E3 ubiquitin-protein ligase RAD18 is 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...

 that in humans is encoded by the RAD18 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...

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Animal models

Model organism

Model organism

A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...

s have been used in the study of RAD18 function. A conditional

Conditional gene knockout

Conditional gene knockout is a relatively new technique, an offshoot of gene knockout technology with the exception that a specific target gene is eliminated from a single organ in the body rather than the whole body as gene knockout technology would entail...

 knockout mouse

Knockout mouse

A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...

 line, called Rad18^{tm1a(EUCOMM)Wtsi}, was generated as part of the EUCOMM

EUCOMM

The European Conditional Mouse Mutagenesis Program or EUCOMM is an EU-funded program to generate a library of mutant mouse embryonic stem cells for research purposes.- Setup :...

 program — a high-throughput mutagenesis

Mutagenesis

Mutagenesis is a process by which the genetic information of an organism is changed in a stable manner, resulting in a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures...

 project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. Mice lacking Rad18 had no significant defects in viability or fertility

Fertility

Fertility is the natural capability of producing offsprings. As a measure, "fertility rate" is the number of children born per couple, person or population. Fertility differs from fecundity, which is defined as the potential for reproduction...

, therefore male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.

Rad18 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Abnormal
Anxiety Open Field (animal test) The Open Field Test is an experiment used to assay general locomotor activity levels and anxiety in rodents in scientific research.- Experimental Design :...	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate Hot plate test The hot plate test is a test of the pain response in animals. It is used in basic pain research and in testing the effectiveness of analgesics by observing the reaction to pain caused by heat. It was proposed by Eddy and Leimbach in 1953....	Normal
Dysmorphology	Normal
Indirect calorimetry	Abnormal
Glucose tolerance test Glucose tolerance test A glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, insulin resistance, and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of...	Normal
Auditory brainstem response Auditory Brainstem Response The auditory brainstem response is an auditory evoked potential extracted from ongoing electrical activity in the brain and recorded via electrodes placed on the scalp. The resulting recording is a series of vertex positive waves of which I through V are evaluated...	Normal
DEXA	Abnormal
Radiography Radiography Radiography is the use of X-rays to view a non-uniformly composed material such as the human body. By using the physical properties of the ray an image can be developed which displays areas of different density and composition....	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma Blood plasma Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...  immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test Micronucleus test A micronucleus test is a test used in toxicological screening for potential genotoxic compounds. There are two major versions of this test, one in vivo and the other In vitro. The in vivo test normally uses mouse bone marrow or mouse peripheral blood. Micronuclei were first used to quantify...	Abnormal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
Salmonella Salmonella Salmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction... infection	Normal
Citrobacter Citrobacter Citrobacter is a genus of Gram-negative coliform bacteria in the Enterobacteriaceae family.The species C. amalonaticus, C. koseri, and C. freundii use solely citrate as a carbon source... infection	Normal
All tests and analysis from

Twenty five tests were carried out and four significant phenotypes were reported:

• Mutant
  Mutant
  In biology and especially genetics, a mutant is an individual, organism, or new genetic character, arising or resulting from an instance of mutation, which is a base-pair sequence change within the DNA of a gene or chromosome of an organism resulting in the creation of a new character or trait not...
  
   male mice had a decreased body weight
  Body weight
  The term body weight is used in daily English speech as well as in the contexts of biological and medical sciences to describe the mass of an organism's body. Body weight is measured in kilograms throughout the world, although in some countries it is still measured in pounds or stones and pounds...
  
   compared to wildtype control mice.
• Mutant male mice showed increased activity, VO2 and energy expenditure, determined by indirect calorimetry.
• Dual-energy X-ray absorptiometry (DEXA) showed mutant male mice had a decrease in fat
  Fat
  Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
  
   mass.
• A micronucleus test
  Micronucleus test
  A micronucleus test is a test used in toxicological screening for potential genotoxic compounds. There are two major versions of this test, one in vivo and the other In vitro. The in vivo test normally uses mouse bone marrow or mouse peripheral blood. Micronuclei were first used to quantify...
  
   found a potential increase in DNA damage in mutant mice.

Interactions

RAD18 has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with HLTF

HLTF

Helicase-like transcription factor is an enzyme that in humans is encoded by the HLTF gene.-Interactions:HLTF has been shown to interact with UBE2N, RAD18 and UBE2V2.-Further reading:...

, UBE2B

UBE2B

Ubiquitin-conjugating enzyme E2 B is a protein that in humans is encoded by the UBE2B gene.-Further reading:...

 and UBE2A

UBE2A

Ubiquitin-conjugating enzyme E2 A is a protein that in humans is encoded by the UBE2A gene.-Interactions:UBE2A has been shown to interact with RAD18 and P53.-Further reading:...

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Further reading