NOS3_HUMAN
ID NOS3_HUMAN Reviewed; 1203 AA.
AC P29474; A0S0A7; A0S0A8; A8KA63; B2RCQ1; E9PFR2; Q13662; Q14251; Q14434;
AC Q548C1; Q6GSL5; Q9UDC6;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 4.
DT 03-AUG-2022, entry version 246.
DE RecName: Full=Nitric oxide synthase, endothelial {ECO:0000305};
DE EC=1.14.13.39 {ECO:0000269|PubMed:1378832};
DE AltName: Full=Constitutive NOS;
DE Short=cNOS;
DE AltName: Full=EC-NOS;
DE AltName: Full=Endothelial NOS;
DE Short=eNOS;
DE AltName: Full=NOS type III;
DE Short=NOSIII;
GN Name=NOS3 {ECO:0000312|HGNC:HGNC:7876};
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), VARIANT GLU-298, CATALYTIC
RP ACTIVITY, AND FUNCTION.
RX PubMed=1378832; DOI=10.1016/s0021-9258(18)42066-2;
RA Janssens S.P., Shimouchi A., Quertermous T., Bloch D.B., Bloch K.D.;
RT "Cloning and expression of a cDNA encoding human endothelium-derived
RT relaxing factor/nitric oxide synthase.";
RL J. Biol. Chem. 267:14519-14522(1992).
RN [2]
RP ERRATUM OF PUBMED:1378832.
RA Janssens S.P., Shimouchi A., Quertermous T., Bloch D.B., Bloch K.D.;
RL J. Biol. Chem. 267:22694-22694(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLU-298.
RX PubMed=1379542; DOI=10.1016/0014-5793(92)80697-f;
RA Marsden P.A., Schappert K.T., Chen H.S., Flowers M., Sundell C.L.,
RA Wilcox J.N., Lamas S., Michel T.;
RT "Molecular cloning and characterization of human endothelial nitric oxide
RT synthase.";
RL FEBS Lett. 307:287-293(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-298.
RX PubMed=7688726; DOI=10.1016/s0021-9258(19)85359-0;
RA Marsden P.A., Heng H.H.Q., Scherer S.W., Stewart R.J., Hall A.V.,
RA Shi X.-M., Tsui L.-C., Schappert K.T.;
RT "Structure and chromosomal localization of the human constitutive
RT endothelial nitric oxide synthase gene.";
RL J. Biol. Chem. 268:17478-17488(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=7509596; DOI=10.1006/bbrc.1994.1146;
RA Nadaud S.A., Bonnardeaux A., Lathrop M., Soubrier F.;
RT "Gene structure, polymorphism and mapping of the human endothelial nitric
RT oxide synthase gene.";
RL Biochem. Biophys. Res. Commun. 198:1027-1033(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-298.
RX PubMed=7519987; DOI=10.1111/j.1432-1033.1994.tb19045.x;
RA Miyahara K., Kawamoto T., Sase K., Yui Y., Toda K., Yang L.X., Hattori R.,
RA Aoyama T., Yamamoto Y., Doi Y., Ogoshi S., Hashimoto K., Kawai C.,
RA Sasayama S., Shizuta Y.;
RT "Cloning and structural characterization of the human endothelial nitric-
RT oxide-synthase gene.";
RL Eur. J. Biochem. 223:719-726(1994).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ENOS13B AND ENOS13C), ALTERNATIVE
RP SPLICING, FUNCTION (ISOFORM ENOS13C), AND VARIANT GLU-298.
RX PubMed=17264164; DOI=10.1096/fj.06-7434com;
RA Lorenz M., Hewing B., Hui J., Zepp A., Baumann G., Bindereif A., Stangl V.,
RA Stangl K.;
RT "Alternative splicing in intron 13 of the human eNOS gene: a potential
RT mechanism for regulating eNOS activity.";
RL FASEB J. 21:1556-1564(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-298.
RC TISSUE=Umbilical vein;
RA Liao J.K.;
RL Submitted (DEC-1993) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLU-298.
RC TISSUE=Platelet;
RA Zhang Y., Freedman J.E.;
RT "The role of phosphatidylinositol-3-oh kinase in platelet-derived nitric
RT oxide release and platelet disaggregation.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-298.
RC TISSUE=Hippocampus, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-298.
RC TISSUE=Spleen;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-112; GLU-298; MET-827;
RP MET-885 AND LEU-982.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-298.
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-298.
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [15]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-298.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [16]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-298.
RC TISSUE=Placenta;
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 [17]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-53.
RC TISSUE=Placenta;
RX PubMed=7514568; DOI=10.1006/geno.1994.1068;
RA Robinson L.J., Weremowicz S., Morton C.C., Michel T.;
RT "Isolation and chromosomal localization of the human endothelial nitric
RT oxide synthase (NOS3) gene.";
RL Genomics 19:350-357(1994).
RN [18]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 411-528 (ISOFORM 1/ENOS13C).
RC TISSUE=Platelet;
RX PubMed=7475956; DOI=10.1016/0024-3205(95)02191-k;
RA Sase K., Michel T.;
RT "Expression of constitutive endothelial nitric oxide synthase in human
RT blood platelets.";
RL Life Sci. 57:2049-2055(1995).
RN [19]
RP PROTEIN SEQUENCE OF 167-175; 531-540; 835-845; 876-881; 886-898; 1001-1005
RP AND 1068-1080, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=7515611; DOI=10.1006/abbi.1994.1232;
RA Garvey E.P., Tuttle J.V., Covington K., Merrill B.M., Wood E.R.,
RA Baylis S.A., Charles I.G.;
RT "Purification and characterization of the constitutive nitric oxide
RT synthase from human placenta.";
RL Arch. Biochem. Biophys. 311:235-241(1994).
RN [20]
RP INTERACTION WITH NOSIP, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=11149895; DOI=10.1096/fj.00-0078com;
RA Dedio J., Koenig P., Wohlfart P., Schroeder C., Kummer W.,
RA Mueller-Esterl W.;
RT "NOSIP, a novel modulator of endothelial nitric oxide synthase activity.";
RL FASEB J. 15:79-89(2001).
