Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
9  structures 62  species 1  interaction 2359  sequences 321  architectures

Family: TB (PF00683)

Summary: TB domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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.

TB domain Provide feedback

This domain is also known as the 8 cysteine domain. This family includes the hybrid domains [1]. This cysteine rich repeat is found in TGF binding protein and fibrillin.

Literature references

  1. Pereira L, D'Alessio M, Ramirez F, Lynch JR, Sykes B, Pangilinan T, Bonadio J; , Hum Mol Genet 1993;2:961-968.: Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. PUBMED:8364578 EPMC:8364578

  2. Yuan X, Downing AK, Knott V, Handford PA , EMBO J 1997;16:6659-6666.: Solution structure of the transforming growth factor beta-binding protein-like module, a domain associated with matrix fibrils. PUBMED:9362480 EPMC:9362480


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR017878

The transforming growth factor beta family of cytokines, are potent and multifunctional signalling molecules. Prior to ligand receptor binding there exist extracellular regulators that target these cytokines and facilitate the formation of morphogen gradients that control developmental processes. Some of these proteins that are known to sequester latent TGF-beta contains a conserved domain, the TGF-beta binding (TB) domain.

The domain is characterised by 8 conserved cysteine residues, which include an unusual cysteine triplet [PUBMED:9362480, PUBMED:14607119]. The TB fold is globular with six beta-strands and two alpha-helices [PUBMED:9362480, PUBMED:14607119, PUBMED:15062093]. The pairing of the eight cysteines is 1-3, 2-6, 4-7, and 5-8, creating a fairly rigid structure. In follistatin and in the first repeat of fibrillin and LTBPs the last disulphide bridge is absent.

Proteins containing a TB domain include:

  • Vertebrate fibrillin-1, 2 and 3. Fibrillins form tissue-specific and temporally regulated microfibril networks. They are implicated in the regulation of TGF-beta signalling.
  • Vertebrate latent TGF-beta binding proteins (LTBPs) 1, 2, 3 and 4 LTBPs regulate TGF-beta signalling by forming a latent complex with the cleaved TGF-beta proproteins.
  • Vertebrate follistatin. It is an extracellular antagonist of various TGF-beta proteins. The TB domain of follistatin mimic a type I receptor of TGF-beta and binds TGF-beta which leads to the formation of a receptor-ligand-antagonist complex [PUBMED:16198295].

Domain organisation

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

Loading domain graphics...

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...

View options

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
(34)
Full
(2359)
Representative proteomes NCBI
(1987)
Meta
(2)
RP15
(138)
RP35
(208)
RP55
(540)
RP75
(1128)
Jalview View  View  View  View  View  View  View  View 
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(34)
Full
(2359)
Representative proteomes NCBI
(1987)
Meta
(2)
RP15
(138)
RP35
(208)
RP55
(540)
RP75
(1128)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

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
(34)
Full
(2359)
Representative proteomes NCBI
(1987)
Meta
(2)
RP15
(138)
RP35
(208)
RP55
(540)
RP75
(1128)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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: Pfam-B_82 (release 2.1)
Previous IDs: TGF-bp;
Type: Family
Author: Bateman A
Number in seed: 34
Number in full: 2359
Average length of the domain: 42.80 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 12.21 %

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 20.9 20.9
Trusted cut-off 21.0 21.0
Noise cut-off 18.7 20.8
Model length: 42
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There is 1 interaction for this family. More...

EGF_CA

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 TB domain has been found. There are 9 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.

Loading structure mapping...