Tubby protein
Encyclopedia
The tubby protein is encoded by the TUB gene. It is an upstream cell signaling
protein
common to multicellular eukaryote
s. The first tubby gene was identified in mice
, and proteins that are homologous
to tubby are known as "tubby-like proteins" (TULPs). They share a common and characteristic tertiary structure
that consists of a beta barrel
packed around an alpha helix
in the central pore. The gene derives its name from its role in metabolism; mice with a mutated tubby gene develop delayed-onset obesity
, sensorineural hearing loss and retinal degeneration
.
barrel surrounding a central alpha helix. Tubby proteins can bind the small cell signaling
molecule phosphatidylinositol
, which is typically localized to the cell membrane
. A similar structural fold to the Tubby like proteins has been identified in the Scramblase
family of proteins.
s and as potential signaling factors coupled to G-protein activity. They are associated with neuron
al differentiation
and development
, and in mammal
s are implicated in three disease processes when mutated
: obesity
, retina
l degeneration, and hearing loss. In mice, mutations in tubby proteins are known to affect life span
and fat
storage as well as carbohydrate
metabolism
. Tubby domains associate with cytoplasmic side of cell membrane
s through binding of different phosphoinositides
; TULP1
; TULP2; TULP3; TULP4;
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
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...
common to multicellular eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s. The first tubby gene was identified in mice
MICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...
, and proteins that are homologous
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...
to tubby are known as "tubby-like proteins" (TULPs). They share a common and characteristic tertiary structure
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
that consists of a beta barrel
Beta barrel
A beta barrel is a large beta-sheet that twists and coils to form a closed structure in which the first strand is hydrogen bonded to the last.Beta-strands in beta-barrels are typically arranged in an antiparallel fashion...
packed around an alpha helix
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
in the central pore. The gene derives its name from its role in metabolism; mice with a mutated tubby gene develop delayed-onset obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, sensorineural hearing loss and retinal degeneration
Retinal degeneration
The term retinal degeneration may refer to:* One of several eye diseases or eye disorders in humans* Progressive retinal atrophy, an eye disease in dogs-See also:*List of human eye diseases and disorders...
.
Structure
Tubby proteins are classified as α+β proteins and have a 12-beta strandedBeta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...
barrel surrounding a central alpha helix. Tubby proteins can bind the small cell signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
molecule phosphatidylinositol
Phosphatidylinositol
Phosphatidylinositol is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes....
, which is typically localized to the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
. A similar structural fold to the Tubby like proteins has been identified in the Scramblase
Scramblase
Scramblase is a protein responsible for the translocation of phospholipids between the two monolayers of a lipid bilayer of a cell membrane. In humans, phospholipid scramblases constitute a family of five homologous proteins that are named as hPLSCR1–hPLSCR5. Scramblases are members of the...
family of proteins.
Function
Tubby proteins have been implicated as transcription factorTranscription 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...
s and as potential signaling factors coupled to G-protein activity. They are associated with neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
al differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
and development
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
, and in mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s are implicated in three disease processes when mutated
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
: obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, 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...
l degeneration, and hearing loss. In mice, mutations in tubby proteins are known to affect life span
Life expectancy
Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...
and 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...
storage as well as carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
. Tubby domains associate with cytoplasmic side of cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s through binding of different phosphoinositides
Phosphatidylinositol
Phosphatidylinositol is a negatively charged phospholipid and a minor component in the cytosolic side of eukaryotic cell membranes....
Human proteins containing this domain
TUBTub
Tub may refer to:* A large round container without a lid - used for washing clothes in, growing plants in, etc.* A shallow, plastic or paper container, typically with a lid or closure.* A bath or Bathtub - a plumbing fixture for bathing....
; TULP1
TULP1
Tubby-related protein 1 is a protein that in humans is encoded by the TULP1 gene.-Further reading:...
; TULP2; TULP3; TULP4;