RN [21]
RP INTERACTION WITH NOSTRIN, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=12446846; DOI=10.1073/pnas.252345399;
RA Zimmermann K., Opitz N., Dedio J., Renne C., Mueller-Esterl W., Oess S.;
RT "NOSTRIN: a protein modulating nitric oxide release and subcellular
RT distribution of endothelial nitric oxide synthase.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:17167-17172(2002).
RN [22]
RP PHOSPHORYLATION AT THR-495 AND SER-1177.
RX PubMed=16126727; DOI=10.1074/jbc.m506374200;
RA David-Dufilho M., Millanvoye-Van Brussel E., Topal G., Walch L., Brunet A.,
RA Rendu F.;
RT "Endothelial thrombomodulin induces Ca2+ signals and nitric oxide synthesis
RT through epidermal growth factor receptor kinase and calmodulin kinase II.";
RL J. Biol. Chem. 280:35999-36006(2005).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=16234328; DOI=10.1242/jcs.02620;
RA Icking A., Matt S., Opitz N., Wiesenthal A., Mueller-Esterl W.,
RA Schilling K.;
RT "NOSTRIN functions as a homotrimeric adaptor protein facilitating
RT internalization of eNOS.";
RL J. Cell Sci. 118:5059-5069(2005).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=16135813; DOI=10.1128/mcb.25.18.8251-8258.2005;
RA Schleicher M., Brundin F., Gross S., Mueller-Esterl W., Oess S.;
RT "Cell cycle-regulated inactivation of endothelial NO synthase through
RT NOSIP-dependent targeting to the cytoskeleton.";
RL Mol. Cell. Biol. 25:8251-8258(2005).
RN [25]
RP PHOSPHORYLATION AT SER-114, AND MUTAGENESIS OF SER-114.
RX PubMed=20213743; DOI=10.1002/jcb.22515;
RA Lee C.-H., Wei Y.-W., Huang Y.-T., Lin Y.-T., Lee Y.-C., Lee K.-H.,
RA Lu P.-J.;
RT "CDK5 phosphorylates eNOS at Ser-113 and regulates NO production.";
RL J. Cell. Biochem. 110:112-117(2010).
RN [26]
RP INTERACTION WITH HSP90AB1.
RX PubMed=23585225; DOI=10.1152/ajplung.00419.2012;
RA Barabutis N., Handa V., Dimitropoulou C., Rafikov R., Snead C., Kumar S.,
RA Joshi A., Thangjam G., Fulton D., Black S.M., Patel V., Catravas J.D.;
RT "LPS induces pp60c-src-mediated tyrosine phosphorylation of Hsp90 in lung
RT vascular endothelial cells and mouse lung.";
RL Am. J. Physiol. 304:L883-L893(2013).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1177, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-33; SER-633; SER-638 AND
RP SER-836, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
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 [30]
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 67-480.
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 [31]
RP X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 66-492.
RX PubMed=18849972; DOI=10.1038/nchembio.115;
RA Garcin E.D., Arvai A.S., Rosenfeld R.J., Kroeger M.D., Crane B.R.,
RA Andersson G., Andrews G., Hamley P.J., Mallinder P.R., Nicholls D.J.,
RA St-Gallay S.A., Tinker A.C., Gensmantel N.P., Mete A., Cheshire D.R.,
RA Connolly S., Stuehr D.J., Aberg A., Wallace A.V., Tainer J.A.,
RA Getzoff E.D.;
RT "Anchored plasticity opens doors for selective inhibitor design in nitric
RT oxide synthase.";
RL Nat. Chem. Biol. 4:700-707(2008).
RN [32] {ECO:0007744|PDB:4D1O, ECO:0007744|PDB:4D1P}
RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 302-721 IN COMPLEXES WITH
RP 5,6,7,8-TETRAHYDROBIOPTERIN; L-ARGININE; HEME AND AN AMINOPYRIDINE
RP INHIBITOR, AND COFACTOR.
RX PubMed=25286850; DOI=10.1107/s1399004714017064;
RA Li H., Jamal J., Plaza C., Pineda S.H., Chreifi G., Jing Q., Cinelli M.A.,
RA Silverman R.B., Poulos T.L.;
RT "Structures of human constitutive nitric oxide synthases.";
RL Acta Crystallogr. D 70:2667-2674(2014).
RN [33]
RP VARIANT GLU-298, AND POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO CORONARY
RP SPASM.
RX PubMed=9737779; DOI=10.1007/s004390050785;
RA Yoshimura M., Yasue H., Nakayama M., Shimasaki Y., Sumida H., Sugiyama S.,
RA Kugiyama K., Ogawa H., Ogawa Y., Saito Y., Miyamoto Y., Nakao K.;
RT "A missense Glu298Asp variant in the endothelial nitric oxide synthase gene
RT is associated with coronary spasm in the Japanese.";
RL Hum. Genet. 103:65-69(1998).
RN [34]
RP VARIANT GLU-298, AND POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO CORONARY
RP SPASM.
RX PubMed=11740345; DOI=10.1097/00008571-200112000-00009;
RA Sofowora G., Dishy V., Xie H.G., Imamura H., Nishimi Y., Morales C.R.,
RA Morrow J.D., Kim R.B., Stein C.M., Wood A.J.;
RT "In-vivo effects of Glu298Asp endothelial nitric oxide synthase
RT polymorphism.";
RL Pharmacogenetics 11:809-814(2001).
RN [35]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-474 AND GLN-602.
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).
CC -!- FUNCTION: Produces nitric oxide (NO) which is implicated in vascular
CC smooth muscle relaxation through a cGMP-mediated signal transduction
CC pathway (PubMed:1378832). NO mediates vascular endothelial growth
CC factor (VEGF)-induced angiogenesis in coronary vessels and promotes
CC blood clotting through the activation of platelets.
CC {ECO:0000269|PubMed:1378832}.
CC -!- FUNCTION: [Isoform eNOS13C]: Lacks eNOS activity, dominant-negative
CC form that may down-regulate eNOS activity by forming heterodimers with
CC isoform 1.
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:1378832};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19898;
CC Evidence={ECO:0000305|PubMed:1378832};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000269|PubMed:25286850};
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; Evidence={ECO:0000269|PubMed:25286850};
CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the
CC enzyme. {ECO:0000269|PubMed:25286850};
CC -!- ACTIVITY REGULATION: Stimulated by calcium/calmodulin. Inhibited by
CC NOSIP and NOSTRIN. {ECO:0000269|PubMed:11149895,
CC ECO:0000269|PubMed:12446846}.
