NOS2_HUMAN
ID NOS2_HUMAN Reviewed; 1153 AA.
AC P35228; A1L3U5; B7ZLY2; O60757; O94994; Q16263; Q16692; Q4TTS5; Q9UD42;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 237.
DE RecName: Full=Nitric oxide synthase, inducible {ECO:0000305};
DE EC=1.14.13.39 {ECO:0000269|PubMed:7504305, ECO:0000269|PubMed:7682706};
DE AltName: Full=Hepatocyte NOS;
DE Short=HEP-NOS;
DE AltName: Full=Inducible NO synthase;
DE Short=Inducible NOS;
DE Short=iNOS;
DE AltName: Full=NOS type II;
DE AltName: Full=Peptidyl-cysteine S-nitrosylase NOS2;
GN Name=NOS2 {ECO:0000312|HGNC:HGNC:7873}; Synonyms=NOS2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC TISSUE=Colon adenocarcinoma;
RX PubMed=7692964; DOI=10.1021/bi00094a017;
RA Sherman P.A., Laubach V.E., Reep B.R., Wood E.R.;
RT "Purification and cDNA sequence of an inducible nitric oxide synthase from
RT a human tumor cell line.";
RL Biochemistry 32:11600-11605(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Liver;
RX PubMed=7682706; DOI=10.1073/pnas.90.8.3491;
RA Geller D.A., Lowenstein C.J., Shapiro R.A., Nussler A.K., di Silvio M.,
RA Wang S.C., Nakayama D.K., Simmons R.L., Snyder S.H., Billiar T.R.;
RT "Molecular cloning and expression of inducible nitric oxide synthase from
RT human hepatocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:3491-3495(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP TISSUE SPECIFICITY, AND INDUCTION BY IL1B.
RC TISSUE=Chondrocyte;
RX PubMed=7504305; DOI=10.1073/pnas.90.23.11419;
RA Charles I.G., Palmer R.M.J., Hickery M.S., Bayliss M.T., Chubb A.P.,
RA Hall V.S., Moss D.W., Moncada S.;
RT "Cloning, characterization, and expression of a cDNA encoding an inducible
RT nitric oxide synthase from the human chondrocyte.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:11419-11423(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Articular chondrocyte;
RX PubMed=7522054; DOI=10.1016/0167-4838(94)90171-6;
RA Maier R., Bilbe G., Rediske J., Lotz M.;
RT "Inducible nitric oxide synthase from human articular chondrocytes: cDNA
RT cloning and analysis of mRNA expression.";
RL Biochim. Biophys. Acta 1208:145-150(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-608, AND FUNCTION.
RC TISSUE=Retina;
RX PubMed=7528017; DOI=10.1006/bbrc.1994.2633;
RA Park C.S., Pardhasaradhi K., Gianotti C., Villegas E., Krishna G.;
RT "Human retina expresses both constitutive and inducible isoforms of nitric
RT oxide synthase mRNA.";
RL Biochem. Biophys. Res. Commun. 205:85-91(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT LEU-608.
RC TISSUE=Glioblastoma;
RX PubMed=7531687; DOI=10.1093/oxfordjournals.jbchem.a124563;
RA Hokari A., Zeniya M., Esumi H.;
RT "Cloning and functional expression of human inducible nitric oxide synthase
RT (NOS) cDNA from a glioblastoma cell line A-172.";
RL J. Biochem. 116:575-581(1994).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Airway epithelium;
RX PubMed=7544004; DOI=10.1073/pnas.92.17.7809;
RA Guo F.H., de Raeve R.H., Rice T.W., Stuehr D.J., Thunnissen F.B.J.M.,
RA Erzurum S.C.;
RT "Continuous nitric oxide synthesis by inducible nitric oxide synthase in
RT normal human airway epithelium in vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7809-7813(1995).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Cardiac myocyte;
RX PubMed=9160867; DOI=10.1006/jmcc.1996.0349;
RA Luss H., Li R.-K., Shapiro R.A., Tzeng E., McGowan F.X., Yoneyama T.,
RA Hatakayama K., Geller D.A., Mickle D.A.G., Simmons R.L., Billiar T.R.;
RT "Dedifferentiated human ventricular cardiac myocytes express inducible
RT nitric oxide synthase mRNA but not protein in response to IL-1, TNF,
RT IFNgamma, and LPS.";
RL J. Mol. Cell. Cardiol. 29:1153-1165(1997).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Ogawa Y., Nishijima S., Goto M., Ida M.;
RT "Cloning and characterization of a novel splice valiant of human inducible
RT nitric oxide synthase.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TRP-221; LEU-608; ALA-747
RP AND CYS-1009.
RG NIEHS SNPs program;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 380-473.
RC TISSUE=Kidney;
RX PubMed=7532248; DOI=10.1038/ki.1994.365;
RA McLay J.S., Chatterjee P., Nicolson A.G., Jardine A.G., McKay N.G.,
RA Ralston S.H., Grabowski P., Haites N.E., Macleod A.M., Hawksworth G.M.;
RT "Nitric oxide production by human proximal tubular cells: a novel
RT immunomodulatory mechanism?";
RL Kidney Int. 46:1043-1049(1994).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 667-831, AND INDUCTION.
