O62699 · NOS2_CANLF
- ProteinNitric oxide synthase, inducible
- GeneNOS2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1154 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2. As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM. Involved in inflammation, enhances the synthesis of pro-inflammatory mediators such as IL6 and IL8.
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
Regulated by calcium/calmodulin.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 107 | Zn2+ (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: C | ||||||
Binding site | 112 | Zn2+ (UniProtKB | ChEBI); ligand shared between homodimeric partners | ||||
Sequence: C | ||||||
Binding site | 197 | Fe (UniProtKB | ChEBI) of heme b (UniProtKB | ChEBI); axial binding residue | ||||
Sequence: C | ||||||
Binding site | 260 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 369 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 370 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 374 | L-arginine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 378 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 459 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 460 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 473 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI) | ||||
Sequence: F | ||||||
Binding site | 488 | heme b (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 542 | FMN (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 543 | FMN (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 544 | FMN (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 546 | FMN (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 547 | FMN (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 588 | FMN (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 589 | FMN (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 625 | FMN (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 632 | FMN (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 658 | FMN (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 747 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 769 | FAD (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 903 | FAD (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 905 | FAD (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 906 | FAD (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 921 | FAD (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 923 | FAD (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 927 | FAD (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 940 | FAD (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 941 | FAD (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 942 | FAD (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 981 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 1014 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 1043 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 1044 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 1050 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 1052 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 1054 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 1087 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNitric oxide synthase, inducible
- EC number
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Caniformia > Canidae > Canis
Accessions
- Primary accessionO62699
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes as discrete foci scattered throughout the cytosol and in the presence of SPSB1 and SPSB4, exhibits a more diffuse cytosolic localization.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000170927 | 1-1154 | Nitric oxide synthase, inducible | |||
Sequence: MACPWKFLFRAKFHQYGMKEEKDINNNVEKPPGATPSPSTQDDLKNHKHHNDSPQPLTETVQKLPESLDKLHATPLSRPQHVRIKNWGNGMTFQDTLHHKAKGDLACKSKSCLGAIMNPKSLTREPRDKPTPPDELLPQAIEFVNQYYSSFKEAKIEEHLARVEAVTKEIETTGTYQLTGDELIFATKQAWRNAPRCIGRIQWSNLQVFDARSCSTAKEMFEHICRHLRYASNNGNIRSAITVFPQRTDGKHDFRVWNAQLIRYAGYQMPDGTILGDPASVEFTQLCIDLGWKPKYGRFDVVPLVLQADGQDPEFFEIPPDLVLEVPMEHPKYEWFRELELKWYALPAVANMLLEVGGLEFPGCPFNGWYMGTEIGVRDFCDVQRYNILEEVGRRMGLETHKLASLWKDRAVIEINVAVLHSFQKQNVTIMDHHSAAESFMKYMQSEYRSRGGCPADWIWLVPPISGSITPVFHQEMLNYVLSPFYYYQVEAWKTHVWQDEKRRPQRRKIQLKVLVKAVLFASMLMRKTMASRVRVTILFATETGKSETLARDLGALFSCAFHPKVLCMDEYKLSHLEEEQLLLVVTSTFGNGDSPGNGEKLKKSLFMLKELTNKFRYAVFGLGSSMYPQFCAFAHDIDHKLSHLGASQLTPGGEGDELNGKEEAFRCWAVQTFKAACDTSDVRGKHCIQIPRLYTSNVTWDPHHYRLLQDSQPLDLNKALSKMHAKNVFTLRLKSQRNLQSPISNRTTLQVELSCEDSQELSYLPGEHLGVFPGNQLALVQGILERVVYSPAPLQPVHLETLSERGSYWVRNNRLPPCSLSQALTYFLDITTPPTHLLLRKLAQLAHQYAERHRLEILCHPSEYNKWKLTNSPTFLEVLEEFPSLRVSAGFLLSQLPILKPRYYSISSSRDCTPMEVHLTVAVLVYPTRDGQGPLHHGVCSTWLSNLKPQDPVPCFVRSAGNFKLPEDPSRPCILIGPGTGIAPFRSFWQQRLHDIKHKGLRGSRMTLVFGCRRPDEDHLYREEMLEMAQSGVLHEVHTAYSRLPGQPKVYVQDILRQQLASQVLRMLHEEQGHLYVCGDVRMARDVAHTLKHLVAAKLSLSEEQVEDYFFQLKSQKRYHEDIFGAVFPYEVKKDGAAKQPSDPRVPAAHGRS | ||||||
Modified residue | 572 | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to proteasomal degradation.