CC -!- SUBUNIT: Homodimer. Interacts with NOSIP and NOSTRIN (PubMed:11149895,
CC PubMed:12446846). Interacts with HSP90AB1 (PubMed:23585225,
CC PubMed:11149895, PubMed:12446846) (By similarity). Forms a complex with
CC ASL, ASS1 and SLC7A1; the complex regulates cell-autonomous L-arginine
CC synthesis and citrulline recycling while channeling extracellular L-
CC arginine to nitric oxide synthesis pathway (By similarity).
CC {ECO:0000250|UniProtKB:P70313, ECO:0000269|PubMed:11149895,
CC ECO:0000269|PubMed:12446846, ECO:0000269|PubMed:23585225}.
CC -!- INTERACTION:
CC P29474; P60709: ACTB; NbExp=3; IntAct=EBI-1391623, EBI-353944;
CC P29474; P63010-2: AP2B1; NbExp=3; IntAct=EBI-1391623, EBI-11529439;
CC P29474; Q8N6T3-3: ARFGAP1; NbExp=3; IntAct=EBI-1391623, EBI-10694449;
CC P29474; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-1391623, EBI-14199987;
CC P29474; Q96FT7-4: ASIC4; NbExp=3; IntAct=EBI-1391623, EBI-9089489;
CC P29474; Q5SZD1: C6orf141; NbExp=3; IntAct=EBI-1391623, EBI-10697767;
CC P29474; Q16543: CDC37; NbExp=4; IntAct=EBI-1391623, EBI-295634;
CC P29474; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-1391623, EBI-350590;
CC P29474; Q8IUI8: CRLF3; NbExp=3; IntAct=EBI-1391623, EBI-2872414;
CC P29474; P35222: CTNNB1; NbExp=4; IntAct=EBI-1391623, EBI-491549;
CC P29474; Q05193: DNM1; NbExp=2; IntAct=EBI-1391623, EBI-713135;
CC P29474; O15287: FANCG; NbExp=3; IntAct=EBI-1391623, EBI-81610;
CC P29474; Q08379: GOLGA2; NbExp=6; IntAct=EBI-1391623, EBI-618309;
CC P29474; Q71DI3: H3C15; NbExp=3; IntAct=EBI-1391623, EBI-750650;
CC P29474; P69905: HBA2; NbExp=2; IntAct=EBI-1391623, EBI-714680;
CC P29474; P61978: HNRNPK; NbExp=3; IntAct=EBI-1391623, EBI-304185;
CC P29474; Q12891: HYAL2; NbExp=3; IntAct=EBI-1391623, EBI-2806068;
CC P29474; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-1391623, EBI-747204;
CC P29474; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-1391623, EBI-714379;
CC P29474; Q14525: KRT33B; NbExp=3; IntAct=EBI-1391623, EBI-1049638;
CC P29474; Q6DKI2: LGALS9C; NbExp=3; IntAct=EBI-1391623, EBI-9088829;
CC P29474; P43364-2: MAGEA11; NbExp=3; IntAct=EBI-1391623, EBI-10178634;
CC P29474; Q8N6F8: METTL27; NbExp=3; IntAct=EBI-1391623, EBI-8487781;
CC P29474; O94851: MICAL2; NbExp=3; IntAct=EBI-1391623, EBI-2804835;
CC P29474; A4FUJ8: MKL1; NbExp=3; IntAct=EBI-1391623, EBI-21250407;
CC P29474; Q8N594: MPND; NbExp=3; IntAct=EBI-1391623, EBI-2512452;
CC P29474; Q8IVI9: NOSTRIN; NbExp=9; IntAct=EBI-1391623, EBI-1391643;
CC P29474; Q6X4W1-6: NSMF; NbExp=3; IntAct=EBI-1391623, EBI-25842707;
CC P29474; O15381-5: NVL; NbExp=3; IntAct=EBI-1391623, EBI-18577082;
CC P29474; Q9NV79: PCMTD2; NbExp=3; IntAct=EBI-1391623, EBI-6309018;
CC P29474; Q16549: PCSK7; NbExp=3; IntAct=EBI-1391623, EBI-8059854;
CC P29474; Q5T2W1: PDZK1; NbExp=3; IntAct=EBI-1391623, EBI-349819;
CC P29474; O75925: PIAS1; NbExp=3; IntAct=EBI-1391623, EBI-629434;
CC P29474; Q96I34: PPP1R16A; NbExp=3; IntAct=EBI-1391623, EBI-710402;
CC P29474; Q6ZMI0-5: PPP1R21; NbExp=3; IntAct=EBI-1391623, EBI-25835994;
CC P29474; P57052: RBM11; NbExp=3; IntAct=EBI-1391623, EBI-741332;
CC P29474; Q9GZR2: REXO4; NbExp=3; IntAct=EBI-1391623, EBI-2856313;
CC P29474; Q96D59: RNF183; NbExp=3; IntAct=EBI-1391623, EBI-743938;
CC P29474; Q8N6K7-2: SAMD3; NbExp=3; IntAct=EBI-1391623, EBI-11528848;
CC P29474; Q8IUW3: SPATA2L; NbExp=3; IntAct=EBI-1391623, EBI-2510414;
CC P29474; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-1391623, EBI-5235340;
CC P29474; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-1391623, EBI-7082156;
CC P29474; P50502: ST13; NbExp=3; IntAct=EBI-1391623, EBI-357285;
CC P29474; Q9BR01-2: SULT4A1; NbExp=3; IntAct=EBI-1391623, EBI-25831443;
CC P29474; Q9NVV9: THAP1; NbExp=3; IntAct=EBI-1391623, EBI-741515;
CC P29474; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-1391623, EBI-11525489;
CC P29474; Q9H347: UBQLN3; NbExp=3; IntAct=EBI-1391623, EBI-25832660;
CC P29474; P58304: VSX2; NbExp=3; IntAct=EBI-1391623, EBI-6427899;
CC P29474; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-1391623, EBI-358545;
CC P29474; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-1391623, EBI-12040603;
CC P29474; Q9UNY5: ZNF232; NbExp=3; IntAct=EBI-1391623, EBI-749023;
CC P29474; P14079: tax; Xeno; NbExp=3; IntAct=EBI-1391623, EBI-9675698;
CC -!- SUBCELLULAR LOCATION: Cell membrane. Membrane, caveola. Cytoplasm,
CC cytoskeleton. Golgi apparatus. Note=Specifically associates with actin
CC cytoskeleton in the G2 phase of the cell cycle; which is favored by
CC interaction with NOSIP and results in a reduced enzymatic activity.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P29474-1; Sequence=Displayed;
CC Name=eNOS13C;
CC IsoId=P29474-2; Sequence=VSP_042625, VSP_042626;
CC Name=eNOS13B;
CC IsoId=P29474-3; Sequence=VSP_045495, VSP_045496;
CC -!- TISSUE SPECIFICITY: Platelets, placenta, liver and kidney.
