NOS3_RAT
ID NOS3_RAT Reviewed; 1202 AA.
AC Q62600; O88672; O89041; Q62734; Q68GV6; Q75NE4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Nitric oxide synthase, endothelial;
DE EC=1.14.13.39;
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15105416; DOI=10.1074/jbc.m401471200;
RA Saitoh F., Tian Q.B., Okano A., Sakagami H., Kondo H., Suzuki T.;
RT "NIDD, a novel DHHC-containing protein, targets neuronal nitric-oxide
RT synthase (nNOS) to the synaptic membrane through a PDZ-dependent
RT interaction and regulates nNOS activity.";
RL J. Biol. Chem. 279:29461-29468(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-288.
RC STRAIN=Sprague-Dawley;
RA Toporsian M., Govindaraju K., Nagi M., Eidelman D., Thibault G., Ward M.E.;
RT "Downregulation of endothelial nitric oxide synthase (NOS III) in rat aorta
RT following in-vivo hypoxia.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-1202.
RC STRAIN=SS/JrHsdMcwi; TISSUE=Heart;
RX PubMed=15808839; DOI=10.1016/j.yjmcc.2005.02.005;
RA Shi Y., Hutchins W., Ogawa H., Chang C.-C., Pritchard K.A. Jr., Zhang C.,
RA Khampang P., Lazar J., Jacob H.J., Rafiee P., Baker J.E.;
RT "Increased resistance to myocardial ischemia in the Brown Norway vs. Dahl S
RT rat: role of nitric oxide synthase and Hsp90.";
RL J. Mol. Cell. Cardiol. 38:625-635(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 473-672 AND 951-1192.
RC TISSUE=Brain;
RA Seidel B., Jiang L., Wolf G.;
RT "Cloning and expression of the rat endothelial nitric oxide synthase.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 633-862.
RC STRAIN=Sprague-Dawley;
RX PubMed=7527874; DOI=10.1038/ki.1994.318;
RA Mohaupt M.G., Elzie J.L., Ahn K.Y., Clapp W.L., Wilcox C.S., Kone B.C.;
RT "Differential expression and induction of mRNAs encoding two inducible
RT nitric oxide synthases in rat kidney.";
RL Kidney Int. 46:653-665(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1015-1132.
RC STRAIN=Sprague-Dawley; TISSUE=Lung;
RA Minchenko A.G., Armstead V.E., Opentanova I.L., Lefer A.M.;
RT "Endothelin-1, endothelin receptors and ecNOS mRNA expression in vital
RT organs during traumatic shock in rats.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1018-1080.
RC STRAIN=Sprague-Dawley; TISSUE=Lung;
RX PubMed=7537461; DOI=10.1152/ajplung.1995.268.4.l589;
RA Kawai N., Bloch D.B., Filippov G., Rabkina D., Suen H.C., Losty P.D.,
RA Janssens S.P., Zapol W.M., de la Monte S., Bloch K.D.;
RT "Constitutive endothelial nitric oxide synthase gene expression is
RT regulated during lung development.";
RL Am. J. Physiol. 268:L589-L595(1995).
RN [8]
RP PHOSPHORYLATION AT THR-494 AND SER-1176.
RX PubMed=10025949; DOI=10.1016/s0014-5793(98)01705-0;
RA Chen Z.P., Mitchelhill K.I., Michell B.J., Stapleton D.,
RA Rodriguez-Crespo I., Witters L.A., Power D.A., Ortiz de Montellano P.R.,
RA Kemp B.E.;
RT "AMP-activated protein kinase phosphorylation of endothelial NO synthase.";
RL FEBS Lett. 443:285-289(1999).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1174 AND SER-1176, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Produces nitric oxide (NO) which is implicated in vascular
CC smooth muscle relaxation through a cGMP-mediated signal transduction
CC pathway. NO mediates vascular endothelial growth factor (VEGF)-induced
CC angiogenesis in coronary vessels and promotes blood clotting through
CC the activation of platelets.
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 -!- 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: Stimulated by calcium/calmodulin. Inhibited by
CC NOSIP and NOSTRIN (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with NOSIP and NOSTRIN (By similarity).
CC Interacts with HSP90AB1 (By similarity). Forms a complex with ASL, ASS1
CC and SLC7A1; the complex regulates cell-autonomous L-arginine synthesis
CC and citrulline recycling while channeling extracellular L-arginine to
CC nitric oxide synthesis pathway (By similarity).
CC {ECO:0000250|UniProtKB:P29474, ECO:0000250|UniProtKB:P70313}.
CC -!- INTERACTION:
CC Q62600; P62157: CALM; Xeno; NbExp=2; IntAct=EBI-7052018, EBI-397403;
CC -!- SUBCELLULAR LOCATION: Membrane, caveola {ECO:0000250}. Cytoplasm,
CC cytoskeleton {ECO:0000250}. Golgi apparatus {ECO:0000250}. Cell
CC membrane {ECO:0000250}. 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 {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed constitutively by vascular endothelium.
CC Detected in alveolar and serosal epithelial cells as well as in
CC endothelial cells in one day old rat. In adult lung, detected in rare
CC endothelial cells.
CC -!- DEVELOPMENTAL STAGE: Detected at high levels in lung during the late
CC fetal and postnatal period and at lower levels in adult.
CC -!- PTM: Phosphorylation by AMPK at Ser-1176 in the presence of Ca(2+)-
CC calmodulin (CaM) activates activity. In absence of Ca(2+)-calmodulin,
CC AMPK also phosphorylates Thr-494, resulting in inhibition of activity.
CC {ECO:0000269|PubMed:10025949}.
CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}.
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DR EMBL; AB176831; BAD15356.1; -; mRNA.
DR EMBL; AF085195; AAC34677.1; -; mRNA.
DR EMBL; AY695391; AAT99567.1; -; mRNA.
DR EMBL; AJ011115; CAA09493.1; -; mRNA.
DR EMBL; AJ011116; CAA09494.1; -; mRNA.
DR EMBL; U02534; AAA96141.1; -; mRNA.
DR EMBL; AF093837; AAC64178.1; -; mRNA.
DR EMBL; U18336; AAC52188.1; -; mRNA.
DR PIR; I51917; I51917.
DR PIR; I56979; I56979.
DR RefSeq; NP_068610.1; NM_021838.2.
DR AlphaFoldDB; Q62600; -.
DR BMRB; Q62600; -.
DR SMR; Q62600; -.
DR CORUM; Q62600; -.
DR DIP; DIP-41833N; -.
DR IntAct; Q62600; 2.
DR MINT; Q62600; -.
DR STRING; 10116.ENSRNOP00000013058; -.
DR BindingDB; Q62600; -.
DR ChEMBL; CHEMBL1075230; -.
DR iPTMnet; Q62600; -.
DR PhosphoSitePlus; Q62600; -.
DR SwissPalm; Q62600; -.
DR PaxDb; Q62600; -.
DR PRIDE; Q62600; -.
DR GeneID; 24600; -.
DR KEGG; rno:24600; -.
DR CTD; 4846; -.
DR RGD; 3186; Nos3.
DR eggNOG; KOG1158; Eukaryota.
DR InParanoid; Q62600; -.
DR OrthoDB; 90349at2759; -.
DR PhylomeDB; Q62600; -.
DR BRENDA; 1.14.13.39; 5301.
DR Reactome; R-RNO-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-RNO-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-RNO-203615; eNOS activation.
DR Reactome; R-RNO-203641; NOSTRIN mediated eNOS trafficking.
DR Reactome; R-RNO-203754; NOSIP mediated eNOS trafficking.
DR Reactome; R-RNO-392154; Nitric oxide stimulates guanylate cyclase.
DR Reactome; R-RNO-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling.
DR SABIO-RK; Q62600; -.
DR PRO; PR:Q62600; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0005901; C:caveola; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005730; C:nucleolus; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR GO; GO:0012506; C:vesicle membrane; IDA:RGD.
DR GO; GO:0003779; F:actin binding; IDA:RGD.
DR GO; GO:0003785; F:actin monomer binding; ISO:RGD.
DR GO; GO:0034618; F:arginine binding; ISO:RGD.
DR GO; GO:0008013; F:beta-catenin binding; IPI:RGD.
DR GO; GO:0045296; F:cadherin binding; IPI:RGD.
DR GO; GO:0005516; F:calmodulin binding; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0051879; F:Hsp90 protein binding; IDA:RGD.
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:RGD.
DR GO; GO:0050998; F:nitric-oxide synthase binding; IPI:RGD.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0097110; F:scaffold protein binding; IPI:RGD.
