Details of the Target

General Information of Target

Target ID LDTP09763
Target Name Cyclic GMP-AMP phosphodiesterase SMPDL3A (SMPDL3A)
Gene Name SMPDL3A
Gene ID 10924
Synonyms
ASML3A; Cyclic GMP-AMP phosphodiesterase SMPDL3A; 2',3'-cGAMP phosphodiesterase SMPDL3A; EC 3.1.4.-; Acid sphingomyelinase-like phosphodiesterase 3a; ASM-like phosphodiesterase 3a; EC 3.6.1.15
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGRQKELVSRCGEMLHIRYRLLRQALAECLGTLILVMFGCGSVAQVVLSRGTHGGFLTIN
LAFGFAVTLGILIAGQVSGAHLNPAVTFAMCFLAREPWIKLPIYTLAQTLGAFLGAGIVF
GLYYDAIWHFADNQLFVSGPNGTAGIFATYPSGHLDMINGFFDQFIGTASLIVCVLAIVD
PYNNPVPRGLEAFTVGLVVLVIGTSMGFNSGYAVNPARDFGPRLFTALAGWGSAVFTTGQ
HWWWVPIVSPLLGSIAGVFVYQLMIGCHLEQPPPSNEEENVKLAHVKHKEQI
Target Bioclass
Enzyme
Family
Acid sphingomyelinase family
Subcellular location
Secreted
Function
Cyclic-nucleotide phosphodiesterase that acts as a negative regulator of innate immunity by mediating degradation of 2',3'-cGAMP, thereby inhibiting the cGAS-STING signaling. Specifically linearizes 2',3'-cGAMP into 2'5'-bond pGpA and further hydrolyzes pGpA to produce GpA. Also has in vitro nucleotide phosphodiesterase activity with nucleoside triphosphates, such as ATP. Has in vitro activity with p-nitrophenyl-TMP. Has lower activity with nucleoside diphosphates, and no activity with nucleoside monophosphates. Has in vitro activity with CDP-choline, giving rise to CMP and phosphocholine. Has in vitro activity with CDP-ethanolamine. Does not have sphingomyelin phosphodiesterase activity.
Uniprot ID
Q92484
Ensemble ID
ENST00000368440.5
HGNC ID
HGNC:17389

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HCT15 SNV: p.V247L .
KYSE510 SNV: p.N243S .
MCC13 SNV: p.P342S .
MDAMB468 SNV: p.P75R .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C62(1.95)  LDD3428  [1]
NHS
 Probe Info  		N.A.  LDD0010  [2]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C170
 Probe Info  		11.16  LDD1850  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 SK-MEL3 C62(1.77)  LDD2594  [1]
 LDCM0023  KB03 SK-MEL-30 C62(2.21)  LDD3012  [1]
 LDCM0024  KB05 SK-MEL3 C62(1.95)  LDD3428  [1]

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 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
3 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587