CC {ECO:0000269|PubMed:7515611}.
CC -!- PTM: Phosphorylation by AMPK at Ser-1177 in the presence of Ca(2+)-
CC calmodulin (CaM) activates activity. In absence of Ca(2+)-calmodulin,
CC AMPK also phosphorylates Thr-495, resulting in inhibition of activity
CC (By similarity). Phosphorylation of Ser-114 by CDK5 reduces activity.
CC {ECO:0000250, ECO:0000269|PubMed:16126727,
CC ECO:0000269|PubMed:20213743}.
CC -!- DISEASE: Note=Variation Asp-298 in NOS3 may be associated with
CC susceptibility to coronary spasm. {ECO:0000269|PubMed:11740345,
CC ECO:0000269|PubMed:9737779}.
CC -!- MISCELLANEOUS: [Isoform eNOS13C]: Lacks eNOS activity. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Nitric oxide synthase entry;
CC URL="https://en.wikipedia.org/wiki/Nitric_oxide_synthase";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/nos3/";
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DR EMBL; M93718; AAA36364.1; -; mRNA.
DR EMBL; M95296; AAA36372.1; -; mRNA.
DR EMBL; L10709; AAA36365.1; -; Genomic_DNA.
DR EMBL; L10693; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10694; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10695; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10696; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10697; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10698; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10699; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10700; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10701; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10702; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10703; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10704; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10705; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10706; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10707; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; L10708; AAA36365.1; JOINED; Genomic_DNA.
DR EMBL; X76303; CAA53950.1; -; Genomic_DNA.
DR EMBL; X76304; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76305; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76306; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76307; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76308; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76309; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76310; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76311; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76312; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76313; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76314; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76315; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; X76316; CAA53950.1; JOINED; Genomic_DNA.
DR EMBL; D26607; BAA05652.1; -; Genomic_DNA.
DR EMBL; DQ256130; ABB79839.1; -; mRNA.
DR EMBL; DQ256131; ABB79840.1; -; mRNA.
DR EMBL; L26914; AAA36374.1; -; Genomic_DNA.
DR EMBL; AF400594; AAK83389.1; -; mRNA.
DR EMBL; AK292928; BAF85617.1; -; mRNA.
DR EMBL; AK315213; BAG37648.1; -; mRNA.
DR EMBL; AK223636; BAD97356.1; -; mRNA.
DR EMBL; AF519768; AAM74944.1; -; Genomic_DNA.
DR EMBL; EU332855; ABY87544.1; -; Genomic_DNA.
DR EMBL; AC010973; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471173; EAW54069.1; -; Genomic_DNA.
DR EMBL; BC063294; AAH63294.1; -; mRNA.
DR EMBL; BC069465; AAH69465.1; -; mRNA.
DR EMBL; L23210; AAA36373.1; -; Genomic_DNA.
DR EMBL; S80791; AAD14336.1; -; mRNA.
DR CCDS; CCDS55182.1; -. [P29474-2]
DR CCDS; CCDS55183.1; -. [P29474-3]
DR CCDS; CCDS5912.1; -. [P29474-1]
DR PIR; A47501; A47501.
DR RefSeq; NP_000594.2; NM_000603.4. [P29474-1]
DR RefSeq; NP_001153581.1; NM_001160109.1.
DR RefSeq; NP_001153582.1; NM_001160110.1. [P29474-3]
DR RefSeq; NP_001153583.1; NM_001160111.1. [P29474-2]
DR RefSeq; XP_016867721.1; XM_017012232.1.
DR PDB; 1M9J; X-ray; 2.43 A; A/B=67-481.
DR PDB; 1M9K; X-ray; 2.01 A; A/B=67-481.
DR PDB; 1M9M; X-ray; 1.96 A; A/B=67-481.
DR PDB; 1M9Q; X-ray; 2.01 A; A/B=67-481.
DR PDB; 1M9R; X-ray; 2.56 A; A/B=67-481.
DR PDB; 1NIW; X-ray; 2.05 A; B/D/F/H=492-511.
DR PDB; 2LL7; NMR; -; B=493-509.
DR PDB; 2MG5; NMR; -; B=495-510.
DR PDB; 2N8J; NMR; -; B=491-512.
DR PDB; 3EAH; X-ray; 2.44 A; A/B=66-492.
DR PDB; 3NOS; X-ray; 2.40 A; A/B=66-492.
DR PDB; 4D1O; X-ray; 1.82 A; A/B=41-480.
DR PDB; 4D1P; X-ray; 1.73 A; A/B=41-480.
DR PDB; 5UO8; X-ray; 2.18 A; A/B/C/D=41-480.
DR PDB; 5UO9; X-ray; 2.19 A; A/B/C/D=41-480.
DR PDB; 5UOA; X-ray; 2.20 A; A/B=41-480.
DR PDB; 5UOB; X-ray; 2.29 A; A/B/C/D=41-480.
DR PDB; 5UOC; X-ray; 2.20 A; A/B/C/D=41-480.
DR PDB; 5VVB; X-ray; 2.15 A; A/B/C/D=41-480.
DR PDB; 5VVC; X-ray; 2.40 A; A/B/C/D=41-480.
DR PDB; 5VVD; X-ray; 2.25 A; A/B/C/D=41-480.
DR PDB; 5XOF; X-ray; 1.96 A; O/P/Q/R=30-36.
DR PDB; 6AV6; X-ray; 2.08 A; A/B/C/D=41-480.
DR PDB; 6AV7; X-ray; 1.92 A; A/B/C/D=41-480.
DR PDB; 6CIE; X-ray; 1.95 A; A/B/C/D=41-480.
