Names & Taxonomy

Uniprot ID:
P35228
Entry Name:
NOS2_HUMAN
Status:
reviewed
Protein Names:
Nitric oxide synthase, inducible (EC 1.14.13.39) (Hepatocyte NOS) (HEP-NOS) (Inducible NO synthase) (Inducible NOS) (iNOS) (NOS type II) (Peptidyl-cysteine S-nitrosylase NOS2)
Gene Names:
NOS2 NOS2A
Gene Names Primary:
NOS2
Organism:
Homo sapiens (Human)

Structure

Length:
1153
Sequence:
MACPWKFLFKTKFHQYAMNGEKDINNNVEKAPCATSSPVTQDDLQYHNLSKQQNESPQPLVETGKKSPESLVKLDATPLSSPRHVRIKNWGSGMTFQDTLHHKAKGILTCRSKSCLGSIMTPKSLTRGPRDKPTPPDELLPQAIEFVNQYYGSFKEAKIEEHLARVEAVTKEIETTGTYQLTGDELIFATKQAWRNAPRCIGRIQWSNLQVFDARSCSTAREMFEHICRHVRYSTNNGNIRSAITVFPQRSDGKHDFRVWNAQLIRYAGYQMPDGSIRGDPANVEFTQLCIDLGWKPKYGRFDVVPLVLQANGRDPELFEIPPDLVLEVAMEHPKYEWFRELELKWYALPAVANMLLEVGGLEFPGCPFNGWYMGTEIGVRDFCDVQRYNILEEVGRRMGLETHKLASLWKDQAVVEINIAVLHSFQKQNVTIMDHHSAAESFMKYMQNEYRSRGGCPADWIWLVPPMSGSITPVFHQEMLNYVLSPFYYYQVEAWKTHVWQDEKRRPKRREIPLKVLVKAVLFACMLMRKTMASRVRVTILFATETGKSEALAWDLGALFSCAFNPKVVCMDKYRLSCLEEERLLLVVTSTFGNGDCPGNGEKLKKSLFMLKELNNKFRYAVFGLGSSMYPRFCAFAHDIDQKLSHLGASQLTPMGEGDELSGQEDAFRSWAVQTFKAACETFDVRGKQHIQIPKLYTSNVTWDPHHYRLVQDSQPLDLSKALSSMHAKNVFTMRLKSRQNLQSPTSSRATILVELSCEDGQGLNYLPGEHLGVCPGNQPALVQGILERVVDGPTPHQTVRLEALDESGSYWVSDKRLPPCSLSQALTYFLDITTPPTQLLLQKLAQVATEEPERQRLEALCQPSEYSKWKFTNSPTFLEVLEEFPSLRVSAGFLLSQLPILKPRFYSISSSRDHTPTEIHLTVAVVTYHTRDGQGPLHHGVCSTWLNSLKPQDPVPCFVRNASGFHLPEDPSHPCILIGPGTGIAPFRSFWQQRLHDSQHKGVRGGRMTLVFGCRRPDEDHIYQEEMLEMAQKGVLHAVHTAYSRLPGKPKVYVQDILRQQLASEVLRVLHKEPGHLYVCGDVRMARDVAHTLKQLVAAKLKLNEEQVEDYFFQLKSQKRYHEDIFGAVFPYEAKKDRVAVQPSSLEMSAL
Proteomes:
UP000005640

Function

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).
Catalytic Activity:
2 L-arginine + 3 NADPH + 4 O(2) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O.
Cofactor:
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413;
Enzyme Regulation:
ENZYME 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).
Cross Reference Drug Bank:
DB01234 DB00997 DB00125 DB00155 DB01110 DB08814
Gene Ontology Go:
cortical cytoskeleton
cytoplasm
cytosol
intracellular
nucleus
perinuclear region of cytoplasm
peroxisome
arginine binding
flavin adenine dinucleotide binding
FMN binding
heme binding
iron ion binding
NADP binding
nitric-oxide synthase activity
protein homodimerization activity
receptor binding
tetrahydrobiopterin binding
arginine catabolic process
blood coagulation
cell redox homeostasis
cellular response to drug
cellular response to interferon-gamma
cellular response to lipopolysaccharide
circadian rhythm
defense response to bacterium
defense response to Gram-negative bacterium
inflammatory response
innate immune response in mucosa
interleukin-6 secretion
interleukin-8 secretion
negative regulation of blood pressure
negative regulation of gene expression
negative regulation of protein catabolic process
nitric oxide biosynthetic process
nitric oxide mediated signal transduction
peptidyl-cysteine S-nitrosylation
positive regulation of guanylate cyclase activity
positive regulation of killing of cells of other organism
positive regulation of leukocyte mediated cytotoxicity
positive regulation of vasodilation
prostaglandin secretion
regulation of cell proliferation
regulation of cellular respiration
regulation of cytokine production involved in inflammatory response
regulation of insulin secretion
response to bacterium
response to hypoxia
superoxide metabolic process
Gene Ontology Biological Process:
arginine catabolic process
blood coagulation
cell redox homeostasis
cellular response to drug
cellular response to interferon-gamma
cellular response to lipopolysaccharide
circadian rhythm
defense response to bacterium
defense response to Gram-negative bacterium
inflammatory response
innate immune response in mucosa
interleukin-6 secretion
interleukin-8 secretion
negative regulation of blood pressure
negative regulation of gene expression
negative regulation of protein catabolic process
nitric oxide biosynthetic process
nitric oxide mediated signal transduction
peptidyl-cysteine S-nitrosylation
positive regulation of guanylate cyclase activity
positive regulation of killing of cells of other organism
positive regulation of leukocyte mediated cytotoxicity
positive regulation of vasodilation
prostaglandin secretion
regulation of cell proliferation
regulation of cellular respiration
regulation of cytokine production involved in inflammatory response
regulation of insulin secretion
response to bacterium
response to hypoxia
superoxide metabolic process
Gene Ontology Molecular Function:
arginine binding
flavin adenine dinucleotide binding
FMN binding
heme binding
iron ion binding
NADP binding
nitric-oxide synthase activity
protein homodimerization activity
receptor binding
tetrahydrobiopterin binding
Gene Ontology Cellular Component:
cortical cytoskeleton
cytoplasm
cytosol
intracellular
nucleus
perinuclear region of cytoplasm
peroxisome
Keywords:
3D-structure
Alternative splicing
Calcium
Calmodulin-binding
Complete proteome
FAD
FMN
Flavoprotein
Heme
Iron
Metal-binding
NADP
Oxidoreductase
Phosphoprotein
Polymorphism
Reference proteome
Zinc
Interacts With:
P04406

Publication

PubMed ID:
7692964 7682706 7504305 7522054 7528017 7531687 7544004 9160867 15489334 7532248 7528267 7558036 9721329 12080081 12433515 19688109 25417112 25180171 10409685 10074942 16959974 24430113