LipidDB-9606-01345

Lipid Modification Database

Tag

Content

LipidDB ID

LipidDB-9606-01345

Entry Name

NOS3_HUMAN

UniProt Accession

P29474; A0S0A7; A0S0A8; A8KA63; B2RCQ1; E9PFR2; Q13662; Q14251; Q14434; Q548C1; Q6GSL5; Q9UDC6;

Theoretical PI

6.94

Molecular Weight

133288.81

Genbank Protein ID

Genbank Nucleotide ID

M93718; M95296; L10709; L10693; L10694; L10695; L10696; L10697; L10698; L10699; L10700; L10701; L10702; L10703; L10704; L10705; L10706; L10707; L10708; X76303; X76304; X76305; X76306; X76307; X76308; X76309; X76310; X76311; X76312; X76313; X76314; X76315; X76316; D26607; DQ256130; DQ256131; L26914; AF400594; AK292928; AK315213; AK223636; AF519768; EU332855; AC010973; CH471173; BC063294; BC069465; L23210; S80791;

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
15	Canonical	AQEPGPPCGLGLGLG	[1]	S-Palmitoylation
26	Canonical	LGLGLGLCGKQGPAT	[1]	S-Palmitoylation

Organism

Homo sapiens (Human)

NCBI Taxa ID

9606

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]

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.
Nucleotide-binding: 649 680 FMN.
Nucleotide-binding: 793 804 FAD.
Nucleotide-binding: 935 945 FAD.
Nucleotide-binding: 1010 1028 NADP.
Nucleotide-binding: 1108 1123 NADP.
Region: 98 486 Interaction with NOSIP.
Region: 491 510 Calmodulin-binding.
Metal binding site: 94 94 Zinc.
Metal binding site: 99 99 Zinc.
Metal binding site: 184 184 Iron (heme axial ligand).
Modified residue: 114 114 Phosphoserine; by CDK5.
Modified residue: 141 141 Phosphoserine.
Modified residue: 495 495 Phosphothreonine; by AMPK.
Modified residue: 633 633 Phosphoserine.
Modified residue: 1175 1175 Phosphothreonine.
Modified residue: 1177 1177 Phosphoserine; by AMPK.

Protein Length

1203 AA.

Protein Sequence
(Canonical)

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

FASTA
(Canonical)

>LipidDB-9606-01345|P29474
MGNLKSVAQEPGPPCGLGLGLGLGLCGKQGPATPAPEPSRAPASLLPPAPEHSPPSSPLT
QPPEGPKFPRVKNWEVGSITYDTLSAQAQQDGPCTPRRCLGSLVFPRKLQGRPSPGPPAP
EQLLSQARDFINQYYSSIKRSGSQAHEQRLQEVEAEVAATGTYQLRESELVFGAKQAWRN
APRCVGRIQWGKLQVFDARDCRSAQEMFTYICNHIKYATNRGNLRSAITVFPQRCPGRGD
FRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDEPP
ELFLLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMST
EIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINVAVLHSYQLAKVTIVDH
HAATASFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYFLSPAFRYQPDPW
KGSAAKGTGITRKKTFKEVANAVKISASLMGTVMAKRVKATILYGSETGRAQSYAQQLGR
LFRKAFDPRVLCMDEYDVVSLEHETLVLVVTSTFGNGDPPENGESFAAALMEMSGPYNSS
PRPEQHKSYKIRFNSISCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYPHF
CAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAQAAFQAACETFCVGEDAKAAA
RDIFSPKRSWKRQRYRLSAQAEGLQLLPGLIHVHRRKMFQATIRSVENLQSSKSTRATIL
VRLDTGGQEGLQYQPGDHIGVCPPNRPGLVEALLSRVEDPPAPTEPVAVEQLEKGSPGGP
PPGWVRDPRLPPCTLRQALTFFLDITSPPSPQLLRLLSTLAEEPREQQELEALSQDPRRY
EEWKWFRCPTLLEVLEQFPSVALPAPLLLTQLPLLQPRYYSVSSAPSTHPGEIHLTVAVL
AYRTQDGLGPLHYGVCSTWLSQLKPGDPVPCFIRGAPSFRLPPDPSLPCILVGPGTGIAP
FRGFWQERLHDIESKGLQPTPMTLVFGCRCSQLDHLYRDEVQNAQQRGVFGRVLTAFSRE
PDNPKTYVQDILRTELAAEVHRVLCLERGHMFVCGDVTMATNVLQTVQRILATEGDMELD
EAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERQLRGAVPWAFDPPGSDT
NSP

Gene Ontology

GO:0005901; C:caveola; IDA:BHF-UCL
GO:0005737; C:cytoplasm; IDA:BHF-UCL
GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW
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:0005886; C:plasma membrane; TAS:Reactome
GO:0003785; F:actin monomer binding; IPI: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:Ensembl
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:Ensembl
GO:0051701; P:interaction with host; TAS:Reactome
GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl
GO:0030324; P:lung development; IEA:Ensembl
GO:0007005; P:mitochondrion organization; ISS:BHF-UCL
GO:0045776; P:negative regulation of blood pressure; IBA:RefGenome
GO:0051926; P:negative regulation of calcium ion transport; IEA:Ensembl
GO:0008285; P:negative regulation of cell proliferation; ISS:BHF-UCL
GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISS:BHF-UCL
GO:0051346; P:negative regulation of hydrolase activity; IEA:Ensembl
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:Ensembl
GO:0006809; P:nitric oxide biosynthetic process; IDA:BHF-UCL
GO:0007263; P:nitric oxide mediated signal transduction; IBA:RefGenome
GO:0046209; P:nitric oxide metabolic process; TAS:Reactome
GO:0001542; P:ovulation from ovarian follicle; IEA:Ensembl
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:0008217; P:regulation of blood pressure; 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:Ensembl
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:Ensembl
GO:0034405; P:response to fluid shear stress; IEP:BHF-UCL
GO:0009408; P:response to heat; NAS:BHF-UCL
GO:0044281; P:small molecule metabolic process; TAS:Reactome
GO:0014806; P:smooth muscle hyperplasia; ISS: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;