DR PDB; 6CIF; X-ray; 2.20 A; A/B/C/D=41-480.
DR PDB; 6NH1; X-ray; 2.22 A; A/B/C/D=41-480.
DR PDB; 6NH2; X-ray; 2.29 A; A/B/C/D=41-480.
DR PDB; 6NH3; X-ray; 2.01 A; A/B/C/D=41-480.
DR PDB; 6NH4; X-ray; 2.27 A; A/B/C/D=41-480.
DR PDB; 6NH5; X-ray; 1.96 A; A/B/C/D=41-480.
DR PDB; 6NH6; X-ray; 2.19 A; A/B/C/D=41-480.
DR PDB; 6NH7; X-ray; 1.90 A; A/B=41-480.
DR PDB; 6NH8; X-ray; 1.80 A; A/B/C/D=41-480.
DR PDB; 6NHF; X-ray; 1.83 A; A/B/C/D=41-480.
DR PDB; 6POU; X-ray; 2.19 A; A/B/C/D/E/F=41-480.
DR PDB; 6POV; X-ray; 2.05 A; A/B/C/D=41-480.
DR PDB; 6POW; X-ray; 2.15 A; A/B/C/D=41-480.
DR PDB; 6POX; X-ray; 2.20 A; A/B/C/D=41-480.
DR PDB; 6POY; X-ray; 2.30 A; A/B/C/D=41-480.
DR PDB; 6POZ; X-ray; 2.20 A; A/B/C/D=41-480.
DR PDB; 6PP0; X-ray; 1.97 A; A/B/C/D=41-480.
DR PDB; 6PP1; X-ray; 1.76 A; A/B/C/D=41-480.
DR PDB; 6PP2; X-ray; 2.02 A; A/B/C/D=41-480.
DR PDB; 6PP3; X-ray; 1.95 A; A/B/C/D=41-480.
DR PDB; 6PP4; X-ray; 2.20 A; A/B/C/D=41-480.
DR PDB; 7M56; X-ray; 1.96 A; A/B=41-480.
DR PDBsum; 1M9J; -.
DR PDBsum; 1M9K; -.
DR PDBsum; 1M9M; -.
DR PDBsum; 1M9Q; -.
DR PDBsum; 1M9R; -.
DR PDBsum; 1NIW; -.
DR PDBsum; 2LL7; -.
DR PDBsum; 2MG5; -.
DR PDBsum; 2N8J; -.
DR PDBsum; 3EAH; -.
DR PDBsum; 3NOS; -.
DR PDBsum; 4D1O; -.
DR PDBsum; 4D1P; -.
DR PDBsum; 5UO8; -.
DR PDBsum; 5UO9; -.
DR PDBsum; 5UOA; -.
DR PDBsum; 5UOB; -.
DR PDBsum; 5UOC; -.
DR PDBsum; 5VVB; -.
DR PDBsum; 5VVC; -.
DR PDBsum; 5VVD; -.
DR PDBsum; 5XOF; -.
DR PDBsum; 6AV6; -.
DR PDBsum; 6AV7; -.
DR PDBsum; 6CIE; -.
DR PDBsum; 6CIF; -.
DR PDBsum; 6NH1; -.
DR PDBsum; 6NH2; -.
DR PDBsum; 6NH3; -.
DR PDBsum; 6NH4; -.
DR PDBsum; 6NH5; -.
DR PDBsum; 6NH6; -.
DR PDBsum; 6NH7; -.
DR PDBsum; 6NH8; -.
DR PDBsum; 6NHF; -.
DR PDBsum; 6POU; -.
DR PDBsum; 6POV; -.
DR PDBsum; 6POW; -.
DR PDBsum; 6POX; -.
DR PDBsum; 6POY; -.
DR PDBsum; 6POZ; -.
DR PDBsum; 6PP0; -.
DR PDBsum; 6PP1; -.
DR PDBsum; 6PP2; -.
DR PDBsum; 6PP3; -.
DR PDBsum; 6PP4; -.
DR PDBsum; 7M56; -.
DR AlphaFoldDB; P29474; -.
DR BMRB; P29474; -.
DR SMR; P29474; -.
DR BioGRID; 110909; 50.
DR CORUM; P29474; -.
DR DIP; DIP-38479N; -.
DR IntAct; P29474; 80.
DR MINT; P29474; -.
DR STRING; 9606.ENSP00000297494; -.
DR BindingDB; P29474; -.
DR ChEMBL; CHEMBL4803; -.
DR DrugBank; DB07001; (3S,5E)-3-propyl-3,4-dihydrothieno[2,3-f][1,4]oxazepin-5(2H)-imine.
DR DrugBank; DB02048; 1,2,4-Triazole-Carboxamidine.
DR DrugBank; DB02911; 2,4-Diamino-6-Phenyl-5,6,7,8,-Tetrahydropteridine.
DR DrugBank; DB02335; 2-Aminothiazoline.
DR DrugBank; DB01997; 3-Bromo-7-Nitroindazole.
DR DrugBank; DB03332; 5,6-Cyclic-Tetrahydropteridine.
DR DrugBank; DB04534; 5-Nitroindazole.
DR DrugBank; DB07244; 5-{4-[(3,5-DIFLUOROBENZYL)AMINO]PHENYL}-6-ETHYLPYRIMIDINE-2,4-DIAMINE.
DR DrugBank; DB03100; 6-Nitroindazole.
DR DrugBank; DB03918; 6S-5,6,7,8-Tetrahydrobiopterin.
DR DrugBank; DB02207; 7-Nitroindazole.
DR DrugBank; DB03065; 7-Nitroindazole-2-Carboxamidine.
DR DrugBank; DB00125; Arginine.
DR DrugBank; DB02994; Cacodylic acid.
DR DrugBank; DB01833; Canavanine.
DR DrugBank; DB00155; Citrulline.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB07388; ETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE.
DR DrugBank; DB03974; L-homoarginine.
DR DrugBank; DB02077; L-N(omega)-nitroarginine-(4R)-amino-L-proline amide.
DR DrugBank; DB01821; L-N(omega)-Nitroarginine-2,4-L-diaminobutyric amide.
DR DrugBank; DB09237; Levamlodipine.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB03144; N(5)-[(hydroxyamino)(imino)methyl]-L-ornithine.
