NOS2_MOUSE
ID NOS2_MOUSE Reviewed; 1144 AA.
AC P29477; O70515; O70516; Q5SXT3; Q6P6A0; Q8R410;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Nitric oxide synthase, inducible;
DE EC=1.14.13.39 {ECO:0000250|UniProtKB:P35228};
DE AltName: Full=Inducible NO synthase;
DE Short=Inducible NOS;
DE Short=iNOS;
DE AltName: Full=Macrophage NOS;
DE Short=MAC-NOS;
DE AltName: Full=NOS type II;
DE AltName: Full=Peptidyl-cysteine S-nitrosylase NOS2;
GN Name=Nos2; Synonyms=Inosl;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1373522; DOI=10.1126/science.1373522;
RA Xie Q.-W., Cho H.J., Calaycay J., Mumford R.A., Swiderek K.M., Lee T.D.,
RA Ding A., Troso T., Nathan C.;
RT "Cloning and characterization of inducible nitric oxide synthase from mouse
RT macrophages.";
RL Science 256:225-228(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1379716; DOI=10.1073/pnas.89.15.6711;
RA Lowenstein C.J., Glatt C.S., Bredt D.S., Snyder S.H.;
RT "Cloned and expressed macrophage nitric oxide synthase contrasts with the
RT brain enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:6711-6715(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1372907; DOI=10.1016/s0021-9258(18)42704-4;
RA Lyons C.R., Orloff G.J., Cunningham J.M.;
RT "Molecular cloning and functional expression of an inducible nitric oxide
RT synthase from a murine macrophage cell line.";
RL J. Biol. Chem. 267:6370-6374(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=7503239; DOI=10.1152/ajprenal.1995.269.5.f718;
RA Kone B.C., Schwoebel J., Turner P., Mohaupt M.G., Cangro C.B.;
RT "Role of NF-kappa B in the regulation of inducible nitric oxide synthase in
RT an MTAL cell line.";
RL Am. J. Physiol. 269:F718-F729(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ARG-211; LEU-967 AND PHE-968.
RC STRAIN=B10.S/J, BALB/cByJ, DBA/2J, NOD/LtJ, and SJL/J; TISSUE=Spleen;
RX PubMed=10438970;
RA Teuscher C., Butterfield R.J., Ma R.Z., Zachary J.F., Doerge R.W.,
RA Blankenhorn E.P.;
RT "Sequence polymorphisms in the chemokines Scya1 (TCA-3), Scya2 (monocyte
RT chemoattractant protein (MCP)-1), and Scya12 (MCP-5) are candidates for
RT eae7, a locus controlling susceptibility to monophasic
RT remitting/nonrelapsing experimental allergic encephalomyelitis.";
RL J. Immunol. 163:2262-2266(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=CD-1;
RA Coge F., Levacher B., Rique H., Leopold O., Boutin J.A., Galizzi J.-P.;
RT "Genomic structure of the murine inducible nitric oxide synthase (i-NOS)
RT gene.";
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ICR;
RA Hagiwara K., Endo Y., Xin H., Takahashi M., Huqun X., Nukiwa T.;
RT "Mouse inducible nitric oxide synthase mRNA.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NMRI; TISSUE=Mammary tumor;
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 [10]
RP PROTEIN SEQUENCE OF 733-744, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [11]
RP EFFECT OF ASPIRIN.
RC TISSUE=Macrophage;
RX PubMed=7544010; DOI=10.1073/pnas.92.17.7926;
RA Amin A.R., Vyas P., Attur M., Leszczynska-Piziak J., Patel I.R.,
RA Weissmann G., Abramson S.B.;
RT "The mode of action of aspirin-like drugs: effect on inducible nitric oxide
RT synthase.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7926-7930(1995).
RN [12]
RP FUNCTION AS NITROSYLASE.
