Lipid Modification Database
Tag Content
LipidDB ID
LipidDB-9913-01347
Entry Name
UniProt Accession
Theoretical PI
6.5
Molecular Weight
133286.77
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
Nitric oxide synthase, endothelial
Protein Synonyms/Alias
1.14.13.39; Constitutive NOS; cNOS; EC-NOS; Endothelial NOS; eNOS; NOS type III; NOSIII;
Gene Name
NOS3
Gene Synonyms/Alias
Created Date
01-APR-1993
 Lipid Modification Sites 
 Position   Sequence Form   Peptide   References   Modification Type 
2
Canonical
******MGNLKSVGQ
[2]
N-Myristoylation
15
Canonical
GQEPGPPCGLGLGLG
[1]
S-Palmitoylation
26
Canonical
LGLGLGLCGKQGPAS
[1]
S-Palmitoylation
Organism
Bos taurus (Bovine)
NCBI Taxa ID
9913
Reference
[1] Robinson LJ, Michel T. Mutagenesis of palmitoylation sites in endothelialnitric oxide synthase identifies a novel motif for dual acylation and subcellulartargeting. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11776-80.[PMID:8524847]
[2] Busconi L, Michel T. Endothelial nitric oxide synthase. N-terminalmyristoylation determines subcellular localization. J Biol Chem. 1993 Apr25;268(12):8410-3.[PMID:7682550]
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: 522 705 Flavodoxin-like.
Domain: 758 1004 FAD-binding FR-type.
Nucleotide-binding: 651 682 FMN.
Nucleotide-binding: 795 806 FAD.
Nucleotide-binding: 937 947 FAD.
Nucleotide-binding: 1012 1030 NADP.
Nucleotide-binding: 1110 1125 NADP.
Region: 100 488 Interaction with NOSIP.
Region: 492 512 Calmodulin-binding.
Metal binding site: 96 96 Zinc.
Metal binding site: 101 101 Zinc.
Metal binding site: 186 186 Iron (heme axial ligand).
Modified residue: 116 116 Phosphoserine; by CDK5.
Modified residue: 143 143 Phosphoserine; by PKA.
Modified residue: 497 497 Phosphothreonine; by AMPK and PKA.
Modified residue: 635 635 Phosphoserine.
Modified residue: 1177 1177 Phosphothreonine.
Modified residue: 1179 1179 Phosphoserine; by AMPK, PDPK1 and PKA.
Protein Length
1205 AA.
Protein Sequence
(Canonical)
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSR APAPATPHAP DHSPAPNSPT  60
LTRPPEGPKF PRVKNWELGS ITYDTLCAQS QQDGPCTPRC CLGSLVLPRK LQTRPSPGPP  120
PAEQLLSQAR DFINQYYSSI KRSGSQAHEE RLQEVEAEVA STGTYHLRES ELVFGAKQAW  180
RNAPRCVGRI QWGKLQVFDA RDCSSAQEMF TYICNHIKYA TNRGNLRSAI TVFPQRAPGR  240
GDFRIWNSQL VRYAGYRQQD GSVRGDPANV EITELCIQHG WTPGNGRFDV LPLLLQAPDE  300
APELFVLPPE LVLEVPLEHP TLEWFAALGL RWYALPAVSN MLLEIGGLEF SAAPFSGWYM  360
STEIGTRNLC DPHRYNILED VAVCMDLDTR TTSSLWKDKA AVEINLAVLH SFQLAKVTIV  420
DHHAATVSFM KHLDNEQKAR GGCPADWAWI VPPISGSLTP VFHQEMVNYI LSPAFRYQPD  480
PWKGSATKGA GITRKKTFKE VANAVKISAS LMGTLMAKRV KATILYASET GRAQSYAQQL  540
GRLFRKAFDP RVLCMDEYDV VSLEHEALVL VVTSTFGNGD PPENGESFAA ALMEMSGPYN  600
SSPRPEQHKS YKIRFNSVSC SDPLVSSWRR KRKESSNTDS AGALGTLRFC VFGLGSRAYP  660
HFCAFARAVD TRLEELGGER LLQLGQGDEL CGQEEAFRGW AKAAFQASCE TFCVGEEAKA  720
AAQDIFSPKR SWKRQRYRLS TQAEGLQLLP GLIHVHRRKM FQATVLSVEN LQSSKSTRAT  780
ILVRLDTAGQ EGLQYQPGDH IGICPPNRPG LVEALLSRVE DPPPPTESVA VEQLEKGSPG  840
GPPPSWVRDP RLPPCTLRQA LTFFLDITSP PSPRLLRLLS TLAEEPSEQQ ELETLSQDPR  900
RYEEWKWFRC PTLLEVLEQF PSVALPAPLL LTQLPLLQPR YYSVSSAPNA HPGEVHLTVA  960
