl:ENSOCUP00000001643.3, ECO:0000313|Proteomes:UP000001811}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thorbecke inbred {ECO:0000313|Ensembl:ENSOCUP00000001643.3,
RC ECO:0000313|Proteomes:UP000001811};
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2] {ECO:0000313|Ensembl:ENSOCUP00000001643.3}
RP IDENTIFICATION.
RC STRAIN=Thorbecke {ECO:0000313|Ensembl:ENSOCUP00000001643.3};
RG Ensembl;
RL Submitted (NOV-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 EMBL; AAGW02049872; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; G1SGE1; -.
DR SMR; G1SGE1; -.
DR PaxDb; 9986-ENSOCUP00000001643; -.
DR Ensembl; ENSOCUT00000001908.3; ENSOCUP00000001643.3; ENSOCUG00000001903.3.
DR eggNOG; KOG1158; Eukaryota.
DR GeneTree; ENSGT00940000159752; -.
DR HOGENOM; CLU_001570_16_0_1; -.
DR InParanoid; G1SGE1; -.
DR TreeFam; TF324410; -.
DR Proteomes; UP000001811; Chromosome 19.
DR Bgee; ENSOCUG00000001903; Expressed in lung and 14 other cell types or tissues.
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:UP000001811}.
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 23..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 23..39
FT /note="Polar residues"
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 1146 AA; 129846 MW; CACC9A1848ABE33C CRC64;
MACPWRFLFK ARSQQYDLTE EKDINNNVGK GTSELCSPAT QDDPKCHSLS KHQDDSPQPP
AATAKKSPES PGKQDVPPSA CPRHVRIRNW GSGMTLQDTL HLKAKEDSTC KSHYCQGAVM
NPKEMIRGPR DRPTPAEELL PQAIEFVNQY YGSFKEAKIE AHLARVEAVT KEIETTGTYQ
LTGDELIFAT KQAWRNAPRC IGRIQWSNLQ VFDARSCSTA QEMFEHICRH LRYATNNGNI
RSAITVFPQR SDGKHDFRVW NSQLIRYAGY HMPDGTIQGD PANTEFTQLC IDLGWKPNFG
RFDVLPLVLQ ADGRDPELFE IPADIVLEVP MEHPKYEWFR ELELKWYALP AVANMLLEAG
GLEFPACPFN GWYMGTEIGV RDFCDVQRYN ILEEVGRRMG LETHRLASLW KDQAVTEINI
AVLHSFQKRN VTIMDHHSAA ESFMKHMQNE YRSRGGCPAD WIWLVPPMSG SITPVFHQEM
LNYILSPFYY YQVEAWKTHA WQDMKKKPQR RRLQFRVLGR TALFASVLMR KTLAVRVRAT
ILFATETGKS EALARDLGDL FGCAFNPTVL CMDEYQLSNL EREQLLLVVT STFGNGDSPG
NGEKLKRSLF MLKELTNKFR YAVFGLGSSM YPQFCAFARD IDQKLCHLGA SQLAPLGEGD
ELSGQEDAFR SWAVQTFKAA CETFGIRGKE RIQIPKLYTS SVTWEPHHYR LVQDSQPLDL
NRALSSLHAK NVMTMKLKSL RNLQSPRSSR ATVLVQLSCE GSPGLSYLPG EHLGVCPSNQ
PALVQGILER VVDCPDPHQT VHLQILAESG SYWVRDKRLP PCSLSQALTY FLDITTPPTQ
LLLQKLSRLA TEEAERQRLV TLCQPSEYNK WKLTNSPTFL EVLEEFPSLR LSAAFLLSQL
PNLKPRYYSI SSSQDHTPTE VHLTVAVVTY RPRGGQGPLH HGVCSTWLSS LKPQDPVPCF
VRSASGFQLP EDPSHPCILI GPGTGIAPFR SFWQQRLHDS EYKGLRGGRM ILVFGCRHPD
EDHLYWEELL EMMQKGVLSG VHTAYSLPGQ PKVYVQDLLR QKLADEVLRV LLEEPGHIYV
CGGVCMARDV ALVLKQLVAA KLSLSEEQVE DYFFLLKSRK RYHEDIFGAA FPYEVQRSEQ
PGDTGL
//