L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (AASDHPPT) is an enzyme that in humans is encoded by the AASDHPPT gene.[1][2][3] It has been suggested that defects in the human gene result in pipecolic acidemia.[3]
The AASDHPPT protein catalyzes the post-translational modification phosphopantetheinylation, in which a 4'-phosphopantetheine (4'-PP) group derived from coenzyme A is covalently attached to target proteins in both cytosol and mitochondria.[4] In the cytosol, these include fatty acid synthase (FASN), aminoadipate semialdehyde dehydrogenase (AASDH), and aldehyde dehydrogenase 1 family member L1 (ALDH1L1), whereas in mitochondria the targets are the mitochondrial acyl carrier protein (mtACP), aldehyde dehydrogenase 1 family member L2 (ALDH1L2), and dehydrogenase/reductase 2 (DHRS2).[4] With the exception of DHRS2, the targets of AASDHPPT contain a acyl carrier protein (ACP) domain, a cofactor domain widespread across bacteria and eukaryotes with roles in the synthesis of fatty acids, polyketides, and nonribosomal peptides.[5]
The protein encoded by this gene is similar to Saccharomyces cerevisiae LYS5, which is required for the activation of the alpha-aminoadipate dehydrogenase in the biosynthetic pathway of lysine. Yeast alpha-aminoadipate dehydrogenase converts alpha-biosynthetic-aminoadipate semialdehyde to alpha-aminoadipate.
References
- ^ Joshi AK, Zhang L, Rangan VS, Smith S (Aug 2003). "Cloning, expression, and characterization of a human 4'-phosphopantetheinyl transferase with broad substrate specificity". J Biol Chem. 278 (35): 33142–9. doi:10.1074/jbc.M305459200. PMID 12815048
- ^ Praphanphoj V, Sacksteder KA, Gould SJ, Thomas GH, Geraghty MT (Apr 2001). "Identification of the alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase gene, the human ortholog of the yeast LYS5 gene". Mol Genet Metab. 72 (4): 336–42. doi:10.1006/mgme.2000.3138. PMID 11286508
- ^ "Entrez Gene: AASDHPPT aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase"
- ^ Norden, Pieter R.; Wedan, Riley J.; Preston, Samuel E. J.; Canfield, Morgan; Graber, Naomi; Longenecker, Jacob Z.; Pentecost, Olivia A.; McLaughlin, Elizabeth; Hart, Madeleine L. (2024-05-10). "Mitochondrial Phosphopantetheinylation is Required for Oxidative Function". bioRxiv 10.1101/2024.05.09.592977
- ^ https://www.ebi.ac.uk/interpro/entry/InterPro/IPR036736/protein/reviewed/taxonomy/uniprot/9606/#table
Further reading
- Rual JF, Venkatesan K, Hao T (2005). "Towards a proteome-scale map of the human protein-protein interaction network.". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026
- Gerhard DS, Wagner L, Feingold EA (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res.. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334
- Mammalian Gene Collection Program Team; Strausberg, R. L.; Feingold, E. A.; Grouse, L. H. et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932
- Zhang QH, Ye M, Wu XY (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.". Genome Res.. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152
- Hu RM, Han ZG, Song HD (2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.". Proc. Natl. Acad. Sci. U.S.A.. 97 (17): 9543–8. Bibcode:2000PNAS...97.9543H. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946
- Lai CH, Chou CY, Ch'ang LY (2000). "Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics.". Genome Res.. 10 (5): 703–13. doi:10.1101/gr.10.5.703. PMC 310876. PMID 10810093