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MGP002110

UniProt Annotations

Entry Information
Gene Namenitric oxide synthase 1 (neuronal)
Protein EntryNOS1_HUMAN
UniProt IDP29475
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=5; Comment=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-terminally truncated protein which possesses enzymatic activity comparable to that of isoform 1. The C-terminally 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. {ECO:0000269|PubMed:9791007}; Name=1; Synonyms=N-NOS-1; IsoId=P29475-1; Sequence=Displayed; Name=2; Synonyms=N-NOS-2; IsoId=P29475-2; Sequence=VSP_003574; Name=3; Synonyms=TN-NOS, TN-NOSB; IsoId=P29475-3; Sequence=VSP_003571; Name=4; Synonyms=TEX2-insertion; IsoId=P29475-4; Sequence=VSP_003572, VSP_003573; Name=5; Synonyms=nNOSmu; IsoId=P29475-5; Sequence=VSP_044916;
Catalytic Activity2 L-arginine + 3 NADPH + 4 O(2) = 2 L- citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O.
CofactorName=5,6,7,8-tetrahydrobiopterin; Xref=ChEBI:CHEBI:15372; Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.;
CofactorName=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD.;
CofactorName=FMN; Xref=ChEBI:CHEBI:58210; Note=Binds 1 FMN.;
CofactorName=heme; Xref=ChEBI:CHEBI:30413;
DomainThe 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). {ECO:0000250}.
Enzyme RegulationStimulated by calcium/calmodulin. Inhibited by n-Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein. Inhibited by NOSIP.
FunctionProduces 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.
InteractionQ08AM6:VAC14; NbExp=5; IntAct=EBI-7164065, EBI-2107455;
PtmUbiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and Hsp40 (in vitro). {ECO:0000250}.
SimilarityBelongs to the NOS family. {ECO:0000305}.
SimilarityContains 1 FAD-binding FR-type domain. {ECO:0000255|PROSITE-ProRule:PRU00716}.
SimilarityContains 1 flavodoxin-like domain. {ECO:0000255|PROSITE-ProRule:PRU00088}.
SimilarityContains 1 PDZ (DHR) domain. {ECO:0000255|PROSITE- ProRule:PRU00143}.
Subcellular LocationCell membrane, sarcolemma; Peripheral membrane protein. Cell projection, dendritic spine {ECO:0000250}. 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). {ECO:0000250}.
SubunitHomodimer. 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. Interacts with VAC14 (By similarity). Interacts with SLC6A4 (By similarity). Interacts (via N-terminal domain) with DLG4 (via N-terminal tandem pair of PDZ domains) (By similarity). {ECO:0000250}.
Tissue SpecificityIsoform 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.
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/nos1/";
Web ResourceName=Wikipedia; Note=Nitric oxide synthase entry; URL="http://en.wikipedia.org/wiki/Nitric_oxide_synthase";
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