RC TISSUE=Glioblastoma;
RX PubMed=7528267; DOI=10.1046/j.1471-4159.1995.64010085.x;
RA Fujisawa H., Ogura T., Hokari A., Weisz A., Yamashita J., Esumi H.;
RT "Inducible nitric oxide synthase in a human glioblastoma cell line.";
RL J. Neurochem. 64:85-91(1995).
RN [15]
RP CHARACTERIZATION.
RX PubMed=7558036; DOI=10.1006/geno.1995.1086;
RA Bloch K.D., Wolfram J.R., Brown D.M., Roberts J.D. Jr., Zapol D.G.,
RA Lepore J.J., Filippov G., Thomas J.E., Jacob H.J., Bloch D.B.;
RT "Three members of the nitric oxide synthase II gene family (NOS2A, NOS2B,
RT and NOS2C) colocalize to human chromosome 17.";
RL Genomics 27:526-530(1995).
RN [16]
RP CHARACTERIZATION.
RX PubMed=9721329;
RA Taylor B.S., Alarcon L.H., Billiar T.R.;
RT "Inducible nitric oxide synthase in the liver: regulation and function.";
RL Biochemistry (Mosc.) 63:766-781(1998).
RN [17]
RP INTERACTION WITH SLC9A3R1.
RX PubMed=12080081; DOI=10.1074/jbc.m205764200;
RA Glynne P.A., Darling K.E.A., Picot J., Evans T.J.;
RT "Epithelial inducible nitric-oxide synthase is an apical EBP50-binding
RT protein that directs vectorial nitric oxide output.";
RL J. Biol. Chem. 277:33132-33138(2002).
RN [18]
RP POLYMORPHISM, AND INVOLVEMENT IN RESISTANCE TO MALARIA.
RX PubMed=12433515; DOI=10.1016/s0140-6736(02)11474-7;
RA Hobbs M.R., Udhayakumar V., Levesque M.C., Booth J., Roberts J.M.,
RA Tkachuk A.N., Pole A., Coon H., Kariuki S., Nahlen B.L., Mwaikambo E.D.,
RA Lal A.L., Granger D.L., Anstey N.M., Weinberg J.B.;
RT "A new NOS2 promoter polymorphism associated with increased nitric oxide
RT production and protection from severe malaria in Tanzanian and Kenyan
RT children.";
RL Lancet 360:1468-1475(2002).
RN [19]
RP FUNCTION.
RX PubMed=19688109; DOI=10.1155/2009/345838;
RA Vuolteenaho K., Koskinen A., Kukkonen M., Nieminen R., Paeivaerinta U.,
RA Moilanen T., Moilanen E.;
RT "Leptin enhances synthesis of proinflammatory mediators in human
RT osteoarthritic cartilage--mediator role of NO in leptin-induced PGE2, IL-6,
RT and IL-8 production.";
RL Mediators Inflamm. 2009:345838-345838(2009).
RN [20]
RP POLYUBIQUITINATION, PROTEASOMAL DEGRADATION, SUBCELLULAR LOCATION,
RP INTERACTION WITH SPSB1; SPSB2; SPSB4; ELOC AND CUL5, MUTAGENESIS OF ASN-27,
RP AND MOTIF DINNN.
RX PubMed=21199876; DOI=10.1074/jbc.m110.190678;
RA Nishiya T., Matsumoto K., Maekawa S., Kajita E., Horinouchi T.,
RA Fujimuro M., Ogasawara K., Uehara T., Miwa S.;
RT "Regulation of inducible nitric-oxide synthase by the SPRY domain- and SOCS
RT box-containing proteins.";
RL J. Biol. Chem. 286:9009-9019(2011).
RN [21]
RP FUNCTION, INTERACTION WITH S100A8; S100A9 AND GAPDH, ASSEMBLY IN THE
RP INOS-S100A8/A9 COMPLEX, AND INDUCTION BY LDL.
RX PubMed=25417112; DOI=10.1016/j.cell.2014.09.032;
RA Jia J., Arif A., Terenzi F., Willard B., Plow E.F., Hazen S.L., Fox P.L.;
RT "Target-selective protein S-nitrosylation by sequence motif recognition.";
RL Cell 159:623-634(2014).
RN [22]
RP INDUCTION.
RX PubMed=25180171; DOI=10.1016/j.redox.2014.06.011;
RA Cortese-Krott M.M., Kulakov L., Oplaender C., Kolb-Bachofen V.,
RA Kroencke K.D., Suschek C.V.;
RT "Zinc regulates iNOS-derived nitric oxide formation in endothelial cells.";
RL Redox Biol. 2:945-954(2014).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 74-504, AND SUBUNIT.
