Chromosome 17

open reading frame In molecular biology, open reading frames (ORFs) 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 readin ...

75 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''C17orf75''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. ''C17orf75'' is also known as SRI2 (sensitization to

ricin Ricin ( ) is a lectin (a carbohydrate-binding protein) and a highly potent toxin produced in the seeds of the castor oil plant, ''Ricinus communis''. The median lethal dose (LD50) of ricin for mice is around 22 micrograms per kilogram of body ...

complex subunit 2) and is a human protein encoding gene located at 17q11.2 on the complementary strand. The protein this gene encodes is also known as NJMU-R1. The ''C17orf75'' gene is ubiquitously expressed at medium-low levels throughout the body and at slightly higher levels in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

and testes. This protein is thought to be part of a complex associated with golgin-mediated

vesicle Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...

capture.

Gene

The ''C17orf75'' gene spans from position 32,328,441 to position 32,342,173 with a length of 13,733

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...

s. The length after

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...

excision is 4,547 nucleotides, and the

coding sequence The coding region of a gene, also known as the coding sequence (CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to no ...

is 1,191 nucleotides in length. ''C17orf75'' has 10 exons.

RNA

''C17orf75'' has 4 transcript isoforms: ''C17orf75'' and 3 predicted isoforms which are ''C17orf75'' transcript variant X1 (4,568 nucleotides in length), ''C17orf75'' transcript variant X2 (4,449 nucleotides in length), and ''C17orf75'' transcript variant X3 (4,464 nucleotides in length).

Protein

Structure

The primary isoform of the protein NJMU-R1 is 396 amino acids long. The theoretical

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

for the protein NJMU-R1 is around 5, and its predicted molecular weight is around 44 kD. This protein has a leucine zipper that is predicted to contribute to a coiled coil in the protein's folded structure. The secondary structure of the protein is predicted to dominated by

helices A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined helices, ...

, with some

beta sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...

s. 3 potential disulfide bridge sites via

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

residues are predicted in the protein.

Post-Translational Modifications

The protein NJMU-R1 has two experimentally determined

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

sites near the N-terminus. Predicted post-translational modifications include

tyrosine sulfation Tyrosine sulfation is a posttranslational modification where a sulfate group is added to a tyrosine residue of a protein molecule. Secreted proteins and extracellular parts of membrane proteins that pass through the Golgi apparatus may be sulfated. ...

O-linked glycosylation ''O''-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine (Ser) or threonine (Thr) residues in a protein. ''O''-glycosylation is a post-translational modification that occurs after the protein has been synthesise ...

, and

GPI anchor Glycosylphosphatidylinositol (), or glycophosphatidylinositol, or GPI in short, is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in ...

attachment.

Tissue Localization

Immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...

staining images show moderate protein levels throughout mouse brain tissues, but the Purkinje layer in the cerebellum shows a distinctly high level of protein concentration, especially as compared to the neighboring granular layer. There are also high protein concentrations in the circumventricular organs of the mouse brain.

Cellular Localization

Within the cell, images have shown the protein to be clustered in the cytosol and near the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...

. Th
PSORTII
tool also predicts that this protein is localized to the cytosol.

Expression Data

RNA sequencing RNA-Seq (named as an abbreviation of RNA sequencing) is a sequencing technique which uses next-generation sequencing (NGS) to reveal the presence and quantity of RNA in a biological sample at a given moment, analyzing the continuously changing c ...

data shows that ''C17orf75'' is expressed highly in the

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...

, and at moderately elevated levels in the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

and

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...

Microarray A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon t ...

data shows that this gene is expressed ubiquitously in most tissues, with moderate-to-high expression in the brain and testes and moderate-to-low expression in all other tissues. Expression levels of C17orf75 are seen to be higher in

colorectal The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being ...

and other cancers, suggesting that C17orf75 may be a

protooncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

or that there is another element of the gene's regulation that is causing these elevated levels. C17orf75_Ortholog_table

Homology

The ''C17orf75'' gene has orthologs as distantly related as amoeba and slime molds that are approximately 1,092,000,000 years old. It is seen in most animals that diverged since then, such as

insect Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body ( head, thorax and abdomen), three pairs ...

s, though, notably, not ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

'',

marine vertebrate Marine vertebrates are vertebrates that live in marine environments. These are the marine fish and the marine tetrapods (primarily seabirds, marine reptiles, and marine mammals). Vertebrates are a subphylum of chordates that have a vertebral c ...

s, marine invertebrates, 14

amphibian Amphibians are tetrapod, four-limbed and ectothermic vertebrates of the Class (biology), class Amphibia. All living amphibians belong to the group Lissamphibia. They inhabit a wide variety of habitats, with most species living within terres ...

s (only frogs/toads and caecilians),

reptile Reptiles, as most commonly defined are the animals in the class Reptilia ( ), a paraphyletic grouping comprising all sauropsids except birds. Living reptiles comprise turtles, crocodilians, squamates (lizards and snakes) and rhynchocephalians ( ...

bird Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweigh ...

s, and

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

Protein Interactions

Research findings show that NJMU-R1 is predicted to be part of a trimer (with FAM91A1 amily With Sequence Similarity 91 Member A1and SRI1), as elicited through

immunoprecipitation Immunoprecipitation (IP) is the technique of precipitating a protein antigen out of solution using an antibody that specifically binds to that particular protein. This process can be used to isolate and concentrate a particular protein from a samp ...

, fractionation, and

mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is use ...

. This trimer has been proposed to promote the Golgi’s capture of vesicles, particularly vesicles involved with the AB toxin, ricin, as knockouts of C17orf75 lead to higher cell susceptibility to ricin.

References

{{reflist Genetics Protein classification Bioinformatics Cell biology Human proteins