Mothers against decapentaplegic homolog 3
Encyclopedia
Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein
that in humans is encoded by the SMAD3 gene
. SMAD3 is a member of the SMAD
family of proteins.
The human SMAD3 gene is located on chromosome
15. It is one of several human homologues
of a gene that was originally discovered in the fruit fly Drosophila melanogaster
.
In mice, mutation of SMAD3 has been linked to colorectal adenocarcinoma, increased systemic inflammation, and accelerated wound
healing. There is no conclusive evidence of similar activity in humans, however. A 2002 study investigated possible links between SMAD3 mutation and cancer
of the pancreas
and parathyroid gland, but found no connection. Increased SMAD3 activity has, however, been implicated in the pathogenesis
of scleroderma
.
Smad3 is also a multifaceted regulator in adipose physiology and the pathogenesis of obesity and type 2 diabetes. Smad3-knockout mice have diminished adiposity, with improved glucose tolerance and insulin sensitivity. Despite their reduced physical activity arising from muscle atrophy
, these Smad3-knockout mice are resistant to high-fat-diet induced obesity.
The herpes simplex
virus
can downregulate SMAD3 using the Lat transcription factor
, even while the virus is in a latent state.
A reference assembly of SMAD3 is available.
of the Drosophila
protein "Mothers against decapentaplegic
". It belongs to the SMAD
family of proteins, which belong to the TGFβ superfamily of modulators. Like many other TGFβ family members, SMAD3 is involved in cell signalling. SMAD3 modulates signals of activin and TGFβ's. Binding of this protein with SMAD4 enables its transmigration into the nucleus where it forms complexes with other proteins and acts as a transcription factor
. SMAD3 is a receptor-regulated SMAD (R-SMAD
).
protein SMA. The name is a combination of the two. During Drosophila research, it was found that a mutation in the gene MAD in the mother repressed the gene decapentaplegic
in the embryo. The phrase "Mothers against" was inspired by organizations formed by mothers to oppose social problems, such as Mothers Against Drunk Driving
(MADD).
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 SMAD3 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...
. SMAD3 is a member of the SMAD
SMAD (protein)
SMADs are intracellular proteins that transduce extracellular signals from transforming growth factor beta ligands to the nucleus where they activate downstream TGF-β gene transcription....
family of proteins.
The human SMAD3 gene is located on chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
15. It is one of several human homologues
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
of a gene that was originally discovered in the fruit fly Drosophila melanogaster
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
.
SMAD3 gene
The human SMAD3 gene is composed of 9 exons over 129,339 base pairs.In mice, mutation of SMAD3 has been linked to colorectal adenocarcinoma, increased systemic inflammation, and accelerated wound
Wound
A wound is a type of injury in which skin is torn, cut or punctured , or where blunt force trauma causes a contusion . In pathology, it specifically refers to a sharp injury which damages the dermis of the skin.-Open:...
healing. There is no conclusive evidence of similar activity in humans, however. A 2002 study investigated possible links between SMAD3 mutation and cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
of the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
and parathyroid gland, but found no connection. Increased SMAD3 activity has, however, been implicated in the pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
of scleroderma
Scleroderma
Systemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
.
Smad3 is also a multifaceted regulator in adipose physiology and the pathogenesis of obesity and type 2 diabetes. Smad3-knockout mice have diminished adiposity, with improved glucose tolerance and insulin sensitivity. Despite their reduced physical activity arising from muscle atrophy
Muscle atrophy
Muscle atrophy, or disuse atrophy, is defined as a decrease in the mass of the muscle; it can be a partial or complete wasting away of muscle. When a muscle atrophies, this leads to muscle weakness, since the ability to exert force is related to mass...
, these Smad3-knockout mice are resistant to high-fat-diet induced obesity.
The herpes simplex
Herpes simplex
Herpes simplex is a viral disease caused by both Herpes simplex virus type 1 and type 2 . Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores or fever...
virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
can downregulate SMAD3 using the Lat transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
, even while the virus is in a latent state.
A reference assembly of SMAD3 is available.
SMAD3 protein
SMAD3, or Mothers against decapentaplegic homolog 3, is a polypeptide that, as its name describes, is a homologHomology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
of the Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
protein "Mothers against decapentaplegic
Mothers against decapentaplegic
Mothers against decapentaplegic is a protein from the SMAD family that was discovered in Drosophila.The SMAD proteins are homologs of both the Drosophila protein "mothers against decapentaplegic" and the C. elegans protein SMA. The name is a combination of the two...
". It belongs to the SMAD
SMAD (protein)
SMADs are intracellular proteins that transduce extracellular signals from transforming growth factor beta ligands to the nucleus where they activate downstream TGF-β gene transcription....
family of proteins, which belong to the TGFβ superfamily of modulators. Like many other TGFβ family members, SMAD3 is involved in cell signalling. SMAD3 modulates signals of activin and TGFβ's. Binding of this protein with SMAD4 enables its transmigration into the nucleus where it forms complexes with other proteins and acts as a transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
. SMAD3 is a receptor-regulated SMAD (R-SMAD
R-SMAD
R-SMAD stands for receptor-regulated SMAD. Smads are transcription factors that transduce extracellular TGF-ß superfamily ligand signaling from cell membrane bound TGF-ß receptors into the nucleus where they activate transcription TGF-ß target genes...
).
Nomenclature
The SMAD proteins are homologs of both the Drosophila protein "mothers against decapentaplegic" (MAD) and the C. elegansCaenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
protein SMA. The name is a combination of the two. During Drosophila research, it was found that a mutation in the gene MAD in the mother repressed the gene decapentaplegic
Decapentaplegic
Decapentaplegic is a key morphogen involved in the development of the fruit fly Drosophila melanogaster. It is known to be necessary for the correct patterning of the fifteen imaginal discs, which are tissues that will become limbs and other organs and structures in the adult fly. It has also been...
in the embryo. The phrase "Mothers against" was inspired by organizations formed by mothers to oppose social problems, such as Mothers Against Drunk Driving
Mothers Against Drunk Driving
Mothers Against Drunk Driving is a non-profit organization in the United States that seeks to stop drunk driving, support those affected by drunk driving, prevent underage drinking, and overall push for stricter alcohol policy...
(MADD).