Nitric oxide synthase, inducible

Function

Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. 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. Involved in inflammation, enhances the synthesis of pro-inflammatory mediators such as IL6 and IL8.

Classification

Family (Pfam)

PF00667 FAD_binding_1, PF00258 Flavodoxin_1, PF00175 NAD_binding_1, PF02898 NO_synthase

InterPro

CysJ-like_FAD-binding, FAD-bd_FR_type, Flavdoxin-like, Flavodoxin/NO_synth, Flavoprot_Pyr_Nucl_cyt_Rdtase, Flavoprotein-like_sf, FNR_nucleotide-bd, NADPH_Cyt_P450_Rdtase_alpha, NOS, NOS_dom_1, NOS_dom_2, NOS_dom_3, NOS_euk, NOS_N, NOS_N_sf, OxRdtase_FAD/NAD-bd, Riboflavin_synthase-like_b-brl

Functional cluster

Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 13

• 1NSI X-ray 2.55A
• 2LL6 NMR
• 2NSI X-ray 3.00A
• 3E7G X-ray 2.20A
• 3EJ8 X-ray 2.55A
• 3HR4 X-ray 2.50A
• 4CX7 X-ray 3.16A
• 4NOS X-ray 2.25A
• 5TP6 NMR
• 5XN3 X-ray 1.34A
• 6JWM X-ray 1.23A
• 6JWN X-ray 1.61A
• … and 1 more

A predicted model is available from AlphaFold.

Gene Ontology · 44

• GO:0030863 cortical cytoskeleton
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0048471 perinuclear region of cytoplasm
• GO:0005782 peroxisomal matrix
• GO:0005777 peroxisome
• GO:0005886 plasma membrane
• GO:0034618 arginine binding
• GO:0005516 calmodulin binding
• GO:0050660 flavin adenine dinucleotide binding
• GO:0010181 FMN binding
• GO:0020037 heme binding
• GO:0046872 metal ion binding
• GO:0050661 NADP binding
• GO:0004517 nitric-oxide synthase activity
• GO:0042803 protein homodimerization activity
• GO:0034617 tetrahydrobiopterin binding
• GO:0045454 cell redox homeostasis
• GO:0007623 circadian rhythm
• GO:0042742 defense response to bacterium
• GO:0050829 defense response to Gram-negative bacterium
• GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
• GO:0006954 inflammatory response
• GO:0002227 innate immune response in mucosa
• GO:0006527 L-arginine catabolic process
• GO:0045776 negative regulation of blood pressure
• GO:0010629 negative regulation of gene expression
• GO:0042177 negative regulation of protein catabolic process
• GO:0006809 nitric oxide biosynthetic process
• GO:0007263 nitric oxide mediated signal transduction
• GO:0018119 peptidyl-cysteine S-nitrosylation
• GO:0032755 positive regulation of interleukin-6 production
• GO:0032757 positive regulation of interleukin-8 production
• GO:0001912 positive regulation of leukocyte mediated cytotoxicity
• GO:0032310 prostaglandin secretion
• GO:0043457 regulation of cellular respiration
• GO:1900015 regulation of cytokine production involved in inflammatory response
• GO:0050796 regulation of insulin secretion
• GO:0009617 response to bacterium
• GO:0009725 response to hormone
• GO:0032496 response to lipopolysaccharide
• GO:0006801 superoxide metabolic process

Disease associations

• malaria, susceptibility to MONDO:0021024

Drugs targeting this protein · 4

• GW-274150 inhibitor
• TILARGININE ACETATE inhibitor
• KD7040 inhibitor
• TILARGININE inhibitor

Related proteins · sequence + function similarity

• Nitric oxide synthase, inducible 0.97
• Nitric oxide synthase, inducible 0.96
• Nitric oxide synthase, inducible 0.96
• Nitric oxide synthase, inducible 0.95
• Nitric oxide synthase, inducible 0.95
• Nitric oxide synthase, inducible 0.95
• Nitric oxide synthase, inducible 0.88
• Nitric oxide synthase, inducible 0.85
• Nitric oxide synthase 0.81
• Nitric oxide synthase, salivary gland 0.79
• Nitric oxide synthase-like protein 0.78
• Nitric oxide synthase, inducible 0.77

Co-cited proteins · studied together in the literature

• Nitric oxide synthase, inducible 1 shared papers
• Nitric oxide synthase 3 2 shared papers
• Leptin 1 shared papers
• Nitric oxide synthase 1 1 shared papers
• Na(+)/H(+) exchange regulatory cofactor NHE-RF1 1 shared papers
• Nitric oxide synthase 1 1 shared papers
• SPRY domain-containing SOCS box protein 1 1 shared papers
• SPRY domain-containing SOCS box protein 4 1 shared papers
• Annexin A5 1 shared papers
• SPRY domain-containing SOCS box protein 2 1 shared papers
• Nitric oxide synthase, inducible 1 shared papers
• Moesin 1 shared papers

Literature · 25 cited papers

• 2-Aminopyridines with a shortened amino sidechain as potent, selective, and highly permeable human neuronal nitric oxide synthase inhibitors. Bioorg. Med. Chem. · 2022
• Target-selective protein S-nitrosylation by sequence motif recognition. Cell · 2014
• Zinc regulates iNOS-derived nitric oxide formation in endothelial cells. Redox Biol. · 2014
• Higher activity of the inducible nitric oxide synthase contributes to very early onset inflammatory bowel disease. Clin. Transl. Gastroenterol. · 2014
• Regulation of inducible nitric-oxide synthase by the SPRY domain- and SOCS box-containing proteins. J. Biol. Chem. · 2011
• Regulation of interdomain interactions by calmodulin in inducible nitric-oxide synthase. J. Biol. Chem. · 2009
• Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage--mediator role of NO in leptin-induced PGE2, IL-6, and IL-8 production. Mediators Inflamm. · 2009
• The consensus coding sequences of human breast and colorectal cancers. Science · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• A new NOS2 promoter polymorphism associated with increased nitric oxide production and protection from severe malaria in Tanzanian and Kenyan children. Lancet · 2002
• Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output. J. Biol. Chem. · 2002
• Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase. J. Biol. Chem. · 1999
• … and 13 more in the literature graph