P79209 · NOS3_SHEEP
- ProteinNitric oxide synthase 3
- GeneNOS3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1205 (go to sequence)
- Protein existenceEvidence at transcript 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 (By similarity).
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 | 96 | Zn2+ (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: C | ||||||
Binding site | 101 | Zn2+ (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: C | ||||||
Binding site | 104 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 186 | Fe (UniProtKB | ChEBI) of heme b (UniProtKB | ChEBI); axial binding residue | ||||
Sequence: C | ||||||
Binding site | 250 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 359 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 360 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 364 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 368 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 369 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 449 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 450 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 463 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: F | ||||||
Binding site | 478 | heme b (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 529 | FMN (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 530 | FMN (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 531 | FMN (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 533 | FMN (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 575 | FMN (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 576 | FMN (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 657 | FMN (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 664 | FMN (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 690 | FMN (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 694 | FMN (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 781 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 803 | FAD (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 939 | FAD (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 941 | FAD (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 942 | FAD (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 957 | FAD (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 959 | FAD (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 1018 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 1051 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 1080 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 1081 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 1087 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 1089 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 1091 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Q |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | caveola | |
Cellular Component | cytoskeleton | |
Cellular Component | Golgi apparatus | |
Molecular Function | calmodulin binding | |
Molecular Function | flavin adenine dinucleotide binding | |
Molecular Function | FMN binding | |
Molecular Function | heme binding | |
Molecular Function | metal ion binding | |
Molecular Function | NADP binding | |
Molecular Function | nitric-oxide synthase activity | |
Biological Process | nitric oxide biosynthetic process |
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 > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Caprinae > Ovis
Accessions
- Primary accessionP79209
- Secondary accessions
Proteomes
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
PTM/Processing
Features
Showing features for initiator methionine, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Chain | PRO_0000170947 | 2-1205 | Nitric oxide synthase 3 | |||
Sequence: GNLKSVGQEPGPPCGLGLGLGFGLCGKQGPASPAPEPSWAPAPATPQAPDHSPAPSSPTLTRPPEGPKFPRVKNWELGSITYDTLCAQSQQDGPCTPRRCLGSLVLPRKLQTRPSQGPPPAEQLLSQARDFINQYYSSIKRSGSQAHEERLQEVEAEVASTGTYHLRESELVFGAKQAWRNAPRCVGRIQWGKLQVFDARDCSSAQEMFTYICNHIKYATNRGNLRLSAITVFPQRTPGRGDFRIWNTQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWSPGNGRFDVLPLLLQAPDEAPELFVLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMSTEIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSMWKDKAAVEINLAVLHSFQPPKVTIVDHHAATVSFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYVLSPAFRYQPDPWKGSAAKGAGITRKKTFKEVANAVKISASLMGTLMAKRVKATILYASETGRAQSYAQQLGRLFRKAFDPRVLCMDEYDVVSLEHEALVLVVTSTFGNGDPPENGESFAAALMEMSGPYNSSPRPEQHRSYKIRFNSVSCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYPHFCAFARAVDTRLEELGGERLGQLGQGGELRGQGEGFRGWGEGASRNAASCETFCVGEEAKAAAQDIFSPKRSWKRQRYRLSTQAEGLQLLPGLIHVHRRKMFQATVLSVENLQSSKSTRATILVRLDTAGQEGLQYQPGDHISPHPPPRSSHRPGQGGPRVAPFSERPLMPRTPPPGGPPPSWVRDPRLPPCTLRQALTFFLDITSPPSPRLLRLLSTLAEEPSEQQELETLSQDPRRYEEWKWFRCPTLLEVLEQFPSVALPAPLLLTQLPLLQPRYYSVSSAPSAHPGEVHLTVAVLALDTSRLCSPLHPAEVVKSGGVWGDKGGLTEGVLARAPSFRLPPDPYVPCILVGPGTGIAPFRGFWQERLHDIESKGLQRAAPTLVFGCRCSQLDHLYRDEVQDAQERGVFGRVLTAFSREPDSPKTYVQDILRTELAAEVHRVLCLERGHMFVCGDVTMATSVLQTVPRILATEGGMELDEAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERHLRGAVPWAFDPPGPDTPGP | ||||||
Modified residue | 116 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 498 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 618 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 636 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 641 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1177 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 1179 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1181 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic 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 (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 (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-20 | Disordered | ||||
Sequence: MGNLKSVGQEPGPPCGLGLG | ||||||
Region | 26-73 | Disordered | ||||
Sequence: CGKQGPASPAPEPSWAPAPATPQAPDHSPAPSSPTLTRPPEGPKFPRV | ||||||
Compositional bias | 35-66 | Pro residues | ||||
Sequence: APEPSWAPAPATPQAPDHSPAPSSPTLTRPPE | ||||||
Region | 100-489 | Interaction with NOSIP | ||||
Sequence: RCLGSLVLPRKLQTRPSQGPPPAEQLLSQARDFINQYYSSIKRSGSQAHEERLQEVEAEVASTGTYHLRESELVFGAKQAWRNAPRCVGRIQWGKLQVFDARDCSSAQEMFTYICNHIKYATNRGNLRLSAITVFPQRTPGRGDFRIWNTQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWSPGNGRFDVLPLLLQAPDEAPELFVLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMSTEIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSMWKDKAAVEINLAVLHSFQPPKVTIVDHHAATVSFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYVLSPAFRYQPDPWKGSAAK | ||||||
Region | 796-850 | Disordered | ||||
Sequence: LQYQPGDHISPHPPPRSSHRPGQGGPRVAPFSERPLMPRTPPPGGPPPSWVRDPR | ||||||
Compositional bias | 830-849 | Pro residues | ||||
Sequence: PLMPRTPPPGGPPPSWVRDP |
Sequence similarities
Belongs to the NOS family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,205
- Mass (Da)132,978
- Last updated2023-11-08 v2
- ChecksumCE5FDDE325A3A07F
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 35-66 | Pro residues | ||||
Sequence: APEPSWAPAPATPQAPDHSPAPSSPTLTRPPE | ||||||
Sequence conflict | 396 | in Ref. 2; AAB40705 | ||||
Sequence: M → L | ||||||
Sequence conflict | 415-416 | in Ref. 2; AAB40705 | ||||
Sequence: PP → LA | ||||||
Compositional bias | 830-849 | Pro residues | ||||
Sequence: PLMPRTPPPGGPPPSWVRDP |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AMGL01089902 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AMGL01089903 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AMGL01089904 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AMGL01089905 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
U76738 EMBL· GenBank· DDBJ | AAB40705.1 EMBL· GenBank· DDBJ | mRNA |