Melatonin receptor 1B
Encyclopedia
Melatonin receptor 1B, also known as MTNR1B, is a protein
that in humans is encoded by the MTNR1B gene
.
, one of two high-affinity forms of a receptor for melatonin
, the primary hormone secreted by the pineal gland
. This gene product is an integral membrane protein
that is a G-protein coupled, 7-transmembrane receptor. It is found primarily in the retina and brain
; however, this detection requires RT-PCR
. It is thought to participate in light-dependent functions in the retina
and may be involved in the neurobiological effects of melatonin.
level and around a 20 percent elevated risk of developing type 2 diabetes. MTNR1B mRNA is expressed in human islets, and immunocytochemistry
confirms that it is primarily localized in beta cell
s in islets
.
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 MTNR1B 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...
.
Function
This gene encodes the MT2 proteinProtein
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...
, one of two high-affinity forms of a receptor for melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
, the primary hormone secreted by the pineal gland
Pineal gland
The pineal gland is a small endocrine gland in the vertebrate brain. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions...
. This gene product is an integral membrane protein
Integral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...
that is a G-protein coupled, 7-transmembrane receptor. It is found primarily in the retina and brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
; however, this detection requires RT-PCR
Reverse transcription polymerase chain reaction
Reverse transcription polymerase chain reaction is a variant of polymerase chain reaction , a laboratory technique commonly used in molecular biology to generate many copies of a DNA sequence, a process termed "amplification"...
. It is thought to participate in light-dependent functions in the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
and may be involved in the neurobiological effects of melatonin.
Clinical significance
Several studies have identified MTNR1B receptor mutations that are associated with increased average blood sugarBlood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
level and around a 20 percent elevated risk of developing type 2 diabetes. MTNR1B mRNA is expressed in human islets, and immunocytochemistry
Immunocytochemistry
Immunocytochemistry is a common laboratory technique that uses antibodies that target specific peptides or protein antigens in the cell via specific epitopes. These bound antibodies can then be detected using several different methods. ICC allows researchers to evaluate whether or not cells in a...
confirms that it is primarily localized in beta cell
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...
s in islets
Islets of Langerhans
The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...
.
MT2R Ligands
The following MT2R ligands have selectivity over MT1R:- Compound 3d: antagonistReceptor antagonistA receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
with sub-nM affinity - Compound 18f: antagonist and compound 18g partial agonistAgonistAn agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
: sub-nM affinity, >100-fold selectivity over MT1 - Compound 14: antagonist
- Compound 13: agonist