Alternative titles; symbols
HGNC Approved Gene Symbol: TBC1D1
Cytogenetic location: 4p14 Genomic coordinates (GRCh38) : 4:37,891,084-38,139,173 (from NCBI)
TBC1D1 is the founding member of a family of proteins sharing a 180- to 200-amino acid TBC domain presumed to have a role in regulating cell growth and differentiation. These proteins share significant homology with TRE2 (USP6; 604334), yeast Bub2, and CDC16 (603461) (White et al., 2000).
By sequencing clones obtained from a size-fractionated adult brain cDNA library, Kikuno et al. (1999) cloned TBC1D1, which they designated KIAA1108. The deduced 763-amino acid protein contains a TBC1 domain. RT-PCR ELISA detected highest TBC1D1 expression in kidney, testis, ovary, and corpus callosum. Expression was intermediate in all other adult and fetal tissues and specific adult brain regions examined.
Using Southern blot analysis of a somatic cell hybrid mapping panel, White et al. (2000) mapped the TBC1D1 gene to chromosome 4p15.1-q21. They mapped the mouse Tbc1d1 gene to a region of chromosome 5 that shows homology of synteny to human chromosome 4p15.1-q21.
For discussion of a possible association between variation in the TBC1D1 gene and susceptibility to obesity, see BMIQ7 (608410).
In the lean Swiss Jim Lambert (SJL) strain of obesity-resistant mice, Chadt et al. (2008) identified a 7-bp deletion in exon 18 of the Tbc1d1 gene that causes a frameshift and results in a truncated protein lacking the TBC Rab-GTPase-activating protein domain. Knockdown of Tbc1d1 in mouse skeletal muscle cells increased fatty acid uptake and oxidation, whereas overexpression of Tbc1d1 had the opposite effect. Recombinant congenic mice lacking Tbc1d1 showed reduced body weight, decreased respiratory quotient, increased fatty acid oxidation, and reduced glucose uptake in isolated skeletal muscle. Chadt et al. (2008) suggested that mutation of Tbc1d1 suppresses high-fat diet-induced obesity by increasing lipid use in skeletal muscle.
Chadt, A., Leicht, K., Deshmukh, A., Jiang, L. Q., Scherneck, S., Bernhardt, U., Dreja, T., Vogel, H., Schmolz, K., Kluge, R., Zierath, J. R., Hultschig, C., Hoeben, R. C., Schurmann, A., Joost, H.-G., Al-Hasani, H. Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity. Nature Genet. 40: 1354-1359, 2008. [PubMed: 18931681] [Full Text: https://doi.org/10.1038/ng.244]
Kikuno, R., Nagase, T., Ishikawa, K., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 6: 197-205, 1999. [PubMed: 10470851] [Full Text: https://doi.org/10.1093/dnares/6.3.197]
White, R. A., Pasztor, L. M., Richardson, P. M., Zon, L. I. The gene encoding TBC1D1 with homology to the tre-2/USP6 oncogene, BUB2, and cdc16 maps to mouse chromosome 5 and human chromosome 4. Cytogenet. Cell Genet. 89: 272-275, 2000. [PubMed: 10965142] [Full Text: https://doi.org/10.1159/000015632]