UniProt functional annotation for P29477



	UniProt functional annotation for P29477

UniProt code: P29477.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7503239). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (PubMed:16373578). As component of the iNOS- S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM (By similarity). Involved in inflammation, enhances the synthesis of proinflammatory mediators such as IL6 and IL8 (By similarity). {ECO:0000250|UniProtKB:P35228, ECO:0000250|UniProtKB:P79290, ECO:0000269|PubMed:16373578, ECO:0000269|PubMed:7503239}.

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: Not stimulated by calcium/calmodulin. Aspirin inhibits expression and function of this enzyme and effects may be exerted at the level of translational/post-translational modification and directly on the catalytic activity.

Subunit: Homodimer (PubMed:10769116, PubMed:11669619). Interacts with SLC9A3R1 (By similarity). Interacts with GAPDH (By similarity). Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9 transnitrosylase complex (By similarity). Interacts with SPSB1, SPSB2 and SPSB4 (PubMed:20603330). Interacts with ELOC and CUL5 in the presence of SPSB1 or SPSB2 or SPSB4 (By similarity). {ECO:0000250|UniProtKB:P35228, ECO:0000269|PubMed:10769116, ECO:0000269|PubMed:11669619, ECO:0000269|PubMed:20603330}.

Subcellular location: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P35228}. Note=Localizes as discrete foci scattered throughout the cytosol and in the presence of SPSB1 and SPSB4, exhibits a more diffuse cytosolic localization. {ECO:0000250|UniProtKB:P35228}.

Tissue specificity: Macrophages.

Induction: By treatment with endotoxins or cytokines. By lipopolysaccharides (LPS) (in vitro). Expression in the liver oscillates in a circadian manner with peak levels occurring during the late night. {ECO:0000269|PubMed:22073225}.

Ptm: Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to proteasomal degradation. {ECO:0000269|PubMed:20603330, ECO:0000269|PubMed:21199876}.

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

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7503239). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (PubMed:16373578). As component of the iNOS- S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM (By similarity). Involved in inflammation, enhances the synthesis of proinflammatory mediators such as IL6 and IL8 (By similarity). {ECO:0000250\|UniProtKB:P35228, ECO:0000250\|UniProtKB:P79290, ECO:0000269\|PubMed:16373578, ECO:0000269\|PubMed:7503239}.


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:		Not stimulated by calcium/calmodulin. Aspirin inhibits expression and function of this enzyme and effects may be exerted at the level of translational/post-translational modification and directly on the catalytic activity.
Subunit:		Homodimer (PubMed:10769116, PubMed:11669619). Interacts with SLC9A3R1 (By similarity). Interacts with GAPDH (By similarity). Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9 transnitrosylase complex (By similarity). Interacts with SPSB1, SPSB2 and SPSB4 (PubMed:20603330). Interacts with ELOC and CUL5 in the presence of SPSB1 or SPSB2 or SPSB4 (By similarity). {ECO:0000250\|UniProtKB:P35228, ECO:0000269\|PubMed:10769116, ECO:0000269\|PubMed:11669619, ECO:0000269\|PubMed:20603330}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000250\|UniProtKB:P35228}. Note=Localizes as discrete foci scattered throughout the cytosol and in the presence of SPSB1 and SPSB4, exhibits a more diffuse cytosolic localization. {ECO:0000250\|UniProtKB:P35228}.
Tissue specificity:		Macrophages.
Induction:		By treatment with endotoxins or cytokines. By lipopolysaccharides (LPS) (in vitro). Expression in the liver oscillates in a circadian manner with peak levels occurring during the late night. {ECO:0000269\|PubMed:22073225}.
Ptm:		Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to proteasomal degradation. {ECO:0000269\|PubMed:20603330, ECO:0000269\|PubMed:21199876}.
Similarity:		Belongs to the NOS family. {ECO:0000305}.