Human Gene NOS2 (ENST00000313735.11_10) from GENCODE V47lift37
  Description: nitric oxide synthase 2 (from RefSeq NM_000625.4)
Gencode Transcript: ENST00000313735.11_10
Gencode Gene: ENSG00000007171.19_15
Transcript (Including UTRs)
   Position: hg19 chr17:26,083,792-26,127,555 Size: 43,764 Total Exon Count: 27 Strand: -
Coding Region
   Position: hg19 chr17:26,084,272-26,125,835 Size: 41,564 Coding Exon Count: 26 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:26,083,792-26,127,555)mRNA (may differ from genome)Protein (1153 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: NOS2_HUMAN
DESCRIPTION: RecName: Full=Nitric oxide synthase, inducible; EC=1.14.13.39; AltName: Full=Hepatocyte NOS; Short=HEP-NOS; AltName: Full=Inducible NO synthase; Short=Inducible NOS; Short=iNOS; AltName: Full=NOS type II; AltName: Full=Peptidyl-cysteine S-nitrosylase NOS2;
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 COX2.
CATALYTIC ACTIVITY: 2 L-arginine + 3 NADPH + 4 O(2) = 2 L- citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O.
COFACTOR: Heme group (By similarity).
COFACTOR: Binds 1 FAD (By similarity).
COFACTOR: Binds 1 FMN (By similarity).
COFACTOR: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme (By similarity).
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).
SUBUNIT: Homodimer. Binds SLC9A3R1.
TISSUE SPECIFICITY: Expressed in the liver, retina, bone cells and airway epithelial cells of the lung. Not expressed in the platelets.
INDUCTION: By endotoxins and cytokines. Induced by IFNG/IFN-gamma acting synergistically with bacterial lipopolysaccharides (LPS), TNF or IL1B/interleukin-1 beta.
POLYMORPHISM: Note=Genetic variations in NOS2 are involved in resistance to malaria [MIM:611162].
SIMILARITY: Belongs to the NOS family.
SIMILARITY: Contains 1 FAD-binding FR-type domain.
SIMILARITY: Contains 1 flavodoxin-like domain.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/nos2a/";
WEB RESOURCE: Name=Wikipedia; Note=Nitric oxide synthase entry; URL="http://en.wikipedia.org/wiki/Nitric_oxide_synthase";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: NOS2
Diseases sorted by gene-association score: malaria* (187), borderline leprosy (22), collagenous colitis (16), chlamydia (15), peyronie's disease (14), spinal cord injury (14), leishmaniasis (13), internal hemorrhoid (13), hemorrhoid (12), gastritis (12), hypertension, essential* (12), pityriasis lichenoides (10), chagas disease (9), hepatopulmonary syndrome (9), mycetoma (9), dystrophinopathies (9), myocarditis (8), cerebral artery occlusion (8), anoxia (8), nervous system disease (8), sleeping sickness (8), impotence (7), visceral leishmaniasis (7), tendinopathy (7), tympanosclerosis (7), retinal vasculitis (7), leukomalacia (7), central nervous system disease (7), crohn's colitis (7), salivary gland adenoid cystic carcinoma (6), pyosalpinx (6), diabetic cataract (6), ureteral obstruction (6), arthus reaction (6), idiopathic achalasia (6), eales disease (6), varicocele (6), enterobiasis (6), pulpitis (6), brain ischemia (6), periventricular leukomalacia (5), orthostatic intolerance (5), vertebral artery occlusion (5), ischemia (4), aortic disease (4), vascular disease (4), pulmonary hypertension (3), colitis (3), colorectal cancer (2), autoinflammation, lipodystrophy, and dermatosis syndrome (2), multiple sclerosis, disease progression, modifier of (1), diabetes mellitus, insulin-dependent (1), primary ciliary dyskinesia (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 2.66 RPKM in Brain - Cortex
Total median expression: 24.02 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -79.80264-0.302 Picture PostScript Text
3' UTR -139.20480-0.290 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003097 - FAD-binding_1
IPR017927 - Fd_Rdtase_FAD-bd
IPR001094 - Flavdoxin
IPR008254 - Flavodoxin/NO_synth
IPR001709 - Flavoprot_Pyr_Nucl_cyt_Rdtase
IPR023173 - NADPH_Cyt_P450_Rdtase_dom3
IPR004030 - NO_synthase_oxygenase_dom
IPR026009 - NOS
IPR012144 - NOS_met
IPR001433 - OxRdtase_FAD/NAD-bd
IPR017938 - Riboflavin_synthase-like_b-brl

