Details of the Target

General Information of Target

Target ID LDTP03491
Target Name Nitric oxide synthase 3 (NOS3)
Gene Name NOS3
Gene ID 4846
Synonyms
Nitric oxide synthase 3; EC 1.14.13.39; Constitutive NOS; cNOS; EC-NOS; NOS type III; NOSIII; Nitric oxide synthase, endothelial; Endothelial NOS; eNOS
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGNLKSVAQEPGPPCGLGLGLGLGLCGKQGPATPAPEPSRAPASLLPPAPEHSPPSSPLT
QPPEGPKFPRVKNWEVGSITYDTLSAQAQQDGPCTPRRCLGSLVFPRKLQGRPSPGPPAP
EQLLSQARDFINQYYSSIKRSGSQAHEQRLQEVEAEVAATGTYQLRESELVFGAKQAWRN
APRCVGRIQWGKLQVFDARDCRSAQEMFTYICNHIKYATNRGNLRSAITVFPQRCPGRGD
FRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDDPP
ELFLLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMST
EIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINVAVLHSYQLAKVTIVDH
HAATASFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYFLSPAFRYQPDPW
KGSAAKGTGITRKKTFKEVANAVKISASLMGTVMAKRVKATILYGSETGRAQSYAQQLGR
LFRKAFDPRVLCMDEYDVVSLEHETLVLVVTSTFGNGDPPENGESFAAALMEMSGPYNSS
PRPEQHKSYKIRFNSISCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYPHF
CAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAQAAFQAACETFCVGEDAKAAA
RDIFSPKRSWKRQRYRLSAQAEGLQLLPGLIHVHRRKMFQATIRSVENLQSSKSTRATIL
VRLDTGGQEGLQYQPGDHIGVCPPNRPGLVEALLSRVEDPPAPTEPVAVEQLEKGSPGGP
PPGWVRDPRLPPCTLRQALTFFLDITSPPSPQLLRLLSTLAEEPREQQELEALSQDPRRY
EEWKWFRCPTLLEVLEQFPSVALPAPLLLTQLPLLQPRYYSVSSAPSTHPGEIHLTVAVL
AYRTQDGLGPLHYGVCSTWLSQLKPGDPVPCFIRGAPSFRLPPDPSLPCILVGPGTGIAP
FRGFWQERLHDIESKGLQPTPMTLVFGCRCSQLDHLYRDEVQNAQQRGVFGRVLTAFSRE
PDNPKTYVQDILRTELAAEVHRVLCLERGHMFVCGDVTMATNVLQTVQRILATEGDMELD
EAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERQLRGAVPWAFDPPGSDT
NSP
Target Type
Clinical trial
Target Bioclass
Enzyme
Family
NOS family
Subcellular location
Cell membrane
Function
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.; [Isoform eNOS13C]: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.
TTD ID
T06046
Uniprot ID
P29474
DrugMap ID
TTCM4B3
Ensemble ID
ENST00000297494.8
HGNC ID
HGNC:7876
ChEMBL ID
CHEMBL4803

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CASKI SNV: p.R202K .
COLO792 SNV: p.E825D; p.V827L .
FTC133 SNV: p.R678W .
HEC1 SNV: p.P580R .
HEC1B Deletion: p.G440AfsTer64 .
IGR1 SNV: p.S765Ter .
JHH7 SNV: p.G1071C .
JURKAT SNV: p.S39N; p.N132I; p.A515V; p.T978M .
KMCH1 SNV: p.G239R; p.R665P .
KMS11 SNV: p.D715N .
KMS27 SNV: p.Y524H .
LU65 SNV: p.R70C .
MEWO SNV: p.G539E DBIA    Probe Info 
MFE319 Insertion: p.C441LfsTer57
SNV: p.G344V;p.Q965R		 .
NALM6 SNV: p.R221Q .
NCIH1048 SNV: p.R782H .
NCIH1155 SNV: p.H1055N .
NCIH1703 SNV: p.G92W; p.S625F .
NCIH446 SNV: p.N598I .
OVK18 SNV: p.I1173T .
RKO SNV: p.P658T .
RL952 Deletion: p.G440AfsTer64 .
SKNSH SNV: p.P42Q .
SNGM Insertion: p.C441LfsTer57 .
SNU5 SNV: p.D287Y .
SSP25 SNV: p.P658L .
T24 SNV: p.S114F .
