NOS1_MOUSE
ID NOS1_MOUSE Reviewed; 1429 AA.
AC Q9Z0J4; Q3UR10; Q64208;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Nitric oxide synthase, brain;
DE EC=1.14.13.39;
DE AltName: Full=Constitutive NOS;
DE AltName: Full=NC-NOS;
DE AltName: Full=NOS type I;
DE AltName: Full=Neuronal NOS;
DE Short=N-NOS;
DE Short=nNOS;
DE AltName: Full=Peptidyl-cysteine S-nitrosylase NOS1;
DE AltName: Full=bNOS;
GN Name=Nos1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS N-NOS-1 AND N-NOS-2).
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=7686743; DOI=10.1006/bbrc.1993.1726;
RA Ogura T., Yokoyama T., Fujisawa H., Kurashima Y., Esumi H.;
RT "Structural diversity of neuronal oxide synthase mRNA in the nervous
RT system.";
RL Biochem. Biophys. Res. Commun. 193:1014-1022(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM NNOS MU).
RC TISSUE=Skeletal muscle;
RX PubMed=8626668; DOI=10.1074/jbc.271.19.11204;
RA Silvagno F., Xia H., Bredt D.S.;
RT "Neuronal nitric-oxide synthase-mu, an alternatively spliced isoform
RT expressed in differentiated skeletal muscle.";
RL J. Biol. Chem. 271:11204-11208(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1320-1429.
RC STRAIN=C57BL/6J; TISSUE=Spinal ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP ALTERNATIVE SPLICING (ISOFORMS NNOS BETA; NNOS GAMMA AND NNOS MU).
RX PubMed=9208206; DOI=10.1159/000111211;
RA Brenman J.E., Xia H., Chao D.S., Black S.M., Bredt D.S.;
RT "Regulation of neuronal nitric oxide synthase through alternative
RT transcripts.";
RL Dev. Neurosci. 19:224-231(1997).
RN [5]
RP INTERACTION WITH DLG4.
RX PubMed=10623522; DOI=10.1006/jmbi.1999.3350;
RA Tochio H., Hung F., Li M., Bredt D.S., Zhang M.;
RT "Solution structure and backbone dynamics of the second PDZ domain of
RT postsynaptic density-95.";
RL J. Mol. Biol. 295:225-237(2000).
RN [6]
RP INTERACTION WITH RASD1 AND CAPON.
RX PubMed=11086993; DOI=10.1016/s0896-6273(00)00095-7;
RA Fang M., Jaffrey S.R., Sawa A., Ye K., Luo X., Snyder S.H.;
RT "Dexras1: a G protein specifically coupled to neuronal nitric oxide
RT synthase via CAPON.";
RL Neuron 28:183-193(2000).
RN [7]
RP INTERACTION WITH HTR4.
RX PubMed=15466885; DOI=10.1242/jcs.01379;
RA Joubert L., Hanson B., Barthet G., Sebben M., Claeysen S., Hong W.,
RA Marin P., Dumuis A., Bockaert J.;
RT "New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a
RT receptor splice variant: roles in receptor targeting.";
RL J. Cell Sci. 117:5367-5379(2004).
RN [8]
RP FUNCTION AS NITROSYLASE.
RX PubMed=17293453; DOI=10.1073/pnas.0611620104;
RA Mustafa A.K., Kumar M., Selvakumar B., Ho G.P., Ehmsen J.T., Barrow R.K.,
RA Amzel L.M., Snyder S.H.;
RT "Nitric oxide S-nitrosylates serine racemase, mediating feedback inhibition
RT of D-serine formation.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2950-2955(2007).
RN [9]
RP INTERACTION WITH SLC6A4.
RX PubMed=17452640; DOI=10.1073/pnas.0610964104;
RA Chanrion B., Mannoury la Cour C., Bertaso F., Lerner-Natoli M.,
RA Freissmuth M., Millan M.J., Bockaert J., Marin P.;
RT "Physical interaction between the serotonin transporter and neuronal nitric
RT oxide synthase underlies reciprocal modulation of their activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:8119-8124(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280; SER-857 AND SER-858, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP INTERACTION WITH ASL; ASS1 AND SLC7A1.
