P70313 · NOS3_MOUSE
- ProteinNitric oxide synthase 3
- GeneNos3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1202 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. May play a significant role in normal and abnormal limb development.
Catalytic activity
- H+ + 2 L-arginine + 3 NADPH + 4 O2 = 4 H2O + 2 L-citrulline + 3 NADP+ + 2 nitric oxideThis reaction proceeds in the forward direction.
CHEBI:15378 + 2 CHEBI:32682 + 3 CHEBI:57783 + 4 CHEBI:15379 = 4 CHEBI:15377 + 2 CHEBI:57743 + 3 CHEBI:58349 + 2 CHEBI:16480
Cofactor
Protein has several cofactor binding sites:
Note: Binds 1 FAD.
Note: Binds 1 FMN.
Note: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.
Activity regulation
Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 93 | Zn2+ (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: C | ||||||
Binding site | 98 | Zn2+ (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: C | ||||||
Binding site | 101 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 183 | Fe (UniProtKB | ChEBI) of heme b (UniProtKB | ChEBI); axial binding residue | ||||
Sequence: C | ||||||
Binding site | 246 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 355 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 356 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 360 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 445 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 446 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 459 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: F | ||||||
Binding site | 474 | heme b (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 525 | FMN (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 526 | FMN (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 527 | FMN (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 529 | FMN (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 571 | FMN (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 572 | FMN (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 653 | FMN (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 660 | FMN (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 686 | FMN (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 690 | FMN (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 775 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 797 | FAD (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 937 | FAD (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 939 | FAD (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 940 | FAD (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 955 | FAD (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 957 | FAD (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 961 | FAD (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 974 | FAD (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 975 | FAD (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 976 | FAD (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 1015 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 1048 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 1077 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 1078 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 1084 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 1086 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 1088 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Q |
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNitric oxide synthase 3
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP70313
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Specifically associates with actin cytoskeleton in the G2 phase of the cell cycle, which is favored by interaction with NOSIP and results in a reduced enzymatic activity.
Keywords
- Cellular component
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 53 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for initiator methionine, lipidation, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Lipidation | 2 | N-myristoyl glycine | ||||
Sequence: G | ||||||
Chain | PRO_0000170944 | 2-1202 | Nitric oxide synthase 3 | |||
Sequence: GNLKSVGQEPGPPCGLGLGLGLGLCGKQGPASPAPEPSQAPAPPSPTRPAPDHSPPLTRPPDGPRFPRVKNWEVGSITYDTLSAQAQQDGPCTSRRCLGSLVFPRKLQSRPTQGPSPTEQLLGQARDFINQYYNSIKRSGSQAHEQRLQEVEAEVAATGTYQLRESELVFGAKQAWRNAPRCVGRIQWGKLQVFDARDCRTAQEMFTYICNHIKYATNRGNLRSAITVFPQRCPGRGDFRIWNSQLIRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDEPPELFTLPPEMVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMSSEIGMRDLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINVAVLHSYQLAKVTIVDHHAATASFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYFLSPAFRYQPDPWKGSAAKGAGITRKKTFKEVANAVKISASLMGTVMAKRVKATILYGSETGRAQSYAQQLGRLFRKAFDPRVLCMDEYDVVSLEHEALVLVVTSTFGNGDPPENGESFAAALMEMSGPYNSSPRPEQHKSYKIRFNSVSCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYPHFCAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAQAAFQAACETFCVGEDAKAAARDIFSPKRSWKRQRYRLSTQAESLQLLPGLTHVHRRKMFQATILSVENLQSSKSTRATILVRLDTGGQEGLQYQPGDHIGVCPPNRPGLVEALLSRVEDPPPSTEPVAVEQLEKGSPGGPPPGWVRDPRLPPCTLRQALTYFLDITSPPSPRLLRLLSTLAEESSEQQELEALSQDPRRYEEWKWFSCPTLLEVLEQFPSVALPAPLILTQLPLLQPRYYSVSSAPSAHPGEIHLTIAVLAYRTQDGLGPLHYGVCSTWMSQLKAGDPVPCFIRGAPSFRLPPDPNLPCILVGPGTGIAPFRGFWQDRLHDIEIKGLQPAPMTLVFGCRCSQLDHLYRDEVLDAQQRGVFGQVLTAFSRDPGSPKTYVQDLLRTELAAEVHRVLCLEQGHMFVCGDVTMATSVLQTVQRILATEGGMELDEAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERQLRGAVPWSFDPPGPEIPGS | ||||||
Lipidation | 15 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Lipidation | 26 | S-palmitoyl cysteine | ||||
Sequence: C | ||||||
Modified residue | 494 | Phosphothreonine; by AMPK | ||||
Sequence: T | ||||||
Modified residue | 614 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 632 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 637 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 835 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1174 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1176 | Phosphoserine; by AMPK | ||||
Sequence: S | ||||||
Modified residue | 1178 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylation by AMPK at Ser-1176 in the presence of Ca2+-calmodulin (CaM) activates activity. In absence of Ca2+-calmodulin, AMPK also phosphorylates Thr-494, resulting in inhibition of activity (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Homodimer. Interacts with NOSIP and NOSTRIN (By similarity).
