Q80Y98 · DDHD2_MOUSE

  • Protein
    Triacylglycerol hydrolase DDHD2
  • Gene
    Ddhd2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Caution

It is uncertain whether Met-1 or Met-31 is the initiator.

Catalytic activity

  • a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H+
    This reaction proceeds in the forward direction.
    EC:3.1.1.3 (UniProtKB | ENZYME | Rhea)
  • 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.

TypeIDPosition(s)Description
Active site351Nucleophile

GO annotations

AspectTerm
Cellular Componentcentriolar satellite
Cellular Componentcytosol
Cellular Componentendoplasmic reticulum-Golgi intermediate compartment
Cellular ComponentGolgi apparatus
Cellular Componentmembrane
Molecular Functionmetal ion binding
Molecular Functiontriacylglycerol lipase activity
Biological Processlipid droplet organization
Biological Processlocomotory behavior
Biological Processmitochondrial fission
Biological Processpositive regulation of mitochondrial fission
Biological Processtriglyceride catabolic process
Biological Processvisual learning

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Triacylglycerol hydrolase DDHD2
  • EC number
  • Short names
    TAG hydrolase
  • Alternative names
    • DDHD domain-containing protein 2
    • Phospholipase DDHD2
      (EC:3.1.1.-) . EC:3.1.1.- (UniProtKB | ENZYME | Rhea)
    • SAM, WWE and DDHD domain-containing protein 1
    • Triglyceride hydrolase DDHD2
    • Triglyceride lipase

Gene names

    • Name
      Ddhd2
    • Synonyms
      Kiaa0725, Samwd1

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
    Q80Y98
  • Secondary accessions
    • E9QKK2
    • Q0VF66
    • Q6A008
    • Q9CVE9

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm, cytosol
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

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.

TypeIDPosition(s)Description
Mutagenesis351Loss 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.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for chain, modified residue.

Type
IDPosition(s)Description
ChainPRO_00003093311-699Triacylglycerol hydrolase DDHD2
Modified residue447Phosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Forms homooligomers and, to a much smaller extent, heterooligomers with DDHD1.

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, domain, compositional bias.

Type
IDPosition(s)Description
Region1-25Disordered
Domain30-112WWE
Domain383-445SAM
Domain484-688DDHD
Region599-635Disordered
Compositional bias610-631Basic 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

Align isoforms (3)
  • Sequence status
    Complete

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.

  • Length
    699
  • Mass (Da)
    79,577
  • Last updated
    2011-07-27 v3
  • Checksum
    BB12F07F9200ACC7
MSSGESHQEQLSQSDPSPSPNSCSSFELIDMDASSSYEPVSPHWFYCKVLDSKELWIPFNSEDSQQLEDAYGSGKDCNERIVPTDGGRYDVHLGERMRYAVYWDELPSEVRRCTWFYKGDKDNKYVPYSESFSQVLEDTYMLAVTLDEWKKKIESPNREIIVLHNPKLMVHYQPIAGSDEWGSTSTEQGRPRSVKRGVENIPVDIHCGEPLQIDHLVFVVHGIGPACDLRFRSIVQCVNDFRSVSLNLLQTHFKKAQENEQIGRVEFLPVNWHSPLHSTGVDIDLQRITLPSINRLRHFTNDTILDVFFYNSPTYCQTIVDTVASEMNRIYTLFLQRNPDFKGGVSIAGHSLGSLILFDILTNQKNSIGDIDSEKGSLSSAEDRGDASTLEEDLKKLQLSEFVTVFEKEKVDREALALCTDRDLQEMGIPLGPRKKILNHFSARKNSVSINRPAMSASEVNISKENGDYLDVGIGQVSVKYPRLNYKPEIFFAFGSPIGMFLTVRGLRRIDPNYKFPTCKGFFNIYHPFDPVAYRIEPMVAPGIEFEPMLIPHHKGRKRMHLELREGLTRMSMDLKNNLLGSLRMAWKSFTRGPYPALQASETAEETEAEPESSSEKSNEANTEEPPVEVKEEAPISVGMLNGGQRIDYVLQEKPIESFNEYLFALQSHLCYWESEDTVLLVLKEIYQTQGVFLDQPLQ

Q80Y98-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-1: M → MRGQKVRFSSFKASAQARPPVRVPHAPSACPARARRPTSARRRSQVSRESPSPHRTSRDTSEDLSAPPALTGSAASAGALLSTAGALRSPRCGDWGAAAGSARPPRPAWESEM
    • 448-528: Missing

Q80Y98-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 283-382: IDLQRITLPSINRLRHFTNDTILDVFFYNSPTYCQTIVDTVASEMNRIYTLFLQRNPDFKGGVSIAGHSLGSLILFDILTNQKNSIGDIDSEKGSLSSAE → M
    • 529-562: Missing

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A1B0GT91A0A1B0GT91_MOUSEDdhd284
A0A1B0GSV3A0A1B0GSV3_MOUSEDdhd2110
A0A1B0GSA5A0A1B0GSA5_MOUSEDdhd2618
A0A1B0GRX3A0A1B0GRX3_MOUSEDdhd284
A0A1B0GS27A0A1B0GS27_MOUSEDdhd2358

Sequence caution

The sequence AAH46229.1 differs from that shown. Reason: Erroneous initiation Extended N-terminus.
The sequence AAI18963.1 differs from that shown. Reason: Frameshift
The sequence BAD32288.1 differs from that shown. Reason: Erroneous initiation Extended N-terminus.

Features

Showing features for alternative sequence, compositional bias, sequence conflict.

Type
IDPosition(s)Description
Alternative sequenceVSP_0291411in isoform 2
Alternative sequenceVSP_029142283-382in isoform 3
Alternative sequenceVSP_029143448-528in isoform 2
Alternative sequenceVSP_029144529-562in isoform 3
Compositional bias610-631Basic and acidic residues
Sequence conflict637in Ref. 1; BAD32288 and 3; AAI18963

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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