RX PubMed=22081021; DOI=10.1038/nm.2544;
RA Erez A., Nagamani S.C., Shchelochkov O.A., Premkumar M.H., Campeau P.M.,
RA Chen Y., Garg H.K., Li L., Mian A., Bertin T.K., Black J.O., Zeng H.,
RA Tang Y., Reddy A.K., Summar M., O'Brien W.E., Harrison D.G., Mitch W.E.,
RA Marini J.C., Aschner J.L., Bryan N.S., Lee B.;
RT "Requirement of argininosuccinate lyase for systemic nitric oxide
RT production.";
RL Nat. Med. 17:1619-1626(2011).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 725-747 IN COMPLEX WITH
RP CALMODULIN.
RA Valentine K.G., Ng H.L., Schneeweis L., Kranz J.K., Frederick K.K.,
RA Alber T., Wand A.J.;
RT "Crystal structure of calmodulin-neuronal nitric oxide synthase complex.";
RL Submitted (DEC-2006) to the PDB data bank.
CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with
CC diverse functions throughout the body. In the brain and peripheral
CC nervous system, NO displays many properties of a neurotransmitter.
CC Probably has nitrosylase activity and mediates cysteine S-nitrosylation
CC of cytoplasmic target proteins such SRR. Isoform NNOS Mu may be an
CC effector enzyme for the dystrophin complex.
CC {ECO:0000269|PubMed:17293453}.
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 -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC Note=Binds 1 FAD. {ECO:0000250};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000250};
CC Note=Binds 1 FMN. {ECO:0000250};
CC -!- COFACTOR:
CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin;
CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000250};
CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the
CC enzyme. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Stimulated by calcium/calmodulin. Inhibited by n-
CC Nos-inhibiting protein (PIN) which may prevent the dimerization of the
CC protein. Inhibited by NOSIP (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with DLG4; the interaction possibly being
CC prevented by the association between NOS1 and CAPON (By similarity).
CC Forms a ternary complex with CAPON and RASD1 (PubMed:11086993). Forms a
CC ternary complex with CAPON and SYN1 (By similarity). Interacts with
CC ZDHHC23 (By similarity). Interacts with NOSIP; which may impair its
CC synaptic location (By similarity). Interacts with HTR4
CC (PubMed:15466885). Interacts with VAC14 (By similarity). Interacts (via
CC N-terminal domain) with DLG4 (via N-terminal tandem pair of PDZ
CC domains) (PubMed:10623522). Interacts with SLC6A4 (PubMed:17452640).
CC Forms a complex with ASL, ASS1 and SLC7A1; the complex regulates cell-
CC autonomous L-arginine synthesis and citrulline recycling while
CC channeling extracellular L-arginine to nitric oxide synthesis pathway
CC (PubMed:22081021). {ECO:0000250|UniProtKB:P29476,
CC ECO:0000269|PubMed:10623522, ECO:0000269|PubMed:11086993,
CC ECO:0000269|PubMed:15466885, ECO:0000269|PubMed:17452640,
CC ECO:0000269|PubMed:22081021, ECO:0000269|Ref.12}.
CC -!- INTERACTION:
CC Q9Z0J4; Q05769: Ptgs2; NbExp=4; IntAct=EBI-397596, EBI-298933;
CC Q9Z0J4; Q60857: Slc6a4; NbExp=4; IntAct=EBI-397596, EBI-15633326;
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma; Peripheral membrane
CC protein. Cell projection, dendritic spine {ECO:0000250}. Note=In
CC skeletal muscle, it is localized beneath the sarcolemma of fast-twitch
CC muscle fiber by associating with the dystrophin glycoprotein complex.
