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Details on Person UniProt:P29474 NOS3

Class:Id	ReferenceGeneProduct:60353
_chainChangeLog	initiator methionine:1 added on Fri February 6 2015;chain:2-1203 added on Fri February 6 2015;initiator methionine:1 for 60353 removed on Fri Nov 03 2023;initiator methionine: for 60353 added on Fri Nov 03 2023;initiator methionine: for 60353 removed on Fri Aug 15 2025;initiator methionine:1 for 60353 added on Fri Aug 15 2025
_displayName	UniProt:P29474 NOS3
_timestamp	2025-08-15 21:24:49
chain	initiator methionine:1 chain:2-1203
checksum	B761A6D40B1A5649
comment	FUNCTION Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.FUNCTION Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.CATALYTIC ACTIVITY 2 L-arginine + 3 NADPH + 4 O2 + H(+) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H2OCOFACTOR Binds 1 FAD.COFACTOR Binds 1 FMN.COFACTOR Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.ACTIVITY REGULATION Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN.SUBUNIT Homodimer. Interacts with NOSIP and NOSTRIN (PubMed:11149895, PubMed:12446846). Interacts with HSP90AB1 (By similarity) (PubMed:11149895, PubMed:12446846, PubMed:23585225). 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).INTERACTION 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.ALTERNATIVE PRODUCTS Platelets, placenta, liver and kidney.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.DISEASE Variation Asp-298 in NOS3 may be associated with susceptibility to coronary spasm.MISCELLANEOUS Lacks eNOS activity.SIMILARITY Belongs to the NOS family.ONLINE INFORMATION Nitric oxide synthase entry
description	recommendedName: fullName evidence="41"Nitric oxide synthase 3 ecNumber evidence="16 27"1.14.13.39 alternativeName: Constitutive NOS shortName: cNOS alternativeName: EC-NOS alternativeName: NOS type III shortName: NOSIII alternativeName: fullName evidence="39"Nitric oxide synthase, endothelial shortName evidence="39"Endothelial NOS shortName evidence="39"eNOS
geneName	NOS3
identifier	P29474
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Calcium Calmodulin-binding Cell membrane Cytoplasm Cytoskeleton Direct protein sequencing FAD Flavoprotein FMN Golgi apparatus Heme Iron Lipoprotein Membrane Metal-binding Myristate NADP Oxidoreductase Palmitate Phosphoprotein Proteomics identification Reference proteome Zinc
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
name	NOS3
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8992000] ENSEMBL:ENSG00000164867 NOS3 [Homo sapiens]
secondaryIdentifier	NOS3_HUMAN A0S0A7 A0S0A8 A8KA63 B2RCQ1 E9PFR2 Q13662 Q14251 Q14434 Q548C1 Q6GSL5 Q9UDC6
sequenceLength	1203
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8972958] UniProt:P29474-1 NOS3 [Homo sapiens] [ReferenceIsoform:8972959] UniProt:P29474-2 NOS3 [Homo sapiens] [ReferenceIsoform:8972960] UniProt:P29474-3 NOS3 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:202114] NOS3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:202139] 2xPalmC-MyrG-p-S1177-NOS3 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:203687] MyrG-NOS3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:203769] 2xPalmC-MyrG-NOS3 [Golgi membrane] [Homo sapiens] [EntityWithAccessionedSequence:534993] 2xPalmC-MyrG-NOS3 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:534995] MyrG-NOS3 [Golgi membrane] [Homo sapiens] [EntityWithAccessionedSequence:534999] MyrG-NOS3 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:535007] 2xPalmC-MyrG-NOS3 [endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:9860783] 2xPalmC-MyrG-p-S1177,S1179-NOS3 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9861341] 2xPalmC-MyrG-p-S633-NOS3 [plasma membrane] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:202118] O-phospho-L-serine at 1177 [ModifiedResidue:203555] N-myristoylglycine at 2 [ModifiedResidue:203580] S-palmitoyl-L-cysteine at 15 [ModifiedResidue:203736] S-palmitoyl-L-cysteine at 26 [ModifiedResidue:9860751] O-phospho-L-serine at 1179 [ModifiedResidue:9861295] O-phospho-L-serine at 633
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No pathways have been reviewed or authored by UniProt:P29474 NOS3 (60353)