The transforming growth factor beta (TGF-β) superfamily is a large family of structurally related cell regulatory 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...

s that was named after its first member, TGF-β1

TGF beta 1

Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines. It is a secreted protein that performs many cellular functions, including the control of cell growth, cell proliferation, cell differentiation and apoptosis...

, originally described in 1983.

Many proteins have since been described as members of the TGF-β superfamily in a variety of species, including invertebrate

Invertebrate

An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...

s as well as vertebrate

Vertebrate

Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s and categorized into 23 distinct gene types that fall into four major subfamilies:

• the 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...
  
  -Vg-related (DVR) related subfamily (including the bone morphogenetic protein
  Bone morphogenetic protein
  Bone morphogenetic proteins are a group of growth factors also known as cytokines and as metabologens . Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue...
  
  s and the growth differentiation factor
  Growth differentiation factor
  Growth differentiation factors are a subfamily of proteins belonging to the transforming growth factor beta superfamily that have functions predominantly in development.-Types:...
  
  s)
• the activin/inhibin subfamily
• the TGF-β subfamily
• a group encompassing various divergent members

Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that controls proliferation, differentiation and other functions in many cell types. TGF-beta-1 is a peptide of 112 amino acid residues derived by proteolytic cleavage from the C-terminal of a precursor protein. These proteins interact with a conserved family of cell surface serine/threonine-specific protein kinase

Serine/threonine-specific protein kinase

Serine/threonine protein kinases phosphorylate the OH group of serine or threonine .At least 125 of the 500+ human protein kinases are serine/threonine kinases .-Regulation:...

 receptors, and generate intracellular signals

Signal transduction

Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

 using a conserved family of proteins called SMAD

SMAD

SMAD may refer to:* Sowjetische Militäradministration in Deutschland* SMAD – proteins involved in cell signaling** R-SMAD – receptor regulated SMAD proteins** I-SMAD – inhibitory SMAD proteins...

s. They play fundamental roles in the regulation of basic biological processes such as growth, 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...

, tissue homeostasis

Homeostasis

Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...

 and regulation of the immune system

Immune system

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

.

Structure

Proteins from the TGF-beta family are only active as homo- or heterodimer; the two chains being linked by a single disulfide bond. From X-ray studies of TGF-beta-2, it is known that all the other cysteines are involved in intrachain disulfide bonds. As shown in the following schematic representation, there are four disulfide bonds in the TGF-beta's and in inhibin beta chains, while the other members of this family lack the first bond.

interchain
|
+------------------------------------------|+
| ||
xxxxcxxxxxCcxxxxxxxxxxxxxxxxxxCxxCxxxxxxxxxxxxxxxxxxxCCxxxxxxxxxxxxxxxxxxxCxCx
| | | | | |
+------+ +--|----------------------------------------+ |
+------------------------------------------+

where 'C' denotes a conserved cysteine involved in a disulfide bond.

Examples

Human genes encoding proteins that contain this domain include:

AMH

Anti-müllerian hormone

Anti-Müllerian hormone also known as AMH is a protein that, in humans, is encoded by the AMH gene. It inhibits the development of the Müllerian ducts in the male embryo. It has also been called Müllerian inhibiting factor , Müllerian-inhibiting hormone , and Müllerian-inhibiting substance...

; ARTN; BMP10; BMP15; BMP2

Bone morphogenetic protein 2

Bone morphogenetic protein 2 or BMP-2 belongs to the TGF-β superfamily of proteins.-Function:BMP-2 like other bone morphogenetic proteins, plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine...

; BMP3

Bone morphogenetic protein 3

Bone morphogenetic protein 3 is a protein that in humans is encoded by the BMP3 gene.The protein encoded by this gene is a member of the transforming growth factor beta superfamily. It, like other bone morphogenetic proteins is known for its ability to induce bone and cartilage development. It is...

; BMP4; BMP5; BMP6; BMP7; BMP8A; BMP8B; GDF1

GDF1

Growth differentiation factor-1 is a protein that in humans is encoded by the GDF1 gene.GDF1 belongs to the transforming growth factor beta superfamily that has a role in left-right patterning and mesoderm induction during embryonic development. It is found in the brain, spinal cord and peripheral...

; GDF10

GDF10

Growth differentiation factor 10 also known as bone morphogenetic protein 3B is a protein that in humans is encoded by the GDF10 gene....

; GDF11

GDF11

Growth differentiation factor 11 also known as bone morphogenetic protein 11 is a protein that in humans is encoded by the GDF11 gene....

; GDF15

GDF15

Growth differentiation factor 15 is a protein belonging to the transforming growth factor beta superfamily that has a role in regulating inflammatory and apoptotic pathways in injured tissues and during disease processes. GDF15 is also known as TGF-PL, MIC-1, PDF, PLAB, and PTGFB. GDF15 mRNA is...

;
GDF2

GDF2

Growth differentiation factor 2 also known as bone morphogenetic protein -9 is a protein that in humans is encoded by the GDF2 gene...

; GDF3

GDF3

Growth differentiation factor-3 , also known as Vg-related gene 2 is protein that in humans is encoded by the GDF3 gene. GDF3 belongs to the transforming growth factor beta superfamily...

; GDF3A; GDF5

GDF5

Growth/differentiation factor 5 is a protein that in humans is encoded by the GDF5 gene.Growth differentiation factor 5 is a protein belonging to the transforming growth factor beta superfamily that is expressed in the developing central nervous system, and has a role in skeletal and joint...

; GDF6

GDF6

Growth differentiation factor 6 is a protein that in humans is encoded by the GDF6 gene.belonging to the transforming growth factor beta superfamily that may regulate patterning of the ectoderm by interacting with bone morphogenetic proteins, and control eye development....

; GDF7

GDF7

Growth differentiation factor 7 is a protein that in humans is encoded by the GDF7 gene.GDF7 belongs to the transforming growth factor beta superfamily that is specifically found in a signaling center known as the roof plate that is located in the developing nervous system of embryos...

; GDF8; GDF9; GDNF; INHA

INHA

Inhibin, alpha, also known as INHA, is a protein which in humans is encoded by the INHA gene.- Function :The inhibin alpha subunit joins either the beta A or beta B subunit to form a pituitary FSH secretion inhibitor. Inhibin has been shown to regulate gonadal stromal cell proliferation...

; INHBA

INHBA

Inhibin, beta A, also known as INHBA, is a protein which in humans is encoded by the INHBA gene. INHBA is a subunit of both activin and inhibin, two closely related glycoproteins with opposing biological effects.- Function :...

; INHBB

INHBB

Inhibin, beta B, also known as INHBB, is a protein which in humans is encoded by the INHBB gene. INHBB is a subunit of both activin and inhibin, two closely related glycoproteins with opposing biological effects.- Inhibin :...

; INHBC

INHBC

Inhibin beta C chain is a protein that in humans is encoded by the INHBC gene.-Further reading:...

; INHBE; LEFTY1; LEFTY2;
MSTN; NODAL

NODAL

Nodal is a protein that in humans is encoded by the NODAL gene. It is a member of the TGF beta superfamily. Like many other members of this superfamily, it is involved in cell differentiation...

; NRTN; PSPN; TGFB1; TGFB2; TGFB3;