Q99LR1 · ABD12_MOUSE

  • Protein
    Lysophosphatidylserine lipase ABHD12
  • Gene
    Abhd12
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Catalytic activity

  • 1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = (9Z)-octadecenoate + H+ + sn-glycero-3-phospho-L-serine
    This 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-inositol
    This reaction proceeds in the forward direction.
  • 1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = (9Z)-octadecenoate + H+ + sn-glycero-3-phosphoethanolamine
    This reaction proceeds in the forward direction.
  • 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + H+ + phosphocholine
    This 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-serine
    This 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.
  • Hydrolyzes glycerol monoesters of long-chain fatty acids.
    EC:3.1.1.23 (UniProtKB | ENZYME | Rhea)
  • 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+ + hexadecanoate
    This reaction proceeds in the forward direction.
  • 1-octadecanoylglycerol + H2O = glycerol + H+ + octadecanoate
    This 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.

TypeIDPosition(s)Description
Active site246Nucleophile
Active site333Charge relay system
Active site372Charge relay system

GO annotations

AspectTerm
Cellular ComponentAMPA glutamate receptor complex
Cellular Componentcytoplasm
Cellular Componentdendrite cytoplasm
Cellular Componentendoplasmic reticulum membrane
Cellular Componentmembrane
Cellular Componentmitochondrion
Molecular Functionacylglycerol lipase activity
Molecular Functionlysophospholipase activity
Molecular Functionpalmitoyl-(protein) hydrolase activity
Biological Processacylglycerol catabolic process
Biological Processadult walking behavior
Biological Processmonoacylglycerol catabolic process
Biological Processphosphatidylserine catabolic process
Biological Processphospholipid catabolic process
Biological Processprotein depalmitoylation
Biological Processregulation of inflammatory response
Biological Processresponse to auditory stimulus

Keywords

Enzyme and pathway databases

Protein family/group databases

Chemistry

Names & Taxonomy

Protein names

  • Recommended name
    Lysophosphatidylserine lipase ABHD12
  • EC number
  • Alternative names
    • 2-arachidonoylglycerol hydrolase ABHD12
    • Abhydrolase domain-containing protein 12
    • Monoacylglycerol lipase ABHD12
      (EC:3.1.1.23
      ) . EC:3.1.1.23 (UniProtKB | ENZYME | Rhea)
    • Oxidized phosphatidylserine lipase ABHD12
      (EC:3.1.-.-
      ) . EC:3.1.-.- (UniProtKB | ENZYME | Rhea)

Gene names

    • Name
      Abhd12

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q99LR1
  • Secondary accessions
    • A2ANB4
    • Q99M06

Proteomes

Organism-specific databases

Subcellular Location

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-74Cytoplasmic
Transmembrane75-95Helical
Topological domain96-398Extracellular

Keywords

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).

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.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for chain, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00000794141-398Lysophosphatidylserine lipase ABHD12
Glycosylation123N-linked (GlcNAc...) asparagine

Post-translational modification

Glycosylated.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Protein-protein interaction databases

Chemistry

Miscellaneous

Structure

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region1-24Disordered

Sequence similarities

Belongs to the serine esterase family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

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.

  • Length
    398
  • Mass (Da)
    45,270
  • Last updated
    2003-11-28 v2
  • Checksum
    B8B23FA97DB4FF45
MRKRTEPVTLEHERCAASGSSSSGSAAAALDADCSLKQNLRLAGKGTAEPHSASDAGMKRALGRRKSLWFRLRKILLCVLGFYIAIPFLVKLCPGIQAKLIFLNFVRVPYFIDLKKPQDQGLNHTCNYYLQPEDDVTIGVWHTIPSVWWKNAQGKDQMWYEDALASNHAIILYLHGNAGTRGGDHRVELYKVLSSLGYHVVTFDYRGWGDSVGTPSERGMTYDALHVFDWIKARSGDNPVYIWGHSLGTGVATNLVRRLCERETPPDALILESPFTNIREEAKSHPFSVIYRYFPGFDWFFLDPITSSGIKFANDENMKHISCPLLILHAEDDPVVPFHLGRKLYNIAAPSRSFRDFKVQFIPFHSDLGYRHKYIYKSPELPRILREFLGKSEPERQH

Q99LR1-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
F7BHM8F7BHM8_MOUSEAbhd1256
D6RFU2D6RFU2_MOUSEAbhd12298
D6RI21D6RI21_MOUSEAbhd1270

Sequence caution

The sequence AAH02138.1 differs from that shown. Reason: Erroneous initiation Extended N-terminus.

Features

Showing features for alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0574931-219in isoform 2
Sequence conflict386in Ref. 3; AAH02138

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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