NOS3
Nitric oxide synthase 3
Also known as: ECNOS, eNOS, NOS3_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P29474
- Gene
- NOS3
- Ensembl
- ENSG00000164867
- Chromosome
- 7
- Canonical length
- 1203 aa
- Protein class
- Cancer-related genes, Disease 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. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]
Canonical amino-acid sequenceUniProt
1203 residues, UniProt reviewed canonical sequence.
>P29474|NOS3
1 MGNLKSVAQE PGPPCGLGLG LGLGLCGKQG PATPAPEPSR APASLLPPAP EHSPPSSPLT
61 QPPEGPKFPR VKNWEVGSIT YDTLSAQAQQ DGPCTPRRCL GSLVFPRKLQ GRPSPGPPAP
121 EQLLSQARDF INQYYSSIKR SGSQAHEQRL QEVEAEVAAT GTYQLRESEL VFGAKQAWRN
181 APRCVGRIQW GKLQVFDARD CRSAQEMFTY ICNHIKYATN RGNLRSAITV FPQRCPGRGD
241 FRIWNSQLVR YAGYRQQDGS VRGDPANVEI TELCIQHGWT PGNGRFDVLP LLLQAPDDPP
301 ELFLLPPELV LEVPLEHPTL EWFAALGLRW YALPAVSNML LEIGGLEFPA APFSGWYMST
361 EIGTRNLCDP HRYNILEDVA VCMDLDTRTT SSLWKDKAAV EINVAVLHSY QLAKVTIVDH
421 HAATASFMKH LENEQKARGG CPADWAWIVP PISGSLTPVF HQEMVNYFLS PAFRYQPDPW
481 KGSAAKGTGI TRKKTFKEVA NAVKISASLM GTVMAKRVKA TILYGSETGR AQSYAQQLGR
541 LFRKAFDPRV LCMDEYDVVS LEHETLVLVV TSTFGNGDPP ENGESFAAAL MEMSGPYNSS
601 PRPEQHKSYK IRFNSISCSD PLVSSWRRKR KESSNTDSAG ALGTLRFCVF GLGSRAYPHF
661 CAFARAVDTR LEELGGERLL QLGQGDELCG QEEAFRGWAQ AAFQAACETF CVGEDAKAAA
721 RDIFSPKRSW KRQRYRLSAQ AEGLQLLPGL IHVHRRKMFQ ATIRSVENLQ SSKSTRATIL
781 VRLDTGGQEG LQYQPGDHIG VCPPNRPGLV EALLSRVEDP PAPTEPVAVE QLEKGSPGGP
841 PPGWVRDPRL PPCTLRQALT FFLDITSPPS PQLLRLLSTL AEEPREQQEL EALSQDPRRY
901 EEWKWFRCPT LLEVLEQFPS VALPAPLLLT QLPLLQPRYY SVSSAPSTHP GEIHLTVAVL
961 AYRTQDGLGP LHYGVCSTWL SQLKPGDPVP CFIRGAPSFR LPPDPSLPCI LVGPGTGIAP
1021 FRGFWQERLH DIESKGLQPT PMTLVFGCRC SQLDHLYRDE VQNAQQRGVF GRVLTAFSRE
1081 PDNPKTYVQD ILRTELAAEV HRVLCLERGH MFVCGDVTMA TNVLQTVQRI LATEGDMELD
1141 EAGDVIGVLR DQQRYHEDIF GLTLRTQEVT SRIRTQSFSL QERQLRGAVP WAFDPPGSDT
1201 NSPLocalizationUniProt · AlphaFold · HPA
Whether an antibody against NOS3 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
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.28
- Highest tissue expression
- 59 nTPM
Expression across tissuesHPA
Tissue
- spleen: 59 nTPM
- heart muscle: 20 nTPM
- adipose tissue: 18 nTPM
- kidney: 18 nTPM
- breast: 13 nTPM
- blood vessel: 11 nTPM
Single-cell type
- early spermatids: 96 nCPM
- late primary spermatocytes: 61 nCPM
- vascular endothelial cells: 56 nCPM
- late spermatids: 48 nCPM
- syncytiotrophoblasts: 29 nCPM
- lymphatic endothelial cells: 28 nCPM
Immune cell
- naive CD4 T-cell: 2.3 nTPM
- T-reg: 2.1 nTPM
- memory CD4 T-cell: 1.7 nTPM
- gdT-cell: 1.1 nTPM
- memory CD8 T-cell: 0.9 nTPM
- naive CD8 T-cell: 0.9 nTPM
Brain region
- thalamus: 25 nTPM
- medulla oblongata: 20 nTPM
- pons: 20 nTPM
- amygdala: 19 nTPM
- midbrain: 18 nTPM
- spinal cord: 17 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about NOS3.
Disease | GeneticClinVar
2 pathogenic / likely-pathogenic of 294 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
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)
- 0.5
- gnomAD pLI
- 0
- gnomAD missense Z
- 2.04
- DepMap mean gene effect
- 0.02
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- angiogenesis
- aortic valve morphogenesis
- blood vessel diameter maintenance
- blood vessel remodeling
- calcium ion transport
- cell redox homeostasis
- endocardial cushion morphogenesis
- endothelial cell migration
- gene expression
- homeostasis of number of cells within a tissue
- in utero embryonic development
- L-arginine catabolic process
- lipopolysaccharide-mediated signaling pathway
- lung development
- mitochondrion organization
- negative regulation of biomineral tissue development
- negative regulation of blood pressure
- negative regulation of calcium ion transport
- negative regulation of cell population proliferation
- negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
- negative regulation of muscle hyperplasia
- negative regulation of platelet activation
- negative regulation of potassium ion transport
- negative regulation of smooth muscle cell proliferation
- nitric oxide biosynthetic process
- nitric oxide mediated signal transduction
- nitric oxide metabolic process
- ovulation from ovarian follicle
- positive regulation of angiogenesis
- positive regulation of blood vessel endothelial cell migration
- positive regulation of gene expression
- positive regulation of Notch signaling pathway
- potassium ion transport
- protein import into nucleus
- pulmonary valve morphogenesis
- regulation of blood pressure
- regulation of nervous system process
- regulation of sodium ion transport
- regulation of systemic arterial blood pressure by endothelin
- regulation of the force of heart contraction by chemical signal
- removal of superoxide radicals
- response to fluid shear stress
- response to heat
- response to hormone
- response to lipopolysaccharide
- smooth muscle hyperplasia
- tetrahydrobiopterin metabolic process
- vasodilation
- ventricular septum morphogenesis
Molecular functions
- actin monomer binding
- arginine binding
- cadmium ion binding
- calmodulin binding
- flavin adenine dinucleotide binding
- FMN binding
- heme binding
- NADP binding
- nitric-oxide synthase activity
- scaffold protein binding
- superoxide-generating NAD(P)H oxidase 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 NOS3 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 NOS3 as an antibody target. Whether an autoantibody or antibody against NOS3 could matter depends on whether native NOS3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
NOS3 is annotated at the cell surface, where native NOS3 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label NOS3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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