P35228 (NOS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nitric oxide synthase, inducible
EC=1.14.13.39

Alternative name(s):
Hepatocyte NOS
Short name=HEP-NOS
Inducible NO synthase
Short name=Inducible NOS
Short name=iNOS
NOS type II
Peptidyl-cysteine S-nitrosylase NOS2

Gene names

Name:	NOS2
Synonyms:	NOS2A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1153 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 COX2.
Catalytic activity	2 L-arginine + 3 NADPH + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O.
Cofactor	Heme group By similarity. Binds 1 FAD By similarity. Binds 1 FMN By similarity. Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme By similarity.
Enzyme 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 structure	Homodimer. Binds SLC9A3R1.
Tissue specificity	Expressed in the liver, retina, bone cells and airway epithelial cells of the lung. Not expressed in the platelets.
Induction	By endotoxins and cytokines. Induced by IFNG/IFN-gamma acting synergistically with bacterial lipopolysaccharides (LPS), TNF or IL1B/interleukin-1 beta. Ref.14
Polymorphism	Note=Genetic variations in NOS2 are involved in resistance to malaria [MIM:611162].
Sequence similarities	Belongs to the NOS family. Contains 1 FAD-binding FR-type domain. Contains 1 flavodoxin-like domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Calcium Calmodulin-binding FAD FMN Heme Iron Metal-binding NADP Zinc
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	arginine catabolic process Inferred from direct assay Ref.3. Source: BHF-UCL blood coagulation Traceable author statement. Source: Reactome cellular response to interferon-gamma Inferred from electronic annotation. Source: Compara cellular response to lipopolysaccharide Inferred from electronic annotation. Source: Compara defense response to Gram-negative bacterium Non-traceable author statement PubMed 18390757. Source: BHF-UCL inflammatory response Inferred from Biological aspect of Ancestor. Source: RefGenome innate immune response in mucosa Non-traceable author statement PubMed 18390757. Source: BHF-UCL interaction with host Traceable author statement. Source: Reactome negative regulation of blood pressure Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of gene expression Inferred from genetic interaction PubMed 12085352. Source: UniProtKB negative regulation of protein catabolic process Inferred from electronic annotation. Source: Compara nitric oxide biosynthetic process Inferred from direct assay Ref.2. Source: UniProtKB nitric oxide mediated signal transduction Inferred from Biological aspect of Ancestor. Source: RefGenome peptidyl-cysteine S-nitrosylation Inferred from sequence or structural similarity. Source: UniProtKB phagosome maturation Traceable author statement. Source: Reactome positive regulation of guanylate cyclase activity Inferred from Biological aspect of Ancestor. Source: RefGenome positive regulation of killing of cells of other organism Inferred from mutant phenotype PubMed 7544003. Source: BHF-UCL positive regulation of leukocyte mediated cytotoxicity Traceable author statement PubMed 10450191. Source: BHF-UCL positive regulation of vasodilation Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of cell proliferation Inferred from electronic annotation. Source: Compara regulation of cellular respiration Traceable author statement PubMed 10450191. Source: BHF-UCL regulation of insulin secretion Inferred from mutant phenotype PubMed 8383325. Source: BHF-UCL response to hypoxia Inferred from electronic annotation. Source: Compara superoxide metabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cortical cytoskeleton Inferred from electronic annotation. Source: Compara cytosol Inferred from mutant phenotype Ref.3. Source: BHF-UCL nucleus Inferred from sequence or structural similarity. Source: BHF-UCL perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara peroxisome Inferred from direct assay PubMed 12085352. Source: UniProtKB
Molecular_function	FMN binding Inferred from sequence or structural similarity. Source: BHF-UCL NADP binding Traceable author statement Ref.3. Source: BHF-UCL NADPH-hemoprotein reductase activity Inferred from Biological aspect of Ancestor. Source: RefGenome arginine binding Inferred from sequence or structural similarity. Source: BHF-UCL flavin adenine dinucleotide binding Inferred from sequence or structural similarity. Source: BHF-UCL heme binding Inferred from sequence or structural similarity. Source: BHF-UCL iron ion binding Inferred from electronic annotation. Source: InterPro nitric-oxide synthase activity Inferred from direct assay Ref.2. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: BHF-UCL tetrahydrobiopterin binding Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P35228-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P35228-2)

