The first member of this family was discovered in mice where a mutation in the tubby gene resulted in a phenotype of delayed-onset obesity, sensorineural hearing loss and retinal degeneration (Kleyn et al.,  1996). Other related genes have usually been named Tubbylike proteins (TLPs or TULPs). TULPs share a common alpha helix +beta sheet protein structure whereby a 12-beta-stranded barrel surrounds a central alpha helix. TLPs are identified through a specific signature of carboxyl terminal tubby domain, required for plasma membrane tethering and an amino terminal F-box domain that communicate as functional SCF-type E3 ligases (Bano et al., 2022).

TLPs are latent cytoplasmic factors whereby the inactive form resides in the cytoplasm, but, when activated, is translocated into the nucleus. Plants appear to possess more tubby-like genes than animals, but their functions are largely unclear except that a few studies have shown that they are involved in stress responses (Wang et al., 2018, Bano et al., 2022). In Arabidopsis, there is evidence that the AtTLP2 protein is translocated into the nucleus by interacting with Nuclear Factor Y subunit C3 (NF-YC3) to function as a transcription factor. RNA-sequence and transactivation assays revealed that TLP2 could activate the UDP-glucose 4-epimerase 1 gene (UGE1) (Wang et al.,  2019).

A more recent study indicates that the CsTLP8 tubby-like protein from cucumber, acts in the ABA signaling pathway and negatively regulates osmotic stresses tolerance during seed germination (Li et al., 2021). In cotton, the GhTULP34 protein has been shown to interact with GhSKP1A, a subunit of the SCF-type complex, to form a functional SCF-type E3 ligase, and then participates in the response to negative regulation of osmotic stress during seed germination and seedling growth (Li et al., 2021). A genome wide survey of the maize genome revealed a total of 15 TLP genes (ZmTLP1-15). This family was classified into four subfamilies based on phylogenetic relationships, protein domains, and motif organization. Gene duplication and chromosomal location analysis indicated that segmental duplication has played a major role in the expansion of the maize TLP family. The ZmTLP genes exhibited differential expression profiles under ABA, NaCl, 42, 4°C, and PEG stress treatment (Yulong et al.,  2015).

Last updated June 2023 by John Gray

References:

Kleyn, P. W.; Fan, W.; et al., (1996 ). "Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family". Cell. 85 (2): 281-290.

Wang M, Xu Z, Kong Y. The tubby-like proteins kingdom in animals and plants. Gene. 2018 Feb 5; 642:16-25. doi:

10.1016/j.gene.2017.10.077. Epub 2017 Nov 3. PMID: 29109004.

Wang M, Xu Z, Ahmed RI, Wang Y, Hu R, Zhou G, Kong Y. Tubby-like Protein 2 regulates homogalacturonan biosynthesis in Arabidopsis seed coat mucilage. Plant Mol Biol. 2019 Mar;99(4-5):421-436. doi: 10.1007/s11103-019-00827-9. Epub 2019 Feb 1. PMID: 30707395.

Li, S., Wang, Z., Wang, F. et al. A tubby-like protein CsTLP8 acts in the ABA signaling pathway and negatively regulates osmotic stresses tolerance during seed germination. BMC Plant Biol 21, 340 (2021). https://doi.org/10.1186/s12870-021-03126-y

Li, Z., Wang,X. et al. GhTULP34, a member of tubby-like proteins, interacts with GhSKP1A to negatively regulate plant osmotic stress, Genomics, 2021 113, Issue 1, Part 2,462-474,

Yulong, C., Wei, D., Baoming, S., Yang, Z., Qing, M., 2015. Genome-wide identification and comparative analysis of the TUBBY-like protein gene family in maize. Genes Genomics 38 (1), 25-36.

Bano N, Aalam S, Bag SK. Tubby-like proteins (TLPs) transcription factor in different regulatory mechanism in plants: a review. Plant Mol Biol. 2022 Dec;110(6):455-468. doi: 10.1007/s11103-022-01301-9. Epub 2022 Oct 18. PMID: 36255595.