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

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s that was named after its first member, TGF-β1, originally described in 1983. They interact with TGF-beta receptors. Many proteins have since been described as members of the TGF-β superfamily in a variety of species, including

invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...

s as well as

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

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

TGF-β Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...

subfamily * The

bone morphogenetic protein Bone morphogenetic proteins (BMPs) 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 piv ...

s and the

growth differentiation factor Growth differentiation factors (GDFs) are a subfamily of proteins belonging to the transforming growth factor beta superfamily that have functions predominantly in development. Types Several members of this subfamily have been described, and name ...

s * The activin and

inhibin Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual ...

subfamilies * The left-right determination factors * 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 A serine/threonine protein kinase () is a kinase enzyme, in particular a protein kinase, that phosphorylates the OH group of the amino-acid residues serine or threonine, which have similar side chains. At least 350 of the 500+ human protei ...

receptors, and generate intracellular

signals In signal processing, a signal is a function that conveys information about a phenomenon. Any quantity that can vary over space or time can be used as a signal to share messages between observers. The ''IEEE Transactions on Signal Processing'' ...

using a conserved family of proteins called SMADs. They play fundamental roles in the regulation of basic biological processes such as growth,

development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped *Photographi ...

, tissue

homeostasis In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...

and regulation of the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

Structure

Proteins from the TGF-beta superfamily 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 superfamily lack the first bond. interchain , +------------------------------------------, + , , , , , , , , , +------+ +--, ----------------------------------------+ , +------------------------------------------+ where 'C' denotes a conserved cysteine involved in a disulfide bond.

Examples

Human genes encoding proteins that contain this domain include:

AMH AMH may refer to: Geography *''Academia Mexicana de la Historia'', the national academy of history, in Mexico *Alaska Marine Highway, ferry services along the southern coast of Alaska and to Washington state *AMH, IATA airport code for Arba Minch ...

; ARTN; BMP2; BMP3;

BMP4 Bone morphogenetic protein 4 is a protein that in humans is encoded by ''BMP4'' gene. BMP4 is found on chromosome 14q22-q23. BMP4 is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamil ...

; BMP5;

BMP6 Bone morphogenetic protein 6 is a protein that in humans is encoded by the ''BMP6'' gene. The protein encoded by this gene is a member of the TGFβ superfamily. Bone morphogenetic proteins are known for their ability to induce the growth of bone ...

;

BMP7 Bone morphogenetic protein 7 or BMP7 (also known as osteogenic protein-1 or OP-1) is a protein that in humans is encoded by the ''BMP7'' gene. Function The protein encoded by this gene is a member of the TGF-β superfamily. Like other members o ...

;

BMP8A Bone morphogenetic protein 8A (BMP8A) is a protein that in humans is encoded by the ''BMP8A'' gene. BMP8A is a polypeptide member of the TGFβ superfamily of proteins. It, like other bone morphogenetic proteins (BMPs), is involved in the develo ...

;

BMP8B Bone morphogenetic protein 8B is a protein that in humans is encoded by the ''BMP8B'' gene. The protein encoded by this gene is a member of the TGF-β superfamily. It has close sequence homology to BMP7 and BMP5 and is believed to play a role ...

;

BMP10 Bone morphogenetic protein 10 (BMP10) is a protein that in humans is encoded by the ''BMP10'' gene. BMP10 is a polypeptide belonging to the TGF-β superfamily of proteins. It is a novel protein that, unlike most other BMP's, is likely to be inv ...

;

BMP15 Bone morphogenetic protein 15 (BMP-15) is a protein that in humans is encoded by the BMP15 gene. It is involved in folliculogenesis, the process in which primordial follicles develop into pre-ovulatory follicles. Structure & Interactions Stru ...

;

GDF1 Growth differentiation factor 1 (GDF1) 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 ...

; GDF2;

GDF3 Growth differentiation factor-3 (GDF3), also known as Vg-related gene 2 (Vgr-2) is protein that in humans is encoded by the ''GDF3'' gene. GDF3 belongs to the transforming growth factor beta (TGF-β) superfamily. It has high similarity to other T ...

;

GDF5 Growth/differentiation factor 5 is a protein that in humans is encoded by the ''GDF5'' gene. The protein encoded by this gene is closely related to the bone morphogenetic protein (BMP) family and is a member of the TGF-beta superfamily. This grou ...

;

GDF6 Growth differentiation factor 6 (GDF6) is a protein that in humans is encoded by the ''GDF6'' gene. Function GDF6 belongs to the transforming growth factor beta superfamily and may regulate patterning of the ectoderm by interacting with bone m ...

; GDF7;

GDF9 Growth/differentiation factor 9 is a protein that in humans is encoded by the ''GDF9'' gene. Growth factors synthesized by ovarian somatic cells directly affect oocyte growth and function. Growth differentiation factor-9 (GDF9) is expressed in o ...

; GDF10;

GDF11 Growth differentiation factor 11 (GDF11) also known as bone morphogenetic protein 11 (BMP-11) is a protein that in humans is encoded by the growth differentiation factor 11 gene. GDF11 is a member of the Transforming growth factor beta family. GD ...

;

GDF15 Growth/differentiation factor 15 (GDF15) was first identified as Macrophage inhibitory cytokine-1 or MIC-1. It is a protein belonging to the transforming growth factor beta superfamily. Under normal conditions, GDF-15 is expressed in low concent ...

;

GDNF Glial cell line-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the ''GDNF'' gene. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particula ...

; INHA;

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 The inhibin beta A ...

;

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. Function Inhibin Inhibin ...

;

INHBC Inhibin beta C chain is a protein that in humans is encoded by the ''INHBC'' gene. This gene encodes the beta C chain of inhibin, a member of the TGF-beta superfamily. This subunit forms heterodimers with beta A and beta B subunits. Inhibins a ...

; INHBE; LEFTY1;

LEFTY2 Left-right determination factor 2 is a protein that in humans is encoded by the LEFTY2 gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generati ...

;

MSTN Myostatin (also known as growth differentiation factor 8, abbreviated GDF8) is a protein that in humans is encoded by the ''MSTN'' gene. Myostatin is a myokine that is produced and released by myocytes and acts on muscle cells to inhibit muscle ...

;

NODAL Nodal homolog is a secretory protein that in humans is encoded by the ''NODAL'' gene which is located on chromosome 10q22.1. It belongs to the transforming growth factor beta superfamily (TGF-β superfamily). Like many other members of this superf ...

; NRTN; PSPN; TGFB1;

TGFB2 Transforming growth factor-beta 2 (TGF-β2) is a secreted protein known as a cytokine that performs many cellular functions and has a vital role during embryonic development (alternative names: Glioblastoma-derived T-cell suppressor factor, G-TSF ...

;

TGFB3 Transforming growth factor beta-3 is a protein that in humans is encoded by the gene. It is a type of protein, known as a cytokine, which is involved in cell differentiation, embryogenesis and development. It belongs to a large family of cytokine ...

;

References

{{Signal transduction Developmental genes and proteins TGFβ domain Protein domains Membrane proteins Protein superfamilies