Summary: Tub family
This is the Wikipedia entry entitled "Tubby protein". More...
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Tubby protein Edit Wikipedia article
A tubby protein expressed in mouse brain
The tubby protein is encoded by the TUB gene. It is an upstream cell signaling protein common to multicellular eukaryotes. The first tubby gene was identified in mice, and proteins that are homologous to tubby are known as "tubby-like proteins" (TULPs). They share a common and characteristic tertiary structure that consists of a beta barrel packed around an alpha helix in the central pore. The gene derives its name from its role in metabolism; mice with a mutated tubby gene develop delayed-onset obesity, sensorineural hearing loss and retinal degeneration.
Tubby proteins are classified as α+β proteins and have a 12-beta stranded barrel surrounding a central alpha helix. Tubby proteins can bind the small cell signaling molecule phosphatidylinositol, which is typically localized to the cell membrane. A similar structural fold to the Tubby like proteins has been identified in the Scramblase family of proteins.
Tubby proteins have been implicated as transcription factors and as potential signaling factors coupled to G-protein activity. They are associated with neuronal differentiation and development, and in mammals are implicated in three disease processes when mutated: obesity, retinal degeneration, and hearing loss. In mice, mutations in tubby proteins are known to affect life span and fat storage as well as carbohydrate metabolism. Tubby domains associate with cytoplasmic side of cell membranes through binding of different phosphoinositides
Human proteins containing this domain
- Noben-Trauth, K.; Naggert, J. K.; North, M. A.; Nishina, P. M. (1996). "A candidate gene for the mouse mutation tubby". Nature 380 (6574): 534–538. Bibcode:1996Natur.380..534N. doi:10.1038/380534a0. PMID 8606774.
- Kleyn, P. W.; Fan, W.; Kovats, S. G.; Lee, J. J.; Pulido, J. C.; Wu, Y.; Berkemeier, L. R.; Misumi, D. J.; Holmgren, L.; Charlat, O.; Woolf, E. A.; Tayber, O.; Brody, T.; Shu, P.; Hawkins, F.; Kennedy, B.; Baldini, L.; Ebeling, C.; Alperin, G. D.; Deeds, J.; Lakey, N. D.; Culpepper, J.; Chen, H.; Glücksmann-Kuis, M. A.; Carlson, G. A.; Duyk, G. M.; Moore, K. J. (1996). "Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family". Cell 85 (2): 281–290. doi:10.1016/S0092-8674(00)81104-6. PMID 8612280.
- Ohlemiller, KK; Hughes, RM; Mosinger-Ogilvie, J; Speck, JD; Grosof, DH; Silverman, MS (1995). "Cochlear and retinal degeneration in the tubby mouse". Neuroreport 6 (6): 845–9. doi:10.1097/00001756-199504190-00005. PMID 7612867.
- Bateman A, Finn RD, Sims PJ, Wiedmer T, Biegert A, Söding J (January 2009). "Phospholipid scramblases and Tubby-like proteins belong to a new superfamily of membrane tethered transcription factors". Bioinformatics 25 (2): 159–62. doi:10.1093/bioinformatics/btn595. PMC 2639001. PMID 19010806.
- Boggon TJ, Shan WS, Santagata S, Myers SC, Shapiro L. (1999). Implication of tubby proteins as transcription factors by structure-based functional analysis. Science 286(5447):2119-25.
- Carroll K, Gomez C, Shapiro L. (2004). Tubby proteins: the plot thickens. Nat Rev Mol Cell Biol5(1):55-63.
- Mukhopadhyay A, Deplancke B, Walhout AJ, Tissenbaum HA. (2005). C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab 2(1):35-42.
- Wang Y, Seburn K, Bechtel L, Lee BY, Szatkiewicz JP, Nishina PM, Naggert JK. (2006). Defective carbohydrate metabolism in mice homozygous for the tubby mutation. Physiol Genomics Epub.
- Cho, W. and Stahelin, R.V. (June 2005). "Membrane-protein interactions in cell signaling and membrane trafficking" (abstract page). Annual Review of Biophysics and Biomolecular Structure 34: 119–151. doi:10.1146/annurev.biophys.33.110502.133337. PMID 15869386. Retrieved 2007-01-23.
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Tub family Provide feedback
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Internal database links
|Similarity to PfamA using HHSearch:||DUF3527|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000007
Tubby, an autosomal recessive mutation, mapping to mouse chromosome 7, was recently found to be the result of a splicing defect in a novel gene with unknown function. This mutation maps to the tub gene [PUBMED:8612280, PUBMED:8606774]. The mouse tubby mutation is the cause of maturity-onset obesity, insulin resistance and sensory deficits. By contrast with the rapid juvenile-onset weight gain seen in diabetes (db) and obese (ob) mice, obesity in tubby mice develops gradually, and strongly resembles the late-onset obesity observed in the human population. Excessive deposition of adipose tissue culminates in a two-fold increase of body weight. Tubby mice also suffer retinal degeneration and neurosensory hearing loss. The tripartite character of the tubby phenotype is highly similar to human obesity syndromes, such as Alstrom and Bardet-Biedl. Although these phenotypes indicate a vital role for tubby proteins, no biochemical function has yet been ascribed to any family member [PUBMED:10591637], although it has been suggested that the phenotypic features of tubby mice may be the result of cellular apoptosis triggered by expression of the mutated tub gene. TUB is the founding-member of the tubby-like proteins, the TULPs. TULPs are found in multicellular organisms from both the plant and animal kingdoms. Ablation of members of this protein family cause disease phenotypes that are indicative of their importance in nervous-system function and development [PUBMED:14708010].
Mammalian TUB is a hydrophilic protein of ~500 residues. The N-terminal (INTERPRO) portion of the protein is conserved neither in length nor sequence, but, in TUB, contains the nuclear localisation signal and may have transcriptional-activation activity. The C-terminal 250 residues are highly conserved. The C-terminal extremity contains a cysteine residue that might play an important role in the normal functioning of these proteins. The crystal structure of the C-terminal core domain from mouse tubby has been determined to 1.9A resolution. This domain is arranged as a 12-stranded, all anti-parallel, closed beta-barrel that surrounds a central alpha helix, (which is at the extreme carboxyl terminus of the protein) that forms most of the hydrophobic core. Structural analyses suggest that TULPs constitute a unique family of bipartite transcription factors [PUBMED:10591637].
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This superfamily contains the scramblase protein family, the Tub family and the DUF567, a family of plant and bacterial proteins of hitherto unknown function. All members are membrane-tethered transcription factors.
The clan contains the following 3 members:Scramblase Tub Tub_2
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Curation and family details
|Author:||Finn RD, Bateman A|
|Number in seed:||11|
|Number in full:||847|
|Average length of the domain:||217.80 aa|
|Average identity of full alignment:||36 %|
|Average coverage of the sequence by the domain:||43.04 %|
|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:||13|
|Download:||download the raw HMM for this family|
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There is 1 interaction 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 Tub domain has been found. There are 7 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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