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Protein

Nitric oxide synthase, brain

Gene

Nos1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Isoform NNOS Mu may be an effector enzyme for the dystrophin complex.1 Publication

Catalytic activityi

2 L-arginine + 3 NADPH + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O.

Cofactori

Protein has several cofactor binding sites:

Activity regulationi

Stimulated by calcium/calmodulin. Inhibited by n-Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein. Inhibited by NOSIP (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi415Iron (heme axial ligand)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi881 – 912FMNPROSITE-ProRule annotationAdd BLAST32
Nucleotide bindingi1027 – 1038FADBy similarityAdd BLAST12
Nucleotide bindingi1170 – 1180FADBy similarityAdd BLAST11
Nucleotide bindingi1245 – 1263NADPBy similarityAdd BLAST19
Nucleotide bindingi1343 – 1358NADPBy similarityAdd BLAST16

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Oxidoreductase
LigandFAD, Flavoprotein, FMN, Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

ReactomeiR-MMU-1222556 ROS, RNS production in phagocytes
R-MMU-392154 Nitric oxide stimulates guanylate cyclase
R-MMU-5578775 Ion homeostasis

Names & Taxonomyi

Protein namesi
Recommended name:
Nitric oxide synthase, brain (EC:1.14.13.39)
Alternative name(s):
Constitutive NOS
NC-NOS
NOS type I
Neuronal NOS
Short name:
N-NOS
Short name:
nNOS
Peptidyl-cysteine S-nitrosylase NOS1
bNOS
Gene namesi
Name:Nos1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:97360 Nos1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Involvement in diseasei

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

Chemistry databases

ChEMBLiCHEMBL4719

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001709221 – 1429Nitric oxide synthase, brainAdd BLAST1429

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei280PhosphoserineCombined sources1
Modified residuei847PhosphoserineBy similarity1
Modified residuei857PhosphoserineCombined sources1
Modified residuei858PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and Hsp40 (in vitro).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9Z0J4
PeptideAtlasiQ9Z0J4
PRIDEiQ9Z0J4

PTM databases

iPTMnetiQ9Z0J4
PhosphoSitePlusiQ9Z0J4

Expressioni

Tissue specificityi

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.

Inductioni

By cholinergic agonists acting at inositol phosphate-linked muscarinic receptors in cardiac myocytes.

Gene expression databases

BgeeiENSMUSG00000029361 Expressed in 177 organ(s), highest expression level in anterior amygdaloid area
CleanExiMM_NOS1
ExpressionAtlasiQ9Z0J4 baseline and differential
GenevisibleiQ9Z0J4 MM

Interactioni

Subunit structurei

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). Interacts (via N-terminal domain) with DLG4 (via N-terminal tandem pair of PDZ domains) (By similarity). Interacts with SLC6A4.By similarity5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201805, 8 interactors
CORUMiQ9Z0J4
DIPiDIP-31556N
IntActiQ9Z0J4, 12 interactors
MINTiQ9Z0J4
STRINGi10090.ENSMUSP00000120421

Chemistry databases

BindingDBiQ9Z0J4

Structurei

Secondary structure

11429
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Z0J4
SMRiQ9Z0J4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Z0J4

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 99PDZPROSITE-ProRule annotationAdd BLAST83
Domaini755 – 935Flavodoxin-likePROSITE-ProRule annotationAdd BLAST181
Domaini990 – 1237FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST248

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 200Interaction with NOSIPBy similarityAdd BLAST200
Regioni163 – 240PIN (nNOS-inhibiting protein) bindingBy similarityAdd BLAST78
Regioni725 – 745Calmodulin-bindingAdd BLAST21
Regioni750 – 769Tetrahydrobiopterin-bindingBy similarityAdd BLAST20

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the NOS family.Curated

Phylogenomic databases

eggNOGiKOG1158 Eukaryota
COG0369 LUCA
COG4362 LUCA
GeneTreeiENSGT00840000129757
HOGENOMiHOG000220884
HOVERGENiHBG000159
InParanoidiQ9Z0J4
KOiK13240
OMAiHNRSRET
PhylomeDBiQ9Z0J4