RX PubMed=16373578; DOI=10.1126/science.1119407;
RA Kim S.F., Huri D.A., Snyder S.H.;
RT "Inducible nitric oxide synthase binds, S-nitrosylates, and activates
RT cyclooxygenase-2.";
RL Science 310:1966-1970(2005).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [14]
RP POLYUBIQUITINATION, PROTEASOMAL DEGRADATION, INTERACTION WITH SPSB1; SPSB2
RP AND SPSB4, MOTIF DINNN, AND MUTAGENESIS OF LYS-22; ASP-23; ASN-25; ASN-27;
RP VAL-28 AND LYS-30.
RX PubMed=20603330; DOI=10.1083/jcb.200912087;
RA Kuang Z., Lewis R.S., Curtis J.M., Zhan Y., Saunders B.M., Babon J.J.,
RA Kolesnik T.B., Low A., Masters S.L., Willson T.A., Kedzierski L., Yao S.,
RA Handman E., Norton R.S., Nicholson S.E.;
RT "The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for
RT proteasomal degradation.";
RL J. Cell Biol. 190:129-141(2010).
RN [15]
RP POLYUBIQUITINATION, AND PROTEASOMAL DEGRADATION.
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 [16]
RP INTERACTION WITH ASL; ASS1 AND HSP90AA1.
RX PubMed=22081021; DOI=10.1038/nm.2544;
RA Erez A., Nagamani S.C., Shchelochkov O.A., Premkumar M.H., Campeau P.M.,
RA Chen Y., Garg H.K., Li L., Mian A., Bertin T.K., Black J.O., Zeng H.,
RA Tang Y., Reddy A.K., Summar M., O'Brien W.E., Harrison D.G., Mitch W.E.,
RA Marini J.C., Aschner J.L., Bryan N.S., Lee B.;
RT "Requirement of argininosuccinate lyase for systemic nitric oxide
RT production.";
RL Nat. Med. 17:1619-1626(2011).
RN [17]
RP INDUCTION.
RX PubMed=22073225; DOI=10.1371/journal.pone.0026954;
RA Niu S., Shingle D.L., Garbarino-Pico E., Kojima S., Gilbert M., Green C.B.;
RT "The circadian deadenylase Nocturnin is necessary for stabilization of the
RT iNOS mRNA in mice.";
RL PLoS ONE 6:E26954-E26954(2011).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 116-496.
RX PubMed=9334294; DOI=10.1126/science.278.5337.425;
RA Crane B.R., Arvai A.S., Gachhui R., Wu C., Ghosh D.K., Getzoff E.D.,
RA Stuehr D.J., Tainer J.A.;
RT "The structure of nitric oxide synthase oxygenase domain and inhibitor
RT complexes.";
RL Science 278:425-431(1997).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 77-496.
RX PubMed=9516116; DOI=10.1126/science.279.5359.2121;
RA Crane B.R., Arvai A.S., Ghosh D.K., Wu C., Getzoff E.D., Stuehr D.J.,
RA Tainer J.A.;
RT "Structure of nitric oxide synthase oxygenase dimer with pterin and
RT substrate.";
RL Science 279:2121-2126(1998).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 77-496.
RX PubMed=10562538; DOI=10.1093/emboj/18.22.6260;
RA Ghosh D.K., Crane B.R., Ghosh S., Wolan D., Gachhui R., Crooks C.,
RA Presta A., Tainer J.A., Getzoff E.D., Stuehr D.J.;
RT "Inducible nitric oxide synthase: role of the N-terminal beta-hairpin hook
RT and pterin-binding segment in dimerization and tetrahydrobiopterin
RT interaction.";
RL EMBO J. 18:6260-6270(1999).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 77-499.
RX PubMed=10562539; DOI=10.1093/emboj/18.22.6271;
RA Crane B.R., Rosenfeld R.J., Arvai A.S., Ghosh D.K., Ghosh S., Tainer J.A.,
RA Stuehr D.J., Getzoff E.D.;
RT "N-terminal domain swapping and metal ion binding in nitric oxide synthase
RT dimerization.";
RL EMBO J. 18:6271-6281(1999).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 77-496, AND SUBUNIT.
