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111  structures 848  species 4  interactions 3712  sequences 19  architectures

Family: TGF_beta (PF00019)

Summary: Transforming growth factor beta like domain

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This is the Wikipedia entry entitled "Transforming growth factor beta superfamily". More...

Transforming growth factor beta superfamily Edit Wikipedia article

Transforming growth factor beta like domain
PDB 1tfg EBI.jpg
Structure of human transforming growth factor-beta 2.[1]
Identifiers
Symbol TGF_beta
Pfam PF00019
InterPro IPR001839
PROSITE PDOC00223
SCOP 1tfg
SUPERFAMILY 1tfg

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.[2]

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]

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 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,[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 family 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; 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

  1. ^ 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. 
  2. ^ 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. 
  3. ^ a b 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ Roberts AB, Sporn MB (1990). Peptide growth factors and their receptors. Berlin: Springer-Verlag. ISBN 3-540-51184-9. 
  7. ^ 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. 

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Literature references

  1. Daopin S, Piez KA, Ogawa Y, Davies DR; , Science 1992;257:369-373.: Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily. PUBMED:1631557 EPMC:1631557

  2. 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

  3. 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.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Cystine-knot (CL0079), which has the following description:

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

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(20)
Full
(3712)
Representative proteomes NCBI
(3220)
Meta
(0)
RP15
(194)
RP35
(298)
RP55
(677)
RP75
(1288)
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Format an alignment

  Seed
(20)
Full
(3712)
Representative proteomes NCBI
(3220)
Meta
(0)
RP15
(194)
RP35
(298)
RP55
(677)
RP75
(1288)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(20)
Full
(3712)
Representative proteomes NCBI
(3220)
Meta
(0)
RP15
(194)
RP35
(298)
RP55
(677)
RP75
(1288)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: TGF-beta;
Type: Domain
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.3 20.3
Trusted cut-off 20.6 20.4
Noise cut-off 19.7 20.1
Model length: 105
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 4 interactions for this family. More...

TGF_beta Kazal_1 Activin_recp PRKCSH

Structures

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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