Family and domain databases

Gene3Di1.20.990.10, 1 hit
3.40.50.360, 1 hit
3.40.50.80, 1 hit
InterProiView protein in InterPro
IPR003097 CysJ-like_FAD-binding
IPR017927 FAD-bd_FR_type
IPR001094 Flavdoxin-like
IPR008254 Flavodoxin/NO_synth
IPR001709 Flavoprot_Pyr_Nucl_cyt_Rdtase
IPR029039 Flavoprotein-like_sf
IPR039261 FNR_nucleotide-bd
IPR023173 NADPH_Cyt_P450_Rdtase_alpha
IPR012144 NOS_euk
IPR004030 NOS_N
IPR036119 NOS_N_sf
IPR001433 OxRdtase_FAD/NAD-bd
IPR001478 PDZ
IPR036034 PDZ_sf
IPR017938 Riboflavin_synthase-like_b-brl
PfamiView protein in Pfam
PF00667 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
PIRSFiPIRSF000333 NOS, 1 hit
PRINTSiPR00369 FLAVODOXIN
PR00371 FPNCR
SMARTiView protein in SMART
SM00228 PDZ, 1 hit
SUPFAMiSSF50156 SSF50156, 1 hit
SSF52218 SSF52218, 1 hit
SSF52343 SSF52343, 1 hit
SSF56512 SSF56512, 1 hit
SSF63380 SSF63380, 1 hit
PROSITEiView protein in PROSITE
PS51384 FAD_FR, 1 hit
PS50902 FLAVODOXIN_LIKE, 1 hit
PS60001 NOS, 1 hit
PS50106 PDZ, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform N-NOS-1 (identifier: Q9Z0J4-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MEEHTFGVQQ IQPNVISVRL FKRKVGGLGF LVKERVSKPP VIISDLIRGG
60 70 80 90 100
AAEQSGLIQA GDIILAVNDR PLVDLSYDSA LEVLRGIASE THVVLILRGP
110 120 130 140 150
EGFTTHLETT FTGDGTPKTI RVTQPLGTPT KAVDLSRQPS ASKDQPLAVD
160 170 180 190 200
RVPGPSNGPQ HAQGRGQGAG SVSQANGVAI DPTMKNTKAN LQDSGEQDEL
210 220 230 240 250
LKEIEPVLSI LTGGGKAVNR GGPAKAEMKD TGIQVDRDLD GKLHKAPPLG
260 270 280 290 300
GENDRVFNDL WGKGNVPVVL NNPYSENEQS PASGKQSPTK NGSPSRCPRF
310 320 330 340 350
LKVKNWETDV VLTDTLHLKS TLETGCTEQI CMGSIMLPSH HIRKSEDVRT
360 370 380 390 400
KDQLFPLAKE FLDQYYSSIK RFGSKAHMDR LEEVNKEIES TSTYQLKDTE
410 420 430 440 450
LIYGAKHAWR NASRCVGRIQ WSKLQVFDAR DCTTAHGMFN YICNHVKYAT
460 470 480 490 500
NKGNLRSAIT IFPQRTDGKH DFRVWNSQLI RYAGYKQPDG STLGDPANVE
510 520 530 540 550
FTEICIQQGW KPPRGRFDVL PLLLQANGND PELFQIPPEL VLEVPIRHPK
560 570 580 590 600
FDWFKDLGLK WYGLPAVSNM LLEIGGLEFS ACPFSGWYMG TEIGVRDYCD
610 620 630 640 650
NSRYNILEEV AKKMDLDMRK TSSLWKDQAL VEINIAVLYS FQSDKVTIVD
660 670 680 690 700
HHSATESFIK HMENEYRCRG GCPADWVWIV PPMSGSITPV FHQEMLNYRL
710 720 730 740 750
TPSFEYQPDP WNTHVWKGTN GTPTKRRAIG FKKLAEAVKF SAKLMGQAMA
760 770 780 790 800
KRVKATILYA TETGKSQAYA KTLCEIFKHA FDAKAMSMEE YDIVHLEHEA
810 820 830 840 850
LVLVVTSTFG NGDPPENGEK FGCALMEMRH PNSVQEERKS YKVRFNSVSS
860 870 880 890 900
YSDSRKSSGD GPDLRDNFES TGPLANVRFS VFGLGSRAYP HFCAFGHAVD
910 920 930 940 950
TLLEELGGER ILKMREGDEL CGQEEAFRTW AKKVFKAACD VFCVGDDVNI
960 970 980 990 1000
EKANNSLISN DRSWKRNKFR LTYVAEAPEL TQGLSNVHKK RVSAARLLSR
1010 1020 1030 1040 1050
QNLQSPKSSR STIFVRLHTN GNQELQYQPG DHLGVFPGNH EDLVNALIER
1060 1070 1080 1090 1100
LEDAPPANHV VKVEMLEERN TALGVISNWK DESRLPPCTI FQAFKYYLDI
1110 1120 1130 1140 1150
TTPPTPLQLQ QFASLATNEK EKQRLLVLSK GLQEYEEWKW GKNPTMVEVL
1160 1170 1180 1190 1200
EEFPSIQMPA TLLLTQLSLL QPRYYSISSS PDMYPDEVHL TVAIVSYHTR
1210 1220 1230 1240 1250
DGEGPVHHGV CSSWLNRIQA DDVVPCFVRG APSFHLPRNP QVPCILVGPG
1260 1270 1280 1290 1300
TGIAPFRSFW QQRQFDIQHK GMNPCPMVLV FGCRQSKIDH IYREETLQAK
1310 1320 1330 1340 1350
NKGVFRELYT AYSREPDRPK KYVQDVLQEQ LAESVYRALK EQGGHIYVCG
1360 1370 1380 1390 1400
DVTMAADVLK AIQRIMTQQG KLSEEDAGVF ISRLRDDNRY HEDIFGVTLR
1410 1420
TYEVTNRLRS ESIAFIEESK KDTDEVFSS
Length:1,429
Mass (Da):160,472
Last modified:May 1, 1999 - v1
Checksum:i3782848D65B41BFC
GO
Isoform N-NOS-2 (identifier: Q9Z0J4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     504-608: Missing.