RX PubMed=10769116; DOI=10.1021/bi992409a;
RA Crane B.R., Arvai A.S., Ghosh S., Getzoff E.D., Stuehr D.J., Tainer J.A.;
RT "Structures of the N(omega)-hydroxy-L-arginine complex of inducible nitric
RT oxide synthase oxygenase dimer with active and inactive pterins.";
RL Biochemistry 39:4608-4621(2000).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF TRP-457 MUTANTS, AND SUBUNIT.
RX PubMed=11669619; DOI=10.1021/bi011183k;
RA Aoyagi M., Arvai A.S., Ghosh S., Stuehr D.J., Tainer J.A., Getzoff E.D.;
RT "Structures of tetrahydrobiopterin binding-site mutants of inducible nitric
RT oxide synthase oxygenase dimer and implicated roles of Trp457.";
RL Biochemistry 40:12826-12832(2001).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 77-496.
RX PubMed=12437348; DOI=10.1021/bi026313j;
RA Rosenfeld R.J., Garcin E.D., Panda K., Andersson G., Aberg A.,
RA Wallace A.V., Morris G.M., Olson A.J., Stuehr D.J., Tainer J.A.,
RA Getzoff E.D.;
RT "Conformational changes in nitric oxide synthases induced by chlorzoxazone
RT and nitroindazoles: crystallographic and computational analyses of
RT inhibitor potency.";
RL Biochemistry 41:13915-13925(2002).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 77-495.
RX PubMed=12464241; DOI=10.1016/s0003-9861(02)00555-6;
RA Fedorov R., Ghosh D.K., Schlichting I.;
RT "Crystal structures of cyanide complexes of P450cam and the oxygenase
RT domain of inducible nitric oxide synthase -- structural models of the
RT short-lived oxygen complexes.";
RL Arch. Biochem. Biophys. 409:25-31(2003).
CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with
CC diverse functions throughout the body (PubMed:7503239). In macrophages,
CC NO mediates tumoricidal and bactericidal actions. Also has nitrosylase
CC activity and mediates cysteine S-nitrosylation of cytoplasmic target
CC proteins such PTGS2/COX2 (PubMed:16373578). As component of the iNOS-
CC S100A8/9 transnitrosylase complex involved in the selective
CC inflammatory stimulus-dependent S-nitrosylation of GAPDH implicated in
CC regulation of the GAIT complex activity and probably multiple targets
CC including ANXA5, EZR, MSN and VIM (By similarity). Involved in
CC inflammation, enhances the synthesis of pro-inflammatory mediators such
CC as IL6 and IL8 (By similarity). {ECO:0000250|UniProtKB:P35228,
CC ECO:0000250|UniProtKB:P79290, ECO:0000269|PubMed:16373578,
CC ECO:0000269|PubMed:7503239}.
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:0000250|UniProtKB:P35228};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19898;
CC Evidence={ECO:0000250|UniProtKB:P35228};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Note=Binds 1 FAD.;
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Note=Binds 1 FMN.;
CC -!- COFACTOR:
CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin;
CC Xref=ChEBI:CHEBI:59560;
CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the
CC enzyme.;
CC -!- ACTIVITY REGULATION: Not stimulated by calcium/calmodulin. Aspirin
CC inhibits expression and function of this enzyme and effects may be
CC exerted at the level of translational/post-translational modification
CC and directly on the catalytic activity.
CC -!- SUBUNIT: Homodimer (PubMed:10769116, PubMed:11669619). Interacts with
CC SLC9A3R1 (By similarity). Interacts with GAPDH (By similarity).
CC Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9
CC transnitrosylase complex (By similarity). Interacts with SPSB1, SPSB2
CC and SPSB4 (PubMed:20603330). Interacts with ELOC and CUL5 in the
CC presence of SPSB1 or SPSB2 or SPSB4 (By similarity). Forms a complex
CC with ASL, ASS1 and HSP90AA1; the complex regulates cell-autonomous L-
CC arginine synthesis and citrulline recycling while channeling
CC extracellular L-arginine to nitric oxide synthesis pathway.