CC In neurons, enriched in dendritic spines (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=N-NOS-1;
CC IsoId=Q9Z0J4-1; Sequence=Displayed;
CC Name=N-NOS-2;
CC IsoId=Q9Z0J4-2; Sequence=VSP_003578;
CC Name=NNOS beta;
CC IsoId=Q9Z0J4-3; Sequence=VSP_003575, VSP_003576;
CC Name=NNOS gamma;
CC IsoId=Q9Z0J4-4; Sequence=VSP_003577;
CC Name=NNOS Mu; Synonyms=Muscle-specific;
CC IsoId=Q9Z0J4-5; Sequence=VSP_003579;
CC -!- TISSUE SPECIFICITY: Widely expressed in the nervous system: expressed
CC in cerebrum, olfactory bulb, hippocampus, midbrain, cerebellum, pons,
CC medulla oblongata, and spinal cord. Also found in skeletal muscle,
CC where it is localized beneath the sarcolemma of fast twitch muscle
CC fibers, and in spleen, heart, kidney, and liver. N-NOS-1 and N-NOS-2
CC are found in all parts of the nervous system. NNOS beta and gamma occur
CC in a region-specific manner in the brain and NNOS beta expression is
CC developmentally regulated. NNOS Mu is only found in mature skeletal and
CC cardiac muscles.
CC -!- INDUCTION: By cholinergic agonists acting at inositol phosphate-linked
CC muscarinic receptors in cardiac myocytes.
CC -!- DOMAIN: The PDZ domain in the N-terminal part of the neuronal isoform
CC participates in protein-protein interaction, and is responsible for
CC targeting nNos to synaptic membranes in muscles. Mediates interaction
CC with VAC14 (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and
CC Hsp40 (in vitro). {ECO:0000250}.
CC -!- DISEASE: Note=In MDX mice (mouse model of dystrophinopathy) the
CC dystrophin complex is disrupted and nNOS is displaced from sarcolemma
CC and accumulates in the cytosol.
CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}.
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DR EMBL; D14552; BAA03415.1; -; mRNA.
DR EMBL; S81982; AAB36469.1; -; mRNA.
DR EMBL; AK141904; BAE24878.1; -; mRNA.
DR CCDS; CCDS19606.1; -. [Q9Z0J4-1]
DR PIR; JN0609; JN0609.
DR RefSeq; NP_032738.1; NM_008712.3. [Q9Z0J4-1]
DR RefSeq; XP_017176196.1; XM_017320707.1.
DR PDB; 2O60; X-ray; 1.55 A; B=725-747.
DR PDBsum; 2O60; -.
DR AlphaFoldDB; Q9Z0J4; -.
DR BMRB; Q9Z0J4; -.
DR SMR; Q9Z0J4; -.
DR BioGRID; 201805; 21.
DR CORUM; Q9Z0J4; -.
DR DIP; DIP-31556N; -.
DR IntAct; Q9Z0J4; 11.
DR MINT; Q9Z0J4; -.
DR STRING; 10090.ENSMUSP00000099617; -.
DR BindingDB; Q9Z0J4; -.
DR ChEMBL; CHEMBL4719; -.
DR iPTMnet; Q9Z0J4; -.
DR PhosphoSitePlus; Q9Z0J4; -.
DR MaxQB; Q9Z0J4; -.
DR PaxDb; Q9Z0J4; -.
DR PeptideAtlas; Q9Z0J4; -.
DR PRIDE; Q9Z0J4; -.
DR ProteomicsDB; 295504; -. [Q9Z0J4-1]
DR ProteomicsDB; 295505; -. [Q9Z0J4-2]
DR ProteomicsDB; 295506; -. [Q9Z0J4-3]
DR ProteomicsDB; 295507; -. [Q9Z0J4-4]
DR ProteomicsDB; 295508; -. [Q9Z0J4-5]
DR ABCD; Q9Z0J4; 2 sequenced antibodies.
DR Antibodypedia; 3691; 951 antibodies from 47 providers.
DR DNASU; 18125; -.