RX PubMed=10409685; DOI=10.1074/jbc.274.30.21276;
RA Li H., Raman C.S., Glaser C.B., Blasko E., Young T.A., Parkinson J.F.,
RA Whitlow M., Poulos T.L.;
RT "Crystal structures of zinc-free and -bound heme domain of human inducible
RT nitric-oxide synthase. Implications for dimer stability and comparison with
RT endothelial nitric-oxide synthase.";
RL J. Biol. Chem. 274:21276-21284(1999).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 82-528, AND SUBUNIT.
RX PubMed=10074942; DOI=10.1038/6675;
RA Fischmann T.O., Hruza A., Niu X.D., Fossetta J.D., Lunn C.A., Dolphin E.,
RA Prongay A.J., Reichert P., Lundell D.J., Narula S.K., Weber P.C.;
RT "Structural characterization of nitric oxide synthase isoforms reveals
RT striking active-site conservation.";
RL Nat. Struct. Biol. 6:233-242(1999).
RN [25]
RP VARIANT [LARGE SCALE ANALYSIS] SER-679.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [26]
RP VARIANT LEU-608, AND CHARACTERIZATION OF VARIANT LEU-608.
RX PubMed=24430113; DOI=10.1038/ctg.2013.17;
RA Dhillon S.S., Mastropaolo L.A., Murchie R., Griffiths C., Thoeni C.,
RA Elkadri A., Xu W., Mack A., Walters T., Guo C., Mack D., Huynh H.,
RA Baksh S., Silverberg M.S., Brumell J.H., Snapper S.B., Muise A.M.;
RT "Higher activity of the inducible nitric oxide synthase contributes to very
RT early onset inflammatory bowel disease.";
RL Clin. Transl. Gastroenterol. 5:E46-E46(2014).
CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with
CC diverse functions throughout the body (PubMed:7531687, PubMed:7544004,
CC PubMed:7682706, PubMed:7504305). In macrophages, NO mediates
CC tumoricidal and bactericidal actions. Also has nitrosylase activity and
CC mediates cysteine S-nitrosylation of cytoplasmic target proteins such
CC PTGS2/COX2 (By similarity). As component of the iNOS-S100A8/9
CC transnitrosylase complex involved in the selective inflammatory
CC stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in
CC regulation of the GAIT complex activity and probably multiple targets
CC including ANXA5, EZR, MSN and VIM (PubMed:25417112). Involved in
CC inflammation, enhances the synthesis of pro-inflammatory mediators such
CC as IL6 and IL8 (PubMed:19688109). {ECO:0000250|UniProtKB:P29477,
CC ECO:0000269|PubMed:19688109, ECO:0000269|PubMed:25417112,
CC ECO:0000269|PubMed:7504305, ECO:0000269|PubMed:7531687,
CC ECO:0000269|PubMed:7544004, ECO:0000269|PubMed:7682706}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + 2 L-arginine + 3 NADPH + 4 O2 = 4 H2O + 2 L-citrulline
CC + 3 NADP(+) + 2 nitric oxide; Xref=Rhea:RHEA:19897,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16480, ChEBI:CHEBI:32682, ChEBI:CHEBI:57743,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.39;
CC Evidence={ECO:0000269|PubMed:7504305, ECO:0000269|PubMed:7682706};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19898;
CC Evidence={ECO:0000305|PubMed:7504305, ECO:0000305|PubMed:7682706};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC Note=Binds 1 FAD. {ECO:0000250};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000250};
CC Note=Binds 1 FMN. {ECO:0000250};
CC -!- COFACTOR:
CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin;
CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000250};
CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the
CC enzyme. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Regulated by calcium/calmodulin. Aspirin inhibits
CC expression and function of this enzyme and effects may be exerted at
CC the level of translational/post-translational modification and directly
CC on the catalytic activity (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer (PubMed:10409685, PubMed:10074942). Interacts with
CC SLC9A3R1 (PubMed:12080081). Interacts with GAPDH; induced by
CC oxidatively-modified low-densitity lipoprotein (LDL(ox))
CC (PubMed:25417112). Interacts with S100A8 and S100A9 to form the iNOS-
CC S100A8/9 transnitrosylase complex (PubMed:25417112). Interacts with
CC SPSB1, SPSB2 and SPSB4 (PubMed:21199876). Interacts with ELOC and CUL5
CC in the presence of SPSB1 or SPSB2 or SPSB4 (PubMed:21199876). Forms a
CC complex with ASL, ASS1 and HSP90AA1; the complex regulates cell-
CC autonomous L-arginine synthesis and citrulline recycling while
CC channeling extracellular L-arginine to nitric oxide synthesis pathway.
CC {ECO:0000250|UniProtKB:P29477, ECO:0000269|PubMed:10074942,
CC ECO:0000269|PubMed:10409685, ECO:0000269|PubMed:12080081,
CC ECO:0000269|PubMed:21199876, ECO:0000269|PubMed:25417112}.
CC -!- INTERACTION:
CC P35228; P04406: GAPDH; NbExp=8; IntAct=EBI-6662224, EBI-354056;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:21199876}.
