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Family Report for: CGI-58_ABHD5_ABHD4

CGI-58_ABHD5_ABHD4



Relationship
Block X
Parent Family : Abhydrolase_6

Comment
Comparative gene identification 58 (CGI-58)/Alpha Beta Hydrolase Domain 5 (ABHD5) NCIE2 functions as an acyltransferase for the synthesis of phosphatidic acid, the major intermediate in membrane and storage lipid biosynthesis. It also functions as a coactivator of adipocyte triglyceride lipase (ATGL, or PNPLA2) (Ghosh et al., 2008)CGI-58 is regulated by its interaction with perilipin 1 (PLIN1) localized on the lipid droplet (LD), and its release is controlled by phosphorylation. Once lipolysis is stimulated by catecholamines, protein kinase A (PKA)-mediated phosphorylation enables the dissociation of the CGI-58/PLIN1 complex, thereby recruiting adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) to initiate fatty acid release. Mutations in CGI-58 were found in Chanarin-Dorfman syndrome. (from OMIM) By examining the critical region for triglyceride storage disease with impaired long-chain fatty acid oxidation, a rare autosomal recessive form of NCIE (242100), on chromosome 3p21, Lefevre et al.(2001) identified several candidate genes, one of which was designated comparative gene identification-58 (human-ABHD5 ). Lefevre et al. (2001) identified 8 different haplotypes and mutations in the human-ABHD5 gene. The disease locus was designated NCIE2. ABHD5_CGI58 is an activator of the adipose triglyceride lipase (TAG lipase, PNPLA2.patatin-like phospholipase domain-containing). ABHD_ CGI-58 proteins orthologs from plants and yeast are weak triglyceride and phospholipid hydrolases. In plants it interacts with peroxisomal transport protein PXA1. PNPLA3/Adiponutrin and ATGL(PNPLA2 patatin) compete for interaction with ABHD5 (Yang et al.). Comparative gene identification 58 (CGI-58)/Alpha Beta Hydrolase Domain 5 (ABHD5) lacks lysophosphatidic acid acyltransferase activity (McMahon et al.). Disruption of the Arabidopsis CGI-58 homologue produces Chanarin-Dorfman-like lipid droplet accumulation in plants (James et al.).ABHD5 is in fact a protease and hydrolyses HDAC4. Through the production of an amino-terminal polypeptide of HDAC4 (HDAC4-NT) in heart, ABHD5 inhibits MEF2-dependent gene expression and thereby controls glucose handling (Jabessa et al. 2019). Two highly conserved ABHD5 amino acids (R299 and G328) enabled ABHD4 (ABHD4 N303R/S332G) to activate ATGL. The corresponding ABHD5 mutations (ABHD5 R299N and ABHD5 G328S) selectively disrupted lipolysis without affecting ATGL lipid droplet translocation or ABHD5 interactions with perilipin proteins and ABHD5 ligands Sanders et al. In Drosophila Pummelig (Puml,colloquial German for chubby) pummelig deletion mutants (puml1) (Hehlert et al.) Pummelig release fatty acids from phosphatidic acid (PA), N-acylphosphatidylethanolamine (NAPE) and phosphatidylglycerol (PG) but does not hydrolyse TG, diolen or monoolein. Pummelig localizes to lipid droplets, mitochondria, and peroxisomes. CIDEC regulates the enzymatic activity of adipose triglyceride lipase via interacting with its activator, CGI-58
2 Disease(s)
NAFLD from mutation T65A_human-ABHD5 in gene_locus human-ABHD5.


Database
Sequences
Interpro
|
PIRSF
|
Pdoc
|
PFam
|
PF12697 (Abhydrolase_6)
Prints
|
Prosite
|
no EC number



Peptide in
|Fasta
Nucleotide in
|Fasta
Alignment with Multalin
|Text only/graphic display
Seed alignment with MAFFT
|No colour/coloured with Mview
Alignment with MAFFT
|No colour/coloured with Mview
Dendrogram
|Graphical display, obtained with the dnd file produced by Clustalw

References
64 more
    Title: Human CIDEC transgene improves lipid metabolism and protects against high-fat diet-induced glucose intolerance in mice
    Gupta A, Balakrishnan B, Karki S, Slayton M, Jash S, Banerjee S, Grahn THM, Jambunathan S, Disney S and Puri V <7 more author(s)>
    Ref: Journal of Biological Chemistry, :102347, 2022 : PubMed

            

    Title: Improved Stability of Human CGI-58 Induced by Phosphomimetic S237E Mutation
    Llamas-Garcia ML, Paez-Perez ED, Benitez-Cardoza CG, Montero-Moran GM, Lara-Gonzalez S
    Ref: ACS Omega, 7:12643, 2022 : PubMed

            

    Title: Structural and functional insights into ABHD5, a ligand-regulated lipase co-activator
    Tseng YY, Sanders MA, Zhang H, Zhou L, Chou CY, Granneman JG
    Ref: Sci Rep, 12:2565, 2022 : PubMed

            

Other Papers


No structure scheme yet for this family

Structures in CGI-58_ABHD5_ABHD4 family (1)

Genes Proteins in CGI-58_ABHD5_ABHD4 family (175)

Fragments of genes in CGI-58_ABHD5_ABHD4 family (10)

Substrates of some enzymes in the CGI-58_ABHD5_ABHD4 family (2)

Inhibitors of some enzymes in the CGI-58_ABHD5_ABHD4 family (8)



Send your questions or comments to :
Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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