UniProt functional annotation for P29475



	UniProt functional annotation for P29475

UniProt code: P29475.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.

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;

Cofactor: Name=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD.;

Cofactor: Name=FMN; Xref=ChEBI:CHEBI:58210; Note=Binds 1 FMN.;

Cofactor: Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin; Xref=ChEBI:CHEBI:59560; Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.;

Activity regulation: Stimulated by calcium/calmodulin. Inhibited by n- Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein. Inhibited by NOSIP.

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. 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}.

Subcellular location: Cell 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}.

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.

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). {ECO:0000250}.

Ptm: Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and Hsp40 (in vitro). {ECO:0000250}.

Similarity: Belongs to the NOS family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.


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;
Cofactor:		Name=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD.;
Cofactor:		Name=FMN; Xref=ChEBI:CHEBI:58210; Note=Binds 1 FMN.;
Cofactor:		Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin; Xref=ChEBI:CHEBI:59560; Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.;
Activity regulation:		Stimulated by calcium/calmodulin. Inhibited by n- Nos-inhibiting protein (PIN) which may prevent the dimerization of the protein. Inhibited by NOSIP.
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. 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}.
Subcellular location:		Cell 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}.
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.
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). {ECO:0000250}.
Ptm:		Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and Hsp40 (in vitro). {ECO:0000250}.
Similarity:		Belongs to the NOS family. {ECO:0000305}.