ID F1LQC7_RAT Unreviewed; 1106 AA. AC F1LQC7; DT 03-MAY-2011, integrated into UniProtKB/TrEMBL. DT 25-MAY-2022, sequence version 2. DT 28-JUN-2023, entry version 90. DE RecName: Full=Nitric oxide synthase {ECO:0000256|PIRNR:PIRNR000333}; DE EC=1.14.13.39 {ECO:0000256|PIRNR:PIRNR000333}; GN Name=Nos3 {ECO:0000313|Ensembl:ENSRNOP00000013058.4, GN ECO:0000313|RGD:3186}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116 {ECO:0000313|Ensembl:ENSRNOP00000013058.4, ECO:0000313|Proteomes:UP000002494}; RN [1] {ECO:0000313|Ensembl:ENSRNOP00000013058.4, ECO:0000313|Proteomes:UP000002494} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000013058.4, RC ECO:0000313|Proteomes:UP000002494}; RX PubMed=15057822; DOI=10.1038/nature02426; RG Rat Genome Sequencing Project Consortium; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [2] {ECO:0007829|PubMed:22673903} RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [3] {ECO:0000313|Ensembl:ENSRNOP00000013058.4} RP IDENTIFICATION. RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000013058.4}; RG Ensembl; RL Submitted (MAR-2023) to UniProtKB. CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with CC diverse functions throughout the body. {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|PIRNR:PIRNR000333}; 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}. 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 AlphaFoldDB; F1LQC7; -. DR Ensembl; ENSRNOT00000013058.5; ENSRNOP00000013058.4; ENSRNOG00000009348.6. DR RGD; 3186; Nos3. DR GeneTree; ENSGT00940000161389; -. DR HOGENOM; CLU_001570_16_0_1; -. DR TreeFam; TF324410; -. DR Proteomes; UP000002494; Chromosome 4. DR Bgee; ENSRNOG00000009348; Expressed in heart and 19 other tissues. DR GO; GO:0005901; C:caveola; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IEA:Ensembl. DR GO; GO:0003785; F:actin monomer binding; 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:InterPro. DR GO; GO:0010181; F:FMN binding; IEA:InterPro. 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:0097110; F:scaffold protein binding; IEA:Ensembl. DR GO; GO:0034617; F:tetrahydrobiopterin binding; IEA:Ensembl. DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl. DR GO; GO:0003180; P:aortic valve morphogenesis; IEA:Ensembl. DR GO; GO:0006527; P:arginine catabolic process; IEA:Ensembl. DR GO; GO:0097746; P:blood vessel diameter maintenance; IEA:Ensembl. DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl. DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl. DR GO; GO:0003203; P:endocardial cushion morphogenesis; IEA:Ensembl. DR GO; GO:0043542; P:endothelial cell migration; IEA:Ensembl. DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl. DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0030324; P:lung development; IEA:Ensembl. DR GO; GO:0070168; P:negative regulation of biomineral tissue development; IEA:Ensembl. DR GO; GO:0051926; P:negative regulation of calcium ion transport; IEA:Ensembl. DR GO; GO:0051346; P:negative regulation of hydrolase activity; IEA:Ensembl. DR GO; GO:0014740; P:negative regulation of muscle hyperplasia; IEA:Ensembl. DR GO; GO:0043267; P:negative regulation of potassium ion transport; IEA:Ensembl. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0006809; P:nitric oxide biosynthetic process; IEA:Ensembl. DR GO; GO:0001542; P:ovulation from ovarian follicle; IEA:Ensembl. DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0031284; P:positive regulation of guanylate cyclase activity; IEA:Ensembl. DR GO; GO:0006813; P:potassium ion transport; IEA:Ensembl. DR GO; GO:0003184; P:pulmonary valve morphogenesis; IEA:Ensembl. DR GO; GO:0042981; P:regulation of apoptotic process; IEA:UniProt. DR GO; GO:0031644; P:regulation of nervous system process; IEA:Ensembl. DR GO; GO:0002028; P:regulation of sodium ion transport; IEA:Ensembl. DR GO; GO:0003100; P:regulation of systemic arterial blood pressure by endothelin; IEA:Ensembl. DR GO; GO:0003057; P:regulation of the force of heart contraction by chemical signal; IEA:Ensembl. DR GO; GO:0019430; P:removal of superoxide radicals; IEA:Ensembl. DR GO; GO:0034405; P:response to fluid shear stress; IEA:Ensembl. DR GO; GO:0014806; P:smooth muscle hyperplasia; IEA:Ensembl. DR GO; GO:0060412; P:ventricular septum morphogenesis; IEA:Ensembl. DR CDD; cd00795; NOS_oxygenase_euk; 1. DR Gene3D; 3.40.50.360; -; 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; 1. 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 1: Evidence at protein level; 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 Proteomics identification {ECO:0007829|PeptideAtlas:F1LQC7}; KW Reference proteome {ECO:0000313|Proteomes:UP000002494}. FT DOMAIN 519..702 FT /note="Flavodoxin-like" FT /evidence="ECO:0000259|PROSITE:PS50902" FT DOMAIN 755..1001 FT /note="FAD-binding FR-type" FT /evidence="ECO:0000259|PROSITE:PS51384" FT REGION 1..70 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 817..843 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1079..1106 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 35..64 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 183 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 1106 AA; 122339 MW; B62810DCB21C897E CRC64; MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSQ APVPPSPTRP APDHSPPLTR PPDGPKFPRV KNWEVGSITY DTLSAQAQQD GPCTPRRCLG SLVFPRKLQS RPTQGPSPTE QLLGQARDFI NQYYNSIKRS GSQAHEQRLQ EVEAEVVATG TYQLRESELV FGAKQAWRNA PRCVGRIQWG KLQVFDARDC RTAQEMFTYI CNHIKYATNR GNLRSAITVF PQRYAGRGDF RIWNSQLVRY AGYRQQDGSV RGDPANVEIT ELCIQHGWTP GNGRFDVLPL LLQAPDEPPE LFTLPPELVL EVPLEHPTLE WFAALGLRWY ALPAVSNMLL EIGGLEFPAA PFSGWYMSSE IGMRDLCDPH RYNILEDVAV CMDLDTRTTS SLWKDKAAVE INVAVLYSYQ LAKVTIVDHH AATASFMKHL ENEQKARGGC PADWAWIVPP ISGSLTPVFH QEMVNYFLSP AFRYQPDPWK GSAAKGTGIT RKKTFKEVAN AVKISASLMG TVMAKRVKAT ILYGSETGRA QSYAQQLGRL FRKAFDPRVL CMDEYDVVSL EHEALVLVVT STFGNGDPPE NGESFAAALM EMSGPYNSSP RPEQHKSYKI RFNSVSCSDP LVSSWRRKRK ESSNTDSAGA LGTLRFCVFG LGSRAYPHFC AFARAVDTRL EELGGERLLQ LGQGDELCGQ EEAFRGWAQA AFQAACETFC VGEDAKAAAR DIFSPKRSWK RQRYRLSTQA ESLQLLPGLT HVHRRKMFQA TILSVENLQS SKSTRATILV RLDTGSQEGL QYQPGDHIGV CPPNRPGLVE ALLSRVEDPP PSTEPVAVEQ LEKGSPGGPP PGWVRDPRLP PCTLRQALTY FLDITSPPSP RLLRLLSTLA EESSEQQELE ALSQDPRRYE EWKWFRCPTL LEVLEQFPSV ALPAPLILTQ LPLLQPRYYS VSSAPSAHPG EIHLTVAVLA YRTQDGLGPL HYGVCSTWMS QLKAGDPVPC FIRGAPSFRL PPDPNLPCIL VGPGTGIAPF RGFWQDRLHD IEIKGLQPAP MTLVFGCRCS QLDHLYRDEV LDAQQRGVFG QVLTAFSRDP GSPKERQLRG AVPWSFDPPT QETPGS //