Ribonuclease 4 is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that in humans is encoded by the ''RNASE4''

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 ...

Ribonuclease 4 with deoxyuridine monophosphate

Function

The

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 ...

encoded by this gene belongs to the

pancreatic The pancreas is an Organ (anatomy), organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...

ribonuclease Ribonuclease (commonly abbreviated RNase) is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the ...

family. Secreted ribonucleases are the only enzyme family that is vertebrate-specific. Among the 13 members of this superfamily, ribonuclease 4 (RNase 4), is the most conserved gene across different vertebrate species. The human form of RNase 4 is an intracellular and plasma enzyme which was first isolated from colon adenocarcinoma cell line HT-29. It can be found in the pancreas, saliva, and the liver, displaying a similar distribution pattern to that of

angiogenin Angiogenin (ANG) also known as ribonuclease 5 is a small 123 amino acid protein that in humans is encoded by the ''ANG'' gene. Angiogenin is a potent stimulator of new blood vessels through the process of angiogenesis. Ang hydrolyzes cellular R ...

(ANG). It plays an important role in

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 ...

cleavage and has marked specificity towards the 3' side of uridine nucleotides.

Alternative splicing Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...

results in two transcript variants encoding the same protein. RNase 4 is co-expressed and shares the same promoter with

(ANG), another member of this superfamily. Each gene splices to a unique downstream exon that contains its complete coding region. RNase 4 has also been studied in its involvement with amyotrophic lateral sclerosis (ALS), a nervous system disease, due to its similarity with ANG which has been associated with ALS pathogenesis.

Structure

Deoxyuridine monophosphate in active site of Ribonuclease 4

RNase 4 features a unique structure compared to its homologous enzymes in the superfamily. It contains 119 amino acid residues making it the shortest known human RNase and contains no ''N-glycosylation'' sites. RNase 4 displays an α + β type polypeptide chain folding and a V-shape with the active site cleft in the middle. It contains three α-helices and four β -strands while the secondary structures are connected by six loops. There are four disulfide bridges located throughout the structure that connect the α-helices, β -strands, and loops. The overall structure of RNase 4 is similar to its homologous enzyme

RNase A Pancreatic ribonuclease family (, ''RNase'', ''RNase I'', ''RNase A'', ''pancreatic RNase'', ''ribonuclease I'', ''endoribonuclease I'', ''ribonucleic phosphatase'', ''alkaline ribonuclease'', ''ribonuclease'', ''gene S glycoproteins'', ''Ceratit ...

, EDN, and angiogenin. A shorter C terminus is a unique feature of RNase 4 which places the carboxy terminus in the pyrimidine recognition site which results in RNase 4 unique specificity. The pyrimidine recognition site is where there are major difference compared to its homologous enzymes. It contains an arginine residue at position 101, a phenylalanine reside at 42, and a threonine residue at 44. These residues contribute to the ribonuclease 4 specificity and are adapted to recognize a uridine-type base over cytidine-containing substrates.

Function

Structure

References

Further reading