NOS2
Nitric oxide synthase, inducible
Also known as: HEP-NOS, iNOS, NOS, NOS2_HUMAN, NOS2A
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P35228
- Gene
- NOS2
- Ensembl
- ENSG00000007171
- Chromosome
- 17
- Canonical length
- 1153 aa
- Protein class
- Cancer-related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
- Quaternary structure
- Homodimer
OverviewNCBI Gene
Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
1153 residues, UniProt reviewed canonical sequence.
>P35228|NOS2
1 MACPWKFLFK TKFHQYAMNG EKDINNNVEK APCATSSPVT QDDLQYHNLS KQQNESPQPL
61 VETGKKSPES LVKLDATPLS SPRHVRIKNW GSGMTFQDTL HHKAKGILTC RSKSCLGSIM
121 TPKSLTRGPR DKPTPPDELL PQAIEFVNQY YGSFKEAKIE EHLARVEAVT KEIETTGTYQ
181 LTGDELIFAT KQAWRNAPRC IGRIQWSNLQ VFDARSCSTA REMFEHICRH VRYSTNNGNI
241 RSAITVFPQR SDGKHDFRVW NAQLIRYAGY QMPDGSIRGD PANVEFTQLC IDLGWKPKYG
301 RFDVVPLVLQ ANGRDPELFE IPPDLVLEVA MEHPKYEWFR ELELKWYALP AVANMLLEVG
361 GLEFPGCPFN GWYMGTEIGV RDFCDVQRYN ILEEVGRRMG LETHKLASLW KDQAVVEINI
421 AVLHSFQKQN VTIMDHHSAA ESFMKYMQNE YRSRGGCPAD WIWLVPPMSG SITPVFHQEM
481 LNYVLSPFYY YQVEAWKTHV WQDEKRRPKR REIPLKVLVK AVLFACMLMR KTMASRVRVT
541 ILFATETGKS EALAWDLGAL FSCAFNPKVV CMDKYRLSCL EEERLLLVVT STFGNGDCPG
601 NGEKLKKSLF MLKELNNKFR YAVFGLGSSM YPRFCAFAHD IDQKLSHLGA SQLTPMGEGD
661 ELSGQEDAFR SWAVQTFKAA CETFDVRGKQ HIQIPKLYTS NVTWDPHHYR LVQDSQPLDL
721 SKALSSMHAK NVFTMRLKSR QNLQSPTSSR ATILVELSCE DGQGLNYLPG EHLGVCPGNQ
781 PALVQGILER VVDGPTPHQT VRLEALDESG SYWVSDKRLP PCSLSQALTY FLDITTPPTQ
841 LLLQKLAQVA TEEPERQRLE ALCQPSEYSK WKFTNSPTFL EVLEEFPSLR VSAGFLLSQL
901 PILKPRFYSI SSSRDHTPTE IHLTVAVVTY HTRDGQGPLH HGVCSTWLNS LKPQDPVPCF
961 VRNASGFHLP EDPSHPCILI GPGTGIAPFR SFWQQRLHDS QHKGVRGGRM TLVFGCRRPD
1021 EDHIYQEEML EMAQKGVLHA VHTAYSRLPG KPKVYVQDIL RQQLASEVLR VLHKEPGHLY
1081 VCGDVRMARD VAHTLKQLVA AKLKLNEEQV EDYFFQLKSQ KRYHEDIFGA VFPYEAKKDR
1141 VAVQPSSLEM SALLocalizationUniProt · AlphaFold · HPA
Whether an antibody against NOS2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.29
- Highest tissue expression
- 20 nTPM
Expression across tissuesHPA
Tissue
- small intestine: 20 nTPM
- appendix: 14 nTPM
- duodenum: 11 nTPM
- rectum: 8.2 nTPM
- colon: 6.3 nTPM
- cerebral cortex: 3.4 nTPM
Single-cell type
- respiratory secretory cells: 53 nCPM
- extravillous trophoblasts: 48 nCPM
- respiratory basal cells: 28 nCPM
- enteric stem cells: 26 nCPM
- ocular epithelial cells: 18 nCPM
- enterocytes: 16 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- cerebral cortex: 2.1 nTPM
- hypothalamus: 1.3 nTPM
- white matter: 1 nTPM
- pons: 0.6 nTPM
- medulla oblongata: 0.5 nTPM
- spinal cord: 0.5 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.76
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.78
- DepMap mean gene effect
- -0.08
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cell redox homeostasis
- cellular response to lipopolysaccharide
- cellular response to type II interferon
- cellular response to xenobiotic stimulus
- circadian rhythm
- defense response to bacterium
- defense response to Gram-negative bacterium
- Fc-gamma receptor signaling pathway involved in phagocytosis
- inflammatory response
- innate immune response in mucosa
- L-arginine catabolic process
- 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 interleukin-6 production
- positive regulation of interleukin-8 production
- prostaglandin secretion
- regulation of cell population proliferation
- regulation of cellular respiration
- regulation of cytokine production involved in inflammatory response
- regulation of insulin secretion
- response to bacterium
- response to hormone
- response to hypoxia
- response to lipopolysaccharide
- superoxide metabolic process
- positive regulation of leukocyte mediated cytotoxicity
Molecular functions
- arginine binding
- calmodulin binding
- flavin adenine dinucleotide binding
- FMN binding
- heme binding
- metal ion binding
- NADP binding
- nitric-oxide synthase activity
- protein homodimerization activity
- tetrahydrobiopterin binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Flavodoxin-like
- Oxidoreductase FAD/NAD(P)-binding
- Flavoprotein pyridine nucleotide cytochrome reductase
- Sulfite reductase [NADPH] flavoprotein alpha-component-like, FAD-binding
- Nitric oxide synthase, N-terminal
- Flavodoxin/nitric oxide synthase
- Nitric-oxide synthase, eukaryote
- FAD-binding domain, ferredoxin reductase-type
- Riboflavin synthase-like beta-barrel
- NADPH-cytochrome p450 reductase, FAD-binding, alpha-helical domain superfamily
- Flavoprotein-like superfamily
- Nitric oxide synthase, N-terminal domain superfamily
- Ferredoxin-NADP reductase (FNR), nucleotide-binding domain
- Nitric oxide synthase, domain 2 superfamily
- Nitric oxide synthase, domain 1 superfamily
- Nitric oxide synthase, domain 3 superfamily
- Nitric Oxide Synthase (NOS)
- Oxidoreductase NAD-binding domain
- Flavodoxin
- FAD binding domain
- Nitric oxide synthase, oxygenase domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of NOS2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads NOS2 as an antibody target. Whether an autoantibody or antibody against NOS2 could matter depends on whether native NOS2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
NOS2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label NOS2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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