CC {ECO:0000250|UniProtKB:P35228, ECO:0000269|PubMed:10769116,
CC ECO:0000269|PubMed:11669619, ECO:0000269|PubMed:20603330,
CC ECO:0000269|PubMed:22081021}.
CC -!- INTERACTION:
CC P29477; Q04207: Rela; NbExp=3; IntAct=EBI-298897, EBI-644400;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P35228}. Note=Localizes as discrete foci
CC scattered throughout the cytosol and in the presence of SPSB1 and
CC SPSB4, exhibits a more diffuse cytosolic localization.
CC {ECO:0000250|UniProtKB:P35228}.
CC -!- TISSUE SPECIFICITY: Macrophages.
CC -!- INDUCTION: By treatment with endotoxins or cytokines. By
CC lipopolysaccharides (LPS) (in vitro). Expression in the liver
CC oscillates in a circadian manner with peak levels occurring during the
CC late night. {ECO:0000269|PubMed:22073225}.
CC -!- PTM: Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to
CC proteasomal degradation. {ECO:0000269|PubMed:20603330,
CC ECO:0000269|PubMed:21199876}.
CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}.
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DR EMBL; M87039; AAA39315.1; -; mRNA.
DR EMBL; M92649; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; M84373; AAA39834.1; -; mRNA.
DR EMBL; U43428; AAC52356.1; -; mRNA.
DR EMBL; AF065919; AAC17914.1; -; mRNA.
DR EMBL; AF065920; AAC17915.1; -; mRNA.
DR EMBL; AF065921; AAC17916.2; -; mRNA.
DR EMBL; AF065922; AAC17917.2; -; mRNA.
DR EMBL; AF065923; AAC17918.2; -; mRNA.
DR EMBL; AF427516; AAL24076.1; -; Genomic_DNA.
DR EMBL; AY090567; AAM11887.1; -; mRNA.
DR EMBL; AL592185; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC062378; AAH62378.1; -; mRNA.
DR CCDS; CCDS25115.1; -.
DR PIR; A43271; A43271.
DR RefSeq; NP_001300850.1; NM_001313921.1.
DR RefSeq; NP_001300851.1; NM_001313922.1.
DR RefSeq; NP_035057.1; NM_010927.4.
DR PDB; 1DD7; X-ray; 2.25 A; A=114-498.
DR PDB; 1DF1; X-ray; 2.35 A; A/B=77-499.
DR PDB; 1DWV; X-ray; 2.35 A; A/B=77-496.
DR PDB; 1DWW; X-ray; 2.35 A; A/B=77-496.
DR PDB; 1DWX; X-ray; 2.60 A; A/B=77-496.
DR PDB; 1JWJ; X-ray; 2.60 A; A/B=66-498.
DR PDB; 1JWK; X-ray; 2.30 A; A/B=66-498.
DR PDB; 1M8D; X-ray; 2.35 A; A/B=65-498.
DR PDB; 1M8E; X-ray; 2.90 A; A/B=65-498.
DR PDB; 1M8H; X-ray; 2.85 A; A/B=65-498.
DR PDB; 1M8I; X-ray; 2.70 A; A/B=65-498.
DR PDB; 1M9T; X-ray; 2.40 A; A/B=65-498.
DR PDB; 1N2N; X-ray; 2.40 A; A/B=77-495.
DR PDB; 1NOC; X-ray; 2.60 A; A=115-498.
DR PDB; 1NOD; X-ray; 2.60 A; A/B=77-499.
DR PDB; 1NOS; X-ray; 2.10 A; A=115-498.
DR PDB; 1QOM; X-ray; 2.70 A; A/B=65-498.
DR PDB; 1QW4; X-ray; 2.40 A; A/B=77-495.
DR PDB; 1QW5; X-ray; 2.70 A; A/B=77-495.
DR PDB; 1R35; X-ray; 2.30 A; A/B=66-498.
DR PDB; 1VAF; X-ray; 2.90 A; A/B=77-495.
