Summary: Transforming growth factor beta like domain
This is the Wikipedia entry entitled "Transforming growth factor beta superfamily". More...
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Transforming growth factor beta superfamily Edit Wikipedia article
|Transforming growth factor beta like domain|
Structure of human transforming growth factor-beta 2.
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.
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:
- 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) 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.
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.
Human genes encoding proteins that contain this domain include:
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;
- Schlunegger MP, Grütter MG (July 1992). "An unusual feature revealed by the crystal structure at 2.2 A resolution of human transforming growth factor-beta 2". Nature 358 (6385): 430–4. doi:10.1038/358430a0. PMID 1641027.
- Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB (June 1983). "Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization". J. Biol. Chem. 258 (11): 7155–60. PMID 6602130.
- Herpin A, Lelong C, Favrel P (May 2004). "Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans". Dev. Comp. Immunol. 28 (5): 461–85. doi:10.1016/j.dci.2003.09.007. PMID 15062644.
- Burt DW (April 1992). "Evolutionary grouping of the transforming growth factor-beta superfamily". Biochem. Biophys. Res. Commun. 184 (2): 590–5. doi:10.1016/0006-291X(92)90630-4. PMID 1575734.
- Burt DW, Law AS (1994). "Evolution of the transforming growth factor-beta superfamily". Prog. Growth Factor Res. 5 (1): 99–118. doi:10.1016/0955-2235(94)90020-5. PMID 8199356.
- Roberts AB, Sporn MB (1990). Peptide growth factors and their receptors. Berlin: Springer-Verlag. ISBN 3-540-51184-9.
- Daopin S, Piez KA, Ogawa Y, Davies DR (July 1992). "Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily". Science 257 (5068): 369–73. doi:10.1126/science.1631557. PMID 1631557.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Transforming growth factor beta like domain Provide feedback
No Pfam abstract.
Griffith DL, Keck PC, Sampath TK, Rueger DC, Carlson WD; , Proc Natl Acad Sci U S A 1996;93:878-883.: Three-dimensional structure of recombinant human osteogenic protein 1: structural paradigm for the transforming growth factor beta superfamily. PUBMED:8570652 EPMC:8570652
Eigenbrot C, Gerber N; , Nat Struct Biol 1997;4:435-438.: X-ray structure of glial cell-derived neurotrophic factor at 1.9 A resolution and implications for receptor binding. PUBMED:9187648 EPMC:9187648
External database links
This tab holds annotation information from the InterPro database.
InterPro entry 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 [PUBMED:8679613].
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. 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.
The regulatory cytokine TGFbeta exerts tumour-suppressive effects, but also modulates cell invasion and immune regulation [PUBMED:18662538]. Misregulation of the TGF-beta signalling pathway can result in tumour development.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||growth factor activity (GO:0008083)|
- the number of sequences which exhibit this architecture
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This example describes an architecture with one
Gladomain, followed by two consecutive
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The cytokine families in this clan have the cystine-knot fold. In this 6 cysteines form three disulphide bridges that are interlinked.
The clan contains the following 9 members:Coagulin Cys_knot DAN Hormone_6 NGF Noggin PDGF Sclerostin TGF_beta
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
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Curation and family details
|Author:||Sonnhammer ELL, Griffiths-Jones SR|
|Number in seed:||20|
|Number in full:||3712|
|Average length of the domain:||95.50 aa|
|Average identity of full alignment:||38 %|
|Average coverage of the sequence by the domain:||29.32 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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There are 4 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the TGF_beta domain has been found. There are 111 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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