CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005789
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Nitric oxide synthase, endothelial 
Protein Synonyms/Alias
 Constitutive NOS; cNOS; EC-NOS; Endothelial NOS; eNOS; NOS type III; NOSIII 
Gene Name
 NOS3 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
494GTGITRKKTFKEVANacetylation[1]
504KEVANAVKISASLMGacetylation[1]
773VENLQSSKSTRATILubiquitination[2]
834VAVEQLEKGSPGGPPubiquitination[2, 3]
904PRRYEEWKWFRCPTLubiquitination[3]
1035RLHDIESKGLQPTPMubiquitination[3]
1085SREPDNPKTYVQDILubiquitination[2, 3]
Reference
 [1] Docosahexaenoic acid improves vascular function via up-regulation of SIRT1 expression in endothelial cells.
 Jung SB, Kwon SK, Kwon M, Nagar H, Jeon BH, Irani K, Yoon SH, Kim CS.
 Biochem Biophys Res Commun. 2013 Jul 19;437(1):114-9. [PMID: 23806688]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. 
Sequence Annotation
 DOMAIN 520 703 Flavodoxin-like.
 DOMAIN 756 1002 FAD-binding FR-type.
 NP_BIND 649 680 FMN (By similarity).
 NP_BIND 793 804 FAD (By similarity).
 NP_BIND 935 945 FAD (By similarity).
 NP_BIND 1010 1028 NADP (By similarity).
 NP_BIND 1108 1123 NADP (By similarity).
 REGION 98 486 Interaction with NOSIP.
 REGION 491 510 Calmodulin-binding (Potential).
 METAL 94 94 Zinc.
 METAL 99 99 Zinc.
 METAL 184 184 Iron (heme axial ligand).
 MOD_RES 114 114 Phosphoserine; by CDK5.
 MOD_RES 141 141 Phosphoserine (By similarity).
 MOD_RES 495 495 Phosphothreonine; by AMPK.
 MOD_RES 633 633 Phosphoserine (By similarity).
 MOD_RES 1175 1175 Phosphothreonine (By similarity).
 MOD_RES 1177 1177 Phosphoserine; by AMPK.
 LIPID 2 2 N-myristoyl glycine (By similarity).
 LIPID 15 15 S-palmitoyl cysteine (By similarity).
 LIPID 26 26 S-palmitoyl cysteine (By similarity).  
Keyword
 3D-structure; Alternative splicing; Calcium; Calmodulin-binding; Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; FAD; FMN; Golgi apparatus; Heme; Iron; Lipoprotein; Membrane; Metal-binding; Myristate; NADP; Oxidoreductase; Palmitate; Phosphoprotein; Polymorphism; Reference proteome; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1203 AA 
Protein Sequence
MGNLKSVAQE PGPPCGLGLG LGLGLCGKQG PATPAPEPSR APASLLPPAP EHSPPSSPLT 60
QPPEGPKFPR VKNWEVGSIT YDTLSAQAQQ DGPCTPRRCL GSLVFPRKLQ GRPSPGPPAP 120
EQLLSQARDF INQYYSSIKR SGSQAHEQRL QEVEAEVAAT GTYQLRESEL VFGAKQAWRN 180
APRCVGRIQW GKLQVFDARD CRSAQEMFTY ICNHIKYATN RGNLRSAITV FPQRCPGRGD 240
FRIWNSQLVR YAGYRQQDGS VRGDPANVEI TELCIQHGWT PGNGRFDVLP LLLQAPDEPP 300
ELFLLPPELV LEVPLEHPTL EWFAALGLRW YALPAVSNML LEIGGLEFPA APFSGWYMST 360
EIGTRNLCDP HRYNILEDVA VCMDLDTRTT SSLWKDKAAV EINVAVLHSY QLAKVTIVDH 420
HAATASFMKH LENEQKARGG CPADWAWIVP PISGSLTPVF HQEMVNYFLS PAFRYQPDPW 480
KGSAAKGTGI TRKKTFKEVA NAVKISASLM GTVMAKRVKA TILYGSETGR AQSYAQQLGR 540
LFRKAFDPRV LCMDEYDVVS LEHETLVLVV TSTFGNGDPP ENGESFAAAL MEMSGPYNSS 600
PRPEQHKSYK IRFNSISCSD PLVSSWRRKR KESSNTDSAG ALGTLRFCVF GLGSRAYPHF 660
CAFARAVDTR LEELGGERLL QLGQGDELCG QEEAFRGWAQ AAFQAACETF CVGEDAKAAA 720
RDIFSPKRSW KRQRYRLSAQ AEGLQLLPGL IHVHRRKMFQ ATIRSVENLQ SSKSTRATIL 780
VRLDTGGQEG LQYQPGDHIG VCPPNRPGLV EALLSRVEDP PAPTEPVAVE QLEKGSPGGP 840
PPGWVRDPRL PPCTLRQALT FFLDITSPPS PQLLRLLSTL AEEPREQQEL EALSQDPRRY 900
EEWKWFRCPT LLEVLEQFPS VALPAPLLLT QLPLLQPRYY SVSSAPSTHP GEIHLTVAVL 960
AYRTQDGLGP LHYGVCSTWL SQLKPGDPVP CFIRGAPSFR LPPDPSLPCI LVGPGTGIAP 1020
FRGFWQERLH DIESKGLQPT PMTLVFGCRC SQLDHLYRDE VQNAQQRGVF GRVLTAFSRE 1080
PDNPKTYVQD ILRTELAAEV HRVLCLERGH MFVCGDVTMA TNVLQTVQRI LATEGDMELD 1140
EAGDVIGVLR DQQRYHEDIF GLTLRTQEVT SRIRTQSFSL QERQLRGAVP WAFDPPGSDT 1200
NSP 1203 
Gene Ontology
 GO:0005901; C:caveola; IDA:BHF-UCL.
 GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
 GO:0000139; C:Golgi membrane; TAS:Reactome.
 GO:0005634; C:nucleus; ISS:BHF-UCL.
 GO:0034618; F:arginine binding; IDA:BHF-UCL.
 GO:0046870; F:cadmium ion binding; NAS:BHF-UCL.
 GO:0050660; F:flavin adenine dinucleotide binding; NAS:BHF-UCL.
 GO:0010181; F:FMN binding; NAS:BHF-UCL.
 GO:0020037; F:heme binding; IDA:BHF-UCL.
 GO:0005506; F:iron ion binding; IEA:InterPro.
 GO:0050661; F:NADP binding; NAS:BHF-UCL.
 GO:0003958; F:NADPH-hemoprotein reductase activity; IBA:RefGenome.
 GO:0004517; F:nitric-oxide synthase activity; IDA:BHF-UCL.
 GO:0034617; F:tetrahydrobiopterin binding; IDA:BHF-UCL.
 GO:0001525; P:angiogenesis; IEA:Compara.
 GO:0006527; P:arginine catabolic process; IDA:BHF-UCL.
 GO:0007596; P:blood coagulation; TAS:Reactome.
 GO:0001974; P:blood vessel remodeling; ISS:BHF-UCL.
 GO:0043542; P:endothelial cell migration; IMP:BHF-UCL.
 GO:0001701; P:in utero embryonic development; IEA:Compara.
 GO:0051701; P:interaction with host; TAS:Reactome.
 GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Compara.
 GO:0030324; P:lung development; IEA:Compara.
 GO:0007005; P:mitochondrion organization; ISS:BHF-UCL.
 GO:0043066; P:negative regulation of apoptotic process; ISS:BHF-UCL.
 GO:0045776; P:negative regulation of blood pressure; IBA:RefGenome.
 GO:0051926; P:negative regulation of calcium ion transport; IEA:Compara.
 GO:0008285; P:negative regulation of cell proliferation; ISS:BHF-UCL.
 GO:0051346; P:negative regulation of hydrolase activity; IEA:Compara.
 GO:0014740; P:negative regulation of muscle hyperplasia; ISS:BHF-UCL.
 GO:0010544; P:negative regulation of platelet activation; NAS:BHF-UCL.
 GO:0043267; P:negative regulation of potassium ion transport; IEA:Compara.
 GO:0006809; P:nitric oxide biosynthetic process; IDA:BHF-UCL.
 GO:0007263; P:nitric oxide mediated signal transduction; IBA:RefGenome.
 GO:0001542; P:ovulation from ovarian follicle; IEA:Compara.
 GO:0090382; P:phagosome maturation; TAS:Reactome.
 GO:0045766; P:positive regulation of angiogenesis; ISS:BHF-UCL.
 GO:0031284; P:positive regulation of guanylate cyclase activity; IMP:BHF-UCL.
 GO:0045909; P:positive regulation of vasodilation; NAS:BHF-UCL.
 GO:0050880; P:regulation of blood vessel size; ISS:BHF-UCL.
 GO:0050999; P:regulation of nitric-oxide synthase activity; TAS:Reactome.
 GO:0002028; P:regulation of sodium ion transport; IEA:Compara.
 GO:0003100; P:regulation of systemic arterial blood pressure by endothelin; IMP:BHF-UCL.
 GO:0003057; P:regulation of the force of heart contraction by chemical signal; IEA:Compara.
 GO:0034405; P:response to fluid shear stress; IEP:BHF-UCL.
 GO:0009408; P:response to heat; NAS:BHF-UCL.
 GO:0014806; P:smooth muscle hyperplasia; ISS:BHF-UCL. 
Interpro
 IPR003097; FAD-binding_1.
 IPR017927; Fd_Rdtase_FAD-bd.
 IPR001094; Flavdoxin.
 IPR008254; Flavodoxin/NO_synth.
 IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
 IPR023173; NADPH_Cyt_P450_Rdtase_dom3.
 IPR004030; NO_synthase_oxygenase_dom.
 IPR026009; NOS.
 IPR012144; NOS_met.
 IPR001433; OxRdtase_FAD/NAD-bd.
 IPR017938; Riboflavin_synthase-like_b-brl. 
Pfam
 PF00667; FAD_binding_1
 PF00258; Flavodoxin_1
 PF00175; NAD_binding_1
 PF02898; NO_synthase 
SMART
  
PROSITE
 PS51384; FAD_FR
 PS50902; FLAVODOXIN_LIKE
 PS60001; NOS 
PRINTS
 PR00369; FLAVODOXIN.
 PR00371; FPNCR.