TOV21G SNV: p.R70S .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C99(2.25)  LDD3311  [1]
BTD
 Probe Info  		C991(0.98)  LDD2100  [2]
IPM
 Probe Info  		C991(4.66)  LDD1701  [2]
CY4
 Probe Info  		N.A.  LDD0247  [3]
W1
 Probe Info  		N.A.  LDD0236  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 A2780 C99(0.99); C648(1.00)  LDD2254  [1]
 LDCM0023  KB03 MDA-MB-231 C991(4.66)  LDD1701  [2]
 LDCM0024  KB05 G361 C99(2.25)  LDD3311  [1]
 LDCM0507  Nucleophilic fragment 16b MDA-MB-231 C991(0.98)  LDD2100  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 12 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Actin, cytoplasmic 1 (ACTB) Actin family P60709
COP9 signalosome complex subunit 3 (COPS3) CSN3 family Q9UNS2
Hyaluronidase-2 (HYAL2) Glycosyl hydrolase 56 family Q12891
Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 (PCMTD2) L-isoaspartyl/D-aspartyl protein methyltransferase family Q9NV79
[F-actin]-monooxygenase MICAL2 (MICAL2) Mical family O94851
MPN domain-containing protein (MPND) Peptidase M67 family Q8N594
Proprotein convertase subtilisin/kexin type 7 (PCSK7) Peptidase S8 family Q16549
E3 SUMO-protein ligase PIAS1 (PIAS1) PIAS family O75925
RNA exonuclease 4 (REXO4) REXO4 family Q9GZR2
Dynamin-1 (DNM1) Dynamin/Fzo/YdjA family Q05193
E3 ubiquitin-protein ligase RNF183 (RNF183) . Q96D59
Methyltransferase-like protein 27 (METTL27) . Q8N6F8
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Hsp90 co-chaperone Cdc37 (CDC37) CDC37 family Q16543
Hemoglobin subunit alpha (HBA1; HBA2) Globin family P69905
Transcription factor
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Zinc finger protein Aiolos (IKZF3) Ikaros C2H2-type zinc-finger protein family Q9UKT9
Zinc finger protein 232 (ZNF232) Krueppel C2H2-type zinc-finger protein family Q9UNY5
Visual system homeobox 2 (VSX2) Paired homeobox family P58304
THAP domain-containing protein 1 (THAP1) THAP1 family Q9NVV9
Cytokine and receptor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cytokine receptor-like factor 3 (CRLF3) Cytokine receptor-like factor 3 family Q8IUI8
Other
Click To Hide/Show 19 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Catenin beta-1 (CTNNB1) Beta-catenin family P35222
Hsc70-interacting protein (ST13) FAM10 family P50502
Golgin subfamily A member 2 (GOLGA2) GOLGA2 family Q08379
Histone H3.2 (H3C15; H3C14; H3C13) Histone H3 family Q71DI3
Keratin, type I cuticular Ha3-II (KRT33B) Intermediate filament family Q14525
Na(+)/H(+) exchange regulatory cofactor NHE-RF3 (PDZK1) NHER family Q5T2W1
Spermatogenesis-associated protein 2-like protein (SPATA2L) SPATA2 family Q8IUW3
Fanconi anemia group G protein (FANCG) . O15287
Galectin-9C (LGALS9C) . Q6DKI2
Heterogeneous nuclear ribonucleoprotein K (HNRNPK) . P61978
Kelch-like protein 20 (KLHL20) . Q9Y2M5
Nostrin (NOSTRIN) . Q8IVI9
Protein phosphatase 1 regulatory subunit 16A (PPP1R16A) . Q96I34
Splicing regulator RBM11 (RBM11) . P57052
Sprouty-related, EVH1 domain-containing protein 1 (SPRED1) . Q7Z699
Sprouty-related, EVH1 domain-containing protein 2 (SPRED2) . Q7Z698
Superkiller complex protein 8 (SKIC8) . Q9GZS3
Ubiquilin-3 (UBQLN3) . Q9H347
Uncharacterized protein C6orf141 (C6orf141) . Q5SZD1

The Drug(s) Related To This Target

Approved
Click To Hide/Show 6 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Doxorubicin Small molecular drug DB00997
Levamlodipine Small molecular drug DB09237
Miconazole Small molecular drug DB01110
Nitric Oxide Small molecular drug DB00435
Pentaerythritol Tetranitrate Small molecular drug DB06154
Sapropterin Small molecular drug DB00360
Phase 3
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Tilarginine Acetate Small molecular drug D06OQI