DR Ensembl; ENSMUST00000142742; ENSMUSP00000120421; ENSMUSG00000029361. [Q9Z0J4-1]
DR Ensembl; ENSMUST00000171055; ENSMUSP00000127432; ENSMUSG00000029361. [Q9Z0J4-1]
DR GeneID; 18125; -.
DR KEGG; mmu:18125; -.
DR UCSC; uc008zfy.2; mouse. [Q9Z0J4-1]
DR CTD; 4842; -.
DR MGI; MGI:97360; Nos1.
DR VEuPathDB; HostDB:ENSMUSG00000029361; -.
DR eggNOG; KOG1158; Eukaryota.
DR GeneTree; ENSGT00940000159357; -.
DR InParanoid; Q9Z0J4; -.
DR PhylomeDB; Q9Z0J4; -.
DR Reactome; R-MMU-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-MMU-392154; Nitric oxide stimulates guanylate cyclase.
DR Reactome; R-MMU-5578775; Ion homeostasis.
DR BioGRID-ORCS; 18125; 0 hits in 70 CRISPR screens.
DR ChiTaRS; Nos1; mouse.
DR EvolutionaryTrace; Q9Z0J4; -.
DR PRO; PR:Q9Z0J4; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9Z0J4; protein.
DR Bgee; ENSMUSG00000029361; Expressed in anterior amygdaloid area and 135 other tissues.
DR ExpressionAtlas; Q9Z0J4; baseline and differential.
DR Genevisible; Q9Z0J4; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0042582; C:azurophil granule; ISO:MGI.
DR GO; GO:0044305; C:calyx of Held; IDA:SynGO.
DR GO; GO:0071944; C:cell periphery; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; IDA:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0001917; C:photoreceptor inner segment; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; ISO:MGI.
DR GO; GO:0099091; C:postsynaptic specialization, intracellular component; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL.
DR GO; GO:0016529; C:sarcoplasmic reticulum; ISO:MGI.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IDA:BHF-UCL.
DR GO; GO:0030141; C:secretory granule; ISO:MGI.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0030315; C:T-tubule; IDA:BHF-UCL.
DR GO; GO:0012506; C:vesicle membrane; ISO:MGI.
DR GO; GO:0030018; C:Z disc; IDA:BHF-UCL.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0046870; F:cadmium ion binding; ISO:MGI.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISO:MGI.
DR GO; GO:0010181; F:FMN binding; ISO:MGI.
DR GO; GO:0020037; F:heme binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0050661; F:NADP binding; ISO:MGI.
DR GO; GO:0070402; F:NADPH binding; ISO:MGI.
DR GO; GO:0004517; F:nitric-oxide synthase activity; IDA:BHF-UCL.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:0017080; F:sodium channel regulator activity; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0006527; P:arginine catabolic process; ISO:MGI.
DR GO; GO:0048148; P:behavioral response to cocaine; ISO:MGI.
DR GO; GO:0006816; P:calcium ion transport; IMP:MGI.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; ISO:MGI.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0045184; P:establishment of protein localization; ISO:MGI.
DR GO; GO:0033555; P:multicellular organismal response to stress; ISO:MGI.
DR GO; GO:0006936; P:muscle contraction; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0045776; P:negative regulation of blood pressure; ISO:MGI.
DR GO; GO:0051926; P:negative regulation of calcium ion transport; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0045822; P:negative regulation of heart contraction; ISO:MGI.
DR GO; GO:0061875; P:negative regulation of hepatic stellate cell contraction; ISO:MGI.
DR GO; GO:0051346; P:negative regulation of hydrolase activity; IMP:MGI.
DR GO; GO:0046676; P:negative regulation of insulin secretion; ISO:MGI.
DR GO; GO:0034760; P:negative regulation of iron ion transmembrane transport; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; IMP:MGI.
DR GO; GO:0051612; P:negative regulation of serotonin uptake; IDA:UniProtKB.
DR GO; GO:0045906; P:negative regulation of vasoconstriction; ISO:MGI.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; ISO:MGI.
DR GO; GO:0018119; P:peptidyl-cysteine S-nitrosylation; IDA:MGI.
