Transforming growth factor beta superfamily

The transforming growth factor beta (TGF-β) superfamily is a large group of structurally related cell regulatory proteins that was named after its first member, TGF-β1, originally described in 1983.^[2] They interact with TGF-beta receptors.

Transforming growth factor beta like domain
Structure of human transforming growth factor-beta 2.[1]
Identifiers
Symbol	TGF_beta
Pfam	PF00019
Pfam clan	CL0079
InterPro	IPR001839
PROSITE	PDOC00223
SCOP2	1tfg / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Many proteins have since been described as members of the TGF-β superfamily in a variety of species, including invertebrates as well as vertebrates and categorized into 23 distinct gene types that fall into four major subfamilies:^[3][4][5]

• The TGF-β subfamily
• The bone morphogenetic proteins and the growth differentiation factors
• The activin and inhibin subfamilies
• The left-right determination factors
• A group encompassing various divergent members

Transforming growth factor-beta (TGF-beta)^[6] 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 receptors, and generate intracellular signals using a conserved family of proteins called SMADs. They play fundamental roles in the regulation of basic biological processes such as growth, development, tissue homeostasis and regulation of the immune system.^[3]

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,^[7] 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
                                                     |
          +------------------------------------------|+
          |                                          ||
xxxxcxxxxxCcxxxxxxxxxxxxxxxxxxCxxCxxxxxxxxxxxxxxxxxxxCCxxxxxxxxxxxxxxxxxxxCxCx
    |      |                  |  |                                        | |
    +------+                  +--|----------------------------------------+ |
                                 +------------------------------------------+

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

Examples

Human genes encoding proteins that contain this domain include:

AMH; ARTN; BMP2; BMP3; BMP4; BMP5; BMP6; BMP7; BMP8A; BMP8B; BMP10; BMP15; GDF1; GDF2; GDF3; GDF5; GDF6; GDF7; GDF9; GDF10; GDF11; GDF15; GDNF; INHA; INHBA; INHBB; INHBC; INHBE; LEFTY1; LEFTY2; MSTN; NODAL; NRTN; PSPN; TGFB1; TGFB2; TGFB3;