TBC1 domain family member 17 (TBC1D17)
The protein contains 648 amino acids for an estimated molecular weight of 72728 Da.
Probable GTPase-activating protein for Rab8; its transient association with Rab8 is mediated by OPTN. Inhibits Rab8-mediated endocytic trafficking, such as of transferrin receptor (TfR) and reduces Rab8 recruitnment to tubules emanating from the endocytic recycling compartment (ERC). Involved in regulation of autophagy. Mediates inhibition of autophagy caused by the OPTN variant GLC1E LYS-50; the function requires its catalytic activity, however, the involved Rab is not known. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs8109661 | |
| dbSNP:rs3745486 |
The reference OMIM entry for this protein is 616659
Tbc1 domain family, member 17; tbc1d17
DESCRIPTION
Small RAB GTPases (see 179508), which are active in their GTP-bound form and inactive in their GDP-bound form, are involved in vesicular trafficking in endocytosis and exocytosis. TBC1D17 functions as a RAB GTPase-activating protein (GAP) that inactivates RAB8 (165040) by catalyzing its GTPase activity (Vaibhava et al., 2012).CLONING
Vaibhava et al. (2012) reported that full-length 648-amino acid human TBC1D17 has an N-terminal NCL1 (CAPN3; 114240)/HT2A (TRIM32; 602290)/LIN41 (TRIM71) (NHL) repeat domain, followed by a catalytic TRE2 (USP6; 604334)/yeast Bub2/CDC16 (603461) (TBC) domain and a proline-rich C-terminal region. TBC1D17 showed a diffuse cytoplasmic localization with concentration in the juxtanuclear region.GENE FUNCTION
Using yeast 2-hybrid and protein pull-down assays, Vaibhava et al. (2012) showed that TBC1D17 interacted with the adaptor protein optineurin (OPTN; 602432). Coexpression of optineurin with TBC1D17 enhanced colocalization of TBC1D17 with transferrin receptor (TFRC; 190010)-positive endocytic vesicles. Optineurin and TB1D17 also interacted with RAB8. Catalytically active TBC1D17, but not an inactive mutant, catalyzed GTP-GDP exchange on RAB8, which inhibited association of RAB8 with endocytic tubules and inhibited transferrin (TF; 190000) uptake in HeLa cells. Overexpression, knockdown, and mutation analyses revealed that optineurin was required to mediate interaction between TBC1D17 and RAB8-GTP.MAPPING
Chalasani et al. (2009) stated that the TBC1D17 gene maps to chromosome 19q13.33. ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616659 was added.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated