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Reviewed, UniProtKB/Swiss-Prot Q9Z0J4 (NOS1_MOUSE)

Last modified January 19, 2010. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Nitric oxide synthase, brain
    EC=1.14.13.39
Alternative name(s):
    bNOS
    NOS type I
    Neuronal NOS
      Short name=N-NOS
      Short name=nNOS
    Constitutive NOS
    NC-NOS
Gene names
Name: Nos1
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length1429 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (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 + n H+ + m O2 = citrulline + nitric oxide + n NADP+.

Cofactor

Heme group By similarity.

Binds 1 FAD By similarity.

Binds 1 FMN By similarity.

Tetrahydrobiopterin (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 structure

Homodimer. 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. Forms a ternary complex with CAPON and RASD1. Interacts with VAC14 By similarity. Ref.4 Ref.5 Ref.6

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.

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. Mediates interaction with VAC14 By similarity.

Involvement in disease

In MDX mice (mouse model of dystrophinopathy) the dystrophin complex is disrupted and nNOS is displaced from sarcolemma and accumulates in the cytosol.

Sequence similarities

Belongs to the NOS family.

Contains 1 FAD-binding FR-type domain.

Contains 1 flavodoxin-like domain.

Contains 1 PDZ (DHR) domain.

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Ontologies

Keywords
   Cellular componentCell membrane
Cell projection
Membrane
   Coding sequence diversityAlternative splicing
   LigandCalmodulin-binding
FAD
FMN
Heme
Iron
Metal-binding
NADP
   Molecular functionOxidoreductase
   Technical term3D-structure
Gene Ontology (GO)
   Biological processexogenous drug catabolic process

Inferred from mutant phenotype. Source: MGI

negative regulation of calcium ion transport

Inferred from mutant phenotype. Source: MGI

negative regulation of hydrolase activity

Inferred from mutant phenotype. Source: MGI

negative regulation of potassium ion transport

Inferred from mutant phenotype. Source: MGI

nitric oxide biosynthetic process

Inferred from direct assay. Source: UniProtKB

oxidation reduction

Inferred from electronic annotation. Source: UniProtKB-KW

peptidyl-cysteine S-nitrosylation

Inferred from direct assay. Source: MGI

regulation of sodium ion transport

Inferred from mutant phenotype. Source: MGI

striated muscle contraction

Inferred from mutant phenotype. Source: MGI

   Cellular componentcytoskeleton

Inferred from direct assay. Source: UniProtKB

dendritic spine

Inferred from electronic annotation. Source: UniProtKB-SubCell

extrinsic to membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

sarcolemma

Inferred from direct assay. Source: UniProtKB

synapse

Inferred from direct assay. Source: MGI

   Molecular functionFAD binding

Inferred from electronic annotation. Source: InterPro

FMN binding

Inferred from electronic annotation. Source: InterPro

NADP or NADPH binding

Inferred from electronic annotation. Source: InterPro

calmodulin binding

Inferred from electronic annotation. Source: UniProtKB-KW

heme binding

Inferred from electronic annotation. Source: InterPro

nitric-oxide synthase activity

Inferred from direct assay. Source: UniProtKB

Complete GO annotation...

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Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform N-NOS-1 (identifier: Q9Z0J4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform N-NOS-2 (identifier: Q9Z0J4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     504-608: Missing.
Isoform NNOS beta (identifier: Q9Z0J4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-230: Missing.
     231-236: TGIQVD → MRGLGS
Isoform NNOS gamma (identifier: Q9Z0J4-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-331: Missing.
Isoform NNOS Mu (identifier: Q9Z0J4-5)

Also known as: Muscle-specific;

The sequence of this isoform differs from the canonical sequence as follows:
     839-839: K → KYPEPLRFFPRKGPSLSHVDSEAHSLVAARDSQHR

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14291429Nitric oxide synthase, brain
PRO_0000170922

Regions

Domain17 – 9983PDZ
Domain755 – 935181Flavodoxin-like
Domain990 – 1237248FAD-binding FR-type
Nucleotide binding881 – 91232FMN By similarity
Nucleotide binding1027 – 103812FAD By similarity
Nucleotide binding1170 – 118011FAD By similarity
Nucleotide binding1245 – 126319NADP By similarity
Nucleotide binding1343 – 135816NADP By similarity
Region1 – 200200Interaction with NOSIP By similarity
Region163 – 24078PIN (nNOS-inhibiting protein) binding By similarity
Region725 – 74521Calmodulin-binding Potential
Region750 – 76920Tetrahydrobiopterin-binding By similarity

Sites

Metal binding4151Iron (heme axial ligand) By similarity

Natural variations

Alternative sequence1 – 331331Missing in isoform NNOS gamma.
VSP_003577
Alternative sequence1 – 230230Missing in isoform NNOS beta.
VSP_003575
Alternative sequence231 – 2366TGIQVD → MRGLGS in isoform NNOS beta.
VSP_003576
Alternative sequence504 – 608105Missing in isoform N-NOS-2.
VSP_003578
Alternative sequence8391K → KYPEPLRFFPRKGPSLSHVD SEAHSLVAARDSQHR in isoform NNOS Mu.
VSP_003579

Secondary structure

1 ... 1429
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform N-NOS-1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 3782848D65B41BFC

FASTA1,429160,472
        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

« Hide

Isoform N-NOS-2.

Checksum: F8532C1457C09EA4
Show »

FASTA1,324148,435
Isoform NNOS beta.

Checksum: 4ACB46D2B44CFEEA
Show »

FASTA1,199136,243
Isoform NNOS gamma.

Checksum: 51C8FA95A3865266
Show »

FASTA1,098125,183
Isoform NNOS Mu (Muscle-specific).

Checksum: 11689C595839D9A7
Show »

FASTA1,463164,343

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References

[1]"Structural diversity of neuronal oxide synthase mRNA in the nervous system."
Ogura T., Yokoyama T., Fujisawa H., Kurashima Y., Esumi H.
Biochem. Biophys. Res. Commun. 193:1014-1022(1993) [PubMed: 7686743] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS N-NOS-1 AND N-NOS-2).
Strain: BALB/c.
Tissue: Brain.
[2]"Neuronal nitric-oxide synthase-mu, an alternatively spliced isoform expressed in differentiated skeletal muscle."
Silvagno F., Xia H., Bredt D.S.
J. Biol. Chem. 271:11204-11208(1996) [PubMed: 8626668] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM NNOS MU).
Tissue: Skeletal muscle.
[3]"Regulation of neuronal nitric oxide synthase through alternative transcripts."
Brenman J.E., Xia H., Chao D.S., Black S.M., Bredt D.S.
Dev. Neurosci. 19:224-231(1997) [PubMed: 9208206] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS NNOS BETA; NNOS GAMMA AND NNOS MU).
[4]"Solution structure and backbone dynamics of the second PDZ domain of postsynaptic density-95."
Tochio H., Hung F., Li M., Bredt D.S., Zhang M.
J. Mol. Biol. 295:225-237(2000) [PubMed: 10623522] [Abstract]
Cited for: INTERACTION WITH DLG4.
[5]"Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON."
Fang M., Jaffrey S.R., Sawa A., Ye K., Luo X., Snyder S.H.
Neuron 28:183-193(2000) [PubMed: 11086993] [Abstract]
Cited for: INTERACTION WITH RASD1 AND CAPON.
[6]"New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a receptor splice variant: roles in receptor targeting."
Joubert L., Hanson B., Barthet G., Sebben M., Claeysen S., Hong W., Marin P., Dumuis A., Bockaert J.
J. Cell Sci. 117:5367-5379(2004) [PubMed: 15466885] [Abstract]
Cited for: INTERACTION WITH HTR4.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		D14552 mRNA. Translation: BAA03415.1.
S81982 mRNA. Translation: AAB36469.1.
IPIIPI00129191.
IPI00229026.
IPI00229027.
IPI00229030.
IPI00309243.
PIRJN0609.
RefSeqNP_032738.1.
UniGeneMm.442195
Mm.44249

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2O60X-ray1.55B725-747[»]
SMRQ9Z0J4. Positions 12-126, 298-716, 750-1413.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-31556N.
STRINGQ9Z0J4.

PTM databases

PhosphoSiteQ9Z0J4.

Proteomic databases

PRIDEQ9Z0J4.

Genome annotation databases

EnsemblENSMUST00000086451; ENSMUSP00000083641; ENSMUSG00000029361; Mus musculus. [Genome view]
ENSMUST00000111935; ENSMUSP00000107566; ENSMUSG00000029361; Mus musculus. [Genome view]
ENSMUST00000111939; ENSMUSP00000107570; ENSMUSG00000029361; Mus musculus. [Genome view]
GeneID18125.
KEGGmmu:18125.
UCSCuc008zfy.1. mouse.

Organism-specific databases

CTD18125.
MGIMGI:97360. Nos1.

Phylogenomic databases

HOVERGENQ9Z0J4.
PhylomeDBQ9Z0J4.

Enzyme and pathway databases

BRENDA1.14.13.39. 244.

Gene expression databases

ArrayExpressQ9Z0J4.
BgeeQ9Z0J4.
CleanExMM_NOS1.
GenevestigatorQ9Z0J4.
GermOnlineENSMUSG00000029361. Mus musculus.

Family and domain databases

InterProIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin-like.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR012144. Nitric-oxide_synthase.
IPR004030. NO_synthase_oxygenase_dom.
IPR001433. OxRdtase_FAD/NAD_bd.
IPR001478. PDZ/DHR/GLGF.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
Gene3DG3DSA:3.90.340.10. NO_synthase_oxygenase_reg. 1 hit.
PfamPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
PF02898. NO_synthase. 1 hit.
PF00595. PDZ. 1 hit.
[Graphical view]
PIRSFPIRSF000333. NOS. 1 hit.
PRINTSPR00369. FLAVODOXIN.
PR00371. FPNCR.
SMARTSM00228. PDZ. 1 hit.
[Graphical view]
PROSITEPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
PS60001. NOS. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio293344.
SOURCESearch...

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Entry information

Entry nameNOS1_MOUSE
AccessionPrimary (citable) accession number: Q9Z0J4
Secondary accession number(s): Q64208
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: January 19, 2010
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents