Angiogenin

Angiogenin

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Angiogenin also known as ribonuclease 5 is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the ANG gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. Angiogenin is a potent stimulator of new blood vessel formation. It hydrolyzes cellular tRNAs
Transfer RNA
Transfer RNA is an adaptor molecule composed of RNA, typically 73 to 93 nucleotides in length, that is used in biology to bridge the three-letter genetic code in messenger RNA with the twenty-letter code of amino acids in proteins. The role of tRNA as an adaptor is best understood by...

 resulting in decreased protein synthesis and is similar to pancreatic ribonuclease
Pancreatic ribonuclease
Pancreatic ribonucleasea are pyrimidine-specific endonucleases found in high quantity in the pancreas of certain mammals and of some reptiles....

.

Function


Angiogenin is a small protein that is implicated in angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...

 (formation of new blood vessels) in tumor growth. However, angiogenin is unique among the many proteins that are involved in angiogenesis in that it is also an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 with an amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 sequence 33% identical to that of bovine pancreatic ribonuclease
Ribonuclease
Ribonuclease 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 EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...

 (RNase) A. Moreover, although Ang has the same general catalytic properties as RNase A – it cleaves preferentially on the 3' side of pyrimidines and follows a transphosphorylation/hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 mechanism – its activity differs markedly both in magnitude and in specificity.

Although angiogenin contains counterparts for the key catalytic residues of bovine pancreatic RNase A, it cleaves standard RNA substrates 105–106 times less efficiently than does RNase A. Despite this apparent weakness, the enzymatic activity of Ang appears to be essential for biological activity: replacements of important active site residues
invariably diminish ribonuclease
Ribonuclease
Ribonuclease 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 EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...

 and angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...

 activities in parallel, and a substitution that increases enzymatic activity also enhances angiogenic potency.

Angiogenin may function as a tRNA-specific ribonuclease
Ribonuclease
Ribonuclease 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 EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...

 that binds to actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...

 on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

, thereby promoting the endothelial invasiveness necessary for blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...

 formation. Angiogenin induces vascularization
Vasculogenesis
Vasculogenesis is the process of blood vessel formation occurring by a de novo production of endothelial cells.-Process:Though similar to angiogenesis, the two are different in one aspect: The term angiogenesis denotes the formation of new blood vessels from pre-existing ones, whereas...

 of normal and malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...

 tissues, and abolishes protein synthesis by specifically hydrolyzing cellular tRNAs.

Gene


Alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...

 results in two transcript variants encoding the same protein. This gene and the gene that encodes ribonuclease, RNase A family, 4 share promoters and 5' exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...

s. Each gene splices to a unique downstream exon that contains its complete coding region.

Further reading