Uncharacterized protein C2orf27 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''C2orf27A

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

''. Although its function is not clearly understood, through the use of bioinformatic analysis more information is being brought to light.

Gene

The

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

is 1,222bp in length and is located at 2q21.2 with a total of five exons in ''

Homo sapiens Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

''. Other sources list ''C2orf27B'' as a paralog but this is unlikely because both genes are located in the same place on

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost ei ...

. It seems to be generally accepted that they are the same gene. Other gene aliases include ''C2orf27'' and chromosome 2

open reading frame In molecular biology, reading frames are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible reading frames ...

27A. The gene is surrounded upstream by POTEKP and downstream by ANKRD30BL.

Protein

The length of the C2orf27 protein sequence is 203 a.a. in length and has a molecular weight of 21.5 kDa with a pI of 5.13 in ''Homo sapiens''. When taking into account the primate orthologs, the molecular weights range from 21.4 to 36.7 kDa with the

isoelectric point The isoelectric point (pI, pH(I), IEP), is the pH at which a molecule carries no net electric charge, electrical charge or is electrically neutral in the statistical mean. The standard nomenclature to represent the isoelectric point is pH(I). Howe ...

ranging from 4.58 to 5.25. This gene is located in the nucleus of the cell and, it doesn't contain any transmembrane regions. Looking at the motifs of the protein sequence, a few important ones are present. All of the repeat sequences are concentrated near the N-terminus of the protein and are highly conserved through all the orthologs. Post-translationally, there are multiple

glycosylation Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...

sites scattered throughout the protein sequence,

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

site positioned at S13, and a

nuclear export signal A nuclear export signal (NES) is a short target peptide containing 4 hydrophobic residues in a protein that targets it for export from the cell nucleus to the cytoplasm through the nuclear pore complex using nuclear transport. It has the opposit ...

located at L80 - V90, which also happens to be within a

coiled coil A coiled coil is a structural motif in proteins in which two to seven alpha-helices are coiled together like the strands of a rope. ( Dimers and trimers are the most common types.) They have been found in roughly 5-10% of proteins and have a ...

region.

Expression

C2orf27 is ubiquitously expressed in most tissues but with increased expression in the brain, pancreas, kidneys, and testis.

Interactions

The protein is said to interaction with another protein called ataxin-1 which was discovered by performing a two hybrid prey pooling (Y2H) approach. They share the similar characteristics of being located in the nucleus of cells and are expressed in the brain.

Structure

The overall structure of this protein is predicted to be composed of both alpha-helices and beta-sheets. The majority of the alpha-helices fall on the N-terminus of the protein and the beta-sheets fall near the C-terminus of the protein. There is a sequence of four prolines located from P185 to P188 has the secondary structure of a type II

polyproline helix A polyproline helix is a type of protein secondary structure which occurs in proteins comprising repeating proline residues. A left-handed polyproline II helix (PPII, poly-Pro II, κ-helix) is formed when sequential residues all adopt (φ,ψ) backb ...

Evolutionary History

This gene is found in primates but is also found at a very poor E-values in other mammals and organisms like fish, invertebrates, fungi, bacteria, or plants. The protein C2orf27, however, is strictly found only in primates like

chimpanzee The chimpanzee (; ''Pan troglodytes''), also simply known as the chimp, is a species of Hominidae, great ape native to the forests and savannahs of tropical Africa. It has four confirmed subspecies and a fifth proposed one. When its close rel ...

gorilla Gorillas are primarily herbivorous, terrestrial great apes that inhabit the tropical forests of equatorial Africa. The genus ''Gorilla'' is divided into two species: the eastern gorilla and the western gorilla, and either four or five su ...

s, and baboons. When comparing the mRNA of ''C2orf27A'' with the exclusion of primates, it is shown that there is a high similarity with a gene called neurobeachin (NBEA
NBEA
When taking a look at this connection between the two, it was found that NBEA was on a different reading frame than ''C2orf27A'' which already begins to rule out any similarity between the two. This was confirmed based upon the fact that when comparing both of these protein sequences, it resulted in a 44% similarity in a 1% query cover. These protein sequences are entirely different suggesting that their functions may not be similar. It was also discovered when comparing the alignment of the sequences, it was shown that a duplication event occurred between NBEA and ''C2orf27A''. NBEA is present on

chromosome 13 Chromosome 13 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 13 spans about 113 million base pairs (the building material of DNA) and represents between 3.5 and 4% of the total DNA i ...

but a section of this mRNA corresponds, with a 96% similarity score, with exons one through four on C2orf27 of chromosome 2. This may be an example of a

gene duplication Gene duplication (or chromosomal duplication or gene amplification) is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene ...

event. Taking all of this into account, the duplication of NBEA into chromosome 2 to form C2orf27 may be the divergence point of the gene becoming strictly present in primates only.

Clinical Significance

C2orf27A has been found to be associated with nonsyndromic

craniosynostosis Craniosynostosis is a condition in which one or more of the fibrous sutures in a young infant's skull prematurely fuses by turning into bone (ossification), thereby changing the growth pattern of the skull. Because the skull cannot expand perpe ...

, a premature fusion of the calvaria. There are two distinct subtypes of this disease and patients with a certain subtype present with an increase in the expression of certain genes characteristic of each subtype. There is subtype A which is associated with increased

insulin-like growth factor The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system (often referred to as the IGF ...

expression, and subtype B which is associated with increased

integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...

expression. There is an increased expression of the gene C2orf27A shown in patients with the subtype B disease. Through a combination of a microarray assay and use of IPA software, C2orf27A has been found to be regulated by the hormone melatonin and linked with a role in cellular movement, the function and development of blood and bone marrow, and cell-mediated response of the immune system. The chimeric fusion of C2orf27A (exon 1) and NBEA (exon 37 and 38) was present in only ovarian cancer samples.

References

{{reflist, 35em Genes Uncharacterized proteins