The sequence of this isoform differs from the canonical sequence as follows:
     264-288: Missing.
     298-311: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1153

1153

Nitric oxide synthase, inducible

PRO_0000170930

Regions

Domain

539 – 677

139

Flavodoxin-like

Domain

730 – 970

241

FAD-binding FR-type

Nucleotide binding

623 – 654

32

FMN By similarity

Nucleotide binding

767 – 778

12

FAD By similarity

Nucleotide binding

903 – 913

11

FAD By similarity

Nucleotide binding

978 – 996

19

NADP By similarity

Nucleotide binding

1076 – 1091

16

NADP By similarity

Region

509 – 529

21

Calmodulin-binding Potential

Sites

Metal binding

110

1

Zinc

Metal binding

115

1

Zinc

Metal binding

200

1

Iron (heme axial ligand)

Amino acid modifications

Modified residue

234

1

Phosphoserine; by PKA Potential

Modified residue

578

1

Phosphoserine; by PKA Potential

Modified residue

892

1

Phosphoserine; by PKA Potential

Natural variations

Alternative sequence

264 – 288

25

Missing in isoform 2.

VSP_003582

Alternative sequence

298 – 311

14

Missing in isoform 2.

VSP_003583

Natural variant

221

1

R → W. Ref.10
Corresponds to variant rs3730017 [ dbSNP | Ensembl ].

VAR_024548

Natural variant

608

1

S → L. Ref.5 Ref.6 Ref.10
Corresponds to variant rs2297518 [ dbSNP | Ensembl ].

VAR_022127

Natural variant

679

1

A → S in a breast cancer sample; somatic mutation. Ref.21

VAR_036302

Natural variant

747

1

T → A. Ref.10
Corresponds to variant rs28944173 [ dbSNP | Ensembl ].

VAR_025020

Natural variant

1009

1

R → C. Ref.10
Corresponds to variant rs28944201 [ dbSNP | Ensembl ].

VAR_025021

Experimental info

Sequence conflict

23

1

D → G in AAA56666. Ref.4

Sequence conflict

154

1

F → L in AAA56666. Ref.4

Sequence conflict

177

1

G → V in AAA56666. Ref.4

Sequence conflict

266

1

R → H in AAC19133. Ref.8

Sequence conflict

423

1

L → I in AAA59171. Ref.2

Sequence conflict

439

1

A → T in AAC19133. Ref.8

Sequence conflict

552

1

A → G in AAI44127. Ref.12

Sequence conflict

676

1

T → I in AAB60366. Ref.7

Sequence conflict

800

1

T → A in AAA56666. Ref.4

Sequence conflict

805

1

A → D in AAA59171. Ref.2

Sequence conflict

831 – 832

2

FL → SP in AAA59171. Ref.2

Sequence conflict

913

1

S → P in AAA56666. Ref.4

Sequence conflict

933

1

R → G in AAA59171. Ref.2

Sequence conflict

933

1

R → G in AAB60366. Ref.7

Sequence conflict

966

1

G → A in AAA59171. Ref.2

Sequence conflict

966

1

G → A in AAB60366. Ref.7

Sequence conflict

987

1

A → V in AAA59171. Ref.2

Secondary structure

1

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1153

Helix Strand Turn

Details...

