Pancreatic ribonuclease family (, ''RNase'', ''RNase I'', ''RNase A'', ''pancreatic RNase'', ''ribonuclease I'', ''endoribonuclease I'', ''ribonucleic phosphatase'', ''alkaline ribonuclease'', ''ribonuclease'', ''gene S glycoproteins'', ''Ceratitis capitata alkaline ribonuclease'', ''SLSG glycoproteins'', ''gene S locus-specific glycoproteins'', ''S-genotype-assocd. glycoproteins'', ''ribonucleate 3'-pyrimidino-oligonucleotidohydrolase'') is a superfamily of

pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The oth ...

-specific

endonucleases In molecular biology, endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain (namely DNA or RNA). Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (with regard to sequence), while many, t ...

found in high quantity in the

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

of certain

mammals A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...

and of some

reptiles Reptiles, as commonly defined, are a group of tetrapods with an ectothermic metabolism and Amniotic egg, amniotic development. Living traditional reptiles comprise four Order (biology), orders: Testudines, Crocodilia, Squamata, and Rhynchocepha ...

. Specifically, the enzymes are involved in endonucleolytic cleavage of 3'-phosphomono

nucleotides Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

and 3'-phosphooligonucleotides ending in C-P or U-P with 2',3'-cyclic phosphate intermediates. Ribonuclease can unwind the

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

helix by complexing with single-stranded RNA; the complex arises by an extended multi-site cation-anion interaction between

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

and

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

residues of the enzyme and phosphate groups of the nucleotides.

Notable family members

Bovine pancreatic ribonuclease is the best-studied member of the family and has served as a model system in work related to

protein folding Protein folding is the physical process by which a protein, after Protein biosynthesis, synthesis by a ribosome as a linear chain of Amino acid, amino acids, changes from an unstable random coil into a more ordered protein tertiary structure, t ...

disulfide bond In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inor ...

formation, protein

crystallography Crystallography is the branch of science devoted to the study of molecular and crystalline structure and properties. The word ''crystallography'' is derived from the Ancient Greek word (; "clear ice, rock-crystal"), and (; "to write"). In J ...

and

spectroscopy Spectroscopy is the field of study that measures and interprets electromagnetic spectra. In narrower contexts, spectroscopy is the precise study of color as generalized from visible light to all bands of the electromagnetic spectrum. Spectro ...

, and

protein dynamics In molecular biology, proteins are generally thought to adopt unique structures determined by their amino acid sequences. However, proteins are not strictly static objects, but rather populate ensembles of (sometimes similar) conformations. Tran ...

. The human genome contains 8 genes that share the structure and function with bovine pancreatic ribonuclease, with 5 additional pseudo-genes. The structure and dynamics of these enzymes are related to their diverse biological functions. Other proteins belonging to the pancreatic ribonuclease superfamily include: bovine seminal vesicle and brain ribonucleases; kidney non-secretory ribonucleases; liver-type ribonucleases; angiogenin, which induces vascularisation of normal and malignant tissues; eosinophil cationic protein, a cytotoxin and helminthotoxin with ribonuclease activity; and frog liver ribonuclease and frog sialic acid-binding lectin. The sequence of pancreatic ribonucleases contains four conserved

s and three amino acid residues involved in the catalytic activity.

Human genes

Human 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 ...

genes 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 ...

encoding proteins containing this

domain A domain is a geographic area controlled by a single person or organization. Domain may also refer to: Law and human geography * Demesne, in English common law and other Medieval European contexts, lands directly managed by their holder rather ...

include: * ANG, * RNASE1, RNASE10, RNASE12, RNASE2, RNASE3, RNASE4,

RNASE6 Ribonuclease A family member k6 is a protein that in humans is encoded by the RNASE6 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 th ...

, RNASE7, and RNASE8.

Cytotoxicity

Some members of the pancreatic ribonuclease family have

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...

effects. Mammalian cells are protected from these effects due to their extremely high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for

ribonuclease inhibitor Ribonuclease inhibitor (RI) is a large (~450 residues, ~49 kDa), acidic (pI ~4.7), leucine-rich repeat protein that forms extremely tight complexes with certain ribonucleases. It is a major cellular protein, comprising ~0.1% of all cellular prote ...

(RI), which protects cellular RNA from degradation by pancreatic ribonucleases. Pancreatic ribonucleases that are not inhibited by RI are approximately as toxic as alpha-sarcin,

diphtheria toxin Diphtheria toxin is an exotoxin secreted mainly by '' Corynebacterium diphtheriae'' but also by ''Corynebacterium ulcerans'' and '' Corynebacterium pseudotuberculosis'', the pathogenic bacterium that causes diphtheria. The toxin gene is enco ...

, or

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 ...

. Two pancreatic ribonucleases isolated from the oocytes of the

Northern leopard frog ''Lithobates pipiens''Integrated Taxonomic Information System nternet2012''Lithobates pipiens'' pdated 2012 Sept; cited 2012 Dec 26Available from: www.itis.gov/ formerly ''Rana pipiens'', commonly known as the northern leopard frog, is a s ...

- amphinase and

ranpirnase Ranpirnase is a ribonuclease enzyme found in the oocytes of the Northern Leopard Frog (''Rana pipiens''). Ranpirnase is a member of the pancreatic ribonuclease (RNase A) protein superfamily and degrades RNA substrates with a sequence preference ...

- are not inhibited by RI and show differential cytotoxicity against

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

cells. Ranpirnase was studied in a Phase III

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

as a treatment candidate for

mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The area most commonly affected is the lining of the lungs and chest wall. Less commonly the lini ...

, but the trial did not demonstrate statistical significance against primary endpoints.

References

{{Portal bar, Biology, border=no Ribonucleases EC 3.1.27 Protein domains