VLAYRTQDGL GPLHYGVCST WLSQLKTGDP VPCFIRGAPS FRLPPDPYVP CILVGPGTGI  1020
APFRGFWQER LHDIESKGLQ PAPMTLVFGC RCSQLDHLYR DEVQDAQERG VFGRVLTAFS  1080
REPDSPKTYV QDILRTELAA EVHRVLCLER GHMFVCGDVT MATSVLQTVQ RILATEGDME  1140
LDEAGDVIGV LRDQQRYHED IFGLTLRTQE VTSRIRTQSF SLQERHLRGA VPWAFDPPGP  1200
DTPGP                                                              1205
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSR APAPATPHAP DHSPAPNSPT  60
LTRPPEGPKF PRVKNWELGS ITYDTLCAQS QQDGPCTPRC CLGSLVLPRK LQTRPSPGPP  120
PAEQLLSQAR DFINQYYSSI KRSGSQAHEE RLQEVEAEVA STGTYHLRES ELVFGAKQAW  180
RNAPRCVGRI QWGKLQVFDA RDCSSAQEMF TYICNHIKYA TNRGNLRSAI TVFPQRAPGR  240
GDFRIWNSQL VRYAGYRQQD GSVRGDPANV EITELCIQHG WTPGNGRFDV LPLLLQAPDE  300
APELFVLPPE LVLEVPLEHP TLEWFAALGL RWYALPAVSN MLLEIGGLEF SAAPFSGWYM  360
STEIGTRNLC DPHRYNILED VAVCMDLDTR TTSSLWKDKA AVEINLAVLH SFQLAKVTIV  420
DHHAATVSFM KHLDNEQKAR GGCPADWAWI VPPISGSLTP VFHQEMVNYI LSPAFRYQPD  480
PWKGSATKGA GITRKKTFKE VANAVKISAS LMGTLMAKRV KATILYASET GRAQSYAQQL  540
GRLFRKAFDP RVLCMDEYDV VSLEHEALVL VVTSTFGNGD PPENGESFAA ALMEMSGPYN  600
SSPRPEQHKS YKIRFNSVSC SDPLVSSWRR KRKESSNTDS AGALGTLRFC VFGLGSRAYP  660
HFCAFARAVD TRLEELGGER LLQLGQGDEL CGQEEAFRGW AKAAFQASCE TFCVGEEAKA  720
AAQDIFSPKR SWKRQRYRLS TQAEGLQLLP GLIHVHRRKM FQATVLSVEN LQSSKSTRAT  780
ILVRLDTAGQ EGLQYQPGDH IGICPPNRPG LVEALLSRVE DPPPPTESVA VEQLEKGSPG  840
GPPPSWVRDP RLPPCTLRQA LTFFLDITSP PSPRLLRLLS TLAEEPSEQQ ELETLSQDPR  900
RYEEWKWFRC PTLLEVLEQF PSVALPAPLL LTQLPLLQPR YYSVSSAPNA HPGEVHLTVA  960
VLAYRTQDGL GPLHYGVCST WLSQLKTGDP VPCFIRGAPS FRLPPDPYVP CILVGPGTGI  1020
APFRGFWQER LHDIESKGLQ PAPMTLVFGC RCSQLDHLYR DEVQDAQERG VFGRVLTAFS  1080
REPDSPKTYV QDILRTELAA EVHRVLCLER GHMFVCGDVT MATSVLQTVQ RILATEGDME  1140
LDEAGDVIGV LRDQQRYHED IFGLTLRTQE VTSRIRTQSF SLQERHLRGA VPWAFDPPGP  1200
DTPGP                                                              1205
FASTA
(Canonical)
>LipidDB-9913-01347|P29473
MGNLKSVGQEPGPPCGLGLGLGLGLCGKQGPASPAPEPSRAPAPATPHAPDHSPAPNSPT
LTRPPEGPKFPRVKNWELGSITYDTLCAQSQQDGPCTPRCCLGSLVLPRKLQTRPSPGPP
PAEQLLSQARDFINQYYSSIKRSGSQAHEERLQEVEAEVASTGTYHLRESELVFGAKQAW
RNAPRCVGRIQWGKLQVFDARDCSSAQEMFTYICNHIKYATNRGNLRSAITVFPQRAPGR
GDFRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDE
APELFVLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFSAAPFSGWYM
STEIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINLAVLHSFQLAKVTIV
DHHAATVSFMKHLDNEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYILSPAFRYQPD
PWKGSATKGAGITRKKTFKEVANAVKISASLMGTLMAKRVKATILYASETGRAQSYAQQL
GRLFRKAFDPRVLCMDEYDVVSLEHEALVLVVTSTFGNGDPPENGESFAAALMEMSGPYN
SSPRPEQHKSYKIRFNSVSCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYP
HFCAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAKAAFQASCETFCVGEEAKA
AAQDIFSPKRSWKRQRYRLSTQAEGLQLLPGLIHVHRRKMFQATVLSVENLQSSKSTRAT
ILVRLDTAGQEGLQYQPGDHIGICPPNRPGLVEALLSRVEDPPPPTESVAVEQLEKGSPG
GPPPSWVRDPRLPPCTLRQALTFFLDITSPPSPRLLRLLSTLAEEPSEQQELETLSQDPR
RYEEWKWFRCPTLLEVLEQFPSVALPAPLLLTQLPLLQPRYYSVSSAPNAHPGEVHLTVA
VLAYRTQDGLGPLHYGVCSTWLSQLKTGDPVPCFIRGAPSFRLPPDPYVPCILVGPGTGI
APFRGFWQERLHDIESKGLQPAPMTLVFGCRCSQLDHLYRDEVQDAQERGVFGRVLTAFS