Show »
Length:1,324
Mass (Da):148,435
Checksum:iF8532C1457C09EA4
GO
Isoform NNOS beta (identifier: Q9Z0J4-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-230: Missing.
     231-236: TGIQVD → MRGLGS

Show »
Length:1,199
Mass (Da):136,243
Checksum:i4ACB46D2B44CFEEA
GO
Isoform NNOS gamma (identifier: Q9Z0J4-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-331: Missing.

Show »
Length:1,098
Mass (Da):125,183
Checksum:i51C8FA95A3865266
GO
Isoform NNOS Mu (identifier: Q9Z0J4-5) [UniParc]FASTAAdd to basket
Also known as: Muscle-specific

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

Show »
Length:1,463
Mass (Da):164,343
Checksum:i11689C595839D9A7
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
S4R255S4R255_MOUSE
Nitric oxide synthase
Nos1
1,425Annotation score:
F8WGF2F8WGF2_MOUSE
Nitric oxide synthase, brain
Nos1
1,463Annotation score:
S4R1D5S4R1D5_MOUSE
Nitric oxide synthase, brain
Nos1
80Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1320K → Q in BAE24878 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0035771 – 331Missing in isoform NNOS gamma. CuratedAdd BLAST331
Alternative sequenceiVSP_0035751 – 230Missing in isoform NNOS beta. CuratedAdd BLAST230
Alternative sequenceiVSP_003576231 – 236TGIQVD → MRGLGS in isoform NNOS beta. Curated6
Alternative sequenceiVSP_003578504 – 608Missing in isoform N-NOS-2. 1 PublicationAdd BLAST105
Alternative sequenceiVSP_003579839K → KYPEPLRFFPRKGPSLSHVD SEAHSLVAARDSQHR in isoform NNOS Mu. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D14552 mRNA Translation: BAA03415.1
S81982 mRNA Translation: AAB36469.1
AK141904 mRNA Translation: BAE24878.1
CCDSiCCDS19606.1 [Q9Z0J4-1]
PIRiJN0609
RefSeqiNP_032738.1, NM_008712.3 [Q9Z0J4-1]
XP_017176196.1, XM_017320707.1 [Q9Z0J4-1]
UniGeneiMm.442195
Mm.44249

Genome annotation databases

EnsembliENSMUST00000142742; ENSMUSP00000120421; ENSMUSG00000029361 [Q9Z0J4-1]
ENSMUST00000171055; ENSMUSP00000127432; ENSMUSG00000029361 [Q9Z0J4-1]
GeneIDi18125
KEGGimmu:18125
UCSCiuc008zfy.2 mouse [Q9Z0J4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D14552 mRNA Translation: BAA03415.1
S81982 mRNA Translation: AAB36469.1
AK141904 mRNA Translation: BAE24878.1
CCDSiCCDS19606.1 [Q9Z0J4-1]
PIRiJN0609
RefSeqiNP_032738.1, NM_008712.3 [Q9Z0J4-1]
XP_017176196.1, XM_017320707.1 [Q9Z0J4-1]
UniGeneiMm.442195
Mm.44249

