C11orf54

C11orf54
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1XCR
Identifiers
Aliases	C11orf54 , PTD012, PTOD012, chromosome 11 open reading frame 54
External IDs	OMIM: 615810; MGI: 1918234; HomoloGene: 8531; GeneCards: C11orf54; OMA:C11orf54 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11q21 Start 93,741,591 bp [1] End 93,764,749 bp [1]
Gene location (Mouse) Chr. Chromosome 9 (mouse) [2] Band 9|9 A2 Start 15,194,633 bp [2] End 15,217,744 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in renal medulla human kidney mucosa of ileum jejunal mucosa liver mucosa of paranasal sinus pancreatic epithelial cell Skeletal muscle tissue of biceps brachii metanephros retinal pigment epithelium Top expressed in parotid gland brown adipose tissue left lobe of liver human kidney transitional epithelium of urinary bladder olfactory epithelium jejunum tunica adventitia of aorta left colon duodenum More reference expression data BioGPS n/a
Gene ontology Molecular function zinc ion binding protein binding hydrolase activity hydrolase activity, acting on ester bonds metal ion binding Cellular component extracellular exosome nucleus nucleoplasm nuclear body Biological process metabolism Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 28970 70984 Ensembl ENSG00000182919 ENSMUSG00000031938 UniProt Q9H0W9 Q91V76 RefSeq (mRNA) NM_001286067 NM_001286068 NM_001286069 NM_001286070 NM_001286071 NM_014039 NM_001351985 NM_001351986 NM_001351988 NM_001351989 NM_001351990 NM_001351991 NM_001351992 NM_001351993 NM_001351987 NM_001369406 NM_001199484 NM_001199485 NM_133732 NM_001359258 RefSeq (protein) NP_001272996 NP_001272997 NP_001272998 NP_001272999 NP_001273000 NP_054758 NP_001338914 NP_001338915 NP_001338916 NP_001338917 NP_001338918 NP_001338919 NP_001338920 NP_001338921 NP_001338922 NP_001356335 NP_001186413 NP_001186414 NP_598493 NP_001346187 Location (UCSC) Chr 11: 93.74 – 93.76 Mb Chr 9: 15.19 – 15.22 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Chromosome 11 open reading frame 54 (C11orf54) is a protein that in humans is encoded by the C11orf54 gene. ^[5] 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. ^[6]

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. ^[6]

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. ^[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

^[6]

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. ^[7] 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. ^[8]

Protein

Primary sequence

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

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. ^[7]

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. ^[10]

Expression & post translational modifications

Image 1: Post-Transcriptional Modifications to C11orf54 protein

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]

Homology

Paralogs

There are no paralogs for C11orf54. ^[5]

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. ^[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

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. ^[7]

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 ^[14]

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

^[15]

References

1. GRCh38: Ensembl release 89: ENSG00000182919 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031938 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: C11orf54 chromosome 11 open reading frame 54".
6. "C11orf54". NCBI Gene. NCBI (National Center for Biotechnology Information).
7. Manjasetty BA, Büssow K, Fieber-Erdmann M, Roske Y, Gobom J, Scheich C, Götz F, Niesen FH, Heinemann U (April 2006). "Crystal structure of Homo sapiens PTD012 reveals a zinc-containing hydrolase fold". Protein Science. 15 (4): 914–20. doi:10.1110/ps.052037006. PMC   2242484 . PMID   16522806.
8. Langton MJ, Serpell CJ, Beer PD (2016). "Anion Recognition in Water: Recent Advances from a Supramolecular and Macromolecular Perspective". Angewandte Chemie International Edition. 55 (6): 1974–87. doi:10.1002/anie.201506589. PMC   4755225 . PMID   26612067.
9. Subramaniam S (1998). "The Biology Workbench--a seamless database and analysis environment for the biologist". Proteins. 32 (1): 1–2. doi:10.1002/(SICI)1097-0134(19980701)32:1<1::AID-PROT1>3.0.CO;2-Q. PMID   9672036. S2CID   1412129.
10. Briesemeister S, Rahnenführer J, Kohlbacher O (2010). "Going from where to why–interpretable prediction of protein subcellular localization". Bioinformatics. 26 (9): 1232–8. doi:10.1093/bioinformatics/btq115. PMC   2859129 . PMID   20299325.
11. Blom N, Gammeltoft S, Brunak S (1999). "Sequence and structure-based prediction of eukaryotic protein phosphorylation sites". Journal of Molecular Biology. 294 (5): 1351–62. doi:10.1006/jmbi.1999.3310. PMID   10600390.
12. Gupta R, Brunak S (2002). "Prediction of glycosylation across the human proteome and the correlation to protein function". Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing: 310–22. doi:10.1142/9789812799623_0029. ISBN   978-981-02-4777-5. PMID   11928486.
13. Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, et al. (January 2015). "Proteomics. Tissue-based map of the human proteome". Science. 347 (6220): 1260419. doi:10.1126/science.1260419. PMID   25613900. S2CID   802377.
14. Percudani, Riccardo; Malatesta, Marco; De Rito, Carlo; Merici, Giovanni; Dell'Accantera, Davide; Quilici, Giacomo; Sansone, Francesco (19 March 2025). "Mapping metabolic coevolution identifies C11orf54 as the missing pentose pathway decarboxylase". Research Square (Preprint). 1. doi:10.21203/rs.3.rs-6141043/v1.
15. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, Lin J, Minguez P, Bork P, von Mering C, Jensen LJ (2013). "STRING v9.1: protein-protein interaction networks, with increased coverage and integration". Nucleic Acids Research. 41 (Database issue): D808–15. doi:10.1093/nar/gks1094. PMC   3531103 . PMID   23203871.

Further reading

• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (September 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC   1083732 . PMID   11256614.
• Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X, Zhong F, He L, Yu J, Yao G, Jiang H, Qian L, Yu Y, Shu H, Chen X, Xu H, Guo M, Pan Z, Chen Y, Ge C, Yang S, Gu J (November 2004). "Large-scale cDNA transfection screening for genes related to cancer development and progression". Proceedings of the National Academy of Sciences of the United States of America. 101 (44): 15724–9. Bibcode:2004PNAS..10115724W. doi: 10.1073/pnas.0404089101 . PMC   524842 . PMID   15498874.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 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.

External links

• Human C11orf54 genome location and C11orf54 gene details page in the UCSC Genome Browser .
• Overview of all the structural information available in the PDB for UniProt : Q9H0W9 (Ester hydrolase C11orf54) at the PDBe-KB .