REPDSPKTYVQDILRTELAAEVHRVLCLERGHMFVCGDVTMATSVLQTVQRILATEGDME
LDEAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERHLRGAVPWAFDPPGP
DTPGP
MGNLKSVGQEPGPPCGLGLGLGLGLCGKQGPASPAPEPSRAPAPATPHAPDHSPAPNSPT
LTRPPEGPKFPRVKNWELGSITYDTLCAQSQQDGPCTPRCCLGSLVLPRKLQTRPSPGPP
PAEQLLSQARDFINQYYSSIKRSGSQAHEERLQEVEAEVASTGTYHLRESELVFGAKQAW
RNAPRCVGRIQWGKLQVFDARDCSSAQEMFTYICNHIKYATNRGNLRSAITVFPQRAPGR
GDFRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDE
APELFVLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFSAAPFSGWYM
STEIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINLAVLHSFQLAKVTIV
DHHAATVSFMKHLDNEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYILSPAFRYQPD
PWKGSATKGAGITRKKTFKEVANAVKISASLMGTLMAKRVKATILYASETGRAQSYAQQL
GRLFRKAFDPRVLCMDEYDVVSLEHEALVLVVTSTFGNGDPPENGESFAAALMEMSGPYN
SSPRPEQHKSYKIRFNSVSCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYP
HFCAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAKAAFQASCETFCVGEEAKA
AAQDIFSPKRSWKRQRYRLSTQAEGLQLLPGLIHVHRRKMFQATVLSVENLQSSKSTRAT
ILVRLDTAGQEGLQYQPGDHIGICPPNRPGLVEALLSRVEDPPPPTESVAVEQLEKGSPG
GPPPSWVRDPRLPPCTLRQALTFFLDITSPPSPRLLRLLSTLAEEPSEQQELETLSQDPR
RYEEWKWFRCPTLLEVLEQFPSVALPAPLLLTQLPLLQPRYYSVSSAPNAHPGEVHLTVA
VLAYRTQDGLGPLHYGVCSTWLSQLKTGDPVPCFIRGAPSFRLPPDPYVPCILVGPGTGI
APFRGFWQERLHDIESKGLQPAPMTLVFGCRCSQLDHLYRDEVQDAQERGVFGRVLTAFS
REPDSPKTYVQDILRTELAAEVHRVLCLERGHMFVCGDVTMATSVLQTVQRILATEGDME
LDEAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERHLRGAVPWAFDPPGP
DTPGP
Gene Ontology
GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW
GO:0005794; C:Golgi apparatus; IDA:BHF-UCL
GO:0005886; C:plasma membrane; IEA:UniProtKB-KW
GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro
GO:0010181; F:FMN binding; IEA:InterPro
GO:0020037; F:heme binding; IEA:InterPro
GO:0005506; F:iron ion binding; IEA:InterPro
GO:0050661; F:NADP binding; IEA:InterPro
GO:0004517; F:nitric-oxide synthase activity; IDA:BHF-UCL
GO:0006527; P:arginine catabolic process; IDA:BHF-UCL
GO:0007596; P:blood coagulation; IEA:UniProtKB-KW
GO:0071499; P:cellular response to laminar fluid shear stress; IMP:BHF-UCL
GO:0007005; P:mitochondrion organization; IMP:BHF-UCL
GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IMP:BHF-UCL
GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; IMP:BHF-UCL
GO:0006809; P:nitric oxide biosynthetic process; IDA:BHF-UCL
GO:0031284; P:positive regulation of guanylate cyclase activity; IMP:BHF-UCL
Interpro
InterPro; IPR003097; FAD-binding_1
InterPro; IPR017927; Fd_Rdtase_FAD-bd
InterPro; IPR001094; Flavdoxin
InterPro; IPR008254; Flavodoxin/NO_synth
InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase
InterPro; IPR029039; Flavoprotein-like
InterPro; IPR023173; NADPH_Cyt_P450_Rdtase_dom3
InterPro; IPR012144; NOS_euk
InterPro; IPR004030; NOS_N
InterPro; IPR001433; OxRdtase_FAD/NAD-bd
InterPro; IPR017938; Riboflavin_synthase-like_b-brl
Pfam
Pfam; PF00667; FAD_binding_1;
Pfam; PF00258; Flavodoxin_1;
Pfam; PF00175; NAD_binding_1;
Pfam; PF02898; NO_synthase;
SMART
PROSITE
PROSITE; PS51384; FAD_FR;
PROSITE; PS50902; FLAVODOXIN_LIKE;
PROSITE; PS60001; NOS;
PRINTS
PRINTS; PR00369; FLAVODOXIN;
PRINTS; PR00371; FPNCR;