Nitric-oxide synthase, eukaryote (IPR012144)

Short name: NOS_euk

Overlapping homologous superfamilies


Family relationships


Nitric oxide synthase (EC: (NOS) enzymes produce nitric oxide (NO) by catalyzing a five-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg). Oxidation of L-Arg to L-citrulline occurs via two successive monooxygenation reactions producing N(omega)-hydroxy-L-arginine as an intermediate. 2 mol of O(2) and 1.5 mol of NADPH are consumed per mole of NO formed [PMID: 8782597].

Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria [PMID: 8782597]. Best studied are mammals, where three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3) [PMID: 7510950]. iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated. The enzymes exist as homodimers, each monomer consisting of two major domains: an N-terminal oxygenase domain, which belongs to the class of haem-thiolate proteins, and a C-terminal reductase domain, which is homologous to NADPH:P450 reductase (EC: The interdomain linker between the oxygenase and reductase domains contains a calmodulin (CaM)-binding sequence. NOSs are the only enzymes known to simultaneously require five bound cofactors animal NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH --> FAD --> FMN --> haem --> O(2).

eNOS localisation to endothelial membranes is mediated by cotranslational N-terminal myristoylation and post-translational palmitoylation [PMID: 9199168]. The subcellular localisation of nNOS in skeletal muscle is mediated by anchoring of nNOS to dystrophin. nNOS contains an additional N-terminal domain, the PDZ domain [PMID: 7535955].

This entry represents all forms of NOS from eukaryotes. For further information see [PMID: 11695891, PMID: 10331866, PMID: 15208315, PMID: 10409685].

GO terms

Biological Process

GO:0006809 nitric oxide biosynthetic process

Molecular Function

GO:0010181 FMN binding
GO:0050661 NADP binding
GO:0005516 calmodulin binding
GO:0050660 flavin adenine dinucleotide binding
GO:0020037 heme binding
GO:0004517 nitric-oxide synthase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.