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Nitric oxide synthase, inducible

ID 7
Name Nitric oxide synthase, inducible
Synonyms
  • EC 1.14.13.39
  • NOS type II
  • Inducible NO synthase
  • Inducible NOS
  • iNOS
  • Hepatocyte NOS
  • HEP- NOS
Gene Name NOS2
Protein Sequence 
>Nitric oxide synthase, inducible
MACPWKFLFKTKFHQYAMNGEKDINNNVEKAPCATSSPVTQDDLQYHNLSKQQNESPQPL
VETGKKSPESLVKLDATPLSSPRHVRIKNWGSGMTFQDTLHHKAKGILTCRSKSCLGSIM
TPKSLTRGPRDKPTPPDELLPQAIEFVNQYYGSFKEAKIEEHLARVEAVTKEIETTGTYQ
LTGDELIFATKQAWRNAPRCIGRIQWSNLQVFDARSCSTAREMFEHICRHVRYSTNNGNI
RSAITVFPQRSDGKHDFRVWNAQLIRYAGYQMPDGSIRGDPANVEFTQLCIDLGWKPKYG
RFDVVPLVLQANGRDPELFEIPPDLVLEVAMEHPKYEWFRELELKWYALPAVANMLLEVG
GLEFPGCPFNGWYMGTEIGVRDFCDVQRYNILEEVGRRMGLETHKLASLWKDQAVVEINI
AVLHSFQKQNVTIMDHHSAAESFMKYMQNEYRSRGGCPADWIWLVPPMSGSITPVFHQEM
LNYVLSPFYYYQVEAWKTHVWQDEKRRPKRREIPLKVLVKAVLFACMLMRKTMASRVRVT
ILFATETGKSEALAWDLGALFSCAFNPKVVCMDKYRLSCLEEERLLLVVTSTFGNGDCPG
NGEKLKKSLFMLKELNNKFRYAVFGLGSSMYPRFCAFAHDIDQKLSHLGASQLTPMGEGD
ELSGQEDAFRSWAVQTFKAACETFDVRGKQHIQIPKLYTSNVTWDPHHYRLVQDSQPLDL
SKALSSMHAKNVFTMRLKSRQNLQSPTSSRATILVELSCEDGQGLNYLPGEHLGVCPGNQ
PALVQGILERVVDGPTPHQTVRLEALDESGSYWVSDKRLPPCSLSQALTYFLDITTPPTQ
LLLQKLAQVATEEPERQRLEALCQPSEYSKWKFTNSPTFLEVLEEFPSLRVSAGFLLSQL
PILKPRFYSISSSRDHTPTEIHLTVAVVTYHTRDGQGPLHHGVCSTWLNSLKPQDPVPCF
VRNASGFHLPEDPSHPCILIGPGTGIAPFRSFWQQRLHDSQHKGVRGGRMTLVFGCRRPD
EDHIYQEEMLEMAQKGVLHAVHTAYSRLPGKPKVYVQDILRQQLASEVLRVLHKEPGHLY
VCGDVRMARDVAHTLKQLVAAKLKLNEEQVEDYFFQLKSQKRYHEDIFGAVFPYEAKKDR
VAVQPSSLEMSAL
Number of Residues 1153
Molecular Weight 131119
Theoretical pI 8.01
GO Classification
Function
calmodulin binding
binding
monooxygenase activity
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD or NADH as one donor, and incorporation of one atom of oxygen
nucleotide binding
nitric-oxide synthase activity
FMN binding
cofactor binding
catalytic activity
coenzyme binding
oxidoreductase activity
NADP binding
ion binding
purine nucleotide binding
cation binding
adenyl nucleotide binding
transition metal ion binding
FAD binding
iron ion binding
tetrapyrrole binding
transporter activity
heme binding
electron transporter activity
protein binding
Process
metabolism
cellular metabolism
physiological process
generation of precursor metabolites and energy
electron transport
biosynthesis
nitric oxide biosynthesis
General Function Inorganic ion transport and metabolism
Specific Function Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions
Pathways Not Available
Reactions
  • L-arginine + n NADPH + n H+ + m O2 = citrulline + nitric oxide + n NADP+
Pfam Domain Function
Signals None
