Q80Y98 · DDHD2_MOUSE
- ProteinTriacylglycerol hydrolase DDHD2
- GeneDdhd2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids699 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Diacylglycerol (DAG) and triacylglycerol (TAG) lipase that is required for proper lipid homeostasis in the central nervous system (PubMed:25267624, PubMed:37832604).
It cooperates with PNPLA2/ATGL in neuronal TAG catabolism and hydrolyzes sn-1,3-DAG downstream of PNPLA2/ATGL (PubMed:37832604).
In vitro, also acts as a phospholipase that hydrolyzes preferentially phosphatidic acids, including 1,2-dioleoyl-sn-phosphatidic acid, phosphatidylcholine and phosphatidylethanolamine. Specifically binds to phosphatidylinositol 3-phosphate (PI3P), phosphatidylinositol 4-phosphate (PI4P), phosphatidylinositol 5-phosphate (PI5P) and possibly phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). May be involved in the maintenance of the endoplasmic reticulum and/or Golgi structures. May regulate the transport between Golgi apparatus and plasma membrane (By similarity).
It cooperates with PNPLA2/ATGL in neuronal TAG catabolism and hydrolyzes sn-1,3-DAG downstream of PNPLA2/ATGL (PubMed:37832604).
In vitro, also acts as a phospholipase that hydrolyzes preferentially phosphatidic acids, including 1,2-dioleoyl-sn-phosphatidic acid, phosphatidylcholine and phosphatidylethanolamine. Specifically binds to phosphatidylinositol 3-phosphate (PI3P), phosphatidylinositol 4-phosphate (PI4P), phosphatidylinositol 5-phosphate (PI5P) and possibly phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). May be involved in the maintenance of the endoplasmic reticulum and/or Golgi structures. May regulate the transport between Golgi apparatus and plasma membrane (By similarity).
Catalytic activity
- a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H+This reaction proceeds in the forward direction.
- a diacylglycerol + H2O = a monoacylglycerol + a fatty acid + H+This reaction proceeds in the forward direction.
- a 1,3-diacylglycerol + H2O = a 1-acylglycerol + a fatty acid + H+This reaction proceeds in the forward direction.
- a 1-acylglycerol + H2O = glycerol + a fatty acid + H+This reaction proceeds in the forward direction.
- 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = di-(9Z)-octadecenoylglycerol + (9Z)-octadecenoate + H+This reaction proceeds in the forward direction.
- di-(9Z)-octadecenoylglycerol + H2O = (9Z-octadecenoyl)-glycerol + (9Z)-octadecenoate + H+This reaction proceeds in the forward direction.
- 1,3-di-(9Z-octadecenoyl)-glycerol + H2O = 1-(9Z-octadecenoyl)-glycerol + (9Z)-octadecenoate + H+
- trihexadecanoylglycerol + H2O = dihexadecanoylglycerol + hexadecanoate + H+This reaction proceeds in the forward direction.
- 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = (9Z-octadecenoyl)-sn-glycero-3-phosphocholine + (9Z)-octadecenoate + H+This reaction proceeds in the forward direction.
- 1-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H+This reaction proceeds in the forward direction.
- 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + (9Z)-octadecenoate + H+This reaction proceeds in the forward direction.
- 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + hexadecanoate + H+This reaction proceeds in the forward direction.
- 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + hexadecanoate + H+This reaction proceeds in the forward direction.
- 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + hexadecanoate + H+This reaction proceeds in the forward direction.
- 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + hexadecanoate + H+This reaction proceeds in the forward direction.
Features
Showing features for active site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Active site | 351 | Nucleophile | |||
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | centriolar satellite | |
Cellular Component | cytosol | |
Cellular Component | endoplasmic reticulum-Golgi intermediate compartment | |
Cellular Component | Golgi apparatus | |
Cellular Component | membrane | |
Molecular Function | metal ion binding | |
Molecular Function | triacylglycerol lipase activity | |
Biological Process | lipid droplet organization | |
Biological Process | locomotory behavior | |
Biological Process | mitochondrial fission | |
Biological Process | positive regulation of mitochondrial fission | |
Biological Process | triglyceride catabolic process | |
Biological Process | visual learning |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTriacylglycerol hydrolase DDHD2
- EC number
- Short namesTAG hydrolase
- 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 accessionQ80Y98
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Cycles between the Golgi apparatus and the cytosol. DDHD2 recruitment to the Golgi/endoplasmic reticulum-Golgi intermediate compartment (ERGIC) is regulated by the levels of phosphoinositides, including PI4P (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Knockout mice display memory and cognitive impairments, and locomotor defects such as significantly shorter stride lengths in gait measurement assays, reductions in rearing behavior, and reduced balance compared to wild-type animals. Mutant mice also show age-dependent increased levels of triacylglycerols in the central nervous system, and accumulation of large lipid droplets in brain neurons. Bulk brain levels of phospholipids are unchanged.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Mutagenesis | 351 | Loss of TAG hydrolase activity. | |||
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 32 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000309331 | 1-699 | Triacylglycerol hydrolase DDHD2 | ||
Modified residue | 447 | Phosphoserine | |||
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Region | 1-25 | Disordered | |||
Domain | 30-112 | WWE | |||
Domain | 383-445 | SAM | |||
Domain | 484-688 | DDHD | |||
Region | 599-635 | Disordered | |||
Compositional bias | 610-631 | Basic and acidic residues | |||
Domain
SAM and DDHD domains together are required for phospholipid binding.
Sequence similarities
Belongs to the PA-PLA1 family.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q80Y98-1
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
- Length699
- Mass (Da)79,577
- Last updated2011-07-27 v3
- ChecksumBB12F07F9200ACC7
Q80Y98-2
- Name2
Q80Y98-3
- Name3
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A1B0GT91 | A0A1B0GT91_MOUSE | Ddhd2 | 84 | ||
A0A1B0GSV3 | A0A1B0GSV3_MOUSE | Ddhd2 | 110 | ||
A0A1B0GSA5 | A0A1B0GSA5_MOUSE | Ddhd2 | 618 | ||
A0A1B0GRX3 | A0A1B0GRX3_MOUSE | Ddhd2 | 84 | ||
A0A1B0GS27 | A0A1B0GS27_MOUSE | Ddhd2 | 358 |
Sequence caution
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Alternative sequence | VSP_029141 | 1 | in isoform 2 | ||
Alternative sequence | VSP_029142 | 283-382 | in isoform 3 | ||
Alternative sequence | VSP_029143 | 448-528 | in isoform 2 | ||
Alternative sequence | VSP_029144 | 529-562 | in isoform 3 | ||
Compositional bias | 610-631 | Basic and acidic residues | |||
Sequence conflict | 637 | in Ref. 1; BAD32288 and 3; AAI18963 | |||
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK173010 EMBL· GenBank· DDBJ | BAD32288.1 EMBL· GenBank· DDBJ | Transcribed RNA | Different initiation | |
AC156990 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC046229 EMBL· GenBank· DDBJ | AAH46229.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC118962 EMBL· GenBank· DDBJ | AAI18963.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AK008529 EMBL· GenBank· DDBJ | BAB25722.1 EMBL· GenBank· DDBJ | mRNA |