Phase 2
Click To Hide/Show 4 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Acclaim Small molecular drug D0J7EH
L-name Small molecular drug D0D3AI
Mtr105 Small molecular drug D0X1RQ
Vas-203 . D0N2JI
Phase 1
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Autologous Cell Based Gene Therapy . D0H3GK
Investigative
Click To Hide/Show 109 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
(5-imino-[1,4]Thiazepan-3-yl)-methanol Small molecular drug D01XOR
(5s,6r)-[Octahydro-quinolin-(2e)-ylidene]Amine Small molecular drug D0K4YY
(5s,6s)-[Octahydro-quinolin-(2e)-ylidene]Amine Small molecular drug D0R9KX
(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin Small molecular drug D04JZV
(S)-2-amino-5-(N-methyl-guanidino)-pentanoic Acid Small molecular drug D0N8EU
(S)-3-propyl-[1,4]Thiazepan-(5e)-ylideneamine Small molecular drug D06VYU
(S)-6-amino-2-(2-imino-ethylamino)-hexanoic Acid Small molecular drug D0T3QN
1,2,4-triazole-carboxamidine Small molecular drug D03RGI
1-(2-amino-benzothiazol-5-yl)-2-ethyl-isothiourea Small molecular drug D00TDJ
1-(2-amino-benzothiazol-6-yl)-2-ethyl-isothiourea Small molecular drug D0X2XQ
124-triazole-carboxamidine Small molecular drug DB02048
1400w Small molecular drug D0AO5D
2,4-diamino-6-phenyl-5,6,7,8,-tetrahydropteridine Small molecular drug D0FK0A
2-amino-4-methylpyridine Small molecular drug D0O3XZ
2-amino-5-(N-nitro-guanidino)-pentanoic Acid Small molecular drug D03FJM
2-aminothiazoline Small molecular drug D01ILO
2-methyl-2,4-pentanediol Small molecular drug D06GOK
2-methyl-[1,4]Thiazepan-(5e)-ylideneamine Small molecular drug D0SB5H
2-propanol, Isopropanol Small molecular drug D0W7LK
24-diamino-6-phenyl-5678-tetrahydropteridine Small molecular drug DB02911
3,4-dimethyl-pyrrolidin-(2z)-ylideneamine Small molecular drug D0G4ZL
3-bromo-1h-indazole-7-carbonitrile Small molecular drug D03EHB
3-bromo-7-nitro-1h-indazole Small molecular drug D0X5QJ
3-bromo-7-nitroindazole Small molecular drug DB01997
3-ethyl-[1,4]Thiazepan-(5e)-ylideneamine Small molecular drug D09NRX
3-methyl-pyrrolidin-(2z)-ylideneamine Small molecular drug D0X6MB
3-methyl-[1,4]Thiazepan-(5e)-ylideneamine Small molecular drug D08WEI
4,5-dimethyl-pyrrolidin-(2z)-ylideneamine Small molecular drug D03JXX
4-ethyl-5,6-dihydro-1h-pyridin-(2z)-ylideneamine Small molecular drug D0Y8DZ
4-ethyl-5-methyl-pyrrolidin-(2z)-ylideneamine Small molecular drug D0X6QY
4-ethyl-pyrrolidin-(2z)-ylideneamine Small molecular drug D02EOF
4-methyl-3,6-dihydro-1h-pyridin-(2z)-ylideneamine Small molecular drug D06PFL
4-methyl-5,6-dihydro-1h-pyridin-(2z)-ylideneamine Small molecular drug D0DI7W
4-methyl-6-propylpyridin-2-amine Small molecular drug D02TMX
4-methyl-piperidin-(2e)-ylideneamine Small molecular drug D0D7PK
4-methyl-pyrrolidin-(2z)-ylideneamine Small molecular drug D0J7NS
5,6-cyclic-tetrahydropteridine Small molecular drug D0P6IL
5-ethyl-3-methyl-pyrrolidin-(2z)-ylideneamine Small molecular drug D0D2WC
5-ethyl-4-methyl-pyrrolidin-(2z)-ylideneamine Small molecular drug D0XJ1C
5-methyl-pyrrolidin-(2z)-ylideneamine Small molecular drug D0D9LT
5-nitroindazole Small molecular drug D0VB2W
56-cyclic-tetrahydropteridine Small molecular drug DB03332
6-(2-fluoropropyl)-4-methylpyridin-2-amine Small molecular drug D07VFC
6-(3-fluoropropyl)-4-methylpyridin-2-amine Small molecular drug D08FXW
6-isobutyl-4-methylpyridin-2-amine Small molecular drug D00EVC
6-nitroindazole Small molecular drug D0Y0FS
6s-5,6,7,8-tetrahydrobiopterin Small molecular drug D03EBE
6s-5678-tetrahydrobiopterin Small molecular drug DB03918
7-(2-nitro-ethyl)-azepan-(2z)-ylideneamine Small molecular drug D03CAJ
7-methyl-[1,4]Thiazepan-(5e)-ylideneamine Small molecular drug D01EHS
