[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS N-NOS-1 AND N-NOS-2). STRAIN=BALB/c; TISSUE=Brain; DOI=10.1006/bbrc.1993.1726; PubMed=7686743 [NCBI, ExPASy, EBI, Israel, Japan] Ogura T., Yokoyama T., Fujisawa H., Kurashima Y., Esumi H.; "Structural diversity of neuronal oxide synthase mRNA in the nervous system."; Biochem. Biophys. Res. Commun. 193:1014-1022(1993).
[2]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM NNOS MU). TISSUE=Skeletal muscle; DOI=10.1074/jbc.271.19.11204; PubMed=8626668 [NCBI, ExPASy, EBI, Israel, Japan] Silvagno F., Xia H., Bredt D.S.; "Neuronal nitric-oxide synthase-mu, an alternatively spliced isoform expressed in differentiated skeletal muscle."; J. Biol. Chem. 271:11204-11208(1996).
[3]	ALTERNATIVE SPLICING (ISOFORMS NNOS BETA; NNOS GAMMA AND NNOS MU). PubMed=9208206 [NCBI, ExPASy, EBI, Israel, Japan] Brenman J.E., Xia H., Chao D.S., Black S.M., Bredt D.S.; "Regulation of neuronal nitric oxide synthase through alternative transcripts."; Dev. Neurosci. 19:224-231(1997).
[4]	INTERACTION WITH DLG4. DOI=10.1006/jmbi.1999.3350; PubMed=10623522 [NCBI, ExPASy, EBI, Israel, Japan] Tochio H., Hung F., Li M., Bredt D.S., Zhang M.; "Solution structure and backbone dynamics of the second PDZ domain of postsynaptic density-95."; J. Mol. Biol. 295:225-237(2000).
[5]	INTERACTION WITH HTR4. DOI=10.1242/jcs.01379; PubMed=15466885 [NCBI, ExPASy, EBI, Israel, Japan] Joubert L., Hanson B., Barthet G., Sebben M., Claeysen S., Hong W., Marin P., Dumuis A., Bockaert J.; "New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a receptor splice variant: roles in receptor targeting."; J. Cell Sci. 117:5367-5379(2004).

Comments

FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Isoform NNOS Mu may be an effector enzyme for the dystrophin complex.
CATALYTIC ACTIVITY: L-arginine + n NADPH + m O₂ = citrulline + nitric oxide + n NADP⁺.
COFACTOR: Heme group (By similarity).
COFACTOR: Binds 1 FAD (By similarity).
COFACTOR: Binds 1 FMN (By similarity).
COFACTOR: Metrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme (By similarity).
ENZYME REGULATION: Stimulated by calcium/calmodulin. Inhibited by n-Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein. Inhibited by NOSIP (By similarity).
SUBUNIT: Homodimer. Forms a ternary complex with CAPON and RASD1. Forms a ternary complex with CAPON and SYN1. Interacts with ZDHHC23. Interacts with NOSIP; which may impair its synaptic location (By similarity). Interacts with DLG4; the interaction possibly being prevented by the association between NOS1 and CAPON. Interacts with HTR4.
SUBCELLULAR LOCATION: Cell membrane, sarcolemma; Peripheral membrane protein. Cell projection, dendritic spine (By similarity). Note=In skeletal muscle, it is localized beneath the sarcolemma of fast-twitch muscle fiber by associating with the dystrophin glycoprotein complex. In neurons, enriched in dendritic spines (By similarity).

ALTERNATIVE PRODUCTS: 5 named isoforms [FASTA] produced by alternative splicing.

Name	N-NOS-1
Isoform ID	Q9Z0J4-1
This is the isoform sequence displayed in this entry.

Name	N-NOS-2
Isoform ID	Q9Z0J4-2
Features which should be applied to build the isoform sequence: VSP_003578.

Name	NNOS beta
Isoform ID	Q9Z0J4-3
Features which should be applied to build the isoform sequence: VSP_003575, VSP_003576.

