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Protein

Nitric oxide synthase, endothelial

Gene

NOS3

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

2 L-arginine + 3 NADPH + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O.

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi96ZincBy similarity1
Metal bindingi101ZincBy similarity1
Metal bindingi186Iron (heme axial ligand)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi651 – 682FMNPROSITE-ProRule annotationAdd BLAST32
Nucleotide bindingi795 – 806FADBy similarityAdd BLAST12
Nucleotide bindingi937 – 947FADBy similarityAdd BLAST11
Nucleotide bindingi1012 – 1030NADPBy similarityAdd BLAST19
Nucleotide bindingi1110 – 1125NADPBy similarityAdd BLAST16

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Oxidoreductase
LigandCalcium, FAD, Flavoprotein, FMN, Heme, Iron, Metal-binding, NADP, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Nitric oxide synthase, endothelial (EC:1.14.13.39)
Alternative name(s):
Constitutive NOS
Short name:
cNOS
EC-NOS
Endothelial NOS
Short name:
eNOS
NOS type III
Short name:
NOSIII
Gene namesi
Name:NOS3
Synonyms:NOS
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Golgi apparatus, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3809

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001709452 – 1205Nitric oxide synthase, endothelialAdd BLAST1204

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Lipidationi15S-palmitoyl cysteineBy similarity1
Lipidationi26S-palmitoyl cysteineBy similarity1
Modified residuei116Phosphoserine; by CDK5By similarity1
Modified residuei497Phosphothreonine; by AMPKBy similarity1
Modified residuei617PhosphoserineBy similarity1
Modified residuei635PhosphoserineBy similarity1
Modified residuei640PhosphoserineBy similarity1
Modified residuei838PhosphoserineBy similarity1
Modified residuei1177PhosphothreonineBy similarity1
Modified residuei1179Phosphoserine; by AMPKBy similarity1
Modified residuei1181PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation by AMPK at Ser-1179 in the presence of Ca2+-calmodulin (CaM) activates activity. In absence of Ca2+-calmodulin, AMPK also phosphorylates Thr-497, resulting in inhibition of activity. Phosphorylation of Ser-116 by CDK5 reduces activity (By similarity).By similarity

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ28969
PRIDEiQ28969

PTM databases

iPTMnetiQ28969

Expressioni

Inductioni

Repressed by proinflammatory cytokines.

Interactioni

Subunit structurei

Homodimer. Interacts with NOSIP and NOSTRIN (By similarity). Interacts with HSP90AB1 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi1149683, 3 interactors
STRINGi9823.ENSSSCP00000017432

Chemistry databases

BindingDBiQ28969

Structurei

3D structure databases

ProteinModelPortaliQ28969
SMRiQ28969
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini522 – 705Flavodoxin-likePROSITE-ProRule annotationAdd BLAST184
Domaini758 – 1004FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST247

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni100 – 488Interaction with NOSIPBy similarityAdd BLAST389
Regioni492 – 512Calmodulin-bindingSequence analysisAdd BLAST21

Sequence similaritiesi

Belongs to the NOS family.Curated

Phylogenomic databases

eggNOGiKOG1158 Eukaryota
COG0369 LUCA
COG4362 LUCA
HOGENOMiHOG000111088
HOVERGENiHBG000159
InParanoidiQ28969
KOiK13242

