SMART: TGFB domain annotation

TGFB Transforming growth factor-beta (TGF-beta) family

SMART accession number:	SM00204
Description:	Family members are active as disulphide-linked homo- or heterodimers. TGFB is a multifunctional peptide that controls proliferation, differentiation, and other functions in many cell types.
Interpro abstract (IPR001839):	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. A number of proteins are known to be related to TGF-beta-1 (PUBMED:1575734), (PUBMED:8199356). Proteins from the TGF-beta family are only active as homo- or heterodimer; the two chains being linked by a single disulphide bond. From X-ray studies of TGF-beta-2 (PUBMED:1631557), it is known that all the other cysteines are involved in intrachain disulphide bonds. As shown in the following schematic representation, there are four disulphide 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 disulphide bond.
GO function:	growth factor activity (GO:0008083)
Family alignment:	View or

There are 1486 TGFB domains in 1486 proteins in SMART's nrdb database.

Click on the following links for more information.

Evolution (species in which this domain is found)
Click on to expand nodes. To display all proteins with a TGFB domain in a specific node, click on it.

This tree shows only several representative species. The complete taxonomic breakdown of all proteins with TGFB domain is also avaliable.

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Go to specific node: Anopheles gambiae, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Hoodless PA, Wrana JL
- Mechanism and function of signaling by the TGF beta superfamily.
- Curr Top Microbiol Immunol. 1998; 228: 235-72
- Padgett RW, Savage C, Das P
- Genetic and biochemical analysis of TGF beta signal transduction.
- Cytokine Growth Factor Rev. 1997; 8: 1-9
- Display abstract
- TGF beta-like ligands are involved in many different developmental processes that pattern a variety of tissues in invertebrates and vertebrates. In the last few years, rapid progress has been made toward elucidating the developmental roles of the TGF beta-like pathways and identifying the novel components involved in transducing their signals, particularly the newly discovered Smads. This rapid progress has been the result of a synergy between classical genetic approaches and biochemical approaches, and this combined approach is likely to propel future understanding of the signaling pathway used by TGF beta.
- Moses HL, Serra R
- Regulation of differentiation by TGF-beta.
- Curr Opin Genet Dev. 1996; 6: 581-6
- Display abstract
- Recent experiments in neural, skeletal, endothelial, and hematopoietic tissues have provided new insights into the way members of the transforming growth factor-beta (TGF-beta) superfamily regulate cellular differentiation. TGF-betas regulate the fate of multipotential stem cells instructively (in the neural crest) by regulating the expression or function of tissue-specific transcription factors, as well as selectively (in the mesenchyme) by regulating the expression of required growth factors and their receptors. During skeletal development, TGF-betas have unique functions and act sequentially to modulate chondrocyte and osteoblast differentiation. Responsiveness to TGF-betas changes as cells differentiate and evidence now suggests that changes in TGF-beta receptor profile may account for some of these differences. Drosophila and transgenic mouse models are now providing useful insights into mechanisms of TGF-beta action in vivo.
- Derynck R et al.
- Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells.
- Nature. 1985; 316: 701-5
- Display abstract
- The partial amino-acid sequence of purified human transforming growth factor-beta (TGF-beta) was used to identify a series of cDNA clones encoding the protein. The cDNA sequence indicates that the 112-amino acid monomeric form of the natural TGF-beta homodimer is derived proteolytically from a much longer precursor polypeptide which may be secreted. TGF-beta messenger RNA is synthesized in various normal and transformed cells.
Disease (disease genes where sequence variants are found in this domain)

Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

Protein	Disease
Left-right determination factor 2 precursor (SRS)(SMART)	OMIM:601877: Left-right axis malformation
Muellerian-inhibiting factor precursor (SRS)(SMART)	OMIM:600957: Persistent Mullerian duct syndrome, type I OMIM:261550:
Glial cell line-derived neurotrophic factor precursor (SRS)(SMART)	OMIM:600837: Hirschsprung disease OMIM:142623:

3D Structures of TGFB domains in PDB

PDB code	Main view	Title
1agq		Glial cell-derived neurotrophic factor from rat
1bmp		Bone morphogenetic protein-7
1es7		Complex between bmp-2 and two bmp receptor ia ectodomains
1kla		Solution structure of tgf-b1, nmr, models 1-17 of 33 structures
1klc		Solution structure of tgf-b1, nmr, minimized average structure
1kld		Solution structure of tgf-b1, nmr, models 18-33 of 33 structures
1ktz		Crystal structure of the human tgf-beta type ii receptor extracellular domain in complex with tgf-beta3
1lx5		Crystal structure of the bmp7/actrii extracellular domain complex
1lxi		Refinement of bmp7 crystal structure
1m4u		Crystal structure of bone morphogenetic protein-7 (bmp-7) in complex with the secreted antagonist noggin
1nys		Crystal structure of activin a bound to the ecd of actriib p41
1nyu		Crystal structure of activin a bound to the ecd of actriib
1reu		Structure of the bone morphogenetic protein 2 mutant l51p
1rew		Structural refinement of the complex of bone morphogenetic protein 2 and its type ia receptor
1s4y		Crystal structure of the activin/actriib extracellular domain
1tfg		An unusual feature revealed by the crystal structure at 2.2 angstroms resolution of human transforming growth factor- beta2
1tgj		Human transforming growth factor-beta 3, crystallized from dioxane
1tgk		Human transforming growth factor beta 3, crystallized from peg 4000
1waq		Crystal structure of human growth and differentiation factor 5 (gdf-5)
1zkz		Crystal structure of bmp9
2arp		Activin a in complex with fs12 fragment of follistatin
2arv		Structure of human activin a
2ask		Structure of human artemin
2b0u		The structure of the follistatin:activin complex
2bhk		Crystal structure of human growth and differentiation factor 5 (gdf5)
2gh0		Growth factor/receptor complex
2goo		Ternary complex of bmp-2 bound to bmpr-ia-ecd and actrii-ecd
2gyr		Crystal structure of human artemin
2gyz		Crystal structure of human artemin
2h62		Crystal structure of a ternary ligand-receptor complex of bmp-2
2h64		Crystal structure of a ternary ligand-receptor complex of bmp-2
2p6a		The structure of the activin:follistatin 315 complex
2pjy		Structural basis for cooperative assembly of the tgf-beta signaling complex
2qcq		Crystal structure of bone morphogenetic protein-3 (bmp-3)
2qcw		Crystal structure of bone morphogenetic protein-6 (bmp-6)
2qj9		Crystal structure analysis of bmp-2 in complex with bmpr-ia variant b1
2qja		Crystal structure analysis of bmp-2 in complex with bmpr-ia variant b12
2qjb		Crystal structure analysis of bmp-2 in complex with bmpr-ia variant ia/ib
2r52		Crystal structure analysis of bone morphogenetic protein-6 (bmp-6)
2r53		Crystal structure analysis of bone morphogenetic protein-6 variant b2 (b2-bmp-6)
2tgi		Crystal structure of transforming growth factor-beta2: an unusual fold for the superfamily
2v5e
3b4v
3bk3		Crystal structure of the complex of bmp-2 and the first von willebrand domain type c of crossveinless-2
3bmp		Human bone morphogenetic protein-2 (bmp-2)
3eo1
3evs
3fub
3hh2

Links (links to other resources describing this domain)
BLOCKS TGF_BETA
PFAM TGF-beta
INTERPRO IPR001839
PROSITE TGFB_DOMAIN

BLOCKS	TGF_BETA
PFAM	TGF-beta
INTERPRO	IPR001839
PROSITE	TGFB_DOMAIN