DR GO; GO:0140196; P:positive regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process; IMP:BHF-UCL.
DR GO; GO:0031284; P:positive regulation of guanylate cyclase activity; IBA:GO_Central.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IMP:BHF-UCL.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISO:MGI.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:1902307; P:positive regulation of sodium ion transmembrane transport; ISO:MGI.
DR GO; GO:0098735; P:positive regulation of the force of heart contraction; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:BHF-UCL.
DR GO; GO:0006813; P:potassium ion transport; IMP:MGI.
DR GO; GO:0008016; P:regulation of heart contraction; ISO:MGI.
DR GO; GO:0050767; P:regulation of neurogenesis; IDA:CACAO.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:0002028; P:regulation of sodium ion transport; IMP:MGI.
DR GO; GO:0043627; P:response to estrogen; ISO:MGI.
DR GO; GO:0009408; P:response to heat; ISO:MGI.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0032496; P:response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0043434; P:response to peptide hormone; ISO:MGI.
DR GO; GO:0098924; P:retrograde trans-synaptic signaling by nitric oxide; IMP:SynGO.
DR GO; GO:0006941; P:striated muscle contraction; IMP:MGI.
DR GO; GO:0099163; P:synaptic signaling by nitric oxide; IDA:SynGO.
DR GO; GO:0042311; P:vasodilation; ISO:MGI.
DR GO; GO:0042178; P:xenobiotic catabolic process; IMP:MGI.
DR Gene3D; 1.20.990.10; -; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR Gene3D; 3.40.50.360; -; 1.
DR Gene3D; 3.40.50.80; -; 1.
DR Gene3D; 3.90.1230.10; -; 1.
DR Gene3D; 3.90.340.10; -; 1.
DR Gene3D; 3.90.440.10; -; 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; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
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 Pfam; PF00595; PDZ; 1.
DR PIRSF; PIRSF000333; NOS; 1.
DR PRINTS; PR00369; FLAVODOXIN.
DR PRINTS; PR00371; FPNCR.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF52218; SSF52218; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF56512; SSF56512; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
DR PROSITE; PS60001; NOS; 1.
DR PROSITE; PS50106; PDZ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calmodulin-binding; Cell membrane;
KW Cell projection; FAD; Flavoprotein; FMN; Heme; Iron; Membrane;
KW Metal-binding; NADP; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Synapse; Ubl conjugation.
FT CHAIN 1..1429
FT /note="Nitric oxide synthase, brain"
FT /id="PRO_0000170922"
FT DOMAIN 17..99
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 755..935
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 990..1237
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..200
FT /note="Interaction with NOSIP"
FT /evidence="ECO:0000250"
FT REGION 114..174
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 163..240
FT /note="PIN (nNOS-inhibiting protein) binding"
FT /evidence="ECO:0000250"
FT REGION 271..298
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 725..745
FT /note="Calmodulin-binding"
FT COMPBIAS 114..143
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 160..174
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..294
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 334
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 415
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:0000250|UniProtKB:P29475"
