Reviewed,
UniProtKB/Swiss-Prot Q9Z0J4 (NOS1_MOUSE)
Last modified
January 19, 2010.
Version 106.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended 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 |
| ||
| Organism | Mus musculus (Mouse) | ||
| Taxonomic identifier | 10090 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 1429 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
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. |
Ontologies
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 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1429 | 1429 | Nitric oxide synthase, brain | PRO_0000170922 | |||||||
Regions | |||||||||||
| Domain | 17 – 99 | 83 | PDZ | ||||||||
| Domain | 755 – 935 | 181 | Flavodoxin-like | ||||||||
| Domain | 990 – 1237 | 248 | FAD-binding FR-type | ||||||||
| Nucleotide binding | 881 – 912 | 32 | FMN By similarity | ||||||||
| Nucleotide binding | 1027 – 1038 | 12 | FAD By similarity | ||||||||
| Nucleotide binding | 1170 – 1180 | 11 | FAD By similarity | ||||||||
| Nucleotide binding | 1245 – 1263 | 19 | NADP By similarity | ||||||||
| Nucleotide binding | 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 | ||||||||
Sites | |||||||||||
| Metal binding | 415 | 1 | Iron (heme axial ligand) By similarity | ||||||||
Natural variations | |||||||||||
| Alternative sequence | 1 – 331 | 331 | Missing in isoform NNOS gamma. | VSP_003577 | |||||||
| Alternative sequence | 1 – 230 | 230 | Missing in isoform NNOS beta. | VSP_003575 | |||||||
| Alternative sequence | 231 – 236 | 6 | TGIQVD → MRGLGS in isoform NNOS beta. | VSP_003576 | |||||||
| Alternative sequence | 504 – 608 | 105 | Missing in isoform N-NOS-2. | VSP_003578 | |||||||
| Alternative sequence | 839 | 1 | K → KYPEPLRFFPRKGPSLSHVD SEAHSLVAARDSQHR in isoform NNOS Mu. | VSP_003579 | |||||||
Secondary structure | |||||||||||
Helix Strand Turn | |||||||||||
| Helix | 731 – 744 | 14 | |||||||||
Sequences
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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. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | D14552 mRNA. Translation: BAA03415.1. S81982 mRNA. Translation: AAB36469.1. | ||||||||||||
| IPI | IPI00129191. IPI00229026. IPI00229027. IPI00229030. IPI00309243. | ||||||||||||
| PIR | JN0609. | ||||||||||||
| RefSeq | NP_032738.1. | ||||||||||||
| UniGene | Mm.442195 Mm.44249 | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
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| SMR | Q9Z0J4. Positions 12-126, 298-716, 750-1413. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| DIP | DIP-31556N. | ||||||||||||
| STRING | Q9Z0J4. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q9Z0J4. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | Q9Z0J4. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENSMUST00000086451; ENSMUSP00000083641; ENSMUSG00000029361; Mus musculus. [Genome view] ENSMUST00000111935; ENSMUSP00000107566; ENSMUSG00000029361; Mus musculus. [Genome view] ENSMUST00000111939; ENSMUSP00000107570; ENSMUSG00000029361; Mus musculus. [Genome view] | ||||||||||||
| GeneID | 18125. | ||||||||||||
| KEGG | mmu:18125. | ||||||||||||
| UCSC | uc008zfy.1. mouse. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 18125. | ||||||||||||
| MGI | MGI:97360. Nos1. | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOVERGEN | Q9Z0J4. | ||||||||||||
| PhylomeDB | Q9Z0J4. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| BRENDA | 1.14.13.39. 244. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q9Z0J4. | ||||||||||||
| Bgee | Q9Z0J4. | ||||||||||||
| CleanEx | MM_NOS1. | ||||||||||||
| Genevestigator | Q9Z0J4. | ||||||||||||
| GermOnline | ENSMUSG00000029361. Mus musculus. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR003097. 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] | ||||||||||||
| Gene3D | G3DSA:3.90.340.10. NO_synthase_oxygenase_reg. 1 hit. | ||||||||||||
| 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. [Graphical view] | ||||||||||||
| PIRSF | PIRSF000333. NOS. 1 hit. | ||||||||||||
| PRINTS | PR00369. FLAVODOXIN. PR00371. FPNCR. | ||||||||||||
| SMART | SM00228. PDZ. 1 hit. [Graphical view] | ||||||||||||
| PROSITE | PS51384. FAD_FR. 1 hit. PS50902. FLAVODOXIN_LIKE. 1 hit. PS60001. NOS. 1 hit. PS50106. PDZ. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| NextBio | 293344. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | NOS1_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q9Z0J4 Secondary accession number(s): Q64208 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
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 |

Clusters with


