Alternative products:Isoform 3 is produced by different alternative splicing events implicating either the untranslated exons TEX1 (TN-NOS) or TEX1B (TN-NOSB) leading to a N-terminus truncated protein which possesses enzymatic activity comparable to that of isoform 1. The C-terminal truncated isoform 4 is produced by insertion of the TEX2 exon between exons 3 and 4 of isoform 1 , leading to a frameshift and a premature stop codon ,Catalytic activity:L-arginine + n NADPH + n H (+) + m O (2) = citrulline + nitric oxide + n NADP (+) . ,cofactor:Binds 1 FAD. ,cofactor:Binds 1 FMN. ,cofactor:Heme group. ,cofactor:Tetrahydrobiopterin (BH4) . May stabilize the dimeric form of the enzyme. ,Disease:Genetic variations in NOS1 gene are associated with susceptibility to infantile hypertrophic pyloric stenosis type 1 (IHPS1) [MIM:179010]. IHPS has an incidence of 1-5 per 1'000 live births in whites and a marked preponderance of males to females (4:1) . IHPS is the most frequent disorder requiring surgery in the first year of life. The disorder is characterized by hypertrophy and hyperplasia of the circular muscle layer of the pylorus , leading to persistent vomiting 2-12 weeks after birth. Defective pyloric relaxation and increased pyloric smooth muscle mass have been suggested to be responsible for gastric-outlet obstruction. ,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. ,enzyme regulation:Stimulated by calcium/calmodulin. Inhibited by n-Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein. Inhibited by NOSIP. ,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. ,online information:Nitric oxide synthase entry ,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. ,subcellular location: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. ,subunit:Homodimer. Interacts with DLG4; the interaction possibly being prevented by the association between NOS1 and CAPON. 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 HTR4. ,tissue specificity:Isoform 1 is ubiquitously expressed: detected in skeletal muscle and brain , also in testis , lung and kidney , and at low levels in heart , adrenal gland and retina. Not detected in the platelets. Isoform 3 is expressed only in testis. Isoform 4 is detected in testis , skeletal muscle , lung , and kidney , at low levels in the brain , but not in the heart and adrenal gland. ,
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