Beta strand

85 – 89

5

Turn

90 – 92

3

Beta strand

95 – 98

4

Helix

100 – 103

4

Beta strand

104 – 106

3

Helix

123 – 125

3

Helix

136 – 152

17

Beta strand

154 – 156

3

Helix

159 – 175

17

Helix

183 – 195

13

Helix

203 – 205

3

Beta strand

210 – 213

4

Helix

220 – 235

16

Helix

236 – 238

3

Beta strand

243 – 246

4

Beta strand

251 – 255

5

Beta strand

261 – 265

5

Beta strand

269 – 271

3

Beta strand

277 – 279

3

Helix

281 – 283

3

Helix

284 – 292

9

Beta strand

307 – 310

4

Beta strand

317 – 319

3

Helix

323 – 325

3

Beta strand

328 – 330

3

Helix

337 – 342

6

Beta strand

345 – 348

4

Beta strand

356 – 359

4

Beta strand

362 – 365

4

Helix

375 – 379

5

Helix

381 – 384

4

Turn

386 – 389

4

Helix

392 – 399

8

Helix

406 – 408

3

Helix

410 – 428

19

Helix

436 – 454

19

Helix

461 – 464

4

Beta strand

467 – 469

3

Helix

470 – 472

3

Helix

474 – 477

4

Beta strand

486 – 491

6

Helix

495 – 498

4

Helix

515 – 534

20

Beta strand

538 – 544

7

Beta strand

546 – 548

3

Helix

549 – 561

13

Turn

562 – 564

3

Beta strand

565 – 571

7

Helix

572 – 574

3

Helix

577 – 581

5

Beta strand

584 – 591

8

Turn

594 – 596

3

Helix

600 – 602

3

Helix

603 – 611

9

Beta strand

620 – 627

8

Beta strand

631 – 633

3

Helix

636 – 648

13

Beta strand

651 – 654

4

Beta strand

657 – 660

4

Helix

665 – 683

19

Helix

689 – 691

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: 47671E5385CB3A52	FASTA	1,153	131,117
	10 20 30 40 50 60 MACPWKFLFK TKFHQYAMNG EKDINNNVEK APCATSSPVT QDDLQYHNLS KQQNESPQPL 70 80 90 100 110 120 VETGKKSPES LVKLDATPLS SPRHVRIKNW GSGMTFQDTL HHKAKGILTC RSKSCLGSIM 130 140 150 160 170 180 TPKSLTRGPR DKPTPPDELL PQAIEFVNQY YGSFKEAKIE EHLARVEAVT KEIETTGTYQ 190 200 210 220 230 240 LTGDELIFAT KQAWRNAPRC IGRIQWSNLQ VFDARSCSTA REMFEHICRH VRYSTNNGNI 250 260 270 280 290 300 RSAITVFPQR SDGKHDFRVW NAQLIRYAGY QMPDGSIRGD PANVEFTQLC IDLGWKPKYG 310 320 330 340 350 360 RFDVVPLVLQ ANGRDPELFE IPPDLVLEVA MEHPKYEWFR ELELKWYALP AVANMLLEVG 370 380 390 400 410 420 GLEFPGCPFN GWYMGTEIGV RDFCDVQRYN ILEEVGRRMG LETHKLASLW KDQAVVEINI 430 440 450 460 470 480 AVLHSFQKQN VTIMDHHSAA ESFMKYMQNE YRSRGGCPAD WIWLVPPMSG SITPVFHQEM 490 500 510 520 530 540 LNYVLSPFYY YQVEAWKTHV WQDEKRRPKR REIPLKVLVK AVLFACMLMR KTMASRVRVT 550 560 570 580 590 600 ILFATETGKS EALAWDLGAL FSCAFNPKVV CMDKYRLSCL EEERLLLVVT STFGNGDCPG 610 620 630 640 650 660 NGEKLKKSLF MLKELNNKFR YAVFGLGSSM YPRFCAFAHD IDQKLSHLGA SQLTPMGEGD 670 680 690 700 710 720 ELSGQEDAFR SWAVQTFKAA CETFDVRGKQ HIQIPKLYTS NVTWDPHHYR LVQDSQPLDL 730 740 750 760 770 780 SKALSSMHAK NVFTMRLKSR QNLQSPTSSR ATILVELSCE DGQGLNYLPG EHLGVCPGNQ 790 800 810 820 830 840 PALVQGILER VVDGPTPHQT VRLEALDESG SYWVSDKRLP PCSLSQALTY FLDITTPPTQ 850 860 870 880 890 900 LLLQKLAQVA TEEPERQRLE ALCQPSEYSK WKFTNSPTFL EVLEEFPSLR VSAGFLLSQL 910 920 930 940 950 960 PILKPRFYSI SSSRDHTPTE IHLTVAVVTY HTRDGQGPLH HGVCSTWLNS LKPQDPVPCF 970 980 990 1000 1010 1020 VRNASGFHLP EDPSHPCILI GPGTGIAPFR SFWQQRLHDS QHKGVRGGRM TLVFGCRRPD 1030 1040 1050 1060 1070 1080 EDHIYQEEML EMAQKGVLHA VHTAYSRLPG KPKVYVQDIL RQQLASEVLR VLHKEPGHLY 1090 1100 1110 1120 1130 1140 VCGDVRMARD VAHTLKQLVA AKLKLNEEQV EDYFFQLKSQ KRYHEDIFGA VFPYEAKKDR 1150 VAVQPSSLEM SAL
	Isoform 2 [UniParc]. Checksum: C1F9624774435571	FASTA	1,114	126,749