Keywords
- PTM
Proteomic databases
Interaction
Subunit
Homodimer. Interacts with NHERF1. Interacts with GAPDH; induced by oxidatively-modified low-densitity lipoprotein (LDL(ox)). Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9 transnitrosylase complex. Interacts with SPSB1, SPSB2 and SPSB4. Interacts with ELOC and CUL5 in the presence of SPSB1 or SPSB2 or SPSB4. 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.
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, motif, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 22-58 | Disordered | ||||
Sequence: KDINNNVEKPPGATPSPSTQDDLKNHKHHNDSPQPLT | ||||||
Motif | 23-27 | DINNN-motif; mediates interaction with SPSB1, SPSB2 and SPSB4 | ||||
Sequence: DINNN | ||||||
Region | 512-532 | Calmodulin-binding | ||||
Sequence: LKVLVKAVLFASMLMRKTMAS | ||||||
Domain | 536-674 | Flavodoxin-like | ||||
Sequence: VTILFATETGKSETLARDLGALFSCAFHPKVLCMDEYKLSHLEEEQLLLVVTSTFGNGDSPGNGEKLKKSLFMLKELTNKFRYAVFGLGSSMYPQFCAFAHDIDHKLSHLGASQLTPGGEGDELNGKEEAFRCWAVQTF | ||||||
Domain | 727-967 | FAD-binding FR-type | ||||
Sequence: KNVFTLRLKSQRNLQSPISNRTTLQVELSCEDSQELSYLPGEHLGVFPGNQLALVQGILERVVYSPAPLQPVHLETLSERGSYWVRNNRLPPCSLSQALTYFLDITTPPTHLLLRKLAQLAHQYAERHRLEILCHPSEYNKWKLTNSPTFLEVLEEFPSLRVSAGFLLSQLPILKPRYYSISSSRDCTPMEVHLTVAVLVYPTRDGQGPLHHGVCSTWLSNLKPQDPVPCFVRSAGNFKLP |
Sequence similarities
Belongs to the NOS family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,154
- Mass (Da)131,847
- Last updated2005-09-13 v2
- ChecksumD6AD3A88AE89E995
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 42-52 | in Ref. 2 | ||||
Sequence: DDLKNHKHHND → KCHSLSKHRDE | ||||||
Sequence conflict | 56 | in Ref. 2; AAC15587 | ||||
Sequence: P → S | ||||||
Sequence conflict | 59-64 | in Ref. 2; AAC15587 | ||||
Sequence: ETVQKL → GTVKTS | ||||||
Sequence conflict | 68-80 | in Ref. 2 | ||||
Sequence: LDKLHATPLSRPQ → TIKPAAPPLACPR | ||||||
Sequence conflict | 91-92 | in Ref. 1; AAC78630 | ||||
Sequence: MT → RS | ||||||
Sequence conflict | 102-104 | in Ref. 1; AAC78630 | ||||
Sequence: KGD → MGV | ||||||
Sequence conflict | 108 | in Ref. 1; AAC78630 | ||||
Sequence: K → T | ||||||
Sequence conflict | 111-115 | in Ref. 1; AAC78630 | ||||
Sequence: SCLGA → LCMGS | ||||||
Sequence conflict | 119 | in Ref. 1; AAC78630 | ||||
Sequence: P → T | ||||||
Sequence conflict | 125-127 | in Ref. 1; AAC78630 | ||||
Sequence: EPR → GPS | ||||||
Sequence conflict | 133-134 | in Ref. 1; AAC78630 | ||||
Sequence: PD → TE | ||||||
Sequence conflict | 149 | in Ref. 1; AAC78630 | ||||
Sequence: S → G | ||||||
Sequence conflict | 169 | in Ref. 1; AAC78630 | ||||
Sequence: E → D | ||||||
Sequence conflict | 394-395 | in Ref. 1; AAC78630 | ||||
Sequence: RR → SK | ||||||
Sequence conflict | 497-499 | in Ref. 1; AAC78630 | ||||
Sequence: VWQ → LWL | ||||||
Sequence conflict | 506-508 | in Ref. 1; AAC78630 | ||||
Sequence: QRR → HRK | ||||||
Sequence conflict | 615 | in Ref. 1; AAC78630 | ||||
Sequence: K → N | ||||||
Sequence conflict | 624-626 | in Ref. 1; AAC78630 | ||||
Sequence: GSS → RSN |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF077821 EMBL· GenBank· DDBJ | AAC78630.1 EMBL· GenBank· DDBJ | mRNA | ||
AF032909 EMBL· GenBank· DDBJ | AAC15587.1 EMBL· GenBank· DDBJ | mRNA |