7-nitro-1h-indazole Small molecular drug D03WOZ
7-nitroindazole Small molecular drug DB02207
7-nitroindazole-2-carboxamidine Small molecular drug D0N5LD
Acetate Ion Small molecular drug D0F2ME
Ap-cav Small molecular drug D01FMS
Arginine Small molecular drug DB00125
Azepan-(2z)-ylideneamine Small molecular drug D08ALG
Cacodylate Ion Small molecular drug D09TVP
Cacodylic Acid Small molecular drug DB02994
Canavanine Small molecular drug DB01833
Citrulline Small molecular drug DB00155
Ethylisothiourea Small molecular drug D0I7VD
Heme Small molecular drug D0UU1I
Hexahydro-cyclopenta[C]Pyrrol-(1z)-ylideneamine Small molecular drug D0LE6N
Hydroxydimethylarsine Oxide Small molecular drug D06YEV
L-2-amino-4-(Guanidinooxy)Butyric Acid Small molecular drug D0V9FZ
L-homoarginine Small molecular drug D0F8VS
L-homoarginine Small molecular drug DB03974
L-nio Small molecular drug D02ELA
N(5)-[(Hydroxyamino)(Imino)Methyl]-l-ornithine Small molecular drug DB03144
N(G)-iminoethylornithine Small molecular drug DB03305
N,N-dimethylarginine Small molecular drug D02DQQ
N-(5-amino-6-oxo-heptyl)-acetamidine Small molecular drug D0V5HI
N-(Chlorophenyl)-n'-hydroxyguanidine Small molecular drug D08DNK
N-(Chlorophenyl)-n'-hydroxyguanidine Small molecular drug DB04559
N-omega-allyl-l-arginine Small molecular drug D0DD9E
N-omega-hydroxy-l-arginine Small molecular drug D0GL9I
N-omega-propargyl-l-arginine Small molecular drug D0L4RU
N-[3-(Aminomethyl)Benzyl]Acetamidine Small molecular drug DB02044
N1,N14-bis((S-methyl)Isothioureido)Tetradecane Small molecular drug D0Z3JI
N1n14-bis((S-methyl)Isothioureido)Tetradecane Small molecular drug DB02979
N5-(1-iminobut-3-enyl)-l-ornithine Small molecular drug D0L5KY
N5-(1-iminobutyl)-l-ornithine Small molecular drug D0GX7G
N5-(1-iminopropyl)-l-ornithine Small molecular drug D04PBI
Nitroarginine Small molecular drug D0GC1Y
Nn-dimethylarginine Small molecular drug DB01686
Piperidin-(2e)-ylideneamine Small molecular drug D0D0TO
Pyrrolidin-(2z)-ylideneamine Small molecular drug D0C1OB
S-(Dimethylarsenic)Cysteine Small molecular drug D08TGY
S-ethyl-n-phenyl-isothiourea Small molecular drug D01TDG
S-ethylisothiourea Small molecular drug DB02234
S-isopropyl-isothiourea Small molecular drug D0J1LO
Se-ethyl-isoselenourea Small molecular drug D02RNH
Ss'-(13-phenylene-bis(12-ethanediyl))Bis-isothiourea Small molecular drug DB03910
Thiocitrulline Small molecular drug D0E0QG
[1,3]Oxazinan-(2e)-ylideneamine Small molecular drug D0M4BM
[1,3]Thiazinan-(2e)-ylideneamine Small molecular drug D0O9II
[1,4]Oxazepan-(3e)-ylideneamine Small molecular drug D0I3ZP
[1,4]Thiazepan-(3e)-ylideneamine Small molecular drug D02TYS
[1,4]Thiazepan-(5e)-ylideneamine Small molecular drug D0N3HU
(3s5e)-3-propyl-34-dihydrothieno[23-f][14]Oxazepin-5(2h)-imine . DB07001
5-{4-[(35-difluorobenzyl)Amino]Phenyl}-6-ethylpyrimidine-24-diamine . DB07244
Ethyl 4-[(4-methylpyridin-2-yl)Amino]Piperidine-1-carboxylate . DB07388
L-n(Omega)-nitroarginine-(4r)-amino-l-proline Amide . DB02077
L-n(Omega)-nitroarginine-24-l-diaminobutyric Amide . DB01821
N-{(3r4s)-4-[(6-amino-4-methylpyridin-2-yl)Methyl]Pyrrolidin-3-yl}-n'-(3-chlorobenzyl)Ethane-12-diamine . DB08019
N-{(3s4s)-4-[(6-amino-4-methylpyridin-2-yl)Methyl]Pyrrolidin-3-yl}-n'-(4-chlorobenzyl)Ethane-12-diamine . DB08018
N-{(4s)-4-amino-5-[(2-aminoethyl)Amino]Pentyl}-n'-nitroguanidine . DB02027
Ss'-(14-phenylene-bis(12-ethanediyl))Bis-isothiourea . DB02141
Discontinued
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
L-nil Small molecular drug D0Y7VJ

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
3 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
4 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.