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Details on Person UniProt:P35228 NOS2
| Class:Id | ReferenceGeneProduct:60486 |
|---|---|
| _chainChangeLog | chain:1-1153 added on Fri February 6 2015 |
| _displayName | UniProt:P35228 NOS2 |
| _timestamp | 2025-02-21 19:09:57 |
| chain | chain:1-1153 |
| checksum | 47671E5385CB3A52 |
| comment | FUNCTION Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (By similarity). As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM (PubMed:25417112). Involved in inflammation, enhances the synthesis of pro-inflammatory mediators such as IL6 and IL8 (PubMed:19688109).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 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 (PubMed:10074942, PubMed:10409685). Interacts with NHERF1 (PubMed:12080081). Interacts with GAPDH; induced by oxidatively-modified low-densitity lipoprotein (LDL(ox)) (PubMed:25417112). Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9 transnitrosylase complex (PubMed:25417112). Interacts with SPSB1, SPSB2 and SPSB4 (PubMed:21199876). Interacts with ELOC and CUL5 in the presence of SPSB1 or SPSB2 or SPSB4 (PubMed:21199876). Forms a complex with ASL, ASS1 and HSP90AA1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway.INTERACTION Localizes as discrete foci scattered throughout the cytosol and in the presence of SPSB1 and SPSB4, exhibits a more diffuse cytosolic localization.ALTERNATIVE PRODUCTS Expressed in the liver, retina, bone cells and airway epithelial cells of the lung. Not expressed in the platelets. Expressed in chondrocytes (PubMed:7504305).INDUCTION By endotoxins and cytokines. Induced by IFNG/IFN-gamma acting synergistically with bacterial lipopolysaccharides (LPS), TNF or IL1B/interleukin-1 beta (PubMed:7504305, PubMed:7528267). Down-regulated by zinc due to inhibition of NF-kappa-B transactivation activity (PubMed:25180171). By oxidatively-modified low-densitity lipoprotein (LDL(ox)) (PubMed:25417112).PTM Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to proteasomal degradation.POLYMORPHISM Genetic variations in NOS2 are involved in resistance to malaria [MIM:611162].SIMILARITY Belongs to the NOS family.ONLINE INFORMATION Nitric oxide synthase entry |
| description | recommendedName: fullName evidence="29"Nitric oxide synthase, inducible ecNumber evidence="21 26"1.14.13.39 alternativeName: Hepatocyte NOS shortName: HEP-NOS alternativeName: Inducible NO synthase shortName: Inducible NOS shortName: iNOS alternativeName: NOS type II alternativeName: Peptidyl-cysteine S-nitrosylase NOS2 |
| geneName | NOS2 NOS2A |
| identifier | P35228 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Calcium Calmodulin-binding Cytoplasm FAD Flavoprotein FMN Heme Iron Metal-binding NADP Oxidoreductase Phosphoprotein Proteomics identification Reference proteome Ubl conjugation Zinc |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [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 |
| name | NOS2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8948476] ENSEMBL:ENSG00000007171 NOS2 [Homo sapiens] |
| secondaryIdentifier | NOS2_HUMAN A1L3U5 B7ZLY2 O60757 O94994 Q16263 Q16692 Q4TTS5 Q9UD42 |
| sequenceLength | 1153 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:151353] UniProt:P35228-2 NOS2 [Homo sapiens] [ReferenceIsoform:403800] UniProt:P35228-1 NOS2 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:202107] NOS2 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9033124] NOS2 [peroxisomal matrix] [Homo sapiens] [EntityWithAccessionedSequence:9636250] NOS2 [nucleoplasm] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P35228 NOS2 (60486)