CC Note=Localizes as discrete foci scattered throughout the cytosol and in
CC the presence of SPSB1 and SPSB4, exhibits a more diffuse cytosolic
CC localization. {ECO:0000269|PubMed:21199876}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P35228-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P35228-2; Sequence=VSP_003582, VSP_003583;
CC -!- TISSUE SPECIFICITY: Expressed in the liver, retina, bone cells and
CC airway epithelial cells of the lung. Not expressed in the platelets.
CC Expressed in chondrocytes (PubMed:7504305).
CC {ECO:0000269|PubMed:7504305}.
CC -!- INDUCTION: By endotoxins and cytokines. Induced by IFNG/IFN-gamma
CC acting synergistically with bacterial lipopolysaccharides (LPS), TNF or
CC IL1B/interleukin-1 beta (PubMed:7528267, PubMed:7504305). Down-
CC regulated by zinc due to inhibition of NF-kappa-B transactivation
CC activity (PubMed:25180171). By oxidatively-modified low-densitity
CC lipoprotein (LDL(ox)) (PubMed:25417112). {ECO:0000269|PubMed:25180171,
CC ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:7504305,
CC ECO:0000269|PubMed:7528267}.
CC -!- PTM: Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to
CC proteasomal degradation. {ECO:0000269|PubMed:21199876}.
CC -!- POLYMORPHISM: Genetic variations in NOS2 are involved in resistance to
CC malaria [MIM:611162]. {ECO:0000269|PubMed:12433515}.
CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/nos2a/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Nitric oxide synthase entry;
CC URL="https://en.wikipedia.org/wiki/Nitric_oxide_synthase";
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DR EMBL; L24553; AAA36375.1; -; mRNA.
DR EMBL; L09210; AAA59171.1; -; mRNA.
DR EMBL; X73029; CAA51512.1; -; mRNA.
DR EMBL; U05810; AAA56666.1; -; mRNA.
DR EMBL; U31511; AAB49041.1; -; mRNA.
DR EMBL; D26525; BAA05531.1; -; mRNA.
DR EMBL; U20141; AAB60366.1; -; mRNA.
DR EMBL; AF068236; AAC19133.1; -; mRNA.
DR EMBL; AB022318; BAA37123.1; -; mRNA.
DR EMBL; DQ060518; AAY43131.1; -; Genomic_DNA.
DR EMBL; EU332854; ABY87543.1; -; Genomic_DNA.
DR EMBL; BC130283; AAI30284.1; -; mRNA.
DR EMBL; BC144126; AAI44127.1; -; mRNA.
DR EMBL; S75615; AAD14179.1; -; mRNA.
DR CCDS; CCDS11223.1; -. [P35228-1]
DR PIR; A49676; A49676.
DR RefSeq; NP_000616.3; NM_000625.4. [P35228-1]
DR RefSeq; XP_011523161.1; XM_011524859.2.
DR PDB; 1NSI; X-ray; 2.55 A; A/B/C/D=74-504.
DR PDB; 2LL6; NMR; -; B=515-531.
DR PDB; 2NSI; X-ray; 3.00 A; A/B/C/D=74-504.
DR PDB; 3E7G; X-ray; 2.20 A; A/B/C/D=82-505.
DR PDB; 3EJ8; X-ray; 2.55 A; A/B/C/D=82-505.
DR PDB; 3HR4; X-ray; 2.50 A; A/C/E/G=503-715.
DR PDB; 4CX7; X-ray; 3.16 A; A/B/C/D=74-504.
DR PDB; 4NOS; X-ray; 2.25 A; A/B/C/D=82-508.
DR PDB; 5TP6; NMR; -; B=507-531.
DR PDB; 5XN3; X-ray; 1.34 A; B=23-28.
DR PDB; 6JWM; X-ray; 1.23 A; B=21-27.
DR PDB; 6JWN; X-ray; 1.61 A; B/D=21-29.
DR PDB; 6KEY; X-ray; 1.24 A; B=22-30.
DR PDBsum; 1NSI; -.
DR PDBsum; 2LL6; -.
DR PDBsum; 2NSI; -.
DR PDBsum; 3E7G; -.
DR PDBsum; 3EJ8; -.
DR PDBsum; 3HR4; -.
DR PDBsum; 4CX7; -.
DR PDBsum; 4NOS; -.
DR PDBsum; 5TP6; -.
DR PDBsum; 5XN3; -.
DR PDBsum; 6JWM; -.
DR PDBsum; 6JWN; -.
DR PDBsum; 6KEY; -.
DR AlphaFoldDB; P35228; -.
DR BMRB; P35228; -.
DR SMR; P35228; -.
DR BioGRID; 110906; 176.
DR ComplexPortal; CPX-52; iNOS-S100A8/A9 complex.
DR CORUM; P35228; -.
DR DIP; DIP-59359N; -.
DR IntAct; P35228; 7.
DR MINT; P35228; -.
DR STRING; 9606.ENSP00000327251; -.
DR BindingDB; P35228; -.
DR ChEMBL; CHEMBL4481; -.
DR DrugBank; DB07003; (2S)-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepin-5-amine.