DR DrugBank; DB03305; N(G)-Iminoethylornithine.
DR DrugBank; DB01686; N,N-dimethylarginine.
DR DrugBank; DB04559; N-(Chlorophenyl)-N'-hydroxyguanidine.
DR DrugBank; DB02044; N-[3-(aminomethyl)benzyl]acetamidine.
DR DrugBank; DB08019; N-{(3R,4S)-4-[(6-amino-4-methylpyridin-2-yl)methyl]pyrrolidin-3-yl}-N'-(3-chlorobenzyl)ethane-1,2-diamine.
DR DrugBank; DB08018; N-{(3S,4S)-4-[(6-AMINO-4-METHYLPYRIDIN-2-YL)METHYL]PYRROLIDIN-3-YL}-N'-(4-CHLOROBENZYL)ETHANE-1,2-DIAMINE.
DR DrugBank; DB02027; N-{(4S)-4-Amino-5-[(2-aminoethyl)amino]pentyl}-N'-nitroguanidine.
DR DrugBank; DB02979; N1,N14-Bis((S-Methyl)Isothioureido)Tetradecane.
DR DrugBank; DB04223; Nitroarginine.
DR DrugBank; DB06154; Pentaerythritol tetranitrate.
DR DrugBank; DB03910; S,S'-(1,3-Phenylene-Bis(1,2-Ethanediyl))Bis-Isothiourea.
DR DrugBank; DB02141; S,S'-(1,4-Phenylene-Bis(1,2-Ethanediyl))Bis-Isothiourea.
DR DrugBank; DB03963; S-(Dimethylarsenic)Cysteine.
DR DrugBank; DB03707; S-Ethyl-N-Phenyl-Isothiourea.
DR DrugBank; DB02234; S-Ethylisothiourea.
DR DrugBank; DB04018; S-Isopropyl-Isothiourea.
DR DrugBank; DB00360; Sapropterin.
DR DrugBank; DB02589; Se-Ethyl-Isoselenourea.
DR DrugCentral; P29474; -.
DR GuidetoPHARMACOLOGY; 1249; -.
DR GlyGen; P29474; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P29474; -.
DR PhosphoSitePlus; P29474; -.
DR SwissPalm; P29474; -.
DR BioMuta; NOS3; -.
DR DMDM; 266648; -.
DR EPD; P29474; -.
DR jPOST; P29474; -.
DR MassIVE; P29474; -.
DR MaxQB; P29474; -.
DR PaxDb; P29474; -.
DR PeptideAtlas; P29474; -.
DR PRIDE; P29474; -.
DR ProteomicsDB; 20158; -.
DR ProteomicsDB; 54576; -. [P29474-1]
DR ProteomicsDB; 54577; -. [P29474-2]
DR Antibodypedia; 3692; 1700 antibodies from 44 providers.
DR DNASU; 4846; -.
DR Ensembl; ENST00000297494.8; ENSP00000297494.3; ENSG00000164867.11. [P29474-1]
DR Ensembl; ENST00000467517.1; ENSP00000420551.1; ENSG00000164867.11. [P29474-3]
DR Ensembl; ENST00000484524.5; ENSP00000420215.1; ENSG00000164867.11. [P29474-2]
DR GeneID; 4846; -.
DR KEGG; hsa:4846; -.
DR MANE-Select; ENST00000297494.8; ENSP00000297494.3; NM_000603.5; NP_000594.2.
DR UCSC; uc003wif.4; human. [P29474-1]
DR CTD; 4846; -.
DR DisGeNET; 4846; -.
DR GeneCards; NOS3; -.
DR HGNC; HGNC:7876; NOS3.
DR HPA; ENSG00000164867; Tissue enhanced (lymphoid).
DR MalaCards; NOS3; -.
DR MIM; 163729; gene+phenotype.
DR neXtProt; NX_P29474; -.
DR OpenTargets; ENSG00000164867; -.
DR PharmGKB; PA254; -.
DR VEuPathDB; HostDB:ENSG00000164867; -.
DR eggNOG; KOG1158; Eukaryota.
DR GeneTree; ENSGT00940000161389; -.
DR InParanoid; P29474; -.
DR OMA; VPFSGWY; -.
DR OrthoDB; 90349at2759; -.
DR PhylomeDB; P29474; -.
DR TreeFam; TF324410; -.
DR BioCyc; MetaCyc:HS09149-MON; -.
DR BRENDA; 1.14.13.39; 2681.
DR PathwayCommons; P29474; -.
DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-HSA-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-HSA-203615; eNOS activation.
DR Reactome; R-HSA-203641; NOSTRIN mediated eNOS trafficking.
DR Reactome; R-HSA-203754; NOSIP mediated eNOS trafficking.
DR Reactome; R-HSA-392154; Nitric oxide stimulates guanylate cyclase.
DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR SignaLink; P29474; -.
DR SIGNOR; P29474; -.
DR BioGRID-ORCS; 4846; 6 hits in 1082 CRISPR screens.
DR ChiTaRS; NOS3; human.
DR EvolutionaryTrace; P29474; -.
DR GeneWiki; Endothelial_NOS; -.
DR GenomeRNAi; 4846; -.
DR Pharos; P29474; Tchem.
DR PRO; PR:P29474; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P29474; protein.
DR Bgee; ENSG00000164867; Expressed in spleen and 95 other tissues.
DR ExpressionAtlas; P29474; baseline and differential.
DR Genevisible; P29474; HS.
DR GO; GO:0005901; C:caveola; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0012506; C:vesicle membrane; IBA:GO_Central.
DR GO; GO:0003785; F:actin monomer binding; IPI:BHF-UCL.
DR GO; GO:0034618; F:arginine binding; IDA:BHF-UCL.
DR GO; GO:0046870; F:cadmium ion binding; NAS:BHF-UCL.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0010181; F:FMN binding; IBA:GO_Central.
DR GO; GO:0020037; F:heme binding; IDA:BHF-UCL.
DR GO; GO:0050661; F:NADP binding; NAS:BHF-UCL.
DR GO; GO:0004517; F:nitric-oxide synthase activity; IDA:BHF-UCL.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0097110; F:scaffold protein binding; IEA:Ensembl.
DR GO; GO:0034617; F:tetrahydrobiopterin binding; IDA:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0003180; P:aortic valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0006527; P:arginine catabolic process; IDA:BHF-UCL.
