Beta-keto L-gulonate decarboxylase is a protein that in humans is encoded by the gene BKGD (previously C11orf54). BKGD exhibits hydrolase activity on p-nitrophenyl acetate and acts on ester bonds, though the overall function is still not fully understood by the scientific community. The protein is highly conserved with the most distant homolog found is in bacteria.

Gene BKGD is located on chromosome 11 at 11q21. The gene consists of 13 exons and spans 23730 bp. BKGD is flanked by TAF1D and MED17.

mRNA The protein ester hydrolase BKGD exists as a monomer and is composed of 315 amino acids. There are 6 isoforms for BKGD. See table 1. - Variant Isoform Length (bp) Accession number 1 ester hydrolase C11orf54 isoform a 2726 NM_001286067.1 2 ester hydrolase C11orf54 isoform a 2589 NM_001286068.1 3 ester hydrolase C11orf54 isoform a 2594 NM_001286069.1 4 ester hydrolase C11orf54 isoform b 2444 NM_014039.3 5 ester hydrolase C11orf54 isoform c 2442 NM_001286070.1 6 ester hydrolase C11orf54 isoform d 2417 NM_001286071.1

The amino acid sequence contains the domain of unknown function 1907. Found in this transcript is the HxHxxxxxxxxxH motif which coordinates the zinc ion involved in the hydrolase activity. An LR nest motif is found at lys262 and Arg263. The LR nest motif forms hydrogen bonds between the NH groups and anions; an acetate anion is coordinated with the LR nest.

Protein Primary sequence Table 2 shows the different characteristics of the protein sequence throughout humans and other orthologs.

Organism Molecular Weight (kilodalton) Isoelectric point High Bias Amino Acids Repeats Human 35.1 5.9 F AEFS Mouse 35.0 5.9 H None 13 Lined Ground Squirrel 35.1 6.0 F,H PAEF Giant Panda 35.2 6.5 F PAEF

Secondary structure The protein of C11orf54 exists as a monomer in solution. The protein assumes a globular shape of 20 beta strands and 4 alpha helices, containing 9 antiparallel beta strands forming a beta screw region. The β-screw region of C11orf54 has structural similarity to the cyclic adenosine 3′,5′-monophosphate (cAMP) binding domain of the regulatory subunit of protein kinase A. A zinc ion is bound to the HxHxxxxxxxxxH motif found in the sequence.

Subcellular localization C11orf54 is predicted to be localized 60.9% in the cytoplasm, 21.7% in the nucleus, 13.0% mitochondrial and 4.3% in the Golgi Apparatus.

Expression & post translational modifications

See image one. The protein is highly expressed in the kidneys and moderately expressed in the adrenal gland, colon, liver, testis and thyroid gland.

Homology Paralogs There are no paralogs for C11orf54.

Orthologs The protein Ester Hydrolase C11orf54 has many orthologs (see table.) It is highly conserved (60-100% identity) in mammals, reptiles, birds, and fish. The protein is moderately conserved (30-59.99% identity) in invertebrates, amphibia, Cnidaria, Mollusca, fungi and bacteria. It is not conserved in archaea. The most distant orthologs are bacteria. Figure 2 shows the unrooted phylogenetic tree of a few of C11orf54's orthologs.

Species Common name Class Accession number Percent identity Divergence (MYA median) Microtus ochrogaster Prairie Vole mammalia XP_005346877.1 87.0 88 Chelonia mydas Green Sea Turtle reptilia XP_007069537.1 72.8 320 Xenopus tropicalis Burmese Python reptilia XP_007434894.1 70.9 320 Python bivittatus Red Junglefowl Ave NP_001264206.1 73.4 320 Gallus gallus Common Cuckoo Ave XP_009564677.1 72.5 320 Cuculus canorus Southern Platyfish Actinopterygii XP_005800827.1 65.2 432 Xiphophorus maculatus Zebrafish Actinopterygii NP_997781.1 62.4 432 Danio rerio Acorn Worm Enteropneusta XP_002738479.1 55.6 627 Saccoglossus kowalevskii Atlantic Horseshoe Crab Merostomata XP_013785734.1 56.6 758 Limulus polyphemus Western Clawed Frog Amphibia XP_012812415.1 55.1 353 Crassostrea gigas Pacific Oyster Bivalvia XP_011412414.1 50.0 758 Tribolium castaneum Red Flour Beetle Insecta XP_968861.1 49.0 758 Drosophila bipectinata Fruitfly Insecta XP_017103988.1 46.0 758 Megachile rotundata Alfalfa leafcutter bee Insecta XP_003702672.1 44.8 758 Zymoseptoria brevis fungi Dothideomycetes KJX93246.1 36.5 1150 Cladophialophora carrionii fungi Dothideomycetes OCT48531.1 35.8 1150 Alternaria alternata fungi Dothideomycetes XP_018384285.1 36.2 1150 Candidatus Pelagibacter ubique bacteria Bacteria WP_075504325.1 34.5 4090 Pelagibacteraceae bacterium bacteria Bacteria OCW82973.1 34.1 4090

Function C11orf54's coordination with a zinc ion through three histidines and an acetate anion is likely to point to a function of the protein being an enzymatic reaction as an ester hydrolase. The protein has a low turnover number when reacted with p-nitrophenyl acetate (0.042 sec−1) as compared to a 1 sec−1 turnover rate found in another enzyme (bovine carbonic anhydrase II) that reacts with p-nitrophenyl acetate.

Recent research has identified C11orf54 as the missing β-keto-L-gulonate decarboxylase in the pentose pathway. The study employing gene coevolution analysis and metabolic network mapping demonstrated that C11orf54 catalyzes the decarboxylation of 3-dehydro-L-gulonate, linking it to sugar metabolism in humans and other metazoans

Interacting proteins Protein Name Abbreviation Ubiquitin C UBC Collagen, type IV, alpha 3 COL4A3 Thyroid Hormone Receptor Interactor 13 TRIP13 DEAD (Asp-Glu-Ala-Asp) box polypeptide 60-like DDX60L Glutamine-fructose-6-phosphate transaminase 2 GFPT2 Superkiller viralicidic activity 2-like (S. cerevisiae) SKIV2L OTU domain, ubiquitin aldehyde binding 1 OTUB1

References

Further reading

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