	10 20 30 40 50 60 MACPWKFLFK TKFHQYAMNG EKDINNNVEK APCATSSPVT QDDLQYHNLS KQQNESPQPL 70 80 90 100 110 120 VETGKKSPES LVKLDATPLS SPRHVRIKNW GSGMTFQDTL HHKAKGILTC RSKSCLGSIM 130 140 150 160 170 180 TPKSLTRGPR DKPTPPDELL PQAIEFVNQY YGSFKEAKIE EHLARVEAVT KEIETTGTYQ 190 200 210 220 230 240 LTGDELIFAT KQAWRNAPRC IGRIQWSNLQ VFDARSCSTA REMFEHICRH VRYSTNNGNI 250 260 270 280 290 300 RSAITVFPQR SDGKHDFRVW NAQLCIDLGW KPNGRDPELF EIPPDLVLEV AMEHPKYEWF 310 320 330 340 350 360 RELELKWYAL PAVANMLLEV GGLEFPGCPF NGWYMGTEIG VRDFCDVQRY NILEEVGRRM 370 380 390 400 410 420 GLETHKLASL WKDQAVVEIN IAVLHSFQKQ NVTIMDHHSA AESFMKYMQN EYRSRGGCPA 430 440 450 460 470 480 DWIWLVPPMS GSITPVFHQE MLNYVLSPFY YYQVEAWKTH VWQDEKRRPK RREIPLKVLV 490 500 510 520 530 540 KAVLFACMLM RKTMASRVRV TILFATETGK SEALAWDLGA LFSCAFNPKV VCMDKYRLSC 550 560 570 580 590 600 LEEERLLLVV TSTFGNGDCP GNGEKLKKSL FMLKELNNKF RYAVFGLGSS MYPRFCAFAH 610 620 630 640 650 660 DIDQKLSHLG ASQLTPMGEG DELSGQEDAF RSWAVQTFKA ACETFDVRGK QHIQIPKLYT 670 680 690 700 710 720 SNVTWDPHHY RLVQDSQPLD LSKALSSMHA KNVFTMRLKS RQNLQSPTSS RATILVELSC 730 740 750 760 770 780 EDGQGLNYLP GEHLGVCPGN QPALVQGILE RVVDGPTPHQ TVRLEALDES GSYWVSDKRL 790 800 810 820 830 840 PPCSLSQALT YFLDITTPPT QLLLQKLAQV ATEEPERQRL EALCQPSEYS KWKFTNSPTF 850 860 870 880 890 900 LEVLEEFPSL RVSAGFLLSQ LPILKPRFYS ISSSRDHTPT EIHLTVAVVT YHTRDGQGPL 910 920 930 940 950 960 HHGVCSTWLN SLKPQDPVPC FVRNASGFHL PEDPSHPCIL IGPGTGIAPF RSFWQQRLHD 970 980 990 1000 1010 1020 SQHKGVRGGR MTLVFGCRRP DEDHIYQEEM LEMAQKGVLH AVHTAYSRLP GKPKVYVQDI 1030 1040 1050 1060 1070 1080 LRQQLASEVL RVLHKEPGHL YVCGDVRMAR DVAHTLKQLV AAKLKLNEEQ VEDYFFQLKS 1090 1100 1110 QKRYHEDIFG AVFPYEAKKD RVAVQPSSLE MSAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line." Sherman P.A., Laubach V.E., Reep B.R., Wood E.R. Biochemistry 32:11600-11605(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Colon adenocarcinoma.
[2]	"Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes." Geller D.A., Lowenstein C.J., Shapiro R.A., Nussler A.K., di Silvio M., Wang S.C., Nakayama D.K., Simmons R.L., Snyder S.H., Billiar T.R. Proc. Natl. Acad. Sci. U.S.A. 90:3491-3495(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[3]	"Cloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte." Charles I.G., Palmer R.M.J., Hickery M.S., Bayliss M.T., Chubb A.P., Hall V.S., Moss D.W., Moncada S. Proc. Natl. Acad. Sci. U.S.A. 90:11419-11423(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Chondrocyte.
[4]	"Inducible nitric oxide synthase from human articular chondrocytes: cDNA cloning and analysis of mRNA expression." Maier R., Bilbe G., Rediske J., Lotz M. Biochim. Biophys. Acta 1208:145-150(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Articular chondrocyte.
[5]	"Human retina expresses both constitutive and inducible isoforms of nitric oxide synthase mRNA." Park C.S., Pardhasaradhi K., Gianotti C., Villegas E., Krishna G. Biochem. Biophys. Res. Commun. 205:85-91(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-608. Tissue: Retina.
[6]	"Cloning and functional expression of human inducible nitric oxide synthase (NOS) cDNA from a glioblastoma cell line A-172." Hokari A., Zeniya M., Esumi H. J. Biochem. 116:575-581(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-608. Tissue: Glioblastoma.
[7]	"Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo." Guo F.H., de Raeve R.H., Rice T.W., Stuehr D.J., Thunnissen F.B.J.M., Erzurum S.C. Proc. Natl. Acad. Sci. U.S.A. 92:7809-7813(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Airway epithelium.
