UniProt functional annotation for P35228

UniProt code: P35228.

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 (PubMed:7531687, PubMed:7544004). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (By similarity). As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM (PubMed:25417112). Involved in inflammation, enhances the synthesis of proinflammatory mediators such as IL6 and IL8 (PubMed:19688109). {ECO:0000250|UniProtKB:P29477, ECO:0000269|PubMed:19688109, ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:7531687, ECO:0000269|PubMed:7544004}.
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:		Regulated 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 (By similarity). {ECO:0000250}.
Subunit:		Homodimer (PubMed:10409685, PubMed:10074942). Interacts with SLC9A3R1 (PubMed:12080081). Interacts with GAPDH; induced by oxidatively-modified low-densitity lipoprotein (LDL(ox)) (PubMed:25417112). Interacts with S100A8 and S100A9 to form the iNOS- S100A8/9 transnitrosylase complex (PubMed:25417112). Interacts with SPSB1, SPSB2 and SPSB4 (PubMed:21199876). Interacts with ELOC and CUL5 in the presence of SPSB1 or SPSB2 or SPSB4 (PubMed:21199876). {ECO:0000269|PubMed:10074942, ECO:0000269|PubMed:10409685, ECO:0000269|PubMed:12080081, ECO:0000269|PubMed:21199876, ECO:0000269|PubMed:25417112}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269|PubMed:21199876}. Note=Localizes as discrete foci scattered throughout the cytosol and in the presence of SPSB1 and SPSB4, exhibits a more diffuse cytosolic localization. {ECO:0000269|PubMed:21199876}.
Tissue specificity:		Expressed in the liver, retina, bone cells and airway epithelial cells of the lung. Not expressed in the platelets.
Induction:		By endotoxins and cytokines. Induced by IFNG/IFN-gamma acting synergistically with bacterial lipopolysaccharides (LPS), TNF or IL1B/interleukin-1 beta (PubMed:7528267). Down-regulated by zinc due to inhibition of NF-kappa-B transactivation activity (PubMed:25180171). By oxidatively-modified low-densitity lipoprotein (LDL(ox)) (PubMed:25417112). {ECO:0000269|PubMed:25180171, ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:7528267}.
Ptm:		Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to proteasomal degradation. {ECO:0000269|PubMed:21199876}.
Polymorphism:		Genetic variations in NOS2 are involved in resistance to malaria [MIM:611162]. {ECO:0000269|PubMed:12433515}.
Similarity:		Belongs to the NOS family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.