Details of the Target

General Information of Target

Target ID LDTP01699
Target Name Acyl-CoA 6-desaturase (FADS2)
Gene Name FADS2
Gene ID 9415
Synonyms
Acyl-CoA 6-desaturase; EC 1.14.19.3; Delta(6) fatty acid desaturase; D6D; Delta(6) desaturase; Delta-6 desaturase; Fatty acid desaturase 2
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGKGGNQGEGAAEREVSVPTFSWEEIQKHNLRTDRWLVIDRKVYNITKWSIQHPGGQRVI
GHYAGEDATDAFRAFHPDLEFVGKFLKPLLIGELAPEEPSQDHGKNSKITEDFRALRKTA
EDMNLFKTNHVFFLLLLAHIIALESIAWFTVFYFGNGWIPTLITAFVLATSQAQAGWLQH
DYGHLSVYRKPKWNHLVHKFVIGHLKGASANWWNHRHFQHHAKPNIFHKDPDVNMLHVFV
LGEWQPIEYGKKKLKYLPYNHQHEYFFLIGPPLLIPMYFQYQIIMTMIVHKNWVDLAWAV
SYYIRFFITYIPFYGILGALLFLNFIRFLESHWFVWVTQMNHIVMEIDQEAYRDWFSSQL
TATCNVEQSFFNDWFSGHLNFQIEHHLFPTMPRHNLHKIAPLVKSLCAKHGIEYQEKPLL
RALLDIIRSLKKSGKLWLDAYLHK
Target Type
Literature-reported
Target Bioclass
Enzyme
Family
Fatty acid desaturase type 1 family
Subcellular location
Endoplasmic reticulum membrane
Function
Involved in the biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors, acting as a fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 6 of the fatty acyl chain. Catalyzes the first and rate limiting step in this pathway which is the desaturation of LA (18:2n-6) and ALA (18:3n-3) into gamma-linoleate (GLA) (18:3n-6) and stearidonate (18:4n-3), respectively. Subsequently, in the biosynthetic pathway of HUFA n-3 series, it desaturates tetracosapentaenoate (24:5n-3) to tetracosahexaenoate (24:6n-3), which is then converted to docosahexaenoate (DHA)(22:6n-3), an important lipid for nervous system function. Desaturates hexadecanate (palmitate) to produce 6Z-hexadecenoate (sapienate), a fatty acid unique to humans and major component of human sebum, that has been implicated in the development of acne and may have potent antibacterial activity. It can also desaturate (11E)-octadecenoate (trans-vaccenoate, the predominant trans fatty acid in human milk) at carbon 6 generating (6Z,11E)-octadecadienoate. In addition to Delta-6 activity, this enzyme exhibits Delta-8 activity with slight biases toward n-3 fatty acyl-CoA substrates.
TTD ID
T64725
Uniprot ID
O95864
DrugMap ID
TTT2VDU
Ensemble ID
ENST00000257261.10
HGNC ID
HGNC:3575
ChEMBL ID
CHEMBL6097

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
Ishikawa (Heraklio) 02 ER SNV: p.A120T .
JURKAT Deletion: p.G56AfsTer31
SNV: p.E243K		 .
MEWO SNV: p.R428K .
MFE319 Deletion: p.P96RfsTer21
SNV: p.A120V		 .
MOLT4 SNV: p.E98Ter; p.Q101H .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 9 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
Alkylaryl probe 2
 Probe Info  		20.00  LDD0389  [1]
TH211
 Probe Info  		Y441(12.97)  LDD0260  [2]
STPyne
 Probe Info  		K28(6.67); K398(5.44); K404(10.00); K42(1.44)  LDD0277  [3]
OPA-S-S-alkyne
 Probe Info  		K108(1.76)  LDD3494  [4]
P11
 Probe Info  		12.38  LDD0201  [5]
Alkylaryl probe 3
 Probe Info  		20.00  LDD0282  [6]
Jackson_1
 Probe Info  		2.95  LDD0121  [7]
Acrolein
 Probe Info  		H76(0.00); H62(0.00)  LDD0223  [8]
Crotonaldehyde
 Probe Info  		N.A.  LDD0219  [8]
PAL-AfBPP Probe
Click To Hide/Show 16 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C027
 Probe Info  		5.90  LDD1733  [9]
C040
 Probe Info  		6.68  LDD1740  [9]
C094
 Probe Info  		24.42  LDD1785  [9]
C161
 Probe Info  		10.48  LDD1841  [9]
C220
 Probe Info  		12.73  LDD1894  [9]
C235
 Probe Info  		17.03  LDD1908  [9]
C275
 Probe Info  		5.54  LDD1945  [9]
C349
 Probe Info  		9.13  LDD2010  [9]
C350
 Probe Info  		22.01  LDD2011  [9]
C353
 Probe Info  		17.39  LDD2014  [9]
C382
 Probe Info  		9.78  LDD2041  [9]
FFF probe11
 Probe Info  		20.00  LDD0471  [10]
FFF probe15
 Probe Info  		20.00  LDD0478  [10]
FFF probe7
 Probe Info  		20.00  LDD0483  [10]
VE-P
 Probe Info  		N.A.  LDD0396  [11]
OEA-DA
 Probe Info  		20.00  LDD0046  [12]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0088  C45 HEK-293T 12.38  LDD0201  [5]
 LDCM0071  Cisar_cp14 MDA-MB-231 2.95  LDD0121  [7]
 LDCM0109  NEM HeLa H76(0.00); H62(0.00)  LDD0223  [8]
 LDCM0099  Phenelzine HEK-293T 20.00  LDD0282  [6]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Zinc finger protein 655 (ZNF655) Krueppel C2H2-type zinc-finger protein family Q8N720
Other
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Keratin, type I cuticular Ha1 (KRT31) Intermediate filament family Q15323
Keratin, type I cytoskeletal 40 (KRT40) Intermediate filament family Q6A162
Notch homolog 2 N-terminal-like protein C (NOTCH2NLC) NOTCH family P0DPK4

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Alpha-linolenic Acid Small molecular drug DB00132

References

1 Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes. bioRxiv, 2020-06.
2 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.
3 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
4 A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell. Nat Commun. 2024 Apr 8;15(1):2997. doi: 10.1038/s41467-024-47033-w.
Mass spectrometry data entry: PXD042888
5 Discovery of Potent and Selective Inhibitors against Protein-Derived Electrophilic Cofactors. J Am Chem Soc. 2022 Mar 30;144(12):5377-5388. doi: 10.1021/jacs.1c12748. Epub 2022 Mar 2.
6 Activity-Based Hydrazine Probes for Protein Profiling of Electrophilic Functionality in Therapeutic Targets. ACS Cent Sci. 2021 Sep 22;7(9):1524-1534. doi: 10.1021/acscentsci.1c00616. Epub 2021 Aug 19.
7 Appendage and Scaffold Diverse Fully Functionalized Small-Molecule Probes via a Minimalist Terminal Alkyne-Aliphatic Diazirine Isocyanide. J Org Chem. 2018 Sep 21;83(18):11245-11253. doi: 10.1021/acs.joc.8b01831. Epub 2018 Aug 31.
8 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
9 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
10 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
11 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.
12 Mapping Protein Targets of Bioactive Small Molecules Using Lipid-Based Chemical Proteomics. ACS Chem Biol. 2017 Oct 20;12(10):2671-2681. doi: 10.1021/acschembio.7b00581. Epub 2017 Sep 20.
Mass spectrometry data entry: PXD007570