Transforming growth factor beta superfamily

Pfam_box
Symbol = TGF_beta
Name = Transforming growth factor beta like domain


width =
caption =
Pfam= PF00019
InterPro= IPR001839
SMART=
PROSITE= PDOC00223
SCOP = 1tfg
TCDB =
OPM family=
OPM protein=
PDB=PDB3|1ktzA:312-412 PDB3|1tgjA:312-412 PDB3|1tgk :312-412PDB3|1tfg :314-414 PDB3|2tgi :314-414 PDB3|1kldA:290-390PDB3|1klcB:290-390 PDB3|1klaA:290-390 PDB3|1nyuB:318-426PDB3|1nysD:318-426 PDB3|2b0uB:318-426 PDB3|1s4yD:318-426PDB3|1m4uL:327-431 PDB3|1bmp :328-431 PDB3|1lxiA:327-431PDB3|1lx5A:327-431 PDB3|1es7A:293-396 PDB3|1rewB:293-396PDB3|1reuA:294-396 PDB3|3bmpA:293-396 PDB3|2bhkA:397-501PDB3|1waqA:397-501 PDB3|1zkzA:324-429 PDB3|1ehuA:290-393PDB3|1ehrA:290-393 PDB3|1agqB:115-211

The transforming growth factor beta (TGF-β) superfamily is a large family of structurally related cell regulatory proteins that was named after its first member, TGF-β1, originally described in 1983 [cite journal |author=Assoian R, Komoriya A, Meyers C, Miller D, Sporn M |title=Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization |journal=J Biol Chem |volume=258 |issue=11 |pages=7155–60 |year=1983 |pmid=6602130] .

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:cite journal |author=Herpin A, Lelong C, Favrel P |title=Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans |journal=Dev Comp Immunol |volume=28 |issue=5 |pages=461–85 |year=2004 |pmid=15062644 |doi=10.1016/j.dci.2003.09.007] cite journal |author=Burt DW |title=Evolutionary grouping of the transforming growth factor-beta superfamily |journal=Biochem. Biophys. Res. Commun. |volume=184 |issue=2 |pages=590–595 |year=1992 |pmid=1575734 |doi=10.1016/0006-291X(92)90630-4] cite journal |author=Burt DW, Law AS |title=Evolution of the transforming growth factor-beta superfamily |journal=Prog. Growth Factor Res. |volume=5 |issue=1 |pages=99–118 |year=1994 |pmid=8199356 |doi=10.1016/0955-2235(94)90020-5] .

* the decapentaplegic-Vg-related (DVR) related subfamily (including the bone morphogenetic proteins and the growth differentiation factors)

* the activin/inhibin subfamily

* the TGF-β subfamily

* a group encompassing various divergent members

Transforming growth factor-beta (TGF-beta)cite book |author=Roberts AB, Sporn MB |title=Peptide growth factors and their receptors |pages=419-475 |year=1990 |isbn=35-405-118-49] 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 molecules 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.

tructure

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-2cite journal |author=Davies DR, Daopin S, Piez KA, Ogawa Y |title=Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily |journal=Science |volume=257 |issue=5068 |pages=369–373 |year=1992 |pmid=1631557 |doi=10.1126/science.1631557] , 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
| | | |
+------+ +--|----------------------------------------+
+------------------------------------------+

'C': conserved cysteine involved in a disulfide bond.

Human proteins containing this domain

AMH; ARTN; BMP10; BMP15; BMP2; BMP3; BMP4; BMP5; BMP6; BMP7; BMP8A; BMP8B; GDF1; GDF10; GDF11; GDF15;
GDF2; GDF3; GDF3A; GDF5; GDF6; GDF7; GDF8; GDF9; GDNF; INHA; INHBA; INHBB; INHBC; INHBE; LEFTY1; LEFTY2;
MSTN; NODAL; NRTN; PSPN; TGFB1; TGFB2; TGFB3;

References