DR DrugBank; DB07007; (3R)-3-[(1,2,3,4-tetrahydroisoquinolin-7-yloxy)methyl]-2,3-dihydrothieno[2,3-f][1,4]oxazepin-5-amine.
DR DrugBank; DB07011; (3S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-3-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PIPERIDINE.
DR DrugBank; DB07405; 1-(6-CYANO-3-PYRIDYLCARBONYL)-5',8'-DIFLUOROSPIRO[PIPERIDINE-4,2'(1'H)-QUINAZOLINE]-4'-AMINE.
DR DrugBank; DB08750; 1-[4-(AMINOMETHYL)BENZOYL]-5'-FLUORO-1'H-SPIRO[PIPERIDINE-4,2'-QUINAZOLIN]-4'-AMINE.
DR DrugBank; DB01997; 3-Bromo-7-Nitroindazole.
DR DrugBank; DB07029; 4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMIDAZOL-1-YL)PHENOXY]-6-METHYLPYRIMIDINE.
DR DrugBank; DB07008; 4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PYRIMIDINE.
DR DrugBank; DB08214; 4-(1H-IMIDAZOL-1-YL)PHENOL.
DR DrugBank; DB07002; 4-({4-[(4-methoxypyridin-2-yl)amino]piperidin-1-yl}carbonyl)benzonitrile.
DR DrugBank; DB01835; 4R-Fluoro-N6-ethanimidoyl-L-lysine.
DR DrugBank; DB06879; 5-(4'-AMINO-1'-ETHYL-5',8'-DIFLUORO-1'H-SPIRO[PIPERIDINE-4,2'-QUINAZOLINE]-1-YLCARBONYL)PICOLINONITRILE.
DR DrugBank; DB04534; 5-Nitroindazole.
DR DrugBank; DB03100; 6-Nitroindazole.
DR DrugBank; DB02207; 7-Nitroindazole.
DR DrugBank; DB00125; Arginine.
DR DrugBank; DB00155; Citrulline.
DR DrugBank; DB01234; Dexamethasone.
DR DrugBank; DB14649; Dexamethasone acetate.
DR DrugBank; DB11327; Dipyrithione.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB07306; ETHYL 4-[(4-CHLOROPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE.
DR DrugBank; DB07388; ETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE.
DR DrugBank; DB05252; Fenoxaprop-ethyl.
DR DrugBank; DB01381; Ginkgo biloba.
DR DrugBank; DB03366; Imidazole.
DR DrugBank; DB05214; KD7040.
DR DrugBank; DB04400; L-erythro-7,8-dihydrobiopterin.
DR DrugBank; DB09237; Levamlodipine.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01017; Minocycline.
DR DrugBank; DB03144; N(5)-[(hydroxyamino)(imino)methyl]-L-ornithine.
DR DrugBank; DB01686; N,N-dimethylarginine.
DR DrugBank; DB03449; N-(4-{2-[(3-chlorobenzyl)amino]ethyl}phenyl)thiophene-2-carboximidamide.
DR DrugBank; DB06916; N-[2-(1,3-BENZODIOXOL-5-YL)ETHYL]-1-[2-(1H-IMIDAZOL-1-YL)-6-METHYLPYRIMIDIN-4-YL]-D-PROLINAMIDE.
DR DrugBank; DB07318; N-[2-(4-AMINO-5,8-DIFLUORO-1,2-DIHYDROQUINAZOLIN-2-YL)ETHYL]-3-FURAMIDE.
DR DrugBank; DB07389; N-[2-(6-AMINO-4-METHYLPYRIDIN-2-YL)ETHYL]-4-CYANOBENZAMIDE.
DR DrugBank; DB02044; N-[3-(aminomethyl)benzyl]acetamidine.
DR DrugBank; DB02644; N-omega-propyl-L-arginine.
DR DrugBank; DB05383; Pimagedine.
DR DrugBank; DB02234; S-Ethylisothiourea.
DR DrugBank; DB03953; Thiocitrulline.
DR DrugBank; DB02462; Thiocoumarin.
DR DrugBank; DB08814; Triflusal.
DR DrugCentral; P35228; -.
DR GuidetoPHARMACOLOGY; 1250; -.
DR iPTMnet; P35228; -.
DR PhosphoSitePlus; P35228; -.
DR SwissPalm; P35228; -.
DR BioMuta; NOS2; -.
DR DMDM; 1352513; -.
DR jPOST; P35228; -.
DR MassIVE; P35228; -.
DR PaxDb; P35228; -.
DR PeptideAtlas; P35228; -.
DR PRIDE; P35228; -.
DR ProteomicsDB; 54993; -. [P35228-1]
DR ProteomicsDB; 54994; -. [P35228-2]
DR Antibodypedia; 4550; 1111 antibodies from 47 providers.
DR DNASU; 4843; -.
DR Ensembl; ENST00000313735.11; ENSP00000327251.6; ENSG00000007171.18. [P35228-1]
DR Ensembl; ENST00000621962.1; ENSP00000482291.1; ENSG00000007171.18. [P35228-2]
DR GeneID; 4843; -.
DR KEGG; hsa:4843; -.
DR MANE-Select; ENST00000313735.11; ENSP00000327251.6; NM_000625.4; NP_000616.3.
DR UCSC; uc002gzu.4; human. [P35228-1]
DR CTD; 4843; -.
DR DisGeNET; 4843; -.
DR GeneCards; NOS2; -.
DR HGNC; HGNC:7873; NOS2.
DR HPA; ENSG00000007171; Group enriched (intestine, lymphoid tissue).
DR MalaCards; NOS2; -.
DR MIM; 163730; gene.
DR MIM; 611162; phenotype.
DR neXtProt; NX_P35228; -.
DR OpenTargets; ENSG00000007171; -.
DR PharmGKB; PA164724093; -.
DR VEuPathDB; HostDB:ENSG00000007171; -.
DR eggNOG; KOG1158; Eukaryota.
DR GeneTree; ENSGT00940000159752; -.
DR HOGENOM; CLU_001570_16_0_1; -.
DR InParanoid; P35228; -.
DR OMA; WFMDAEI; -.
DR OrthoDB; 90349at2759; -.
DR PhylomeDB; P35228; -.
DR TreeFam; TF324410; -.
DR BioCyc; MetaCyc:HS00205-MON; -.
DR BRENDA; 1.14.13.39; 2681.
DR PathwayCommons; P35228; -.
DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-HSA-392154; Nitric oxide stimulates guanylate cyclase.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR Reactome; R-HSA-9636249; Inhibition of nitric oxide production.
DR SignaLink; P35228; -.
DR SIGNOR; P35228; -.
DR BioGRID-ORCS; 4843; 10 hits in 1076 CRISPR screens.
DR ChiTaRS; NOS2; human.
DR EvolutionaryTrace; P35228; -.
DR GeneWiki; Nitric_oxide_synthase_2_(inducible); -.
DR GenomeRNAi; 4843; -.
DR Pharos; P35228; Tchem.
DR PRO; PR:P35228; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P35228; protein.
DR Bgee; ENSG00000007171; Expressed in cartilage tissue and 96 other tissues.
DR ExpressionAtlas; P35228; baseline and differential.
DR Genevisible; P35228; HS.
DR GO; GO:0030863; C:cortical cytoskeleton; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IMP:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0012506; C:vesicle membrane; IBA:GO_Central.
DR GO; GO:0034618; F:arginine binding; ISS:BHF-UCL.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:BHF-UCL.
DR GO; GO:0010181; F:FMN binding; ISS:BHF-UCL.
DR GO; GO:0020037; F:heme binding; ISS:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050661; F:NADP binding; TAS:BHF-UCL.
DR GO; GO:0004517; F:nitric-oxide synthase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL.
DR GO; GO:0034617; F:tetrahydrobiopterin binding; ISS:BHF-UCL.
DR GO; GO:0006527; P:arginine catabolic process; IDA:BHF-UCL.
DR GO; GO:0045454; P:cell redox homeostasis; TAS:Reactome.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0042742; P:defense response to bacterium; IMP:BHF-UCL.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; NAS:BHF-UCL.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0002227; P:innate immune response in mucosa; NAS:BHF-UCL.
DR GO; GO:0045776; P:negative regulation of blood pressure; IBA:GO_Central.
DR GO; GO:0010629; P:negative regulation of gene expression; IGI:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IBA:GO_Central.
DR GO; GO:0018119; P:peptidyl-cysteine S-nitrosylation; ISS:UniProtKB.
DR GO; GO:0031284; P:positive regulation of guanylate cyclase activity; IBA:GO_Central.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:UniProtKB.
DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; IMP:BHF-UCL.
DR GO; GO:0001912; P:positive regulation of leukocyte mediated cytotoxicity; TAS:BHF-UCL.
DR GO; GO:0032310; P:prostaglandin secretion; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0043457; P:regulation of cellular respiration; TAS:BHF-UCL.
DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; IDA:UniProtKB.
DR GO; GO:0050796; P:regulation of insulin secretion; IMP:BHF-UCL.
DR GO; GO:0009617; P:response to bacterium; NAS:UniProtKB.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0006801; P:superoxide metabolic process; ISS:UniProtKB.
DR Gene3D; 1.20.990.10; -; 1.
DR Gene3D; 3.40.50.360; -; 2.
DR Gene3D; 3.40.50.80; -; 1.
DR Gene3D; 3.90.1230.10; -; 1.
DR Gene3D; 3.90.340.10; -; 1.
DR Gene3D; 3.90.440.10; -; 1.
DR InterPro; IPR003097; CysJ-like_FAD-binding.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR001094; Flavdoxin-like.
DR InterPro; IPR008254; Flavodoxin/NO_synth.
DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR023173; NADPH_Cyt_P450_Rdtase_alpha.
DR InterPro; IPR044943; NOS_dom_1.
DR InterPro; IPR044940; NOS_dom_2.
DR InterPro; IPR044944; NOS_dom_3.
DR InterPro; IPR012144; NOS_euk.
