Q99LR1 · ABD12_MOUSE
- ProteinLysophosphatidylserine lipase ABHD12
- GeneAbhd12
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids398 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes (PubMed:23297193, PubMed:25580854, PubMed:30420694).
Represents a major lysophosphatidylserine lipase in the brain, thereby playing a key role in the central nervous system (PubMed:23297193).
Also able to hydrolyze oxidized phosphatidylserine; oxidized phosphatidylserine is produced in response to severe inflammatory stress and constitutes a proapoptotic 'eat me' signal (PubMed:30643283).
Also has monoacylglycerol (MAG) lipase activity: hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator of endocannabinoid signaling pathways (PubMed:18096503).
Has a strong preference for very-long-chain lipid substrates; substrate specificity is likely due to improved catalysis and not improved substrate binding (PubMed:30237167).
Represents a major lysophosphatidylserine lipase in the brain, thereby playing a key role in the central nervous system (PubMed:23297193).
Also able to hydrolyze oxidized phosphatidylserine; oxidized phosphatidylserine is produced in response to severe inflammatory stress and constitutes a proapoptotic 'eat me' signal (PubMed:30643283).
Also has monoacylglycerol (MAG) lipase activity: hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator of endocannabinoid signaling pathways (PubMed:18096503).
Has a strong preference for very-long-chain lipid substrates; substrate specificity is likely due to improved catalysis and not improved substrate binding (PubMed:30237167).
Catalytic activity
- 1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = (9Z)-octadecenoate + H+ + sn-glycero-3-phospho-L-serineThis reaction proceeds in the forward direction.
- 1-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1'-sn-glycerol) + H2O = (9Z)-octadecenoate + H+ + sn-glycero-3-phospho-(1'-sn-glycerol)This reaction proceeds in the forward direction.
- 1-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = (9Z)-octadecenoate + H+ + sn-glycero-3-phospho-1D-myo-inositolThis reaction proceeds in the forward direction.
- 1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = (9Z)-octadecenoate + H+ + sn-glycero-3-phosphoethanolamineThis reaction proceeds in the forward direction.
- 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + H+ + phosphocholineThis reaction proceeds in the forward direction.
- 2-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H+This reaction proceeds in the forward direction.
- 1-hexadecanoyl-sn-glycero-3-phospho-L-serine + H2O = H+ + hexadecanoate + sn-glycero-3-phospho-L-serineThis reaction proceeds in the forward direction.
- 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H+This reaction proceeds in the forward direction.
- 1-decanoylglycerol + H2O = decanoate + glycerol + H+
- 1-dodecanoylglycerol + H2O = dodecanoate + glycerol + H+
- 1-tetradecanoylglycerol + H2O = glycerol + H+ + tetradecanoate
- 2-hexadecanoylglycerol + H2O = glycerol + H+ + hexadecanoate
- 1-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H+This reaction proceeds in the forward direction.
- 2-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H+
- 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H+This reaction proceeds in the forward direction.
- 1-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H+
- 1-hexadecanoylglycerol + H2O = glycerol + H+ + hexadecanoateThis reaction proceeds in the forward direction.
- 1-octadecanoylglycerol + H2O = glycerol + H+ + octadecanoateThis reaction proceeds in the forward direction.
- 1-octadecanoyl-2-(9,10-epoxyoctadecanoyl)-sn-glycero-3-phospho-L-serine + H2O = 1-octadecanoyl-sn-glycero-3-phosphoserine + 9,10-epoxyoctadecanoate + H+
- 1-octadecanoyl-2-(10-hydroxyoctadecanoyl)-sn-glycero-3-phospho-L-serine + H2O = 1-octadecanoyl-sn-glycero-3-phosphoserine + 10-hydroxyoctadecanoate + H+
- 1-hexadecanoyl-2-(10-hydroxyoctadecanoyl)-sn-glycero-3-phospho-L-serine + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-L-serine + 10-hydroxyoctadecanoate + H+
Activity regulation
Selectively inhibited by DO264 (N-3-pyridyl-N'-(1-[3-chloro-4-{2-chloro-4-(trifluoromethoxy)phenoxy}pyridine-2-yl]piperidin-4-yl)thiourea).