Pfam Domains:
PF00175 - Oxidoreductase NAD-binding domain
PF00258 - Flavodoxin
PF00667 - FAD binding domain
PF02898 - Nitric oxide synthase, oxygenase domain

SCOP Domains:
63380 - Riboflavin synthase domain-like
52218 - Flavoproteins
52343 - Ferredoxin reductase-like, C-terminal NADP-linked domain
56512 - Nitric oxide (NO) synthase oxygenase domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1NSI - X-ray MuPIT 2LL6 - NMR MuPIT 2NSI - X-ray MuPIT 3E7G - X-ray MuPIT 3EJ8 - X-ray MuPIT 3HR4 - X-ray MuPIT 4NOS - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P35228
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003958 NADPH-hemoprotein reductase activity
GO:0004517 nitric-oxide synthase activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0005516 calmodulin binding
GO:0010181 FMN binding
GO:0016491 oxidoreductase activity
GO:0020037 heme binding
GO:0034617 tetrahydrobiopterin binding
GO:0034618 arginine binding
GO:0042803 protein homodimerization activity
GO:0046872 metal ion binding
GO:0050660 flavin adenine dinucleotide binding
GO:0050661 NADP binding

Biological Process:
GO:0001666 response to hypoxia
GO:0001912 positive regulation of leukocyte mediated cytotoxicity
GO:0002227 innate immune response in mucosa
GO:0006527 arginine catabolic process
GO:0006625 protein targeting to peroxisome
GO:0006801 superoxide metabolic process
GO:0006809 nitric oxide biosynthetic process
GO:0007263 nitric oxide mediated signal transduction
GO:0007623 circadian rhythm
GO:0009617 response to bacterium
GO:0010629 negative regulation of gene expression
GO:0018119 peptidyl-cysteine S-nitrosylation
GO:0019221 cytokine-mediated signaling pathway
GO:0031284 positive regulation of guanylate cyclase activity
GO:0032310 prostaglandin secretion
GO:0032496 response to lipopolysaccharide
GO:0035690 cellular response to drug
GO:0042127 regulation of cell proliferation
GO:0042177 negative regulation of protein catabolic process
GO:0042742 defense response to bacterium
GO:0043457 regulation of cellular respiration
GO:0045454 cell redox homeostasis
GO:0045776 negative regulation of blood pressure
GO:0050796 regulation of insulin secretion
GO:0050829 defense response to Gram-negative bacterium
GO:0051712 positive regulation of killing of cells of other organism
GO:0055114 oxidation-reduction process
GO:0071222 cellular response to lipopolysaccharide
GO:0071346 cellular response to interferon-gamma
GO:0072604 interleukin-6 secretion
GO:0072606 interleukin-8 secretion
GO:1900015 regulation of cytokine production involved in inflammatory response

Cellular Component:
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005777 peroxisome
GO:0005782 peroxisomal matrix
GO:0005829 cytosol
GO:0030863 cortical cytoskeleton
GO:0048471 perinuclear region of cytoplasm


-  Descriptions from all associated GenBank mRNAs
  AK310926 - Homo sapiens cDNA, FLJ17968.
U20141 - Human inducible nitric oxide synthase mRNA, complete cds.
D26525 - Homo sapiens mRNA for inducible type of nitric oxide synthase, complete cds.
U31511 - Human inducible nitric oxide synthase (NOS) mRNA, complete cds.
HV708936 - JP 2012506450-A/34: Methods for treating eye disorders.
L09210 - Homo sapiens inducible nitric oxide synthase mRNA, complete cds.
X73029 - H.sapiens mRNA for nitric oxide synthase.
AF068236 - Homo sapiens inducible nitric oxide synthase (NOS) mRNA, complete cds.
JD364715 - Sequence 345739 from Patent EP1572962.
JD451597 - Sequence 432621 from Patent EP1572962.
JD534464 - Sequence 515488 from Patent EP1572962.
JD364720 - Sequence 345744 from Patent EP1572962.
JD398127 - Sequence 379151 from Patent EP1572962.
BC130283 - Homo sapiens nitric oxide synthase 2, inducible, mRNA (cDNA clone MGC:163155 IMAGE:40146314), complete cds.
BC144126 - Homo sapiens nitric oxide synthase 2, inducible, mRNA (cDNA clone MGC:177663 IMAGE:9052646), complete cds.
U05810 - Human inducible nitric oxide synthase mRNA, complete cds.
JD362659 - Sequence 343683 from Patent EP1572962.
JD269110 - Sequence 250134 from Patent EP1572962.
JD435741 - Sequence 416765 from Patent EP1572962.
L24553 - Homo sapiens inducible nitric oxide synthase mRNA, complete cds.
JD105506 - Sequence 86530 from Patent EP1572962.
AB022318 - Homo sapiens mRNA for inducible nitric oxide synthase, complete cds.
HQ258688 - Synthetic construct Homo sapiens clone IMAGE:100072718 nitric oxide synthase 2, inducible (NOS2) gene, encodes complete protein.
JD221797 - Sequence 202821 from Patent EP1572962.
AK304252 - Homo sapiens cDNA FLJ60219 complete cds, highly similar to Nitric oxide synthase, inducible (EC 1.14.13.39).
JD314018 - Sequence 295042 from Patent EP1572962.
S75615 - iNOS=nitric oxide synthase [human, renal proximal tubular cells, mRNA Partial, 283 nt].
S76479 - calcium-calmodulin independent nitric oxide synthase iNOS [human, Epstein-Barr virus-transformed Burkitt's lymphoma cell line, Akata, mRNA, 180 nt].
JD390129 - Sequence 371153 from Patent EP1572962.
JD227443 - Sequence 208467 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCyc Knowledge Library
PWY-4983 - citrulline-nitric oxide cycle

Reactome (by CSHL, EBI, and GO)

Protein P35228 (Reactome details) participates in the following event(s):

R-HSA-9033233 PEX5S,L binds cargo proteins containing PTS1
R-HSA-418436 Nitric Oxide Synthase (NOS) produces Nitric Oxide (NO)
R-HSA-9033236 PEX5S,L:Cargo binds PEX13:PEX14 of PEX13:PEX14:PEX2:PEX10:PEX12 (Docking and Translocation Complex)
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-9033241 Peroxisomal protein import
R-HSA-392154 Nitric oxide stimulates guanylate cyclase
R-HSA-1222556 ROS, RNS production in phagocytes
R-HSA-449147 Signaling by Interleukins
R-HSA-392499 Metabolism of proteins
R-HSA-418346 Platelet homeostasis
R-HSA-168249 Innate Immune System
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-109582 Hemostasis
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A1L3U5, B7ZLY2, ENST00000313735.1, ENST00000313735.10, ENST00000313735.2, ENST00000313735.3, ENST00000313735.4, ENST00000313735.5, ENST00000313735.6, ENST00000313735.7, ENST00000313735.8, ENST00000313735.9, NM_000625, NOS2 , NOS2A, NOS2_HUMAN, O60757, O94994, P35228, Q16263, Q16692, Q4TTS5, Q9UD42, uc317pme.1, uc317pme.2
UCSC ID: ENST00000313735.11_10
RefSeq Accession: NM_000625.4
Protein: P35228 (aka NOS2_HUMAN)

-  Gene Model Information
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.