human-ABHD5

 
Homo sapiens (Human) 39.1 kDa Comparative gene identification 58 (CGI-58)/Alpha Beta Hydrolase Domain 5 (ABHD5)

Comment
Comparative gene identification 58 (CGI-58)/Alpha Beta Hydrolase Domain 5 (ABHD5) 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).The Family in ESTHER is CGI-58_ABHD5_ABHD4. Mutations in ABDH5 CGI-58 where found in patients with Chanarin-Dorfman syndrome. First mutations were described by Lefevre et al.(2001). They identified several candidate genes, one of which, designated comparative gene identification-58. Many more mutations. have been described since then (see below). The disease locus was designated NLSDI (neutral lipid storage disease with ichtyosis). Symptoms are close to NLSMD (neutral lipid storage disease with myopathy) which is due to mutations in patatin-like phospholipase domain-containing protein-2 (adipose triglyceride lipase; ATGL (PNPLA2); not an alpha beta hydrolase (Fischer et al.)). But NLSMD do not show ichtyolisis and in NLSDI myopathy is milder. However ABDH5 interacts and activates ATGL (Yamaguchi et al.). ABDH5 interacts also with perilipin. Mutations affecting the carboxyl terminus of perilipin increase lipolysis by failing to sequester ABHD5. Comparative gene identification 58 (CGI-58)/Alpha Beta Hydrolase Domain 5 (ABHD5) lacks lysophosphatidic acid acyltransferase activity (McMahon et al.) ABHD5 lacks a serine residue in a conserved sequence (GXSXG) that normally harbors the nucleophilic component of the catalytic triad


Relationship
Block X
Homo sapiens position in NCBI Life Tree :
N link to NCBI taxonomic web page and E link to ESTHER gene locus found in this strain.
> cellular organisms: N E > Eukaryota: N E > Opisthokonta: N E > Metazoa: N E > Eumetazoa: N E > Bilateria: N E > Deuterostomia: N E > Chordata: N E > Craniata: N E > Vertebrata: N E > Gnathostomata: N E > Teleostomi: N E > Euteleostomi: N E > Sarcopterygii: N E > Dipnotetrapodomorpha: N E > Tetrapoda: N E > Amniota: N E > Mammalia: N E > Theria: N E > Eutheria: N E > Boreoeutheria: N E > Euarchontoglires: N E > Primates: N E > Haplorrhini: N E > Simiiformes: N E > Catarrhini: N E > Hominoidea: N E > Hominidae: N E > Homininae: N E > Homo: N E > Homo sapiens: N E

Molecular evidence
Database
44 mutations: Table (ordered Natural and SD mutagenesis) (e.g. : S115G_human-ABHD5, R184X_human-ABHD5, IVS6-1G>A_human-ABHD5 ... more)
1 structure:
5A4H: Solution structure of the lipid droplet anchoring peptide of CGI-58 bound to DPC micelles
No kinetic
Disease: NAFLD - Chanarin-Dorfman syndrome -

Inhibitor: SR-4995 , SR-3133 , SR-3134 , SR-4559 ,
>3 Genbank links 2 more: AF151816, BC021958, AL606838
3 UniProt : Q8WTS1, C9J1D1, C9JBM3
1 Structure : 5A4H
3 UniProtTrembl : Q8WTS1, C9J1D1, C9JBM3
3 Interpro : Q8WTS1, C9J1D1, C9JBM3
3 Prodom : Q8WTS1, C9J1D1, C9JBM3
3 Pfam : Q8WTS1, C9J1D1, C9JBM3
3 PIRSF : Q8WTS1, C9J1D1, C9JBM3
3 SUPERFAM : Q8WTS1, C9J1D1, C9JBM3
3 QuickSwissBlast : Q8WTS1, C9J1D1, C9JBM3
1 EntrezGene : 51099
1 SNP : 51099
1 UniGene : 19385
1 HUGO HGNC : 21396
2 OMIM : 604780, 275630
1 Ensembl : ENSG00000011198
 
Sequence
Graphical view for this peptide sequence: human-ABHD5
Colored MSA for CGI-58_ABHD5_ABHD4 (raw)
MAAEEEEVDSADTGERSGWLTGWLPTWCPTSISHLKEAEEKMLKCVPCTY
KKEPVRISNGNKIWTLKFSHNISNKTPLVLLHGFGGGLGLWALNFGDLCT
NRPVYAFDLLGFGRSSRPRFDSDAEEVENQFVESIEEWRCALGLDKMILL
GHNLGGFLAAAYSLKYPSRVNHLILVEPWGFPERPDLADQDRPIPVWIRA
LGAALTPFNPLAGLRIAGPFGLSLVQRLRPDFKRKYSSMFEDDTVTEYIY
HCNVQTPSGETASKNMTIPYGWAKRPMLQRIGKMHPDIPVSVIFGARSCI
DGNSGTSIQSLRPHSYVKTIAILGAGHYVYADQPEEFNQKVKEICDTVD
Legend This sequence has been compared to family alignement (MSA)
red => minority aminoacid
blue => majority aminoacid
color intensity => conservation rate
title => sequence position(MSA position)aminoacid rate
Catalytic site
Catalytic site in the MSA

MAAEEEEVDSADTGERSGWLTGWLPTWCPTSISHLKEAEEKMLKCVPCTY
KKEPVRISNGNKIWTLKFSHNISNKTPLVLLHGFGGGLGLWALNFGDLCT
NRPVYAFDLLGFGRSSRPRFDSDAEEVENQFVESIEEWRCALGLDKMILL
GHNLGGFLAAAYSLKYPSRVNHLILVEPWGFPERPDLADQDRPIPVWIRA
LGAALTPFNPLAGLRIAGPFGLSLVQRLRPDFKRKYSSMFEDDTVTEYIY
HCNVQTPSGETASKNMTIPYGWAKRPMLQRIGKMHPDIPVSVIFGARSCI
DGNSGTSIQSLRPHSYVKTIAILGAGHYVYADQPEEFNQKVKEICDTVD

no DNA




References
93 more
    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

            

    Title: The lipid droplet-associated protein ABHD5 protects the heart through proteolysis of HDAC4
    Jebessa ZH, Shanmukha Kumar D, Dewenter M, Lehmann LH, Xu C, Schreiter F, Siede D, Gong XM, Worst BC and Backs J <14 more author(s)>
    Ref: Nat Metab, 1:1157, 2019 : PubMed

            


Other Papers


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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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