DR InterPro; IPR004030; NOS_N.
DR InterPro; IPR036119; NOS_N_sf.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR Pfam; PF00667; FAD_binding_1; 1.
DR Pfam; PF00258; Flavodoxin_1; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR Pfam; PF02898; NO_synthase; 1.
DR PIRSF; PIRSF000333; NOS; 1.
DR PRINTS; PR00369; FLAVODOXIN.
DR PRINTS; PR00371; FPNCR.
DR SUPFAM; SSF52218; SSF52218; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF56512; SSF56512; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
DR PROSITE; PS60001; NOS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Calmodulin-binding; Cytoplasm;
KW FAD; Flavoprotein; FMN; Heme; Iron; Metal-binding; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc.
FT CHAIN 1..1153
FT /note="Nitric oxide synthase, inducible"
FT /id="PRO_0000170930"
FT DOMAIN 539..677
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 730..970
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 509..529
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT MOTIF 23..27
FT /note="DINNN-motif; mediates interaction with SPSB1, SPSB2
FT and SPSB4"
FT /evidence="ECO:0000269|PubMed:21199876"
FT BINDING 110
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 118
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 200
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 263
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 372
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 373
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 377
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 463
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 476
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 491
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 623..654
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 767..778
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 903..913
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 978..996
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 1076..1091
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 234
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT MOD_RES 575
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q06518"
FT MOD_RES 578
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT MOD_RES 892
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT VAR_SEQ 264..288
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.9"
FT /id="VSP_003582"
FT VAR_SEQ 298..311
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.9"
FT /id="VSP_003583"
FT VARIANT 221
FT /note="R -> W (in dbSNP:rs3730017)"
FT /evidence="ECO:0000269|Ref.10"
FT /id="VAR_024548"
FT VARIANT 608
FT /note="S -> L (found in patients with very early onset
FT inflammatory bowel disease; increases NOS2 activity;
FT dbSNP:rs2297518)"
FT /evidence="ECO:0000269|PubMed:24430113,
FT ECO:0000269|PubMed:7528017, ECO:0000269|PubMed:7531687,
FT ECO:0000269|Ref.10"
FT /id="VAR_022127"
FT VARIANT 679
FT /note="A -> S (in a breast cancer sample; somatic mutation;
FT dbSNP:rs769900089)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036302"
FT VARIANT 747
FT /note="T -> A (in dbSNP:rs28944173)"
FT /evidence="ECO:0000269|Ref.10"
FT /id="VAR_025020"
FT VARIANT 1009
FT /note="R -> C (in dbSNP:rs28944201)"
FT /evidence="ECO:0000269|Ref.10"
FT /id="VAR_025021"
FT MUTAGEN 27
FT /note="N->A: Loss of interaction with SPSB1 and SPSB4."
FT /evidence="ECO:0000269|PubMed:21199876"
FT CONFLICT 23
FT /note="D -> G (in Ref. 4; AAA56666)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="F -> L (in Ref. 4; AAA56666)"
FT /evidence="ECO:0000305"
FT CONFLICT 177
FT /note="G -> V (in Ref. 4; AAA56666)"
FT /evidence="ECO:0000305"
FT CONFLICT 266
FT /note="R -> H (in Ref. 8; AAC19133)"
FT /evidence="ECO:0000305"
FT CONFLICT 423
FT /note="L -> I (in Ref. 2; AAA59171)"
FT /evidence="ECO:0000305"
FT CONFLICT 439
FT /note="A -> T (in Ref. 8; AAC19133)"
FT /evidence="ECO:0000305"
FT CONFLICT 552
FT /note="A -> G (in Ref. 12; AAI44127)"
FT /evidence="ECO:0000305"
FT CONFLICT 676
FT /note="T -> I (in Ref. 7; AAB60366)"
FT /evidence="ECO:0000305"
FT CONFLICT 800
FT /note="T -> A (in Ref. 4; AAA56666)"
FT /evidence="ECO:0000305"
FT CONFLICT 805
FT /note="A -> D (in Ref. 2; AAA59171)"
FT /evidence="ECO:0000305"
FT CONFLICT 831..832
FT /note="FL -> SP (in Ref. 2; AAA59171)"
FT /evidence="ECO:0000305"
FT CONFLICT 913
