Endothelin receptor type B, also known as ET_B 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 EDNRB 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

Endothelin receptor type B is a G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

 which activates a phosphatidylinositol-calcium second messenger system. Its ligand, endothelin

Endothelin

Endothelins are proteins that constrict blood vessels and raise blood pressure. They are normally kept in balance by other mechanisms, but when they are over-expressed, they contribute to high blood pressure and heart disease....

, consists of a family of three potent vasoactive peptides: ET₁, ET₂, and ET₃. A splice variant, named SVR, has been described; the sequence of the ETB-SVR receptor is identical to ETRB except for the intracellular C-terminal domain. While both splice variants bind ET₁, they exhibit different responses upon binding which suggests that they may be functionally distinct.

Regulation

In melanocytic

Melanocyte

-External links: - "Eye: fovea, RPE" - "Integument: pigmented skin"...

 cells the EDNRB gene is regulated by the microphthalmia-associated transcription factor

Microphthalmia-associated transcription factor

Microphthalmia-associated transcription factor is a basic helix-loop-helix leucine zipper transcription factor involved in melanocyte and osteoclast development.-Clinical significance:...

. Mutations in either gene are links to Waardenburg syndrome

Waardenburg syndrome

Waardenburg syndrome Waardenburg syndrome Waardenburg syndrome (also Waardenburg­ Shah Syndrome, Waardenburg-Klein syndrome, Mende's syndrome II, Van der Hoeve-Halbertsma-Waardenburg syndrome, Ptosis-Epicanthus syndrome, Van der Hoeve-Halbertsma-Gualdi syndrome, Waardenburg type Pierpont,[5] Van...

.

Clinical signficance

The multigenic disorder, Hirschsprung disease type 2, is due to mutation in endothelin receptor type B gene.

In horse

Horse

The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...

s, a mutation in the middle of the EDNRB gene, Ile118Lys, when homozygous, causes Lethal White Syndrome

Lethal white syndrome

Lethal white syndrome , also called overo lethal white syndrome , lethal white overo , and overo lethal white foal syndrome , is an autosomal genetic disorder most prevalent in the American Paint Horse...

. In this mutation, a mismatch in the DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 replication causes isoleucine

Isoleucine

Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....

 to be made instead of lysine

Lysine

Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

. The resulting EDNRB protein is unable to fulfill its role in the development of the embryo, limiting the migration of the melanocyte and enteric neuron precursors. A single copy of the EDNRB mutation, the heterozygous state, produces an identifiable and completely benign spotted coat color

Equine coat color

Horses exhibit a diverse array of coat colors and distinctive markings. A specialized vocabulary has evolved to describe them.While most horses remain the same color throughout life, a few, over the course of several years, will develop a different coat color from that with which they were born...

 called frame overo

Overo

Overo refers to several genetically unrelated pinto coloration patterns of white-over-dark body markings in horses, and is a term used by the American Paint Horse Association to classify a set of pinto patterns that are not Tobiano...

.

Interactions

Endothelin receptor type B 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 Caveolin 1.

Further reading