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UniProt functional annotation for P29474 | ||
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| UniProt code: P29474. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| 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. |
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| Function: | |
[Isoform eNOS13C]: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1. |
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| Catalytic activity: | |
Reaction=H(+) + 2 L-arginine + 3 NADPH + 4 O2 = 4 H2O + 2 L-citrulline + 3 NADP(+) + 2 nitric oxide; Xref=Rhea:RHEA:19897, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16480, ChEBI:CHEBI:32682, ChEBI:CHEBI:57743, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.39; |
| Cofactor: | |
Name=heme; Xref=ChEBI:CHEBI:30413; |
| Cofactor: | |
Name=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD.; |
| Cofactor: | |
Name=FMN; Xref=ChEBI:CHEBI:58210; Note=Binds 1 FMN.; |
| Cofactor: | |
Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin; Xref=ChEBI:CHEBI:59560; Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.; |
| Activity regulation: | |
Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN. {ECO:0000269|PubMed:11149895, ECO:0000269|PubMed:12446846}. |
| Subunit: | |
Homodimer. Interacts with NOSIP and NOSTRIN. Interacts with HSP90AB1 (PubMed:23585225). {ECO:0000269|PubMed:11149895, ECO:0000269|PubMed:12446846, ECO:0000269|PubMed:23585225}. |
| Subcellular location: | |
Cell membrane. Membrane, caveola. Cytoplasm, cytoskeleton. Golgi apparatus. 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. |
| Tissue specificity: | |
Platelets, placenta, liver and kidney. {ECO:0000269|PubMed:7515611}. |
| Ptm: | |
Phosphorylation by AMPK at Ser-1177 in the presence of Ca(2+)- calmodulin (CaM) activates activity. In absence of Ca(2+)-calmodulin, AMPK also phosphorylates Thr-495, resulting in inhibition of activity (By similarity). Phosphorylation of Ser-114 by CDK5 reduces activity. {ECO:0000250, ECO:0000269|PubMed:16126727, ECO:0000269|PubMed:20213743}. |
| Disease: | |
Note=Variation Asp-298 in NOS3 may be associated with susceptibility to coronary spasm. {ECO:0000269|PubMed:11740345, ECO:0000269|PubMed:9737779}. |
| Miscellaneous: | |
[Isoform eNOS13C]: Lacks eNOS activity. {ECO:0000305}. |
| Similarity: | |
Belongs to the NOS family. {ECO:0000305}. |
Annotations taken from UniProtKB at the EBI.