DR PDB; 2BHJ; X-ray; 3.20 A; A=77-498.
DR PDB; 2NOD; X-ray; 2.60 A; A/B=77-499.
DR PDB; 2NOS; X-ray; 2.30 A; A=115-498.
DR PDB; 2ORO; X-ray; 2.00 A; A=114-498.
DR PDB; 2ORP; X-ray; 1.97 A; A=114-498.
DR PDB; 2ORQ; X-ray; 2.10 A; A=114-498.
DR PDB; 2ORR; X-ray; 2.00 A; A=114-498.
DR PDB; 2ORS; X-ray; 2.00 A; A=114-498.
DR PDB; 2ORT; X-ray; 1.87 A; A=114-498.
DR PDB; 2Y37; X-ray; 2.60 A; A/B=66-498.
DR PDB; 3DWJ; X-ray; 2.75 A; A/B=66-496.
DR PDB; 3E65; X-ray; 2.05 A; A/B=66-498.
DR PDB; 3E67; X-ray; 2.60 A; A/B=66-498.
DR PDB; 3E68; X-ray; 2.20 A; A/B=66-498.
DR PDB; 3E6L; X-ray; 2.30 A; A/B=66-498.
DR PDB; 3E6N; X-ray; 2.40 A; A/B=66-498.
DR PDB; 3E6O; X-ray; 2.60 A; A/B=66-498.
DR PDB; 3E6T; X-ray; 2.50 A; A/B=66-498.
DR PDB; 3E7I; X-ray; 2.90 A; A/B=66-498.
DR PDB; 3E7M; X-ray; 2.00 A; A/B=66-498.
DR PDB; 3E7T; X-ray; 2.60 A; A/B=66-498.
DR PDB; 3EAI; X-ray; 2.20 A; A/B=66-498.
DR PDB; 3EBD; X-ray; 2.40 A; A/B=66-498.
DR PDB; 3EBF; X-ray; 2.29 A; A/B=66-498.
DR PDB; 3GOF; X-ray; 1.45 A; C/D=503-518.
DR PDB; 3NOD; X-ray; 2.70 A; A/B=77-499.
DR PDB; 3NQS; X-ray; 2.20 A; A/B=66-498.
DR PDB; 3NW2; X-ray; 2.80 A; A/B=77-499.
DR PDB; 4JS9; X-ray; 2.78 A; A/B=66-496.
DR PDB; 4UX6; X-ray; 3.00 A; A=77-100, B=108-496.
DR PDBsum; 1DD7; -.
DR PDBsum; 1DF1; -.
DR PDBsum; 1DWV; -.
DR PDBsum; 1DWW; -.
DR PDBsum; 1DWX; -.
DR PDBsum; 1JWJ; -.
DR PDBsum; 1JWK; -.
DR PDBsum; 1M8D; -.
DR PDBsum; 1M8E; -.
DR PDBsum; 1M8H; -.
DR PDBsum; 1M8I; -.
DR PDBsum; 1M9T; -.
DR PDBsum; 1N2N; -.
DR PDBsum; 1NOC; -.
DR PDBsum; 1NOD; -.
DR PDBsum; 1NOS; -.
DR PDBsum; 1QOM; -.
DR PDBsum; 1QW4; -.
DR PDBsum; 1QW5; -.
DR PDBsum; 1R35; -.
DR PDBsum; 1VAF; -.
DR PDBsum; 2BHJ; -.
DR PDBsum; 2NOD; -.
DR PDBsum; 2NOS; -.
DR PDBsum; 2ORO; -.
DR PDBsum; 2ORP; -.
DR PDBsum; 2ORQ; -.
DR PDBsum; 2ORR; -.
DR PDBsum; 2ORS; -.
DR PDBsum; 2ORT; -.
DR PDBsum; 2Y37; -.
DR PDBsum; 3DWJ; -.
DR PDBsum; 3E65; -.
DR PDBsum; 3E67; -.
DR PDBsum; 3E68; -.
DR PDBsum; 3E6L; -.
