UniProt functional annotation for P29476

UniProt code: P29476.

Organism: Rattus norvegicus (Rat).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.
 
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. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.
 
Catalytic activity: Reaction=H(+) + 2 L-arginine + 3 NADPH + 4 O2 = 4 H2O + 2 L-citrulline + 3 NADP(+) + 2 nitric oxide; Xref=Rhea:RHEA:19897, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16480, ChEBI:CHEBI:32682, ChEBI:CHEBI:57743, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.39;
Cofactor: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
Cofactor: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250}; Note=Binds 1 FAD. {ECO:0000250};
Cofactor: Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000250}; Note=Binds 1 FMN. {ECO:0000250};
Cofactor: Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin; Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000250}; Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme. {ECO:0000250};
Activity regulation: Stimulated by calcium/calmodulin. Inhibited by n- Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein (By similarity). Inhibited by NOSIP. {ECO:0000250, ECO:0000269|PubMed:15548660}.
Subunit: Homodimer. Interacts with DLG4; the interaction possibly being prevented by the association between NOS1 and CAPON (By similarity). 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. Interacts with HTR4 (By similarity). Interacts with SLC6A4 (By similarity). Interacts with VAC14. Interacts (via N-terminal domain) with DLG4 (via N-terminal tandem pair of PDZ domains). {ECO:0000250, ECO:0000269|PubMed:11086993, ECO:0000269|PubMed:11867766, ECO:0000269|PubMed:15105416, ECO:0000269|PubMed:15548660, ECO:0000269|PubMed:17161399, ECO:0000269|PubMed:23300088}.
Subcellular location: Cell membrane, sarcolemma {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. 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 (By similarity). In neurons, enriched in dendritic spines. {ECO:0000250, ECO:0000269|PubMed:15548660}.
Tissue specificity: Isoform N-NOS-1 is expressed in brain and colorectum. Found in the Auerbach's plexus of the enteric nervous system. Isoform PNNOS is expressed in the penis, urethra, prostate, and skeletal muscle, and coexists with the cerebellar nnos in the pelvic plexus, bladder and liver, and is detectable in the cerebellum. {ECO:0000269|PubMed:7520037}.
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 (By similarity). Mediates interaction with VAC14. {ECO:0000250, ECO:0000269|PubMed:17161399}.
Ptm: Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and Hsp40 (in vitro). {ECO:0000269|PubMed:15466472}.
Similarity: Belongs to the NOS family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.