Target Information
| Target General Information | Top | |||||
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| Target ID |
T81452
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| Target Name |
Monoacylglycerol lipase ABHD6 (ABHD6)
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| Synonyms |
Abhydrolase domain-containing protein 6; 2-arachidonoylglycerol hydrolase
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| Gene Name |
ABHD6
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| Target Type |
Patented-recorded target
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[1] | ||||
| Function |
Lipase that preferentially hydrolysis medium-chain saturated monoacylglycerols including 2-arachidonoylglycerol. Through 2-arachidonoylglycerol degradation may regulate endocannabinoid signaling pathways. Also has a lysophosphatidyl lipase activity with a preference for lysophosphatidylglycerol among other lysophospholipids. Also able to degrade bis(monoacylglycero)phosphate (BMP) and constitutes the major enzyme for BMP catabolism. BMP, also known as lysobisphosphatidic acid, is enriched in late endosomes and lysosomes and plays a key role in the formation of intraluminal vesicles and in lipid sorting.
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| BioChemical Class |
Carboxylic ester hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.1.1.23
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| Sequence |
MDLDVVNMFVIAGGTLAIPILAFVASFLLWPSALIRIYYWYWRRTLGMQVRYVHHEDYQF
CYSFRGRPGHKPSILMLHGFSAHKDMWLSVVKFLPKNLHLVCVDMPGHEGTTRSSLDDLS IDGQVKRIHQFVECLKLNKKPFHLVGTSMGGQVAGVYAAYYPSDVSSLCLVCPAGLQYST DNQFVQRLKELQGSAAVEKIPLIPSTPEEMSEMLQLCSYVRFKVPQQILQGLVDVRIPHN NFYRKLFLEIVSEKSRYSLHQNMDKIKVPTQIIWGKQDQVLDVSGADMLAKSIANCQVEL LENCGHSVVMERPRKTAKLIIDFLASVHNTDNNKKLD Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: B-Octylglucoside | Ligand Info | |||||
| Structure Description | Crystal structure of human Monoacylglycerol Lipase ABHD6 in complex with oleic acid and octyl glucoside | PDB:7OTS | ||||
| Method | X-ray diffraction | Resolution | 1.79 Å | Mutation | Yes | [2] |
| PDB Sequence |
TLGMQVRYVH
54 HEDYQFCYSF64 RGRPGHKPSI74 LMLHGFSAHK84 DMWLSVVKFL94 PKNLHLVCVD 104 MPGHEGTTRS114 SLDDLSIDGQ124 VKRIHQFVEC134 LKLNKKPFHL144 VGTAMGGQVA 154 GVYAAYYPSD164 VSSLCLVCPA174 GLQYSTDNQF184 VQRLKELQGS194 AAVEKIPLIP 204 STPEEMSEML214 QLCSYVRFKV224 PQQILQGLVD234 VRIPHNNFYR244 KLFLEIVSEK 254 SRYSLHQNMD264 KIKVPTQIIW274 GKQDQVLDVS284 GADMLAKSIA294 NCQVELLENC 304 GHSVVMERPR314 KTAKLIIDFL324 ASVHNTDNNK334 KL
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| Ligand Name: Oleic acid | Ligand Info | |||||
| Structure Description | Crystal structure of human Monoacylglycerol Lipase ABHD6 in complex with oleic acid and octyl glucoside | PDB:7OTS | ||||
| Method | X-ray diffraction | Resolution | 1.79 Å | Mutation | Yes | [2] |
| PDB Sequence |
TLGMQVRYVH
54 HEDYQFCYSF64 RGRPGHKPSI74 LMLHGFSAHK84 DMWLSVVKFL94 PKNLHLVCVD 104 MPGHEGTTRS114 SLDDLSIDGQ124 VKRIHQFVEC134 LKLNKKPFHL144 VGTAMGGQVA 154 GVYAAYYPSD164 VSSLCLVCPA174 GLQYSTDNQF184 VQRLKELQGS194 AAVEKIPLIP 204 STPEEMSEML214 QLCSYVRFKV224 PQQILQGLVD234 VRIPHNNFYR244 KLFLEIVSEK 254 SRYSLHQNMD264 KIKVPTQIIW274 GKQDQVLDVS284 GADMLAKSIA294 NCQVELLENC 304 GHSVVMERPR314 KTAKLIIDFL324 ASVHNTDNNK334 KL
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GLY79
3.749
PHE80
2.815
THR147
4.905
ALA148
3.174
MET149
3.209
ALA174
4.297
PHE184
4.105
VAL185
3.818
LEU188
3.546
LYS189
3.826
GLN192
3.578
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| Epoxide hydrolase 3 (EPHX3) | 22.143 (62/280) | 1.86E-08 | |
| Protein ABHD11 (ABHD11) | 23.308 (62/266) | 1.21E-06 |
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Retrograde endocannabinoid signaling | hsa04723 | Affiliated Target |
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| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Retrograde endocannabinoid signaling | |||||
| References | Top | |||||
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| REF 1 | A patent review of Monoacylglycerol Lipase (MAGL) inhibitors (2013-2017).Expert Opin Ther Pat. 2017 Dec;27(12):1341-1351. | |||||
| REF 2 | Crystal structure of human Monoacylglycerol Lipase ABHD6 in complex with oleic acid and octyl glucoside | |||||
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