FAHD1 explained

Fumarylacetoacetate hydrolase domain-containing protein 1, also known as FLJ36880 protein, is an enzyme that in humans is encoded by the FAHD1 gene on chromosome 16.^[1]

Structure

The FAHD1 gene encodes for a 24-kDa protein that is localized to the mitochondrion and belongs to the fumarylacetoacetate hydrolase family of proteins.^[2] The structure of FAHD1 has been resolved using X-ray crystallography at 2.2-Å resolution. The overall structure is similar to the C-terminal domain of the bifunctional enzyme HpcE from Escherichia coli C, fumarylacetoacetate hydrolase from Mus musculus and to YcgM (Apc5008) from E. coli 1262.^[2] A number of conserved amino acids including Asp-102 and Arg-106 of FAHD1 appear to be important for its catalytic activity.^[3]

Function

The FAHD1 protein has been shown to function as an oxaloacetate decarboxylase in eukaryotes.^[4] The FAHD1 protein probably also functions as an acylpyruvase, having been shown to catalyze the hydrolysis of acetylpyruvate and fumarylpyruvate in in vitro experiments.^[2] Mg(2+) was required for maximal enzyme activity.^[3]

Further reading

• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination. . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 10.1101/gr.143000 . 310948 .
• Daniels RJ, Peden JF, Lloyd C . Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16. . Hum. Mol. Genet. . 10 . 4 . 339–52 . 2001 . 11157797 . 10.1093/hmg/10.4.339 . etal. free .
• Wiemann S, Weil B, Wellenreuther R . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 10.1101/gr.GR1547R . 311072 . etal.
• Simpson JC, Wellenreuther R, Poustka A . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. . EMBO Rep. . 1 . 3 . 287–92 . 2001 . 11256614 . 10.1093/embo-reports/kvd058 . 1083732 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Lehner B, Sanderson CM . A protein interaction framework for human mRNA degradation. . Genome Res. . 14 . 7 . 1315–23 . 2004 . 15231747 . 10.1101/gr.2122004 . 442147 .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Wiemann S, Arlt D, Huber W . From ORFeome to biology: a functional genomics pipeline. . Genome Res. . 14 . 10B . 2136–44 . 2004 . 15489336 . 10.1101/gr.2576704 . 528930 . etal.
• Manjasetty BA, Niesen FH, Delbrück H . X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880. . Biol. Chem. . 385 . 10 . 935–42 . 2005 . 15551868 . 10.1515/BC.2004.122 . 16759973 . etal.
• Mehrle A, Rosenfelder H, Schupp I . The LIFEdb database in 2006. . Nucleic Acids Res. . 34 . Database issue . D415–8 . 2006 . 16381901 . 10.1093/nar/gkj139 . 1347501 . etal.

Notes and References

1. Web site: Entrez Gene: FAHD1 fumarylacetoacetate hydrolase domain containing 1.
2. Manjasetty BA, Niesen FH, Delbrück H, Götz F, Sievert V, Büssow K, Behlke J, Heinemann U . X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880 . Biol. Chem. . 385 . 10 . 935–42 . 2004 . 15551868 . 10.1515/BC.2004.122 . 16759973 .
3. Pircher H, Straganz GD, Ehehalt D, Morrow G, Tanguay RM, Jansen-Dürr P . Identification of human fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) as a novel mitochondrial acylpyruvase . J. Biol. Chem. . 286 . 42 . 36500–8 . 2011 . 21878618 . 3196145 . 10.1074/jbc.M111.264770 . free .
4. Pircher H, von Grafenstein S, Diener T, Metzger C, Albertini E, Taferner A, Unterluggauer H, Kramer C, Liedl KR, Jansen-Dürr P . Identification of FAH domain-containing protein 1 (FAHD1) as oxaloacetate decarboxylase . J. Biol. Chem. . 290 . 11 . 6755–62 . 2015 . 25575590 . 10.1074/jbc.M114.609305 . 4358102. free .