FT /note="S -> P (in Ref. 4; AAA56666)"
FT /evidence="ECO:0000305"
FT CONFLICT 933
FT /note="R -> G (in Ref. 2; AAA59171 and 7; AAB60366)"
FT /evidence="ECO:0000305"
FT CONFLICT 966
FT /note="G -> A (in Ref. 2; AAA59171 and 7; AAB60366)"
FT /evidence="ECO:0000305"
FT CONFLICT 987
FT /note="A -> V (in Ref. 2; AAA59171)"
FT /evidence="ECO:0000305"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:3E7G"
FT TURN 90..92
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 100..103
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:4NOS"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 136..152
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:1NSI"
FT HELIX 159..175
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 183..195
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 210..213
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 220..235
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 251..255
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 261..265
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 284..292
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 307..310
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 337..342
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 345..348
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 356..359
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 375..379
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 381..384
FT /evidence="ECO:0007829|PDB:3E7G"
FT TURN 386..389
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 392..399
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 410..428
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 436..454
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 461..464
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 467..469
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 474..477
FT /evidence="ECO:0007829|PDB:3E7G"
FT STRAND 486..491
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 495..498
FT /evidence="ECO:0007829|PDB:3E7G"
FT HELIX 515..534
FT /evidence="ECO:0007829|PDB:3HR4"
FT STRAND 538..544
FT /evidence="ECO:0007829|PDB:3HR4"
FT STRAND 546..548
FT /evidence="ECO:0007829|PDB:3HR4"
FT HELIX 549..561
FT /evidence="ECO:0007829|PDB:3HR4"
FT TURN 562..564
FT /evidence="ECO:0007829|PDB:3HR4"
FT STRAND 565..571
FT /evidence="ECO:0007829|PDB:3HR4"
FT HELIX 572..574
FT /evidence="ECO:0007829|PDB:3HR4"
FT HELIX 577..581
FT /evidence="ECO:0007829|PDB:3HR4"
FT STRAND 584..591
FT /evidence="ECO:0007829|PDB:3HR4"
FT TURN 594..596
FT /evidence="ECO:0007829|PDB:3HR4"
FT HELIX 600..602
FT /evidence="ECO:0007829|PDB:3HR4"
FT HELIX 603..611
FT /evidence="ECO:0007829|PDB:3HR4"
FT STRAND 620..627
FT /evidence="ECO:0007829|PDB:3HR4"
FT STRAND 631..633
FT /evidence="ECO:0007829|PDB:3HR4"
FT HELIX 636..648
FT /evidence="ECO:0007829|PDB:3HR4"
FT STRAND 651..654
FT /evidence="ECO:0007829|PDB:3HR4"
FT STRAND 657..660
FT /evidence="ECO:0007829|PDB:3HR4"
FT HELIX 665..683
FT /evidence="ECO:0007829|PDB:3HR4"
FT HELIX 689..691
FT /evidence="ECO:0007829|PDB:3HR4"
SQ SEQUENCE 1153 AA; 131117 MW; 47671E5385CB3A52 CRC64;
MACPWKFLFK TKFHQYAMNG EKDINNNVEK APCATSSPVT QDDLQYHNLS KQQNESPQPL
VETGKKSPES LVKLDATPLS SPRHVRIKNW GSGMTFQDTL HHKAKGILTC RSKSCLGSIM
TPKSLTRGPR DKPTPPDELL PQAIEFVNQY YGSFKEAKIE EHLARVEAVT KEIETTGTYQ
LTGDELIFAT KQAWRNAPRC IGRIQWSNLQ VFDARSCSTA REMFEHICRH VRYSTNNGNI
RSAITVFPQR SDGKHDFRVW NAQLIRYAGY QMPDGSIRGD PANVEFTQLC IDLGWKPKYG
RFDVVPLVLQ ANGRDPELFE IPPDLVLEVA MEHPKYEWFR ELELKWYALP AVANMLLEVG
GLEFPGCPFN GWYMGTEIGV RDFCDVQRYN ILEEVGRRMG LETHKLASLW KDQAVVEINI
AVLHSFQKQN VTIMDHHSAA ESFMKYMQNE YRSRGGCPAD WIWLVPPMSG SITPVFHQEM
LNYVLSPFYY YQVEAWKTHV WQDEKRRPKR REIPLKVLVK AVLFACMLMR KTMASRVRVT
ILFATETGKS EALAWDLGAL FSCAFNPKVV CMDKYRLSCL EEERLLLVVT STFGNGDCPG
NGEKLKKSLF MLKELNNKFR YAVFGLGSSM YPRFCAFAHD IDQKLSHLGA SQLTPMGEGD
ELSGQEDAFR SWAVQTFKAA CETFDVRGKQ HIQIPKLYTS NVTWDPHHYR LVQDSQPLDL
SKALSSMHAK NVFTMRLKSR QNLQSPTSSR ATILVELSCE DGQGLNYLPG EHLGVCPGNQ
PALVQGILER VVDGPTPHQT VRLEALDESG SYWVSDKRLP PCSLSQALTY FLDITTPPTQ
LLLQKLAQVA TEEPERQRLE ALCQPSEYSK WKFTNSPTFL EVLEEFPSLR VSAGFLLSQL
PILKPRFYSI SSSRDHTPTE IHLTVAVVTY HTRDGQGPLH HGVCSTWLNS LKPQDPVPCF
VRNASGFHLP EDPSHPCILI GPGTGIAPFR SFWQQRLHDS QHKGVRGGRM TLVFGCRRPD
EDHIYQEEML EMAQKGVLHA VHTAYSRLPG KPKVYVQDIL RQQLASEVLR VLHKEPGHLY
VCGDVRMARD VAHTLKQLVA AKLKLNEEQV EDYFFQLKSQ KRYHEDIFGA VFPYEAKKDR
VAVQPSSLEM SAL