FT BINDING 478
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 587
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 588
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 592
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 677
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 678
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 691
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 706
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P29475"
FT BINDING 881..912
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 1027..1038
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 1170..1180
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 1245..1263
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 1343..1358
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 847
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29476"
FT MOD_RES 857
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 858
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..331
FT /note="Missing (in isoform NNOS gamma)"
FT /evidence="ECO:0000305"
FT /id="VSP_003577"
FT VAR_SEQ 1..230
FT /note="Missing (in isoform NNOS beta)"
FT /evidence="ECO:0000305"
FT /id="VSP_003575"
FT VAR_SEQ 231..236
FT /note="TGIQVD -> MRGLGS (in isoform NNOS beta)"
FT /evidence="ECO:0000305"
FT /id="VSP_003576"
FT VAR_SEQ 504..608
FT /note="Missing (in isoform N-NOS-2)"
FT /evidence="ECO:0000303|PubMed:7686743"
FT /id="VSP_003578"
FT VAR_SEQ 839
FT /note="K -> KYPEPLRFFPRKGPSLSHVDSEAHSLVAARDSQHR (in isoform
FT NNOS Mu)"
FT /evidence="ECO:0000303|PubMed:8626668"
FT /id="VSP_003579"
FT CONFLICT 1320
FT /note="K -> Q (in Ref. 3; BAE24878)"
FT /evidence="ECO:0000305"
FT HELIX 731..744
FT /evidence="ECO:0007829|PDB:2O60"
SQ SEQUENCE 1429 AA; 160472 MW; 3782848D65B41BFC CRC64;
MEEHTFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA
GDIILAVNDR PLVDLSYDSA LEVLRGIASE THVVLILRGP EGFTTHLETT FTGDGTPKTI
RVTQPLGTPT KAVDLSRQPS ASKDQPLAVD RVPGPSNGPQ HAQGRGQGAG SVSQANGVAI
DPTMKNTKAN LQDSGEQDEL LKEIEPVLSI LTGGGKAVNR GGPAKAEMKD TGIQVDRDLD
GKLHKAPPLG GENDRVFNDL WGKGNVPVVL NNPYSENEQS PASGKQSPTK NGSPSRCPRF
LKVKNWETDV VLTDTLHLKS TLETGCTEQI CMGSIMLPSH HIRKSEDVRT KDQLFPLAKE
FLDQYYSSIK RFGSKAHMDR LEEVNKEIES TSTYQLKDTE LIYGAKHAWR NASRCVGRIQ
WSKLQVFDAR DCTTAHGMFN YICNHVKYAT NKGNLRSAIT IFPQRTDGKH DFRVWNSQLI
RYAGYKQPDG STLGDPANVE FTEICIQQGW KPPRGRFDVL PLLLQANGND PELFQIPPEL
VLEVPIRHPK FDWFKDLGLK WYGLPAVSNM LLEIGGLEFS ACPFSGWYMG TEIGVRDYCD
NSRYNILEEV AKKMDLDMRK TSSLWKDQAL VEINIAVLYS FQSDKVTIVD HHSATESFIK
HMENEYRCRG GCPADWVWIV PPMSGSITPV FHQEMLNYRL TPSFEYQPDP WNTHVWKGTN
GTPTKRRAIG FKKLAEAVKF SAKLMGQAMA KRVKATILYA TETGKSQAYA KTLCEIFKHA
FDAKAMSMEE YDIVHLEHEA LVLVVTSTFG NGDPPENGEK FGCALMEMRH PNSVQEERKS
YKVRFNSVSS YSDSRKSSGD GPDLRDNFES TGPLANVRFS VFGLGSRAYP HFCAFGHAVD
TLLEELGGER ILKMREGDEL CGQEEAFRTW AKKVFKAACD VFCVGDDVNI EKANNSLISN
DRSWKRNKFR LTYVAEAPEL TQGLSNVHKK RVSAARLLSR QNLQSPKSSR STIFVRLHTN
GNQELQYQPG DHLGVFPGNH EDLVNALIER LEDAPPANHV VKVEMLEERN TALGVISNWK
DESRLPPCTI FQAFKYYLDI TTPPTPLQLQ QFASLATNEK EKQRLLVLSK GLQEYEEWKW
GKNPTMVEVL EEFPSIQMPA TLLLTQLSLL QPRYYSISSS PDMYPDEVHL TVAIVSYHTR
DGEGPVHHGV CSSWLNRIQA DDVVPCFVRG APSFHLPRNP QVPCILVGPG TGIAPFRSFW
QQRQFDIQHK GMNPCPMVLV FGCRQSKIDH IYREETLQAK NKGVFRELYT AYSREPDRPK
KYVQDVLQEQ LAESVYRALK EQGGHIYVCG DVTMAADVLK AIQRIMTQQG KLSEEDAGVF
ISRLRDDNRY HEDIFGVTLR TYEVTNRLRS ESIAFIEESK KDTDEVFSS
