# C11orf54

Chromosome 11 open reading frame 54 (C11orf54) is a protein that in humans is encoded by the C11orf54 gene. The "Homo sapiens" gene, C11orf54 is also known as PTD012 and PTOD12. C11orf54 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

C11orf54 is located on chromosome 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.

## mRNA

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.
| 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 |