[8]	"Dedifferentiated human ventricular cardiac myocytes express inducible nitric oxide synthase mRNA but not protein in response to IL-1, TNF, IFNgamma, and LPS." Luss H., Li R.-K., Shapiro R.A., Tzeng E., McGowan F.X., Yoneyama T., Hatakayama K., Geller D.A., Mickle D.A.G., Simmons R.L., Billiar T.R. J. Mol. Cell. Cardiol. 29:1153-1165(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Cardiac myocyte.
[9]	"Cloning and characterization of a novel splice valiant of human inducible nitric oxide synthase." Ogawa Y., Nishijima S., Goto M., Ida M. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[10]	NIEHS SNPs program Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TRP-221; LEU-608; ALA-747 AND CYS-1009.
[11]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[12]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[13]	"Nitric oxide production by human proximal tubular cells: a novel immunomodulatory mechanism?" McLay J.S., Chatterjee P., Nicolson A.G., Jardine A.G., McKay N.G., Ralston S.H., Grabowski P., Haites N.E., Macleod A.M., Hawksworth G.M. Kidney Int. 46:1043-1049(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 380-473. Tissue: Kidney.
[14]	"Inducible nitric oxide synthase in a human glioblastoma cell line." Fujisawa H., Ogura T., Hokari A., Weisz A., Yamashita J., Esumi H. J. Neurochem. 64:85-91(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 667-831, INDUCTION. Tissue: Glioblastoma.
[15]	"Three members of the nitric oxide synthase II gene family (NOS2A, NOS2B, and NOS2C) colocalize to human chromosome 17." Bloch K.D., Wolfram J.R., Brown D.M., Roberts J.D. Jr., Zapol D.G., Lepore J.J., Filippov G., Thomas J.E., Jacob H.J., Bloch D.B. Genomics 27:526-530(1995) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[16]	"Inducible nitric oxide synthase in the liver: regulation and function." Taylor B.S., Alarcon L.H., Billiar T.R. Biokhimiia 63:766-781(1998) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[17]	"Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output." Glynne P.A., Darling K.E.A., Picot J., Evans T.J. J. Biol. Chem. 277:33132-33138(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SLC9A3R1.
[18]	"A new NOS2 promoter polymorphism associated with increased nitric oxide production and protection from severe malaria in Tanzanian and Kenyan children." Hobbs M.R., Udhayakumar V., Levesque M.C., Booth J., Roberts J.M., Tkachuk A.N., Pole A., Coon H., Kariuki S., Nahlen B.L., Mwaikambo E.D., Lal A.L., Granger D.L., Anstey N.M., Weinberg J.B. Lancet 360:1468-1475(2002) [PubMed] [Europe PMC] [Abstract] Cited for: POLYMORPHISM, INVOLVEMENT IN RESISTANCE TO MALARIA.
[19]	"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." Li H., Raman C.S., Glaser C.B., Blasko E., Young T.A., Parkinson J.F., Whitlow M., Poulos T.L. J. Biol. Chem. 274:21276-21284(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 74-504.
[20]	"Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation." Fischmann T.O., Hruza A., Niu X.D., Fossetta J.D., Lunn C.A., Dolphin E., Prongay A.J., Reichert P., Lundell D.J., Narula S.K., Weber P.C. Nat. Struct. Biol. 6:233-242(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 82-528.
[21]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-679.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