Transmembrane Regions None
Essentiality Non-Essential
GenBank Protein ID 292242 Link_out
UniProtKB ID P35228 Link_out
UniProtKB Entry Name NOS2_HUMAN Link_out
PDB ID 2NSI Link_out
PDB File show
3D Structure View 3D Structure
Cellular Location Not Available
Gene Sequence 
>3462 bp
ATGGCCTGTCCTTGGAAATTTCTGTTCAAGACCAAATTCCACCAGTATGCAATGAATGGG
GAAAAAGACATCAACAACAATGTGGAGAAAGCCCCCTGTGCCACCTCCAGTCCAGTGACA
CAGGATGACCTTCAGTATCACAACCTCAGCAAGCAGCAGAATGAGTCCCCGCAGCCCCTC
GTGGAGACGGGAAAGAAGTCTCCAGAATCTCTGGTCAAGCTGGATGCAACCCCATTGTCC
TCCCCACGGCATGTGAGGATCAAAAACTGGGGCAGCGGGATGACTTTCCAAGACACACTT
CACCATAAGGCCAAAGGGATTTTAACTTGCAGGTCCAAATCTTGCCTGGGGTCCATTATG
ACTCCCAAAAGTTTGACCAGAGGACCCAGGGACAAGCCTACCCCTCCAGATGAGCTTCTA
CCTCAAGCTATCGAATTTGTCAACCAATATTACGGCTCCTTCAAAGAGGCAAAAATAGAG
GAACATCTGGCCAGGGTGGAAGCGGTAACAAAGGAGATAGAAACAACAGGAACCTACCAA
CTGACGGGAGATGAGCTCATCTTCGCCACCAAGCAGGCCTGGCGCAATGCCCCACGCTGC
ATTGGGAGGATCCAGTGGTCCAACCTGCAGGTCTTCGATGCCCGCAGCTGTTCCACTGCC
CGGGAAATGTTTGAACACATCTGCAGACACGTGCGTTACTCCACCAACAATGGCAACATC
AGGTCGGCCATCACCGTGTTCCCCCAGCGGAGTGATGGCAAGCACGACTTCCGGGTGTGG
AATGCTCAGCTCATCCGCTATGCTGGCTACCAGATGCCAGATGGCAGCATCAGAGGGGAC
CCTGCCAACGTGGAATTCACTCAGCTGTGCATCGACCTGGGCTGGAAGCCCAAGTACGGC
CGCTTCGATGTGGTCCCCCTGGTCCTGCAGGCCAATGGCCGTGACCCTGAGCTCTTCGAA
ATCCCACCTGACCTTGTGCTTGAGGTGGCCATGGAACATCCCAAATACGAGTGGTTTCGG
GAACTGGAGCTAAAGTGGTACGCCCTGCCTGCAGTGGCCAACATGCTGCTTGAGGTGGGC
GGCCTGGAGTTCCCAGGGTGCCCCTTCAATGGCTGGTACATGGGCACAGAGATCGGAGTC
CGGGACTTCTGTGACGTCCAGCGCTACAACATCCTGGAGGAAGTGGGCAGGAGAATGGGC
CTGGAAACGCACAAGCTGGCCTCGCTCTGGAAAGACCAGGCTGTCGTTGAGATCAACATT
GCTGTGATCCATAGTTTTCAGAAGCAGAATGTGACCATCATGGACCACCACTCGGCTGCA
GAATCCTTCATGAAGTACATGCAGAATGAATACCGGTCCCGTGGGGGCTGCCCGGCAGAC
TGGATTTGGCTGGTCCCTCCCATGTCTGGGAGCATCACCCCCGTGTTTCACCAGGAGATG
CTGAACTACGTCCTGTCCCCTTTCTACTACTATCAGGTAGAGGCCTGGAAAACCCATGTC
TGGCAGGACGAGAAGCGGAGACCCAAGAGAAGAGAGATTCCATTGAAAGTCTTGGTCAAA
GCTGTGCTCTTTGCCTGTATGCTGATGCGCAAGACAATGGCGTCCCGAGTCAGAGTCACC
ATCCTCTTTGCGACAGAGACAGGAAAATCAGAGGCGCTGGCCTGGGACCTGGGGGCCTTA
TTCAGCTGTGCCTTCAACCCCAAGGTTGTCTGCATGGATAAGTACAGGCTGAGCTGCCTG
GAGGAGGAACGGCTGCTGTTGGTGGTGACCAGTACGTTTGGCAATGGAGACTGCCCTGGC
AATGGAGAGAAACTGAAGAAATCGCTCTTCATGCTGAAAGAGCTCAACAACAAATTCAGG
TACGCTGTGTTTGGCCTCGGCTCCAGCATGTACCCTCGGTTCTGCGCCTTTGCTCATGAC
ATTGATCAGAAGCTGTCCCACCTGGGGGCCTCTCAGCTCACCCCGATGGGAGAAGGGGAT
GAGCTCAGTGGGCAGGAGGACGCCTTCCGCAGCTGGGCCGTGCAAACCTTCAAGGCAGCC
TGTGAGACGTTTGATGTCCGAGGCAAACAGCACATTCAGATCCCCAAGCTCTACACCTCC
AATGTGACCTGGGACCCGCACCACTACAGGCTCGTGCAGGACTCACAGCCTTTGGACCTC
AGCAAAGCCCTCAGCAGCATGCATGCCAAGAACGTGTTCACCATGAGGCTCAAATCTCGG
CAGAATCTACAAAGTCCGACATCCAGCCGTGCCACCATCCTGGTGGAACTCTCCTGTGAG