DR GO; GO:0097746; P:blood vessel diameter maintenance; ISS:BHF-UCL.
DR GO; GO:0001974; P:blood vessel remodeling; ISS:BHF-UCL.
DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl.
DR GO; GO:0045454; P:cell redox homeostasis; TAS:Reactome.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
DR GO; GO:0043542; P:endothelial cell migration; IMP:BHF-UCL.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; ISS:BHF-UCL.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0007005; P:mitochondrion organization; ISS:BHF-UCL.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; ISS:BHF-UCL.
DR GO; GO:0045776; P:negative regulation of blood pressure; IBA:GO_Central.
DR GO; GO:0051926; P:negative regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:BHF-UCL.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISS:BHF-UCL.
DR GO; GO:0051346; P:negative regulation of hydrolase activity; IEA:Ensembl.
DR GO; GO:0014740; P:negative regulation of muscle hyperplasia; ISS:BHF-UCL.
DR GO; GO:0010544; P:negative regulation of platelet activation; NAS:BHF-UCL.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; IEA:Ensembl.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl.
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:0001542; P:ovulation from ovarian follicle; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:BHF-UCL.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:BHF-UCL.
DR GO; GO:0031284; P:positive regulation of guanylate cyclase activity; IMP:BHF-UCL.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IC:BHF-UCL.
DR GO; GO:0006813; P:potassium ion transport; IEA:Ensembl.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0008217; P:regulation of blood pressure; NAS:BHF-UCL.
DR GO; GO:0031644; P:regulation of nervous system process; ISS:ARUK-UCL.
DR GO; GO:0002028; P:regulation of sodium ion transport; IEA:Ensembl.
DR GO; GO:0003100; P:regulation of systemic arterial blood pressure by endothelin; IMP:BHF-UCL.
DR GO; GO:0003057; P:regulation of the force of heart contraction by chemical signal; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IDA:BHF-UCL.
DR GO; GO:0034405; P:response to fluid shear stress; IEP:BHF-UCL.
DR GO; GO:0009408; P:response to heat; NAS:BHF-UCL.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0032496; P:response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0014806; P:smooth muscle hyperplasia; ISS:BHF-UCL.
DR GO; GO:0042311; P:vasodilation; NAS:BHF-UCL.
DR GO; GO:0060412; P:ventricular septum morphogenesis; IEA:Ensembl.
DR Gene3D; 1.20.990.10; -; 1.
DR Gene3D; 3.40.50.360; -; 1.
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;
KW Cell membrane; Cytoplasm; Cytoskeleton; Direct protein sequencing; FAD;
KW Flavoprotein; FMN; Golgi apparatus; Heme; Iron; Lipoprotein; Membrane;
KW Metal-binding; Myristate; NADP; Oxidoreductase; Palmitate; Phosphoprotein;
KW Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P29473"
FT CHAIN 2..1203
FT /note="Nitric oxide synthase, endothelial"
FT /id="PRO_0000170943"
FT DOMAIN 520..703
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 756..1002
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 98..486
FT /note="Interaction with NOSIP"
FT /evidence="ECO:0000269|PubMed:11149895"
FT REGION 491..510
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 35..65
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 94
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 102
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000269|PubMed:25286850,
FT ECO:0007744|PDB:4D1O"
FT BINDING 184
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:0000269|PubMed:25286850,
FT ECO:0007744|PDB:4D1O"
FT BINDING 247
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:25286850,
FT ECO:0007744|PDB:4D1O"
FT BINDING 356
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:25286850,
FT ECO:0007744|PDB:4D1O"
FT BINDING 357
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:25286850,
FT ECO:0007744|PDB:4D1O"
FT BINDING 361
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:25286850,
FT ECO:0007744|PDB:4D1O"
FT BINDING 366
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000269|PubMed:25286850,
FT ECO:0007744|PDB:4D1O"
FT BINDING 446
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000269|PubMed:25286850,
FT ECO:0007744|PDB:4D1O"
FT BINDING 447
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000269|PubMed:25286850,
FT ECO:0007744|PDB:4D1O"
FT BINDING 460
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000269|PubMed:25286850,
FT ECO:0007744|PDB:4D1O"
FT BINDING 475
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000269|PubMed:25286850,
FT ECO:0007744|PDB:4D1O"
FT BINDING 649..680
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 793..804
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 935..945
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 1010..1028
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 1108..1123
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 33
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 114
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:20213743"
FT MOD_RES 495
FT /note="Phosphothreonine; by AMPK"
FT /evidence="ECO:0000269|PubMed:16126727"
FT MOD_RES 615
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70313"
FT MOD_RES 633
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 638
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 836
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1175
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P70313"
FT MOD_RES 1177
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:16126727,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1179
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70313"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT LIPID 15
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 26
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 584..625
FT /note="ESFAAALMEMSGPYNSSPRPEQHKSYKIRFNSISCSDPLVSS -> EGLTLW
FT PRLECSSTITAHCSLNLLDSSNPPTSTSQVVGTTGACHDA (in isoform
FT eNOS13C)"
FT /evidence="ECO:0000303|PubMed:17264164"
FT /id="VSP_042625"
FT VAR_SEQ 585..614
FT /note="SFAAALMEMSGPYNSSPRPEQHKSYKIRFN -> RWGFAMLPRLVSNSWVQA
FT IHLPRPPKVLRL (in isoform eNOS13B)"
FT /evidence="ECO:0000303|PubMed:17264164"
FT /id="VSP_045495"
FT VAR_SEQ 615..1203
FT /note="Missing (in isoform eNOS13B)"
FT /evidence="ECO:0000303|PubMed:17264164"
FT /id="VSP_045496"
FT VAR_SEQ 626..1203
FT /note="Missing (in isoform eNOS13C)"
FT /evidence="ECO:0000303|PubMed:17264164"
FT /id="VSP_042626"
FT VARIANT 112
FT /note="R -> Q (in dbSNP:rs3918166)"
FT /evidence="ECO:0000269|Ref.12"
FT /id="VAR_031218"
FT VARIANT 298
FT /note="D -> E (in dbSNP:rs1799983)"
FT /evidence="ECO:0000269|PubMed:11740345,
FT ECO:0000269|PubMed:12853948, ECO:0000269|PubMed:1378832,
FT ECO:0000269|PubMed:1379542, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17264164,
FT ECO:0000269|PubMed:7519987, ECO:0000269|PubMed:7688726,
FT ECO:0000269|PubMed:9737779, ECO:0000269|Ref.11,
FT ECO:0000269|Ref.12, ECO:0000269|Ref.13, ECO:0000269|Ref.15,
FT ECO:0000269|Ref.8, ECO:0000269|Ref.9"
FT /id="VAR_008037"
FT VARIANT 474
FT /note="R -> C (found in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs145805216)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036303"
FT VARIANT 602
FT /note="R -> Q (found in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs145168353)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036304"
FT VARIANT 665
FT /note="R -> H (in dbSNP:rs7792133)"
FT /id="VAR_061377"
FT VARIANT 827
FT /note="V -> M (in dbSNP:rs3918232)"
FT /evidence="ECO:0000269|Ref.12"
FT /id="VAR_031219"
FT VARIANT 885
FT /note="R -> M (in dbSNP:rs3918201)"
FT /evidence="ECO:0000269|Ref.12"
FT /id="VAR_031220"
FT VARIANT 982
FT /note="Q -> L (in dbSNP:rs3918234)"
FT /evidence="ECO:0000269|Ref.12"
FT /id="VAR_031221"
FT MUTAGEN 114
FT /note="S->A: Reduced nitrite (NO) production."
