Reactome | UniProt:P35228 NOS2

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UniProt:P35228 NOS2 Show undefined attributes

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
crossReference	[DatabaseIdentifier:12816082] ZINC target:P35228 [DatabaseIdentifier:12456391] RefSeq:NP_000616.3 [DatabaseIdentifier:12285569] Pharos - Targets:P35228 [DatabaseIdentifier:12264819] PRO:P35228 [DatabaseIdentifier:12178527] PDB:3EJ8 [DatabaseIdentifier:12178526] PDB:4CX7 [DatabaseIdentifier:12173928] PDB:5TP6 [DatabaseIdentifier:12178525] PDB:4NOS [DatabaseIdentifier:12178528] PDB:3E7G [DatabaseIdentifier:12178523] PDB:1NSI [DatabaseIdentifier:12154026] PDB:6JWM [DatabaseIdentifier:12178524] PDB:2NSI [DatabaseIdentifier:12173982] PDB:2LL6 [DatabaseIdentifier:12173977] PDB:3HR4 [DatabaseIdentifier:12154025] PDB:6JWN [DatabaseIdentifier:12154024] PDB:5XN3 [DatabaseIdentifier:12154023] PDB:6KEY [DatabaseIdentifier:12125264] OpenTargets:ENSG00000007171 [DatabaseIdentifier:11850332] IntEnz:1.14.13.39 [DatabaseIdentifier:11840722] HPA:ENSG00000007171-NOS2 [DatabaseIdentifier:11832040] HMDB Protein:HMDBP00926 [DatabaseIdentifier:11803127] GlyGen:P35228 [DatabaseIdentifier:11787649] GeneCards:NOS2 [DatabaseIdentifier:11778738] Guide to Pharmacology - Targets:1250 [DatabaseIdentifier:11752638] ENSEMBL:ENST00000313735 [DatabaseIdentifier:11629939] ENSEMBL:ENSP00000327251 [DatabaseIdentifier:11513814] ENSEMBL:ENSG00000007171
databaseName	UniProt
dbId	60486
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
displayName	UniProt:P35228 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:9939033] Weiser, Joel, 2025-02-21
moleculeType	Protein
name	NOS2
otherIdentifier	11724403_at 11752035_a_at 11752213_a_at 1418_at 1419_g_at 16842517 1948_f_at 210037_PM_s_at 210037_s_at 2576342 3714422 3714424 3748390 3748392 3750338 3750346 3750375 3750376 3750377 3750378 3750379 3750380 3750381 3750382 3750383 3750384 3750385 3750386 3750388 3750391 3750393 3750396 3750397 3750398 3750399 3750401 3750403 3750404 3750405 3750406 3750407 3750409 3750410 3750411 3750412 3750413 3750415 3750416 3750417 3750418 3750419 3750421 3750422 3750423 4843 8013536 A_21_P0011583 A_23_P502464 D29675_at D29675_s_at GE61880 GO:0001666 GO:0001912 GO:0002227 GO:0002376 GO:0004517 GO:0005515 GO:0005516 GO:0005634 GO:0005654 GO:0005737 GO:0005777 GO:0005782 GO:0005829 GO:0005856 GO:0005886 GO:0006520 GO:0006527 GO:0006801 GO:0006809 GO:0006954 GO:0007263 GO:0007623 GO:0009617 GO:0009725 GO:0010181 GO:0010629 GO:0016491 GO:0018119 GO:0020037 GO:0030863 GO:0032310 GO:0032496 GO:0032755 GO:0032757 GO:0034617 GO:0034618 GO:0038096 GO:0042127 GO:0042177 GO:0042742 GO:0042803 GO:0043457 GO:0045454 GO:0045776 GO:0046872 GO:0048471 GO:0050660 GO:0050661 GO:0050796 GO:0050829 GO:0071222 GO:0071346 GO:0071466 GO:0098542 GO:1900015 HMNXSV003004158 HMNXSV003026794 HMNXSV003051116 ILMN_1747882 ILMN_1748765 ILMN_2322831 PH_hs_0027962 TC17002562.hg TC17002894.hg X85781_s_at g404048_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-9033124] NOS2 [peroxisomal matrix] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9636250] NOS2 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-202107] NOS2 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:12764317] UCSC:P35228 NOS2 [ReferenceDNASequence:12110595] OMIM:163730 NOS2 [ReferenceDNASequence:12092189] NCBI Gene:4843 NOS2 [ReferenceDNASequence:12008096] Monarch:4843 NOS2 [ReferenceDNASequence:11915590] KEGG:hsa:4843 NOS2 [ReferenceDNASequence:11819294] HGNC:7873 NOS2 [ReferenceDNASequence:11440985] dbSNP Gene:4843 NOS2 [ReferenceDNASequence:11413520] CTD Gene:4843 NOS2 [ReferenceDNASequence:11403377] COSMIC - genes:NOS2 NOS2 [ReferenceDNASequence:11378307] BioGPS Gene:4843 NOS2 [ReferenceDNASequence:ensembl:ENSG00000007171] ENSEMBL:ENSG00000007171 NOS2
referenceTranscript	[ReferenceRNASequence:12637856] RefSeq:NM_000625.4 NOS2
schemaClass	ReferenceGeneProduct
secondaryIdentifier	NOS2_HUMAN A1L3U5 B7ZLY2 O60757 O94994 Q16263 Q16692 Q4TTS5 Q9UD42
sequenceLength	1153
species	[Species:48887] Homo sapiens
stId	uniprot:P35228
url	http://purl.uniprot.org/uniprot/P35228

Referrals

(interactor)	[UndirectedInteraction:11277035] UniProt:P35228 <-> UniProt:P05109 (IntAct) [UndirectedInteraction:11277033] UniProt:P35228 <-> UniProt:P06702 (IntAct) [UndirectedInteraction:11277031] UniProt:P35228 <-> UniProt:P04406 (IntAct)
(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-9033124] NOS2 [peroxisomal matrix] [EntityWithAccessionedSequence:R-HSA-9636250] NOS2 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-202107] NOS2 [cytosol]

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