Details of the Target

General Information of Target

Target ID LDTP05040
Target Name Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (GNAS)
Gene Name GNAS
Gene ID 2778
Synonyms
GNAS1; GSP; Guanine nucleotide-binding protein G(s) subunit alpha isoforms short; Adenylate cyclase-stimulating G alpha protein
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQM
RILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELA
NPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLD
KIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFND
VTAIIFVVASSSYNMVIREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEK
VLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCY
PHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL
Target Bioclass
Transporter and channel
Family
G-alpha family, G(s) subfamily
Subcellular location
Cell membrane
Function
Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. Stimulates the Ras signaling pathway via RAPGEF2.
Uniprot ID
P63092
Ensemble ID
ENST00000265620.11
HGNC ID
HGNC:4392
ChEMBL ID
CHEMBL4377

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
AGS SNV: p.F219V .
HCT116 SNV: p.Y318C .
HCT15 SNV: p.K338N .
HT115 SNV: p.A175V .
ICC3 SNV: p.R201H .
KURAMOCHI SNV: p.R160C .
MCAS SNV: p.R317C .
OZ SNV: p.R201H .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 16 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		13.10  LDD0402  [1]
CHEMBL5175495
 Probe Info  		7.01  LDD0196  [2]
TH211
 Probe Info  		Y318(20.00); Y311(10.47); Y360(6.40)  LDD0260  [3]
STPyne
 Probe Info  		K338(6.25); K34(7.66)  LDD0277  [4]
BTD
 Probe Info  		C3(6.39)  LDD1699  [5]
Probe 1
 Probe Info  		Y190(36.13); Y311(10.86); Y318(17.98); Y339(28.04)  LDD3495  [6]
ATP probe
 Probe Info  		K211(0.00); K216(0.00)  LDD0199  [7]
4-Iodoacetamidophenylacetylene
 Probe Info  		C3(0.00); C379(0.00); C174(0.00)  LDD0038  [8]
IA-alkyne
 Probe Info  		C379(0.00); C174(0.00); C3(0.00); C359(0.00)  LDD0036  [8]
Lodoacetamide azide
 Probe Info  		C3(0.00); C379(0.00); C174(0.00); C359(0.00)  LDD0037  [8]
JW-RF-010
 Probe Info  		N.A.  LDD0026  [9]
TFBX
 Probe Info  		C3(0.00); C379(0.00)  LDD0027  [9]
IPM
 Probe Info  		N.A.  LDD0005  [10]
Phosphinate-6
 Probe Info  		C359(0.00); C3(0.00)  LDD0018  [11]
AOyne
 Probe Info  		15.00  LDD0443  [12]
NAIA_5
 Probe Info  		C162(0.00); C174(0.00); C237(0.00); C365(0.00)  LDD2223  [13]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STS-2
 Probe Info  		N.A.  LDD0139  [14]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0548  1-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-2-nitroethan-1-one MDA-MB-231 C3(1.02)  LDD2142  [5]
 LDCM0519  1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-2-nitroethan-1-one MDA-MB-231 C3(1.21)  LDD2112  [5]
 LDCM0502  1-(Cyanoacetyl)piperidine MDA-MB-231 C3(0.90)  LDD2095  [5]
 LDCM0537  2-Cyano-N,N-dimethylacetamide MDA-MB-231 C3(1.09)  LDD2130  [5]
 LDCM0524  2-Cyano-N-(2-morpholin-4-yl-ethyl)-acetamide MDA-MB-231 C3(0.99)  LDD2117  [5]
 LDCM0539  3-(4-Isopropylpiperazin-1-yl)-3-oxopropanenitrile MDA-MB-231 C3(0.66)  LDD2132  [5]
 LDCM0538  4-(Cyanoacetyl)morpholine MDA-MB-231 C3(0.89)  LDD2131  [5]
 LDCM0545  Acetamide MDA-MB-231 C3(0.90)  LDD2138  [5]
 LDCM0156  Aniline NCI-H1299 15.00  LDD0403  [1]
 LDCM0498  BS-3668 MDA-MB-231 C3(0.51)  LDD2091  [5]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C3(3.30); C379(1.54)  LDD1702  [5]
 LDCM0625  F8 Ramos C3(1.24); C379(0.56); 1.02  LDD2187  [15]
 LDCM0572  Fragment10 Ramos C3(1.78); C379(0.55)  LDD2189  [15]
 LDCM0573  Fragment11 Ramos C3(4.23); C379(0.49)  LDD2190  [15]
 LDCM0574  Fragment12 Ramos C3(0.86); C379(0.59)  LDD2191  [15]
 LDCM0575  Fragment13 Ramos C3(0.97); C379(0.84)  LDD2192  [15]
 LDCM0576  Fragment14 Ramos C3(0.72); C379(0.35); 0.84  LDD2193  [15]
 LDCM0579  Fragment20 Ramos C3(1.24); C379(0.55)  LDD2194  [15]
 LDCM0580  Fragment21 Ramos C3(0.98); C379(0.72)  LDD2195  [15]
 LDCM0582  Fragment23 Ramos C3(0.75); C379(1.40)  LDD2196  [15]
 LDCM0578  Fragment27 Ramos C3(0.92); C379(0.88)  LDD2197  [15]
 LDCM0586  Fragment28 Ramos C3(0.76); C379(0.88)  LDD2198  [15]
 LDCM0588  Fragment30 Ramos C3(1.41); C379(0.96)  LDD2199  [15]
 LDCM0589  Fragment31 Ramos C3(0.83); C379(0.87)  LDD2200  [15]
 LDCM0590  Fragment32 Ramos C3(2.20); C379(0.52)  LDD2201  [15]
 LDCM0468  Fragment33 Ramos C3(1.11); C379(0.66)  LDD2202  [15]
 LDCM0596  Fragment38 Ramos C3(1.04); C379(0.83)  LDD2203  [15]
 LDCM0566  Fragment4 Ramos C3(1.13); C379(0.67)  LDD2184  [15]
 LDCM0610  Fragment52 Ramos C3(1.14); C379(1.28)  LDD2204  [15]
 LDCM0614  Fragment56 Ramos C3(2.27); C379(1.10)  LDD2205  [15]
 LDCM0569  Fragment7 Ramos C3(1.23); C379(0.91); 0.76  LDD2186  [15]
 LDCM0571  Fragment9 Ramos C3(1.16); C379(0.66)  LDD2188  [15]
 LDCM0022  KB02 Ramos C3(3.58); C379(0.97)  LDD2182  [15]
 LDCM0023  KB03 MDA-MB-231 C379(10.92); C3(5.66)  LDD1701  [5]
 LDCM0024  KB05 Ramos C3(1.91); C379(0.84)  LDD2185  [15]
 LDCM0509  N-(4-bromo-3,5-dimethylphenyl)-2-nitroacetamide MDA-MB-231 C3(0.89)  LDD2102  [5]
 LDCM0528  N-(4-bromophenyl)-2-cyano-N-phenylacetamide MDA-MB-231 C3(0.78)  LDD2121  [5]
 LDCM0496  Nucleophilic fragment 11a MDA-MB-231 C3(0.74)  LDD2089  [5]
 LDCM0497  Nucleophilic fragment 11b MDA-MB-231 C379(0.65)  LDD2090  [5]
 LDCM0499  Nucleophilic fragment 12b MDA-MB-231 C3(0.96)  LDD2092  [5]
 LDCM0501  Nucleophilic fragment 13b MDA-MB-231 C3(1.27)  LDD2094  [5]
 LDCM0505  Nucleophilic fragment 15b MDA-MB-231 C3(1.14)  LDD2098  [5]
 LDCM0506  Nucleophilic fragment 16a MDA-MB-231 C3(0.93)  LDD2099  [5]
 LDCM0507  Nucleophilic fragment 16b MDA-MB-231 C3(1.34)  LDD2100  [5]
 LDCM0511  Nucleophilic fragment 18b MDA-MB-231 C3(1.06)  LDD2104  [5]
 LDCM0512  Nucleophilic fragment 19a MDA-MB-231 C3(1.77)  LDD2105  [5]
 LDCM0514  Nucleophilic fragment 20a MDA-MB-231 C379(1.31)  LDD2107  [5]
 LDCM0515  Nucleophilic fragment 20b MDA-MB-231 C3(1.03)  LDD2108  [5]
 LDCM0521  Nucleophilic fragment 23b MDA-MB-231 C3(0.87)  LDD2114  [5]
 LDCM0527  Nucleophilic fragment 26b MDA-MB-231 C3(0.90)  LDD2120  [5]
 LDCM0531  Nucleophilic fragment 28b MDA-MB-231 C3(1.11)  LDD2124  [5]
 LDCM0532  Nucleophilic fragment 29a MDA-MB-231 C3(0.94)  LDD2125  [5]
 LDCM0533  Nucleophilic fragment 29b MDA-MB-231 C3(1.36)  LDD2126  [5]
 LDCM0535  Nucleophilic fragment 30b MDA-MB-231 C3(1.01); C379(0.95)  LDD2128  [5]
 LDCM0542  Nucleophilic fragment 37 MDA-MB-231 C3(0.94)  LDD2135  [5]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C3(1.23)  LDD2136  [5]
 LDCM0211  Nucleophilic fragment 3b MDA-MB-231 C3(1.33)  LDD1700  [5]
 LDCM0546  Nucleophilic fragment 40 MDA-MB-231 C3(1.24)  LDD2140  [5]
 LDCM0547  Nucleophilic fragment 41 MDA-MB-231 C3(0.91)  LDD2141  [5]
 LDCM0549  Nucleophilic fragment 43 MDA-MB-231 C3(1.01)  LDD2143  [5]
 LDCM0551  Nucleophilic fragment 5b MDA-MB-231 C3(8.20)  LDD2145  [5]
 LDCM0552  Nucleophilic fragment 6a MDA-MB-231 C3(0.98)  LDD2146  [5]
 LDCM0553  Nucleophilic fragment 6b MDA-MB-231 C3(2.11)  LDD2147  [5]
 LDCM0556  Nucleophilic fragment 8a MDA-MB-231 C3(0.52)  LDD2150  [5]
 LDCM0627  NUDT7-COV-1 HEK-293T C3(0.69)  LDD2206  [16]
 LDCM0628  OTUB2-COV-1 HEK-293T C3(0.74)  LDD2207  [16]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
2'5'-dideoxy-adenosine 3'-monophosphate Small molecular drug DB06843
Colforsin Small molecular drug DB02587

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 Charting the Chemical Space of Acrylamide-Based Inhibitors of zDHHC20. ACS Med Chem Lett. 2022 Sep 26;13(10):1648-1654. doi: 10.1021/acsmedchemlett.2c00336. eCollection 2022 Oct 13.
3 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
4 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
5 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
6 An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome. Anal Chem. 2021 Jul 27;93(29):10334-10342. doi: 10.1021/acs.analchem.1c01935. Epub 2021 Jul 12.
7 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
8 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
9 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
10 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
11 DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202205348. doi: 10.1002/anie.202205348. Epub 2022 Aug 22.
Mass spectrometry data entry: PXD033004
12 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
13 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
14 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.
15 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
16 Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening. J Am Chem Soc. 2019 Jun 5;141(22):8951-8968. doi: 10.1021/jacs.9b02822. Epub 2019 May 22.