Summary: Tubby C 2
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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Tubby C 2 Provide feedback
The structure of this family has been solved. It comprises a 12-stranded beta barrel with a central C-terminal alpha helix. This helix is thought to be a transmembrane helix. It is structurally similar to the C-terminal domain of the Tubby protein . In plants it plays a role in defense against pathogens .
Bateman A, Finn RD, Sims PJ, Wiedmer T, Biegert A, Soding J;, Bioinformatics. 2009;25:159-162.: Phospholipid scramblases and Tubby-like proteins belong to a new superfamily of membrane tethered transcription factors. PUBMED:19010806 EPMC:19010806
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR007612
The structure of this domain has been solved. It comprises a 12-stranded beta barrel with a central C-terminal alpha helix. This helix is thought to be a transmembrane helix. It is structurally similar to the C-terminal domain of the Tubby protein [PUBMED:19010806]. In plants it plays a role in defense against pathogens [PUBMED:18346188].
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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
|Seed source:||Pfam-B_4998 (release 7.5)|
|Author:||Waterfield DI, Finn RD, Eberhardt R|
|Number in seed:||16|
|Number in full:||987|
|Average length of the domain:||155.80 aa|
|Average identity of full alignment:||24 %|
|Average coverage of the sequence by the domain:||85.77 %|
|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:||7|
|Download:||download the raw HMM for this family|
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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_2 domain has been found. There are 2 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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