Family and domain databases

Gene3Di1.20.990.10, 1 hit
3.40.50.360, 1 hit
InterProiView protein in InterPro
IPR003097 FAD-binding_1
IPR017927 Fd_Rdtase_FAD-bd
IPR001094 Flavdoxin-like
IPR008254 Flavodoxin/NO_synth
IPR001709 Flavoprot_Pyr_Nucl_cyt_Rdtase
IPR029039 Flavoprotein-like_sf
IPR023173 NADPH_Cyt_P450_Rdtase_alpha
IPR012144 NOS_euk
IPR004030 NOS_N
IPR036119 NOS_N_sf
IPR001433 OxRdtase_FAD/NAD-bd
IPR017938 Riboflavin_synthase-like_b-brl
PfamiView protein in Pfam
PF00667 FAD_binding_1, 1 hit
PF00258 Flavodoxin_1, 1 hit
PF00175 NAD_binding_1, 1 hit
PF02898 NO_synthase, 1 hit
PIRSFiPIRSF000333 NOS, 1 hit
PRINTSiPR00369 FLAVODOXIN
PR00371 FPNCR
SUPFAMiSSF52218 SSF52218, 1 hit
SSF56512 SSF56512, 1 hit
SSF63380 SSF63380, 1 hit
PROSITEiView protein in PROSITE
PS51384 FAD_FR, 1 hit
PS50902 FLAVODOXIN_LIKE, 1 hit
PS60001 NOS, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q28969-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PATPAPEPSR APAPATPHAP
60 70 80 90 100
EHSPAPNSPT LTRPPEGPKF PRVKNWEVGS ITYDTLCAQS QQDGPCTPRR
110 120 130 140 150
CLGSLVLPRK LQSRPSPGPP PAEQLLSQAR DFINQYYSSI KRSGSQAHEE
160 170 180 190 200
RLQEVEAEVA TTGTYHLGES ELVFGAKQAW RNAPRCVGRI QWGKLQVFDA
210 220 230 240 250
RDCSSAQEMF TYICNHIKYA TNRGNLRSAI TVFPQRTPGR GDFRIWNSQL
260 270 280 290 300
VRYAGYRQQD GSVRGDPANV EITELCIQHG WTPGNGRFDV LPLLLQAPDE
310 320 330 340 350
PPELFALPPE LVLEVPLEHP TLEWFAALGL RWYALPAVSN MLLEIGGLEF
360 370 380 390 400
PAAPFSGWYM STEIGTRNLC DPHRYNILED VAVCMDLDTR TTSSLWKDKA
410 420 430 440 450
AVEINLAVLH SYQLAKVTIV DHHAATASFM KHLENEQKAR GGCPADWAWI
460 470 480 490 500
VPPISGSLTP VFHQEMVNYV LSPAFRYQPD PWKGSAAKGT GIARKKTFKE
510 520 530 540 550
VANAVKISAS LMATVMPKRV KASILYASET VRAQSYAQQL GRLFRKAFDP
560 570 580 590 600
RVLCMDEYDV VSLEHETLVL VVTSTFGNGD PPENGESFAA ALMEMSGPYN
610 620 630 640 650
GSPRPEQHRS YKIRFNSVSC SDPLVSSWRR KRKESSNTDS AGALGTLRFC
660 670 680 690 700
VFGLGSRAYP HFCAFARAVD TRLEELGGER LLQLGQGDEL CGQEEAFRGW
710 720 730 740 750
AQAAFQASCE TFCVGEDAKA AARDIFSPKR SWKRQRYRLS AQVEGLQLLP
760 770 780 790 800
GLVHVHRRKM FQATVLSVEN LQSSKSTRAT ILVRLDTEGQ EGLQYQPGDH
810 820 830 840 850
IGICPPNRTG LVEALLSRVE DPTPPTESVG VEQLEKGSPG GPPPSWVRDP
860 870 880 890 900
RLPPYTLRQA LTFFLDITSP PSPRLLRVLS TLAEEPSEQQ ELETLSQDPR
910 920 930 940 950
RYEEWKWFRC PTLLEVLEQF PSVALPTPLL LTQLALLQPR YYSVSSAPST
960 970 980 990 1000
YPGEIHPTVA VLAYRTQDGL GPLHYGVCST WLGQLKPGDP VPCFIRAAPS
1010 1020 1030 1040 1050
FRLPPDPSLP CILVGPGTGI APFRGFWQER LHDIESKGLQ PAPMTLVFGC
1060 1070 1080 1090 1100
RCSQLDHLYR DEVQDAQQRG VFGRVLTAFS REPDSPKTYV QDILRTELAA
1110 1120 1130 1140 1150
EVHRVLCLER GHMFVCGDVT MATSVLQTVQ RILATEGNME LDEAGDVIGV
1160 1170 1180 1190 1200
LRDQQRYHED IFGLTLRTQE VTSRIRTQSF SLQERHLRGA VPWTFDPPGP

DTPGP
Length:1,205
Mass (Da):133,406
Last modified:January 23, 2007 - v4
Checksum:iC5B8B5E61AADAACF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U59924 mRNA Translation: AAB39539.1
U33832 mRNA Translation: AAA84933.1
RefSeqiNP_999460.1, NM_214295.1
UniGeneiSsc.16364

Genome annotation databases

GeneIDi397557
KEGGissc:397557

Similar proteinsi

Entry informationi

Entry nameiNOS3_PIG
AccessioniPrimary (citable) accession number: Q28969
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: May 23, 2018
This is version 147 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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