Protein family
The tubby protein is encoded by the TUB genecell 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 .[ 1] [ 2] [ 3]
Structure
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.[ 4]
Function
Tubby proteins have been implicated as transcription factors [ 5] G-protein activity.[ 6] neuronal differentiation and development , and in mammals are implicated in three disease processes when mutated : obesity , retinal degeneration, and hearing loss .[ 5] life span and fat storage[ 7] carbohydrate metabolism .[ 8] cell membranes through binding of different phosphoinositides [ 9]
Human proteins containing this domain
TUB ; TULP1 ; TULP2 ; TULP3 ; TULP4 ;
External links
References
^ 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 . S2CID 4272027 . ^ 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 . S2CID 15670925 . ^ 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 . S2CID 8311280 . ^ 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 . ^ a b 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. doi :10.1126/science.286.5447.2119 . PMID 10591637 . ^ Carroll, K; Gomez, C; Shapiro, L (2004). "Tubby proteins: the plot thickens". Nat Rev Mol Cell Biol . 5 (1): 55– 63. doi :10.1038/nrm1278 . PMID 14708010 . S2CID 7065010 . ^ 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. doi :10.1016/j.cmet.2005.06.004 PMID 16054097 . ^ 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 . 27 (2): 131– 40. doi :10.1152/physiolgenomics.00239.2005 . PMID 16849632 . ^ Cho, W. & Stahelin, R.V. (June 2005). "Membrane-protein interactions in cell signaling and membrane trafficking". Annual Review of Biophysics and Biomolecular Structure . 34 : 119– 151. doi :10.1146/annurev.biophys.33.110502.133337 . PMID 15869386 .