Interacts with HSP90AB1 (By similarity).
Forms a complex with ASL, ASS1 and SLC7A1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway
Interacts with HSP90AB1 (By similarity).
Forms a complex with ASL, ASS1 and SLC7A1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-70 | Disordered | ||||
Sequence: MGNLKSVGQEPGPPCGLGLGLGLGLCGKQGPASPAPEPSQAPAPPSPTRPAPDHSPPLTRPPDGPRFPRV | ||||||
Compositional bias | 35-64 | Pro residues | ||||
Sequence: APEPSQAPAPPSPTRPAPDHSPPLTRPPDG | ||||||
Region | 97-485 | Interaction with NOSIP | ||||
Sequence: RCLGSLVFPRKLQSRPTQGPSPTEQLLGQARDFINQYYNSIKRSGSQAHEQRLQEVEAEVAATGTYQLRESELVFGAKQAWRNAPRCVGRIQWGKLQVFDARDCRTAQEMFTYICNHIKYATNRGNLRSAITVFPQRCPGRGDFRIWNSQLIRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDEPPELFTLPPEMVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMSSEIGMRDLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINVAVLHSYQLAKVTIVDHHAATASFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYFLSPAFRYQPDPWKGSAAK | ||||||
Region | 490-509 | Calmodulin-binding | ||||
Sequence: TRKKTFKEVANAVKISASLM | ||||||
Domain | 519-702 | Flavodoxin-like | ||||
Sequence: ATILYGSETGRAQSYAQQLGRLFRKAFDPRVLCMDEYDVVSLEHEALVLVVTSTFGNGDPPENGESFAAALMEMSGPYNSSPRPEQHKSYKIRFNSVSCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYPHFCAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAQAAF | ||||||
Domain | 755-1001 | FAD-binding FR-type | ||||
Sequence: RKMFQATILSVENLQSSKSTRATILVRLDTGGQEGLQYQPGDHIGVCPPNRPGLVEALLSRVEDPPPSTEPVAVEQLEKGSPGGPPPGWVRDPRLPPCTLRQALTYFLDITSPPSPRLLRLLSTLAEESSEQQELEALSQDPRRYEEWKWFSCPTLLEVLEQFPSVALPAPLILTQLPLLQPRYYSVSSAPSAHPGEIHLTIAVLAYRTQDGLGPLHYGVCSTWMSQLKAGDPVPCFIRGAPSFRLP | ||||||
Region | 817-843 | Disordered | ||||
Sequence: EDPPPSTEPVAVEQLEKGSPGGPPPGW |
Sequence similarities
Belongs to the NOS family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,202
- Mass (Da)132,916
- Last updated2011-07-27 v4
- ChecksumE1F65C43601F0937
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
E9Q9X4 | E9Q9X4_MOUSE | Nos3 | 1106 |
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 35-64 | Pro residues | ||||
Sequence: APEPSQAPAPPSPTRPAPDHSPPLTRPPDG | ||||||
Sequence conflict | 50 | in Ref. 1; AAC52766 | ||||
Sequence: P → A | ||||||
Sequence conflict | 298 | in Ref. 1; AAC52766 | ||||
Sequence: P → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U53142 EMBL· GenBank· DDBJ | AAC52766.1 EMBL· GenBank· DDBJ | mRNA | ||
BC052636 EMBL· GenBank· DDBJ | AAH52636.1 EMBL· GenBank· DDBJ | mRNA | ||
AF045940 EMBL· GenBank· DDBJ | AAC02553.1 EMBL· GenBank· DDBJ | Genomic DNA |