FT /evidence="ECO:0000269|PubMed:20213743"
FT CONFLICT 53
FT /note="S -> R (in Ref. 17; AAA36373)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="S -> G (in Ref. 10; BAG37648)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="K -> R (in Ref. 10; BAF85617)"
FT /evidence="ECO:0000305"
FT CONFLICT 489
FT /note="G -> S (in Ref. 18; AAD14336)"
FT /evidence="ECO:0000305"
FT CONFLICT 567
FT /note="V -> W (in Ref. 5; CAA53950)"
FT /evidence="ECO:0000305"
FT CONFLICT 1150
FT /note="R -> RQ (in Ref. 6; BAA05652)"
FT /evidence="ECO:0000305"
FT CONFLICT 1194
FT /note="D -> E (in Ref. 5; CAA53950)"
FT /evidence="ECO:0000305"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:4D1P"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 84..87
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:3NOS"
FT STRAND 104..107
FT /evidence="ECO:0007829|PDB:6NH3"
FT HELIX 120..137
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:6NH7"
FT HELIX 144..160
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 167..179
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 204..219
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:6NH7"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 257..259
FT /evidence="ECO:0007829|PDB:6AV6"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 268..276
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 291..294
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:6NH7"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 323..326
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 329..332
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 340..343
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 346..349
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 359..363
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 365..368
FT /evidence="ECO:0007829|PDB:4D1P"
FT TURN 370..373
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 376..382
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 394..412
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 420..438
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 445..448
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 454..456
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 458..461
FT /evidence="ECO:0007829|PDB:4D1P"
FT STRAND 465..467
FT /evidence="ECO:0007829|PDB:6CIE"
FT STRAND 470..474
FT /evidence="ECO:0007829|PDB:4D1P"
FT HELIX 496..506
FT /evidence="ECO:0007829|PDB:1NIW"
FT HELIX 507..509
FT /evidence="ECO:0007829|PDB:1NIW"
SQ SEQUENCE 1203 AA; 133275 MW; B761A6D40B1A5649 CRC64;
MGNLKSVAQE PGPPCGLGLG LGLGLCGKQG PATPAPEPSR APASLLPPAP EHSPPSSPLT
QPPEGPKFPR VKNWEVGSIT YDTLSAQAQQ DGPCTPRRCL GSLVFPRKLQ GRPSPGPPAP
EQLLSQARDF INQYYSSIKR SGSQAHEQRL QEVEAEVAAT GTYQLRESEL VFGAKQAWRN
APRCVGRIQW GKLQVFDARD CRSAQEMFTY ICNHIKYATN RGNLRSAITV FPQRCPGRGD
FRIWNSQLVR YAGYRQQDGS VRGDPANVEI TELCIQHGWT PGNGRFDVLP LLLQAPDDPP
ELFLLPPELV LEVPLEHPTL EWFAALGLRW YALPAVSNML LEIGGLEFPA APFSGWYMST
EIGTRNLCDP HRYNILEDVA VCMDLDTRTT SSLWKDKAAV EINVAVLHSY QLAKVTIVDH
HAATASFMKH LENEQKARGG CPADWAWIVP PISGSLTPVF HQEMVNYFLS PAFRYQPDPW
KGSAAKGTGI TRKKTFKEVA NAVKISASLM GTVMAKRVKA TILYGSETGR AQSYAQQLGR
LFRKAFDPRV LCMDEYDVVS LEHETLVLVV TSTFGNGDPP ENGESFAAAL MEMSGPYNSS
PRPEQHKSYK IRFNSISCSD PLVSSWRRKR KESSNTDSAG ALGTLRFCVF GLGSRAYPHF
CAFARAVDTR LEELGGERLL QLGQGDELCG QEEAFRGWAQ AAFQAACETF CVGEDAKAAA
RDIFSPKRSW KRQRYRLSAQ AEGLQLLPGL IHVHRRKMFQ ATIRSVENLQ SSKSTRATIL
VRLDTGGQEG LQYQPGDHIG VCPPNRPGLV EALLSRVEDP PAPTEPVAVE QLEKGSPGGP
PPGWVRDPRL PPCTLRQALT FFLDITSPPS PQLLRLLSTL AEEPREQQEL EALSQDPRRY
EEWKWFRCPT LLEVLEQFPS VALPAPLLLT QLPLLQPRYY SVSSAPSTHP GEIHLTVAVL
AYRTQDGLGP LHYGVCSTWL SQLKPGDPVP CFIRGAPSFR LPPDPSLPCI LVGPGTGIAP
FRGFWQERLH DIESKGLQPT PMTLVFGCRC SQLDHLYRDE VQNAQQRGVF GRVLTAFSRE
PDNPKTYVQD ILRTELAAEV HRVLCLERGH MFVCGDVTMA TNVLQTVQRI LATEGDMELD
EAGDVIGVLR DQQRYHEDIF GLTLRTQEVT SRIRTQSFSL QERQLRGAVP WAFDPPGSDT
NSP