GATGGCCAAGGCCTGAACTACCTGCCGGGGGAGCACCTTGGGGTTTGCCCAGGCAACCAG
CCGGCCCTGGTCCAAGGCATCCTGGAGCGAGTGGTGGATGGCCCCACACCCCACCAGACA
GTGCGCCTGGAGGACCTGGATGAGAGTGGCAGCTACTGGGTCAGTGACAAGAGGCTGCCC
CCCTGCTCACTCAGCCAGGCCCTCACCTACTCCCCGGACATCACCACACCCCCAACCCAG
CTGCTGCTCCAAAAGCTGGCCCAGGTGGCCACAGAAGAGCCTGAGAGACAGAGGCTGGAG
GCCCTGTGCCAGCCCTCAGAGTACAGCAAGTGGAAGTTCACCAACAGCCCCACATTCCTG
GAGGTGCTAGAGGAGTTCCCGTCCCTGCGGGTGTCTGCTGGCTTCCTGCTTTCCCAGCTC
CCCATTCTGAAGCCCAGGTTCTACTCCATCAGCTCCTCCCGGGATCACACGCCCACGGAG
ATCCACCTGACTGTGGCCGTGGTCACCTACCACACCGGAGATGGCCAGGGTCCCCTGCAC
CACGGTGTCTGCAGCACATGGCTCAACAGCCTGAAGCCCCAAGACCCAGTGCCCTGCTTT
GTGCGGAATGCCAGCGCCTTCCACCTCCCCGAGGATCCCTCCCATCCTTGCATCCTCATC
GGGCCTGGCACAGGCATCGTGCCCTTCCGCAGTTTCTGGCAGCAACGGCTCCATGACTCC
CAGCACAAGGGAGTGCGGGGAGGCCGCATGACCTTGGTGTTTGGGTGCCGCCGCCCAGAT
GAGGACCACATCTACCAGGAGGAGATGCTGGAGATGGCCCAGAAGGGGGTGCTGCATGCG
GTGCACACAGCCTATTCCCGCCTGCCTGGCAAGCCCAAGGTCTATGTTCAGGACATCCTG
CGGCAGCAGCTGGCCAGCGAGGTGCTCCGTGTGCTCCACAAGGAGCCAGGCCACCTCTAT
GTTTGCGGGGATGTGCGCATGGCCCGGGACGTGGCCCACACCCTGAAGCAGCTGGTGGCT
GCCAAGCTGAAATTGAATGAGGAGCAGGTCGAGGACTATTTCTTTCAGCTCAAGAGCCAG
AAGCGCTATCACGAAGATATCTTCGGTGCTGTATTTCCTTACGAGGCGAAGAAGGACAGG
GTGGCGGTGCAGCCCAGCAGCCTGGAGATGTCAGCGCTCTGA
GenBank Gene ID L09210 Link_out
GeneCard ID NOS2A Link_out
GenAtlas ID NOS2A Link_out
HGNC ID HGNC:7873 Link_out
HPRD ID 01225
IUPHAR ID Not Available
Guide to Pharmacology ID Not Available
Chromosome Location Not Available
Locus 17q11.2-q12
SNPs NOS2 Link_out
General References
  1. Geller DA, Lowenstein CJ, Shapiro RA, Nussler AK, Di Silvio M, Wang SC, Nakayama DK, Simmons RL, Snyder SH, Billiar TR: Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3491-5. Pubmed
  2. Sherman PA, Laubach VE, Reep BR, Wood ER: Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line. Biochemistry. 1993 Nov 2;32(43):11600-5. Pubmed
  3. Charles IG, Palmer RM, Hickery MS, Bayliss MT, Chubb AP, Hall VS, Moss DW, Moncada S: Cloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11419-23. Pubmed
  4. Maier R, Bilbe G, Rediske J, Lotz M: Inducible nitric oxide synthase from human articular chondrocytes: cDNA cloning and analysis of mRNA expression. Biochim Biophys Acta. 1994 Sep 21;1208(1):145-50. Pubmed
  5. Park CS, Pardhasaradhi K, Gianotti C, Villegas E, Krishna G: Human retina expresses both constitutive and inducible isoforms of nitric oxide synthase mRNA. Biochem Biophys Res Commun. 1994 Nov 30;205(1):85-91. Pubmed
  6. Hokari A, Zeniya M, Esumi H: Cloning and functional expression of human inducible nitric oxide synthase (NOS) cDNA from a glioblastoma cell line A-172. J Biochem (Tokyo). 1994 Sep;116(3):575-81. Pubmed
