Tubulin-specific chaperone D (TBCD)
The protein contains 1192 amino acids for an estimated molecular weight of 132600 Da.
Tubulin-folding protein implicated in the first step of the tubulin folding pathway and required for tubulin complex assembly. Involved in the regulation of microtubule polymerization or depolymerization, it modulates microtubule dynamics by capturing GTP-bound beta-tubulin (TUBB). Its ability to interact with beta tubulin is regulated via its interaction with ARL2. Acts as a GTPase-activating protein (GAP) for ARL2. Induces microtubule disruption in absence of ARL2. Increases degradation of beta tubulin, when overexpressed in polarized cells. Promotes epithelial cell detachment, a process antagonized by ARL2. Induces tight adherens and tight junctions disassembly at the lateral cell membrane (PubMed:10722852, PubMed:10831612, PubMed:11847227, PubMed:20740604, PubMed:27666370, PubMed:28158450). Required for correct assembly and maintenance of the mitotic spindle, and proper progression of mitosis (PubMed:27666370). Involved in neuron morphogenesis (PubMed:27666374). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
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.
This protein is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| PEBAT | |
| PEBAT | |
| PEBAT | |
| PEBAT | |
| PEBAT | |
| PEBAT | |
| dbSNP:rs2292971 | |
| PEBAT | |
| PEBAT | |
| PEBAT | |
| dbSNP:rs3214033 | |
| PEBAT | |
| dbSNP:rs8072406 | |
| PEBAT | |
| PEBAT | |
| PEBAT | |
| dbSNP:rs2292969 |
Biological Process
Adherens junction assembly
Bicellular tight junction assembly
Cell morphogenesis involved in neuron differentiation
Microtubule cytoskeleton organization
Mitotic cell cycle
Negative regulation of cell-substrate adhesion
Negative regulation of microtubule polymerization
Post-chaperonin tubulin folding pathway
Protein folding
Tubulin complex assembly
Cellular Component
Adherens junction
Bicellular tight junction
Centrosome
Cytoplasm
Lateral plasma membrane
Microtubule
The reference OMIM entry for this protein is 604649
Tubulin-specific chaperone d; tbcd
See TBCC (602971) for background information on microtubules and tubulin-specific chaperones.
CLONING
By screening human brain cDNAs for the potential to encode proteins larger than 50 kD, Nagase et al. (1999) isolated a TBCD cDNA, which they called KIAA0988. The deduced 1,192-amino acid full-length TBCD protein shares 80.5% amino acid sequence identity with bovine tubulin-folding cofactor D across 1,188 amino acids. RT-PCR followed by ELISA detected TBCD expression at varying levels in all human tissues examined, namely brain, spinal cord, liver, pancreas, kidney, spleen, heart, lung, skeletal muscle, testis, ovary, fetal brain, and fetal liver. Within the brain, TBCD expression was found in all regions tested, namely amygdala, corpus callosum, cerebellum, caudate nucleus, hippocampus, substantia nigra, subthalamic nucleus, and thalamus.GENE FUNCTION
By immunofluorescence microscopy analysis, Martin et al. (2000) demonstrated that overexpression of TBCD correlated with microtubule depolymerization and a progressive loss of microtubules, leading to a rapid drop in levels of alpha-tubulin (191110) but not beta-tubulin (TUBB; 191130). The results showed that TBCD modulates microtubule dynamics by capturing GTP-bound TUBB. The interactions did not lead to apoptosis. Using HeLa cells, Tian et al. (2010) showed that binding of TBCD to the GTPase-activating protein ARL2 (604649) inhibited the microtubule-depolymerizing effect of overexpressed human TBCD.MAPPING
Nagase et al. (1999) noted that the UniGene database gives chromosome 17 as the map location of the TBCD gene. Hartz (2013) mapped the TBCD gene to chromosome 17q25.3 based on an alignment of the TBCD sequence (GenBank GENBANK AJ006417) with the genomic sequence (GRCh37). In linkage and association studies of Gilles de la Tourette syndrome (GTS; 137580), Paschou et al. (2004) reported linkage disequilibrium results suggesting involvement of the TBCD gene in the disorder. ... More on the omim web site
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 604649 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).