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 246 | Nucleophile | ||||
Sequence: S | ||||||
Active site | 333 | Charge relay system | ||||
Sequence: D | ||||||
Active site | 372 | Charge relay system | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | AMPA glutamate receptor complex | |
Cellular Component | cytoplasm | |
Cellular Component | dendrite cytoplasm | |
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | membrane | |
Cellular Component | mitochondrion | |
Molecular Function | acylglycerol lipase activity | |
Molecular Function | lysophospholipase activity | |
Molecular Function | palmitoyl-(protein) hydrolase activity | |
Biological Process | acylglycerol catabolic process | |
Biological Process | adult walking behavior | |
Biological Process | monoacylglycerol catabolic process | |
Biological Process | phosphatidylserine catabolic process | |
Biological Process | phospholipid catabolic process | |
Biological Process | protein depalmitoylation | |
Biological Process | regulation of inflammatory response | |
Biological Process | response to auditory stimulus |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameLysophosphatidylserine lipase ABHD12
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ99LR1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Single-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-74 | Cytoplasmic | ||||
Sequence: MRKRTEPVTLEHERCAASGSSSSGSAAAALDADCSLKQNLRLAGKGTAEPHSASDAGMKRALGRRKSLWFRLRK | ||||||
Transmembrane | 75-95 | Helical | ||||
Sequence: ILLCVLGFYIAIPFLVKLCPG | ||||||
Topological domain | 96-398 | Extracellular | ||||
Sequence: IQAKLIFLNFVRVPYFIDLKKPQDQGLNHTCNYYLQPEDDVTIGVWHTIPSVWWKNAQGKDQMWYEDALASNHAIILYLHGNAGTRGGDHRVELYKVLSSLGYHVVTFDYRGWGDSVGTPSERGMTYDALHVFDWIKARSGDNPVYIWGHSLGTGVATNLVRRLCERETPPDALILESPFTNIREEAKSHPFSVIYRYFPGFDWFFLDPITSSGIKFANDENMKHISCPLLILHAEDDPVVPFHLGRKLYNIAAPSRSFRDFKVQFIPFHSDLGYRHKYIYKSPELPRILREFLGKSEPERQH |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice are viable and were born at the expected Mendelian frequency (PubMed:23297193).
Young mice (less than 6 months old) are mostly normal in their behavior; however, as these animals age, they develop an array of phenotypes, including defective auditory and motor behavior, with concomitant cellular pathology indicative of a neuroinflammatory response (PubMed:23297193).
Mice show heightened immunological responses (PubMed:30420694).
Metabolomic characterization of brain tissue show striking elevations in a series of lysophosphatidylserine (LPS) lipids that occur before the onset of neuroinflammatory and behavioral defects (PubMed:23297193).
Brain tissues accumulate oxidized phosphatidylserine lipids in response to severe inflammatory stress (PubMed:30643283).
Young mice (less than 6 months old) are mostly normal in their behavior; however, as these animals age, they develop an array of phenotypes, including defective auditory and motor behavior, with concomitant cellular pathology indicative of a neuroinflammatory response (PubMed:23297193).
Mice show heightened immunological responses (PubMed:30420694).
Metabolomic characterization of brain tissue show striking elevations in a series of lysophosphatidylserine (LPS) lipids that occur before the onset of neuroinflammatory and behavioral defects (PubMed:23297193).
Brain tissues accumulate oxidized phosphatidylserine lipids in response to severe inflammatory stress (PubMed:30643283).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 19 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000079414 | 1-398 | Lysophosphatidylserine lipase ABHD12 | |||
Sequence: MRKRTEPVTLEHERCAASGSSSSGSAAAALDADCSLKQNLRLAGKGTAEPHSASDAGMKRALGRRKSLWFRLRKILLCVLGFYIAIPFLVKLCPGIQAKLIFLNFVRVPYFIDLKKPQDQGLNHTCNYYLQPEDDVTIGVWHTIPSVWWKNAQGKDQMWYEDALASNHAIILYLHGNAGTRGGDHRVELYKVLSSLGYHVVTFDYRGWGDSVGTPSERGMTYDALHVFDWIKARSGDNPVYIWGHSLGTGVATNLVRRLCERETPPDALILESPFTNIREEAKSHPFSVIYRYFPGFDWFFLDPITSSGIKFANDENMKHISCPLLILHAEDDPVVPFHLGRKLYNIAAPSRSFRDFKVQFIPFHSDLGYRHKYIYKSPELPRILREFLGKSEPERQH | ||||||
Glycosylation | 123 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-24 | Disordered | ||||
Sequence: MRKRTEPVTLEHERCAASGSSSSG |
Sequence similarities
Belongs to the serine esterase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q99LR1-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length398
- Mass (Da)45,270
- Last updated2003-11-28 v2
- ChecksumB8B23FA97DB4FF45
Q99LR1-2
- Name2
- Differences from canonical
- 1-219: Missing
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_057493 | 1-219 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 386 | in Ref. 3; AAH02138 | ||||
Sequence: R → W |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL808125 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL954712 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH466519 EMBL· GenBank· DDBJ | EDL28584.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC002138 EMBL· GenBank· DDBJ | AAH02138.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC002263 EMBL· GenBank· DDBJ | AAH02263.1 EMBL· GenBank· DDBJ | mRNA |