Name	NNOS gamma
Isoform ID	Q9Z0J4-4
Features which should be applied to build the isoform sequence: VSP_003577.

Name	NNOS Mu
Synonyms	Muscle-specific
Isoform ID	Q9Z0J4-5
Features which should be applied to build the isoform sequence: VSP_003579.

TISSUE SPECIFICITY: Widely expressed in the nervous system: expressed in cerebrum, olfactory bulb, hippocampus, midbrain, cerebellum, pons, medulla oblongata, and spinal cord. Also found in skeletal muscle, where it is localized beneath the sarcolemma of fast twitch muscle fibers, and in spleen, heart, kidney, and liver. N-NOS-1 and N-NOS-2 are found in all parts of the nervous system. NNOS beta and gamma occur in a region-specific manner in the brain and NNOS beta expression is developmentally regulated. NNOS Mu is only found in mature skeletal and cardiac muscles.
INDUCTION: By cholinergic agonists acting at inositol phosphate-linked muscarinic receptors in cardiac myocytes.
DOMAIN: The PDZ domain in the N-terminal part of the neuronal isoform participates in protein-protein interaction, and is responsible for targeting nNos to synaptic membranes in muscles.
DISEASE: In MDX mice (mouse model of dystrophinopathy) the dystrophin complex is disrupted and nNOS is displaced from sarcolemma and accumulates in the cytosol.
SIMILARITY: Belongs to the NOS family.
SIMILARITY: Contains 1 FAD-binding FR-type domain.
SIMILARITY: Contains 1 flavodoxin-like domain.
SIMILARITY: Contains 1 PDZ (DHR) domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

D14552; BAA03415.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S81982; AAB36469.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

JN0609; JN0609.

NP_032738.1; -.

3D structure databases

PDB

2O60; X-ray; 1.55 A; B=725-747.

[ExPASy / RCSB / EBI]

PDBsum

2O60; -.

SMR

Q9Z0J4; 12-126, 299-718, 963-1397.

ModBase

Q9Z0J4.

Protein-protein interaction databases

IntAct

Q9Z0J4; -.

PTM databases

PhosphoSite

Q9Z0J4; -.

Organism-specific databases

MGI

MGI:97360; Nos1.

Gene expression databases

ArrayExpress

Q9Z0J4; -.

CleanEx

MM_NOS1; -.

GermOnline

ENSMUSG00000029361; Mus musculus.

Ontologies

GO:0005856;	Cellular component: cytoskeleton (inferred from direct assay from UniProtKB).
GO:0042383;	Cellular component: sarcolemma (inferred from direct assay from MGI).
GO:0045202;	Cellular component: synapse (inferred from direct assay from MGI).
GO:0004517;	Molecular function: nitric-oxide synthase activity (inferred from direct assay from UniProtKB).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0042738;	Biological process: exogenous drug catabolic process (inferred from mutant phenotype from MGI).
GO:0051926;	Biological process: negative regulation of calcium ion transport (inferred from mutant phenotype from MGI).
GO:0051346;	Biological process: negative regulation of hydrolase activity (inferred from mutant phenotype from MGI).
GO:0043267;	Biological process: negative regulation of potassium ion transport (inferred from mutant phenotype from MGI).
GO:0006809;	Biological process: nitric oxide biosynthetic process (inferred from direct assay from UniProtKB).
GO:0002028;	Biological process: regulation of sodium ion transport (inferred from mutant phenotype from MGI).
GO:0006941;	Biological process: striated muscle contraction (inferred from mutant phenotype from MGI).
QuickGo view.

Family and domain databases

InterPro

IPR003097; FAD-binding_1.
IPR001094; Flavdoxin_like.
IPR008254; Flavodoxin/NO_synth.
IPR001709; FPN_cyt_redctse.
IPR004030; NO_synthase_oxygenase_reg.
IPR012144; NOS.
IPR001433; OxRdtase_FAD/NAD_bd.
IPR001478; PDZ.
Graphical view of domain structure.