DR GO; GO:0034617; F:tetrahydrobiopterin binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0003180; P:aortic valve morphogenesis; ISO:RGD.
DR GO; GO:0006527; P:arginine catabolic process; ISO:RGD.
DR GO; GO:0097746; P:blood vessel diameter maintenance; ISO:RGD.
DR GO; GO:0001974; P:blood vessel remodeling; ISO:RGD.
DR GO; GO:0060348; P:bone development; IEP:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
DR GO; GO:0034605; P:cellular response to heat; IEP:RGD.
DR GO; GO:0071403; P:cellular response to high density lipoprotein particle stimulus; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IEP:RGD.
DR GO; GO:0071286; P:cellular response to magnesium ion; IEP:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IMP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:1904648; P:cellular response to rotenone; IEP:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IMP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISO:RGD.
DR GO; GO:0043542; P:endothelial cell migration; ISO:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; ISO:RGD.
DR GO; GO:0045776; P:negative regulation of blood pressure; IBA:GO_Central.
DR GO; GO:0051926; P:negative regulation of calcium ion transport; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0051346; P:negative regulation of hydrolase activity; ISO:RGD.
DR GO; GO:0014740; P:negative regulation of muscle hyperplasia; ISO:RGD.
DR GO; GO:0043267; P:negative regulation of potassium ion transport; ISO:RGD.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IMP:RGD.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IBA:GO_Central.
DR GO; GO:0001542; P:ovulation from ovarian follicle; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0031284; P:positive regulation of guanylate cyclase activity; ISO:RGD.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISO:RGD.
DR GO; GO:0031644; P:regulation of nervous system process; ISO:RGD.
DR GO; GO:0002028; P:regulation of sodium ion transport; ISO:RGD.
DR GO; GO:0003100; P:regulation of systemic arterial blood pressure by endothelin; ISO:RGD.
DR GO; GO:0003057; P:regulation of the force of heart contraction by chemical signal; ISO:RGD.
DR GO; GO:0019430; P:removal of superoxide radicals; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0048678; P:response to axon injury; IEP:RGD.
DR GO; GO:1901556; P:response to candesartan; IEP:RGD.
DR GO; GO:0009743; P:response to carbohydrate; IEP:RGD.
DR GO; GO:0051412; P:response to corticosterone; IEP:RGD.
DR GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR GO; GO:0036017; P:response to erythropoietin; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IDA:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0034405; P:response to fluid shear stress; ISO:RGD.
DR GO; GO:0009750; P:response to fructose; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0055093; P:response to hyperoxia; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:1901654; P:response to ketone; IEP:RGD.
DR GO; GO:1903576; P:response to L-arginine; IEP:RGD.
DR GO; GO:0010288; P:response to lead ion; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0071000; P:response to magnetism; IEP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0046689; P:response to mercury ion; IEP:RGD.
DR GO; GO:0010038; P:response to metal ion; IEP:RGD.
DR GO; GO:1901558; P:response to metformin; IEP:RGD.
DR GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:1901652; P:response to peptide; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:1902074; P:response to salt; IEP:RGD.
DR GO; GO:1990478; P:response to ultrasound; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0060041; P:retina development in camera-type eye; IEP:RGD.
DR GO; GO:0007165; P:signal transduction; IMP:RGD.
DR GO; GO:0014806; P:smooth muscle hyperplasia; ISO:RGD.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISO:RGD.