  7. Guo FH, De Raeve HR, Rice TW, Stuehr DJ, Thunnissen FB, Erzurum SC: Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7809-13. Pubmed
  8. Luss H, Li RK, Shapiro RA, Tzeng E, McGowan FX, Yoneyama T, Hatakeyama K, Geller DA, Mickle DA, Simmons RL, Billiar TR: Dedifferentiated human ventricular cardiac myocytes express inducible nitric oxide synthase mRNA but not protein in response to IL-1, TNF, IFNgamma, and LPS. J Mol Cell Cardiol. 1997 Apr;29(4):1153-65. Pubmed
  9. McLay JS, Chatterjee P, Nicolson AG, Jardine AG, McKay NG, Ralston SH, Grabowski P, Haites NE, MacLeod AM, Hawksworth GM: Nitric oxide production by human proximal tubular cells: a novel immunomodulatory mechanism? Kidney Int. 1994 Oct;46(4):1043-9. Pubmed
  10. Bloch KD, Wolfram JR, Brown DM, Roberts JD Jr, Zapol DG, Lepore JJ, Filippov G, Thomas JE, Jacob HJ, Bloch DB: Three members of the nitric oxide synthase II gene family (NOS2A, NOS2B, and NOS2C) colocalize to human chromosome 17. Genomics. 1995 Jun 10;27(3):526-30. Pubmed
  11. Taylor BS, Alarcon LH, Billiar TR: Inducible nitric oxide synthase in the liver: regulation and function. Biochemistry (Mosc). 1998 Jul;63(7):766-81. Pubmed
  12. Glynne PA, Darling KE, Picot J, Evans TJ: Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output. J Biol Chem. 2002 Sep 6;277(36):33132-8. Epub 2002 Jun 21. Pubmed
  13. Li H, Raman CS, Glaser CB, Blasko E, Young TA, Parkinson JF, Whitlow M, Poulos TL: Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase. J Biol Chem. 1999 Jul 23;274(30):21276-84. Pubmed
  14. Fischmann TO, Hruza A, Niu XD, Fossetta JD, Lunn CA, Dolphin E, Prongay AJ, Reichert P, Lundell DJ, Narula SK, Weber PC: Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation. Nat Struct Biol. 1999 Mar;6(3):233-42. Pubmed
Drugs
# DrugBank ID Drug Name Drug Type Drug Groups
1 DB07003 (2S)-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepin-5-amine small molecule experimental
2 DB07007 (3R)-3-[(1,2,3,4-tetrahydroisoquinolin-7-yloxy)methyl]-2,3-dihydrothieno[2,3-f][1,4]oxazepin-5-amine small molecule experimental
3 DB07011 (3S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-3-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PIPERIDINE small molecule experimental
4 DB02692 (6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin small molecule experimental
5 DB07405 1-(6-CYANO-3-PYRIDYLCARBONYL)-5',8'-DIFLUOROSPIRO[PIPERIDINE-4,2'(1'H)-QUINAZOLINE]-4'-AMINE small molecule experimental
6 DB08750 1-[4-(AMINOMETHYL)BENZOYL]-5'-FLUORO-1'H-SPIRO[PIPERIDINE-4,2'-QUINAZOLIN]-4'-AMINE small molecule experimental
7 DB01997 3-Bromo-7-Nitroindazole small molecule experimental
8 DB07002 4-({4-[(4-methoxypyridin-2-yl)amino]piperidin-1-yl}carbonyl)benzonitrile small molecule experimental
9 DB07029 4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMIDAZOL-1-YL)PHENOXY]-6-METHYLPYRIMIDINE small molecule experimental
10 DB07008 4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PYRIMIDINE small molecule experimental
11 DB08214 4-(1H-IMIDAZOL-1-YL)PHENOL small molecule experimental
12 DB01835 4r-Fluoro-N6-Ethanimidoyl-L-Lysine small molecule experimental
13 DB06879 5-(4'-AMINO-1'-ETHYL-5',8'-DIFLUORO-1'H-SPIRO[PIPERIDINE-4,2'-QUINAZOLINE]-1-YLCARBONYL)PICOLINONITRILE small molecule experimental
14 DB04534 5-Nitroindazole small molecule experimental
15 DB03100 6-Nitroindazole small molecule experimental
16 DB02207 7-Nitroindazole small molecule experimental
17 DB03271 7,8-Dihydro-L-Biopterin small molecule experimental
18 DB04400 7,8-Dihydrobiopterin small molecule experimental
19 DB02533 Aminoguanidine small molecule experimental
20 DB01234 Dexamethasone small molecule approved, investigational
21 DB07306 ETHYL 4-[(4-CHLOROPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE small molecule experimental
22 DB07388 ETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE small molecule experimental
23 DB02234 Ethylisothiourea small molecule experimental
24 DB03014 Heme small molecule experimental
25 DB00125 L-Arginine small molecule approved, nutraceutical
26 DB00155 L-Citrulline small molecule approved, nutraceutical
27 DB03953 L-Thiocitrulline small molecule experimental
28 DB01110 Miconazole small molecule approved, investigational
29 DB02044 N-(3-(Aminomethyl)Benzyl)Acetamidine small molecule experimental
30 DB03449 N-(4-(2-((3-Chlorophenylmethyl)Amino)Ethyl)Phenyl)-2-Thiophecarboxamidine small molecule experimental
31 DB06916 N-[2-(1,3-BENZODIOXOL-5-YL)ETHYL]-1-[2-(1H-IMIDAZOL-1-YL)-6-METHYLPYRIMIDIN-4-YL]-D-PROLINAMIDE small molecule experimental
32 DB07318 N-[2-(4-AMINO-5,8-DIFLUORO-1,2-DIHYDROQUINAZOLIN-2-YL)ETHYL]-3-FURAMIDE small molecule experimental
33 DB07389 N-[2-(6-AMINO-4-METHYLPYRIDIN-2-YL)ETHYL]-4-CYANOBENZAMIDE small molecule experimental
34 DB03144 N-Omega-Hydroxy-L-Arginine small molecule experimental
35 DB02644 N-Omega-Propyl-L-Arginine small molecule experimental
36 DB01686 N,N-dimethylarginine small molecule experimental
37 DB02539 S-Ethylisothiourea small molecule experimental
38 DB02462 Thiocoumarin small molecule experimental
39 DB08814 Triflusal small molecule approved