Gene3D

G3DSA:3.90.340.10; NO_synthase_oxygenase_reg; 1.

Pfam

PF00667; FAD_binding_1; 1.
PF00258; Flavodoxin_1; 1.
PF00175; NAD_binding_1; 1.
PF02898; NO_synthase; 1.
PF00595; PDZ; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF000333; NOS; 1.

PRINTS

PR00369; FLAVODOXIN.
PR00371; FPNCR.

SMART

SM00228; PDZ; 1.
SMART graphical view of domain structure.

PROSITE

PS51384; FAD_FR; 1.
PS50902; FLAVODOXIN_LIKE; 1.
PS60001; NOS; 1.
PS50106; PDZ; 1.
PROSITE graphical view of domain structure (profiles).

BLOCKS

Q9Z0J4.

Genome annotation databases

Ensembl

ENSMUSG00000029361; Mus musculus. [Contig view]

GeneID

18125; -.

KEGG

mmu:18125; -.

Phylogenomic databases

HOGENOM

Q9Z0J4; -.

HOVERGEN

Q9Z0J4; -.

Other

Nos1; Mus musculus.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Alternative splicing; Calmodulin-binding; Cell membrane; Cell projection; FAD; FMN; Heme; Iron; Membrane; Metal-binding; NADP; Oxidoreductase.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 1429`	`1429`	`Nitric oxide synthase, brain.`	`PRO_0000170922`
`DOMAIN`	`17 99`	`83`	`PDZ.`
`DOMAIN`	`755 935`	`181`	`Flavodoxin-like.`
`DOMAIN`	`990 1237`	`248`	`FAD-binding FR-type.`
`NP_BIND`	`881 912`	`32`	`FMN (By similarity).`
`NP_BIND`	`1027 1038`	`12`	`FAD (By similarity).`
`NP_BIND`	`1170 1180`	`11`	`FAD (By similarity).`
`NP_BIND`	`1245 1263`	`19`	`NADP (By similarity).`
`NP_BIND`	`1343 1358`	`16`	`NADP (By similarity).`
`REGION`	`1 200`	`200`	`Interaction with NOSIP (By similarity).`
`REGION`	`163 240`	`78`	`PIN (nNOS-inhibiting protein) binding (By similarity).`
`REGION`	`725 745`	`21`	`Calmodulin-binding (Potential).`
`REGION`	`750 769`	`20`	`Tetrahydrobiopterin-binding (By similarity).`
`METAL`	`415 415`		`Iron (heme axial ligand) (By similarity).`
`VAR_SEQ`	`1 331`		`Missing (in isoform NNOS gamma).`	`VSP_003577`
`VAR_SEQ`	`1 230`		`Missing (in isoform NNOS beta).`	`VSP_003575`
`VAR_SEQ`	`231 236`		`TGIQVD -> MRGLGS (in isoform NNOS beta).`	`VSP_003576`
`VAR_SEQ`	`504 608`		`Missing (in isoform N-NOS-2).`	`VSP_003578`
`VAR_SEQ`	`839 839`		`K -> KYPEPLRFFPRKGPSLSHVDSEAHSLVAARDSQHR (in isoform NNOS Mu).`	`VSP_003579`

Sequence information

Length: 1429 AA [This is the length of the unprocessed precursor]

Molecular weight: 160472 Da [This is the MW of the unprocessed precursor]

CRC64: 3782848D65B41BFC [This is a checksum on the sequence]

        10         20         30         40         50         60 
MEEHTFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG AAEQSGLIQA 

        70         80         90        100        110        120 
GDIILAVNDR PLVDLSYDSA LEVLRGIASE THVVLILRGP EGFTTHLETT FTGDGTPKTI 

       130        140        150        160        170        180 
RVTQPLGTPT KAVDLSRQPS ASKDQPLAVD RVPGPSNGPQ HAQGRGQGAG SVSQANGVAI 