Nitric oxide synthase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L24553 mRNA. Translation: AAA36375.1.
L09210 mRNA. Translation: AAA59171.1.
X73029 mRNA. Translation: CAA51512.1.
U05810 mRNA. Translation: AAA56666.1.
U31511 mRNA. Translation: AAB49041.1.
D26525 mRNA. Translation: BAA05531.1.
U20141 mRNA. Translation: AAB60366.1.
AF068236 mRNA. Translation: AAC19133.1.
AB022318 mRNA. Translation: BAA37123.1.
DQ060518 Genomic DNA. Translation: AAY43131.1.
EU332854 Genomic DNA. Translation: ABY87543.1.
BC130283 mRNA. Translation: AAI30284.1.
BC144126 mRNA. Translation: AAI44127.1.
S75615 mRNA. Translation: AAD14179.1.

IPI

IPI00017304.
IPI00220339.

PIR

A49676.

RefSeq

NP_000616.3. NM_000625.4.

UniGene

Hs.709191.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NSI	X-ray	2.55	A/B/C/D	74-504	[»]
2LL6	NMR	-	B	515-531	[»]
2NSI	X-ray	3.00	A/B/C/D	74-504	[»]
3E7G	X-ray	2.20	A/B/C/D	82-505	[»]
3EJ8	X-ray	2.55	A/B/C/D	82-505	[»]
3HR4	X-ray	2.50	A/C/E/G	503-715	[»]
4NOS	X-ray	2.25	A/B/C/D	82-508	[»]

ProteinModelPortal

P35228.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59359N.

PTM databases

PhosphoSite

P35228.

Polymorphism databases

DMDM

1352513.

Proteomic databases

PaxDb

P35228.

PRIDE

P35228.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000313735; ENSP00000327251; ENSG00000007171.

GeneID

4843.

KEGG

hsa:4843.

UCSC

uc002gzu.3. human.

Organism-specific databases

CTD

4843.

GeneCards

GC17M026083.

H-InvDB

HIX0027239.

HGNC

HGNC:7873. NOS2.

HPA

CAB002014.

MIM

163730. gene.
611162. phenotype.

neXtProt

NX_P35228.

PharmGKB

PA164724093.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4362.

HOVERGEN

HBG000159.

InParanoid

P35228.

KO

K13241.

OMA

KFTNSPT.

OrthoDB

EOG4D26P1.

PhylomeDB

P35228.

Enzyme and pathway databases

BioCyc

MetaCyc:HS00205-MONOMER.

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.
il12_2pathway. IL12-mediated signaling events.
il23pathway. IL23-mediated signaling events.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.

Reactome

REACT_116125. Disease.
REACT_604. Hemostasis.

SignaLink

P35228.

Gene expression databases

ArrayExpress

P35228.

Bgee

P35228.

CleanEx

HS_NOS2.

Genevestigator

P35228.

GermOnline

ENSG00000007171. Homo sapiens.

Family and domain databases

Gene3D

1.20.990.10. 1 hit.
3.90.340.10. 1 hit.

InterPro

IPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR004030. NO_synthase_oxygenase_dom.
IPR026009. NOS.
IPR012144. NOS_met.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]

PANTHER

PTHR19384:SF5. PTHR19384:SF5. 1 hit.

Pfam

PF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
PF02898. NO_synthase. 1 hit.
[Graphical view]

PIRSF

PIRSF000333. NOS. 1 hit.

PRINTS

PR00369. FLAVODOXIN.
PR00371. FPNCR.

SUPFAM

SSF56512. NO_synthase_oxygenase_reg. 1 hit.
SSF63380. Riboflavin_synthase_like_b-brl. 1 hit.

PROSITE

PS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
PS60001. NOS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P35228.

ChEMBL

CHEMBL4481.

ChiTaRS

NOS2. human.

DrugBank

DB01234. Dexamethasone.
DB00741. Hydrocortisone.
DB00125. L-Arginine.
DB00155. L-Citrulline.

EvolutionaryTrace

P35228.

GenomeRNAi

4843.

NextBio

18662.

SOURCE

Search...

Entry information

Entry name

NOS2_HUMAN

Accession

Primary (citable) accession number: P35228
Secondary accession number(s): A1L3U5 , B7ZLY2, O60757, O94994, Q16263, Q16692, Q4TTS5, Q9UD42

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1996
Last modified:	May 29, 2013
This is version 161 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.