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2O60X-ray1.55B725-747[»]
ProteinModelPortaliQ9Z0J4
SMRiQ9Z0J4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201805, 8 interactors
CORUMiQ9Z0J4
DIPiDIP-31556N
IntActiQ9Z0J4, 12 interactors
MINTiQ9Z0J4
STRINGi10090.ENSMUSP00000120421

Chemistry databases

BindingDBiQ9Z0J4
ChEMBLiCHEMBL4719

PTM databases

iPTMnetiQ9Z0J4
PhosphoSitePlusiQ9Z0J4

Proteomic databases

PaxDbiQ9Z0J4
PeptideAtlasiQ9Z0J4
PRIDEiQ9Z0J4

Protocols and materials databases

DNASUi18125
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000142742; ENSMUSP00000120421; ENSMUSG00000029361 [Q9Z0J4-1]
ENSMUST00000171055; ENSMUSP00000127432; ENSMUSG00000029361 [Q9Z0J4-1]
GeneIDi18125
KEGGimmu:18125
UCSCiuc008zfy.2 mouse [Q9Z0J4-1]

Organism-specific databases

CTDi4842
MGIiMGI:97360 Nos1

Phylogenomic databases

eggNOGiKOG1158 Eukaryota
COG0369 LUCA
COG4362 LUCA
GeneTreeiENSGT00840000129757
HOGENOMiHOG000220884
HOVERGENiHBG000159
InParanoidiQ9Z0J4
KOiK13240
OMAiHNRSRET
PhylomeDBiQ9Z0J4

Enzyme and pathway databases

ReactomeiR-MMU-1222556 ROS, RNS production in phagocytes
R-MMU-392154 Nitric oxide stimulates guanylate cyclase
R-MMU-5578775 Ion homeostasis

Miscellaneous databases

EvolutionaryTraceiQ9Z0J4
PROiPR:Q9Z0J4
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029361 Expressed in 177 organ(s), highest expression level in anterior amygdaloid area
CleanExiMM_NOS1
ExpressionAtlasiQ9Z0J4 baseline and differential
GenevisibleiQ9Z0J4 MM

Family and domain databases

Gene3Di1.20.990.10, 1 hit
3.40.50.360, 1 hit
3.40.50.80, 1 hit
InterProiView protein in InterPro
IPR003097 CysJ-like_FAD-binding
IPR017927 FAD-bd_FR_type
IPR001094 Flavdoxin-like
IPR008254 Flavodoxin/NO_synth
IPR001709 Flavoprot_Pyr_Nucl_cyt_Rdtase
IPR029039 Flavoprotein-like_sf
IPR039261 FNR_nucleotide-bd
IPR023173 NADPH_Cyt_P450_Rdtase_alpha
IPR012144 NOS_euk
IPR004030 NOS_N
IPR036119 NOS_N_sf
IPR001433 OxRdtase_FAD/NAD-bd
IPR001478 PDZ
IPR036034 PDZ_sf
IPR017938 Riboflavin_synthase-like_b-brl
PfamiView protein in Pfam
PF00667 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
PIRSFiPIRSF000333 NOS, 1 hit
PRINTSiPR00369 FLAVODOXIN
PR00371 FPNCR
SMARTiView protein in SMART
SM00228 PDZ, 1 hit
SUPFAMiSSF50156 SSF50156, 1 hit
SSF52218 SSF52218, 1 hit
SSF52343 SSF52343, 1 hit
SSF56512 SSF56512, 1 hit
SSF63380 SSF63380, 1 hit
PROSITEiView protein in PROSITE
PS51384 FAD_FR, 1 hit
PS50902 FLAVODOXIN_LIKE, 1 hit
PS60001 NOS, 1 hit
PS50106 PDZ, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNOS1_MOUSE
AccessioniPrimary (citable) accession number: Q9Z0J4
Secondary accession number(s): Q3UR10, Q64208
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: November 7, 2018
This is version 189 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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