DR PDBsum; 3E6N; -.
DR PDBsum; 3E6O; -.
DR PDBsum; 3E6T; -.
DR PDBsum; 3E7I; -.
DR PDBsum; 3E7M; -.
DR PDBsum; 3E7T; -.
DR PDBsum; 3EAI; -.
DR PDBsum; 3EBD; -.
DR PDBsum; 3EBF; -.
DR PDBsum; 3GOF; -.
DR PDBsum; 3NOD; -.
DR PDBsum; 3NQS; -.
DR PDBsum; 3NW2; -.
DR PDBsum; 4JS9; -.
DR PDBsum; 4UX6; -.
DR AlphaFoldDB; P29477; -.
DR SMR; P29477; -.
DR BioGRID; 201806; 9.
DR ComplexPortal; CPX-53; iNOS-S100A8/A9 complex.
DR DIP; DIP-31080N; -.
DR IntAct; P29477; 2.
DR MINT; P29477; -.
DR STRING; 10090.ENSMUSP00000018610; -.
DR BindingDB; P29477; -.
DR ChEMBL; CHEMBL3464; -.
DR DrugCentral; P29477; -.
DR iPTMnet; P29477; -.
DR PhosphoSitePlus; P29477; -.
DR SwissPalm; P29477; -.
DR MaxQB; P29477; -.
DR PaxDb; P29477; -.
DR PRIDE; P29477; -.
DR ProteomicsDB; 293704; -.
DR Antibodypedia; 4550; 1111 antibodies from 47 providers.
DR DNASU; 18126; -.
DR Ensembl; ENSMUST00000018610; ENSMUSP00000018610; ENSMUSG00000020826.
DR GeneID; 18126; -.
DR KEGG; mmu:18126; -.
DR UCSC; uc007kkc.1; mouse.
DR CTD; 4843; -.
DR MGI; MGI:97361; Nos2.
DR VEuPathDB; HostDB:ENSMUSG00000020826; -.
DR eggNOG; KOG1158; Eukaryota.
DR GeneTree; ENSGT00940000159752; -.
DR HOGENOM; CLU_001570_16_0_1; -.
DR InParanoid; P29477; -.
DR OMA; WFMDAEI; -.
DR OrthoDB; 90349at2759; -.
DR PhylomeDB; P29477; -.
DR TreeFam; TF324410; -.
DR BRENDA; 1.14.13.39; 3474.
DR Reactome; R-MMU-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-MMU-392154; Nitric oxide stimulates guanylate cyclase.
DR Reactome; R-MMU-9033241; Peroxisomal protein import.
DR BioGRID-ORCS; 18126; 4 hits in 76 CRISPR screens.
DR EvolutionaryTrace; P29477; -.
DR PRO; PR:P29477; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P29477; protein.
DR Bgee; ENSMUSG00000020826; Expressed in ectoplacental cone and 40 other tissues.
DR ExpressionAtlas; P29477; baseline and differential.
DR Genevisible; P29477; MM.
DR GO; GO:0030863; C:cortical cytoskeleton; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0005777; C:peroxisome; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0012506; C:vesicle membrane; ISO:MGI.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0034618; F:arginine binding; IDA:BHF-UCL.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0045296; F:cadherin binding; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; TAS:UniProtKB.
DR GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; ISO:MGI.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:BHF-UCL.
DR GO; GO:0010181; F:FMN binding; IDA:BHF-UCL.
DR GO; GO:0020037; F:heme binding; IDA:BHF-UCL.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0004517; F:nitric-oxide synthase activity; IDA:BHF-UCL.
DR GO; GO:0050998; F:nitric-oxide synthase binding; ISO:MGI.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0034617; F:tetrahydrobiopterin binding; IDA:BHF-UCL.
DR GO; GO:0006527; P:arginine catabolic process; IDA:BHF-UCL.
DR GO; GO:0001974; P:blood vessel remodeling; ISO:MGI.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:MGI.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IDA:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0019934; P:cGMP-mediated signaling; ISO:MGI.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IMP:MGI.