       190        200        210        220        230        240 
DPTMKNTKAN LQDSGEQDEL LKEIEPVLSI LTGGGKAVNR GGPAKAEMKD TGIQVDRDLD 

       250        260        270        280        290        300 
GKLHKAPPLG GENDRVFNDL WGKGNVPVVL NNPYSENEQS PASGKQSPTK NGSPSRCPRF 

       310        320        330        340        350        360 
LKVKNWETDV VLTDTLHLKS TLETGCTEQI CMGSIMLPSH HIRKSEDVRT KDQLFPLAKE 

       370        380        390        400        410        420 
FLDQYYSSIK RFGSKAHMDR LEEVNKEIES TSTYQLKDTE LIYGAKHAWR NASRCVGRIQ 

       430        440        450        460        470        480 
WSKLQVFDAR DCTTAHGMFN YICNHVKYAT NKGNLRSAIT IFPQRTDGKH DFRVWNSQLI 

       490        500        510        520        530        540 
RYAGYKQPDG STLGDPANVE FTEICIQQGW KPPRGRFDVL PLLLQANGND PELFQIPPEL 

       550        560        570        580        590        600 
VLEVPIRHPK FDWFKDLGLK WYGLPAVSNM LLEIGGLEFS ACPFSGWYMG TEIGVRDYCD 

       610        620        630        640        650        660 
NSRYNILEEV AKKMDLDMRK TSSLWKDQAL VEINIAVLYS FQSDKVTIVD HHSATESFIK 

       670        680        690        700        710        720 
HMENEYRCRG GCPADWVWIV PPMSGSITPV FHQEMLNYRL TPSFEYQPDP WNTHVWKGTN 

       730        740        750        760        770        780 
GTPTKRRAIG FKKLAEAVKF SAKLMGQAMA KRVKATILYA TETGKSQAYA KTLCEIFKHA 

       790        800        810        820        830        840 
FDAKAMSMEE YDIVHLEHEA LVLVVTSTFG NGDPPENGEK FGCALMEMRH PNSVQEERKS 

       850        860        870        880        890        900 
YKVRFNSVSS YSDSRKSSGD GPDLRDNFES TGPLANVRFS VFGLGSRAYP HFCAFGHAVD 

       910        920        930        940        950        960 
TLLEELGGER ILKMREGDEL CGQEEAFRTW AKKVFKAACD VFCVGDDVNI EKANNSLISN 

       970        980        990       1000       1010       1020 
DRSWKRNKFR LTYVAEAPEL TQGLSNVHKK RVSAARLLSR QNLQSPKSSR STIFVRLHTN 

      1030       1040       1050       1060       1070       1080 
GNQELQYQPG DHLGVFPGNH EDLVNALIER LEDAPPANHV VKVEMLEERN TALGVISNWK 

      1090       1100       1110       1120       1130       1140 
DESRLPPCTI FQAFKYYLDI TTPPTPLQLQ QFASLATNEK EKQRLLVLSK GLQEYEEWKW 

      1150       1160       1170       1180       1190       1200 
GKNPTMVEVL EEFPSIQMPA TLLLTQLSLL QPRYYSISSS PDMYPDEVHL TVAIVSYHTR 

      1210       1220       1230       1240       1250       1260 
DGEGPVHHGV CSSWLNRIQA DDVVPCFVRG APSFHLPRNP QVPCILVGPG TGIAPFRSFW 

      1270       1280       1290       1300       1310       1320 
QQRQFDIQHK GMNPCPMVLV FGCRQSKIDH IYREETLQAK NKGVFRELYT AYSREPDRPK 

      1330       1340       1350       1360       1370       1380 
KYVQDVLQEQ LAESVYRALK EQGGHIYVCG DVTMAADVLK AIQRIMTQQG KLSEEDAGVF 

      1390       1400       1410       1420 
ISRLRDDNRY HEDIFGVTLR TYEVTNRLRS ESIAFIEESK KDTDEVFSS

Q9Z0J4 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools