From Wikipedia, the free encyclopedia
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 .
[1]
[2]
[3]
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]
Tubby proteins have been implicated as
transcription factors
[5] and as potential signaling factors coupled to
G-protein activity.
[6] 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 .
[5] In mice, mutations in tubby proteins are known to affect
life span and
fat storage
[7] as well as
carbohydrate
metabolism .
[8] Tubby domains associate with cytoplasmic side of
cell membranes through binding of different
phosphoinositides
[9]
Human proteins containing this domain
TUB ;
TULP1 ;
TULP2 ;
TULP3 ;
TULP4 ;
^ 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 .