DR GO; GO:0007199; P:G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
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; IDA:BHF-UCL.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IBA:GO_Central.
DR GO; GO:0018119; P:peptidyl-cysteine S-nitrosylation; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; ISO:MGI.
DR GO; GO:0032310; P:prostaglandin secretion; ISS:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI.
DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0008016; P:regulation of heart contraction; ISO:MGI.
DR GO; GO:0050796; P:regulation of insulin secretion; ISO:MGI.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0001666; P:response to hypoxia; IDA:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0006801; P:superoxide metabolic process; IMP:MGI.
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; Calmodulin-binding; Cytoplasm; Direct protein sequencing;
KW FAD; Flavoprotein; FMN; Heme; Iron; Metal-binding; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc.
FT CHAIN 1..1144
FT /note="Nitric oxide synthase, inducible"
FT /id="PRO_0000170934"
FT DOMAIN 533..671
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 724..964
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 37..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..523
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:20603330"
FT COMPBIAS 41..59
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 104
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 109
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 112
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 194
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 257
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 366
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 367
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 371
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 457
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 470
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 485
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 617..648
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 761..772
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 897..907
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 972..990
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 1070..1085
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 569
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q06518"
FT VARIANT 211
FT /note="C -> R (in strain: NOD/LtJ)"
FT /evidence="ECO:0000269|PubMed:10438970"
FT VARIANT 967
FT /note="P -> L (in strain: SJL/J)"
FT /evidence="ECO:0000269|PubMed:10438970"
FT VARIANT 968
FT /note="S -> F (in strain: BALB/CBYJ)"
FT /evidence="ECO:0000269|PubMed:10438970"
FT MUTAGEN 22
FT /note="K->A: Reduced interaction with SPSB2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT MUTAGEN 23
FT /note="D->A: Significant loss of interaction with SPSB2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT MUTAGEN 25
FT /note="N->A,Q: Significant loss of interaction with SPSB2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT MUTAGEN 27
FT /note="N->A,Q: Loss of interaction with SPSB2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT MUTAGEN 28
FT /note="V->A: Reduced interaction with SPSB2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT MUTAGEN 30
FT /note="K->A: Reduced interaction with SPSB2."
FT /evidence="ECO:0000269|PubMed:20603330"
FT CONFLICT 19
FT /note="K -> T (in Ref. 4; AAC52356)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="T -> TP (in Ref. 7; AAM11887 and 9; AAH62378)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="A -> V (in Ref. 2; M92649)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="S -> T (in Ref. 7; AAM11887 and 9; AAH62378)"
FT /evidence="ECO:0000305"
FT CONFLICT 844
FT /note="A -> G (in Ref. 2; M92649)"
FT /evidence="ECO:0000305"
FT CONFLICT 1075
