NO synthase-1 (calmodulin NO synthase, NADPH diaphorase, neuronal NO synthase, nNOS)
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Function
- produces nitric oxide (NO), a messenger molecule with diverse functions throughout the body
- in brain & peripheral nervous system, NO displays many properties of a neurotransmitter
- stimulated by Ca+2/calmodulin
- interacts with DLG4; the interaction possibly being prevented by the association between NOS1 & CAPON
- forms a ternary complex with CAPON & RASD1
- forms a ternary complex with CAPON & SYN1
- interacts with ZDHHC23
- interacts with NOSIPwhich may impair its synaptic location
- interacts with HTR4 (putative)
L-arginine + n NADPH + m O2
<-->
citrulline + nitric oxide + n NADP+
Cofactor:
- heme group
- binds 1 FAD
- binds 1 FMN
- betrahydrobiopterin (BH4)
Kinetics:
- half maximal activity at Ca+2 of 160 nM
- intraneuronal Ca+2 is typically 100 nM
Structure
- homodimer
- PDZ domain in the N-terminal part of the neuronal isoform participates in protein-protein interaction, & is responsible for targeting NOS1 to synaptic membranes in muscles
- belongs to the NOS family
- contains 1 flavodoxin-like domain
- contains 1 PDZ (DHR) domain
Compartment
- cell membrane, sarcolemma
- cell projection, dendritic spine
- in skeletal muscle, localized beneath the sarcolemma of fast-twitch muscle fiber by associating with the dystrophin glycoprotein complex
- in neurons, enriched in dendritic spines (putative)
Alternative splicing
named isoforms=4
Expression
- isoform 1 is ubiquitously expressed:
- detected in skeletal muscle & brain, also in testis, lung & kidney
- low levels in heart, adrenal gland & retina
- not detected in the platelets
- isoform 3 is expressed only in testis
- isoform 4
- detected in testis, skeletal muscle, lung, & kidney
- low levels in the brain,
- not detected in heart or adrenal gland
Pathology
- genetic variations in NOS1 gene are associated with susceptibility to infantile hypertrophic pyloric stenosis type 1
Notes
- inhibited by n-Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein
- inhibited by NOSIP
More general terms
Additional terms
References
- ↑ Bredt DS, Snyder SH. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci U S A. 1990 Jan;87(2):682-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1689048
- ↑ Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci. 1991 Feb;14(2):60-7. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1708538
- ↑ Snyder SH, Bredt DS. Nitric oxide as a neuronal messenger. Trends Pharmacol Sci. 1991 Apr;12(4):125-8. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1712138
- ↑ Crossin KL. Nitric oxide (NO): a versatile second messenger in brain. Trends Biochem Sci. 1991 Mar;16(3):81-2. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1711724
- ↑ Vincent SR, Hope BT. Neurons that say NO. Trends Neurosci. 1992 Mar;15(3):108-13. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1373918
- ↑ Prince RC, Gunson DE. Rising interest in nitric oxide synthase. Trends Biochem Sci. 1993 Feb;18(2):35-6. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7683828
- ↑ UniProt http://www.uniprot.org/uniprot/P29475.html