Chromosome 11open reading frame 54 (C11orf54) is aprotein that in humans is encoded by theC11orf54gene.[5] The "Homo sapiens" gene, C11orf54 is also known as PTD012 and PTOD12. C11orf54 exhibitshydrolase 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 distanthomolog found is in bacteria.[6]
C11orf54 is located onchromosome 11 at 11q21. Common aliases of the gene are PTD012 and PT0D12. The gene consists 13 exons and spans 23730 bp. C11orf54 is flanked by TAF1D and MED17.[6]
The protein ester hydrolase c11orf54 exists as a monomer and is composed of 315 amino acids. There are 6 isoforms for C11orf54. See table 1.[6]
| 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 thedomain of unknown function 1907. Found in this transcript is the HxHxxxxxxxxxH motif which coordinates the zinc ion involved in the hydrolase activity.[7] AnLR 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.[8]
Table 2 shows the different characteristics of the protein sequence throughout humans and other orthologs.[9]
| 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 |
The protein of C11orf54 exists as a monomer in solution. The protein assumes a globular shape of 20beta strands and 4alpha 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.[7]
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.[10]
See image one.[11][12] The protein is highly expressed in the kidneys and moderately expressed in the adrenal gland, colon, liver, testis and thyroid gland.[13]
There are no paralogs for C11orf54.[5]
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.[9] The most distant orthologs are bacteria. Figure 2 shows the unrooted phylogenetic tree of a few of C11orf54's orthologs.[5]
| 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 |
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 withp-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 withp-nitrophenyl acetate.[7]
Recent research has identifiedC11orf54 as the missingβ-keto-L-gulonate decarboxylase in thepentose pathway. The study employing genecoevolution analysis andmetabolic network mapping demonstrated that C11orf54 catalyzes the decarboxylation of 3-dehydro-L-gulonate, linking it to sugar metabolism in humans and other metazoans[14]
| 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 |