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 Calcium; Calmodulin-binding; Cell membrane; Cytoplasm; Cytoskeleton; 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..1202
FT /note="Nitric oxide synthase, endothelial"
FT /id="PRO_0000170946"
FT DOMAIN 519..702
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 755..1001
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 1..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 97..485
FT /note="Interaction with NOSIP"
FT /evidence="ECO:0000250"
FT REGION 489..509
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT REGION 817..843
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..64
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 98
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 101
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 183
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 246
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 355
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 356
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 360
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 445
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 446
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 459
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 474
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 648..679
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 792..803
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 1009..1027
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 1107..1122
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 494
FT /note="Phosphothreonine; by AMPK"
FT /evidence="ECO:0000269|PubMed:10025949"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70313"
FT MOD_RES 632
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29473"
FT MOD_RES 637
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT MOD_RES 835
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT MOD_RES 1174
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1176
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:10025949,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 1178
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 CONFLICT 232..233
FT /note="QR -> PS (in Ref. 2; AAC34677)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="R -> S (in Ref. 2; AAC34677)"
FT /evidence="ECO:0000305"
FT CONFLICT 298..304
FT /note="Missing (in Ref. 3; AAT99567)"
FT /evidence="ECO:0000305"
FT CONFLICT 600
FT /note="P -> L (in Ref. 4; CAA09493)"
FT /evidence="ECO:0000305"
FT CONFLICT 735
FT /note="R -> G (in Ref. 3; AAT99567)"
FT /evidence="ECO:0000305"
FT CONFLICT 739
FT /note="Q -> P (in Ref. 3; AAT99567)"
FT /evidence="ECO:0000305"
FT CONFLICT 748
FT /note="R -> G (in Ref. 1; BAD15356)"
FT /evidence="ECO:0000305"
FT CONFLICT 771
FT /note="S -> T (in Ref. 3; AAT99567)"
FT /evidence="ECO:0000305"
FT CONFLICT 852..854
FT /note="CTL -> GTV (in Ref. 5; AAA96141)"
FT /evidence="ECO:0000305"
FT CONFLICT 966
FT /note="G -> V (in Ref. 1; BAD15356)"
FT /evidence="ECO:0000305"
FT CONFLICT 997..998
FT /note="SF -> FL (in Ref. 3; AAT99567)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1202 AA; 133290 MW; 52E905C3134E244D CRC64;
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSQ APVPPSPTRP APDHSPPLTR
PPDGPKFPRV KNWEVGSITY DTLSAQAQQD GPCTPRRCLG SLVFPRKLQS RPTQGPSPTE
QLLGQARDFI NQYYNSIKRS GSQAHEQRLQ EVEAEVVATG TYQLRESELV FGAKQAWRNA
PRCVGRIQWG KLQVFDARDC RTAQEMFTYI CNHIKYATNR GNLRSAITVF PQRYAGRGDF
RIWNSQLVRY AGYRQQDGSV RGDPANVEIT ELCIQHGWTP GNGRFDVLPL LLQAPDEPPE
LFTLPPELVL EVPLEHPTLE WFAALGLRWY ALPAVSNMLL EIGGLEFPAA PFSGWYMSSE
IGMRDLCDPH RYNILEDVAV CMDLDTRTTS SLWKDKAAVE INVAVLYSYQ LAKVTIVDHH
AATASFMKHL ENEQKARGGC PADWAWIVPP ISGSLTPVFH QEMVNYFLSP AFRYQPDPWK
GSAAKGTGIT RKKTFKEVAN AVKISASLMG TVMAKRVKAT ILYGSETGRA QSYAQQLGRL
FRKAFDPRVL CMDEYDVVSL EHEALVLVVT STFGNGDPPE NGESFAAALM EMSGPYNSSP
RPEQHKSYKI RFNSVSCSDP LVSSWRRKRK ESSNTDSAGA LGTLRFCVFG LGSRAYPHFC
AFARAVDTRL EELGGERLLQ LGQGDELCGQ EEAFRGWAQA AFQAACETFC VGEDAKAAAR
DIFSPKRSWK RQRYRLSTQA ESLQLLPRLT HVHRRKMFQA TILSVENLQS SKSTRATILV
RLDTGSQEGL QYQPGDHIGV CPPNRPGLVE ALLSRVEDPP PSTEPVAVEQ LEKGSPGGPP
PGWVRDPRLP PCTLRQALTY FLDITSPPSP RLLRLLSTLA EESSEQQELE ALSQDPRRYE
EWKWFRCPTL LEVLEQFPSV ALPAPLILTQ LPLLQPRYYS VSSAPSAHPG EIHLTVAVLA
YRTQDGLGPL HYGVCSTWMS QLKAGDPVPC FIRGAPSFRL PPDPNLPCIL VGPGTGIAPF
RGFWQDRLHD IEIKGLQPAP MTLVFGCRCS QLDHLYRDEV LDAQQRGVFG QVLTAFSRDP
GSPKTYVQDL LRTELAAEVH RVLCLEQGHM FVCGDVTMAT SVLQTVQRIL ATEGSMELDE
AGDVIGVLRD QQRYHEDIFG LTLRTQEVTS RIRTQSFSLQ ERQLRGAVPW SFDPPTQETP
GS