FT /note="I -> V (in Ref. 9; AAH62378)"
FT /evidence="ECO:0000305"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:3E7M"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:3E7M"
FT STRAND 89..92
FT /evidence="ECO:0007829|PDB:3E7M"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:3E7M"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:1QOM"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:3E7M"
FT HELIX 130..146
FT /evidence="ECO:0007829|PDB:2ORT"
FT TURN 147..150
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 153..170
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 177..189
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 195..199
FT /evidence="ECO:0007829|PDB:2ORT"
FT STRAND 204..207
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:2BHJ"
FT HELIX 214..229
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:2ORT"
FT STRAND 237..240
FT /evidence="ECO:0007829|PDB:2ORT"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:2ORT"
FT STRAND 255..259
FT /evidence="ECO:0007829|PDB:2ORT"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:2ORP"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:2BHJ"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:2ORP"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 278..286
FT /evidence="ECO:0007829|PDB:2ORT"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:1DF1"
FT STRAND 301..304
FT /evidence="ECO:0007829|PDB:2ORT"
FT STRAND 311..313
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:2ORT"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 332..334
FT /evidence="ECO:0007829|PDB:2ORO"
FT TURN 335..337
FT /evidence="ECO:0007829|PDB:2ORO"
FT STRAND 339..342
FT /evidence="ECO:0007829|PDB:2ORT"
FT STRAND 350..353
FT /evidence="ECO:0007829|PDB:2ORT"
FT STRAND 356..359
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 369..373
FT /evidence="ECO:0007829|PDB:3E7M"
FT HELIX 375..378
FT /evidence="ECO:0007829|PDB:3E7M"
FT TURN 380..383
FT /evidence="ECO:0007829|PDB:3E7M"
FT HELIX 386..392
FT /evidence="ECO:0007829|PDB:3E7M"
FT HELIX 400..402
FT /evidence="ECO:0007829|PDB:3E7M"
FT HELIX 415..422
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 430..442
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 455..458
FT /evidence="ECO:0007829|PDB:3E7M"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:3E7M"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:3E7M"
FT HELIX 468..471
FT /evidence="ECO:0007829|PDB:3E7M"
FT STRAND 480..485
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 489..492
FT /evidence="ECO:0007829|PDB:2ORT"
FT HELIX 509..517
FT /evidence="ECO:0007829|PDB:3GOF"
SQ SEQUENCE 1144 AA; 130575 MW; 0735BE676113457F CRC64;
MACPWKFLFK VKSYQSDLKE EKDINNNVKK TPCAVLSPTI QDDPKSHQNG SPQLLTGTAQ
NVPESLDKLH VTSTRPQYVR IKNWGSGEIL HDTLHHKATS DFTCKSKSCL GSIMNPKSLT
RGPRDKPTPL EELLPHAIEF INQYYGSFKE AKIEEHLARL EAVTKEIETT GTYQLTLDEL
IFATKMAWRN APRCIGRIQW SNLQVFDARN CSTAQEMFQH ICRHILYATN NGNIRSAITV
FPQRSDGKHD FRLWNSQLIR YAGYQMPDGT IRGDAATLEF TQLCIDLGWK PRYGRFDVLP
LVLQADGQDP EVFEIPPDLV LEVTMEHPKY EWFQELGLKW YALPAVANML LEVGGLEFPA
CPFNGWYMGT EIGVRDFCDT QRYNILEEVG RRMGLETHTL ASLWKDRAVT EINVAVLHSF
QKQNVTIMDH HTASESFMKH MQNEYRARGG CPADWIWLVP PVSGSITPVF HQEMLNYVLS
PFYYYQIEPW KTHIWQNEKL RPRRREIRFR VLVKVVFFAS MLMRKVMASR VRATVLFATE
TGKSEALARD LATLFSYAFN TKVVCMDQYK ASTLEEEQLL LVVTSTFGNG DCPSNGQTLK
KSLFMLRELN HTFRYAVFGL GSSMYPQFCA FAHDIDQKLS HLGASQLAPT GEGDELSGQE
DAFRSWAVQT FRAACETFDV RSKHHIQIPK RFTSNATWEP QQYRLIQSPE PLDLNRALSS
IHAKNVFTMR LKSQQNLQSE KSSRTTLLVQ LTFEGSRGPS YLPGEHLGIF PGNQTALVQG
ILERVVDCPT PHQTVCLEVL DESGSYWVKD KRLPPCSLSQ ALTYFLDITT PPTQLQLHKL
ARFATDETDR QRLEALCQPS EYNDWKFSNN PTFLEVLEEF PSLHVPAAFL LSQLPILKPR
YYSISSSQDH TPSEVHLTVA VVTYRTRDGQ GPLHHGVCST WIRNLKPQDP VPCFVRSVSG
FQLPEDPSQP CILIGPGTGI APFRSFWQQR LHDSQHKGLK GGRMSLVFGC RHPEEDHLYQ
EEMQEMVRKR VLFQVHTGYS RLPGKPKVYV QDILQKQLAN EVLSVLHGEQ GHLYICGDVR
MARDVATTLK KLVATKLNLS EEQVEDYFFQ LKSQKRYHED IFGAVFSYGA KKGSALEEPK
ATRL
