Ask about this productRelated genes to: TBC1D19 antibody
- Gene:
- TBC1D19 NIH gene
- Name:
- TBC1 domain family member 19
- Previous symbol:
- -
- Synonyms:
- FLJ11082
- Chromosome:
- 4p15.2
- Locus Type:
- gene with protein product
- Date approved:
- 2005-01-05
- Date modifiied:
- 2015-11-18
Related products to: TBC1D19 antibody
Related articles to: TBC1D19 antibody
- The tubulin poly-glutamylase complex (TPGC) is comprised of TTLL1 and at least five associated proteins that promote the addition of glutamate residues to carboxy-terminal tails of tubulin subunits comprising microtubules. Despite its discovery two decades ago, the enzyme has been refractory to characterization owing to its complex multimeric nature and the inability to detect poly-glutamylase activity after assembling the six-subunit complex. We now show that TPGC is the key enzyme driving centriolar and ciliary poly-glutamylation. We identified two additional TPGC subunits, TBC1D19 and KIAA1841, and showed that both components play an essential role in the assembly of the eight-subunit holo-enzyme. We were able to reconstitute the activity of TPGC with all eight subunits. TBC1D19 and KIAA1841 were essential for TPGC activity, and loss of TBC1D19 strongly compromised multiple tubulin modifications, including axonemal poly-glutamylation. TBC1D19 loss also abolished transport of ARL13B and other ciliary membrane proteins, abrogating primary cilium assembly. Structural predictions suggested an essential role for TBC1D19 and KIAA1841 in complex assembly, microtubule binding, and preferential poly-glutamylation of α-tubulin. We found that TBC1D19 loss abrogated the ciliary localization of phosphatidyl inositol phosphatase, INPP5E, which coincided with cilium instability. Ciliogenesis in TBC1D19 null cells could be restored through inhibition of a specific phosphatidyl inositol phosphate (PIP) kinase, PIP5K1C, suggesting that TBC1D19 is required to maintain PIP homeostasis during ciliogenesis. Collectively, our data show that TPGC is a multi-functional enzyme essential for cilium assembly and maintenance. - Source: PubMed
Publication date: 2026/05/15
Badarudeen BinshadCollado LorenChiang Hung-JuWang LeiSanchez IrmaDynlacht Brian David - The tubulin poly-glutamylase complex (TPGC) is comprised of TTLL1 and at least five associated proteins that promote the addition of glutamate residues to tubulin tails of microtubules. Despite its discovery two decades ago, the enzyme has been refractory to characterization owing to its complex multimeric nature and the inability to detect poly-glutamylase activity after assembling the six-subunit complex. We now show that TPGC is the key enzyme driving centriolar and ciliary poly-glutamylation. We identified two novel TPGC subunits, TBC1D19 and KIAA1841, and showed that both components play an essential role in the assembly of the eight-subunit holo-enzyme. Remarkably, we were able to reconstitute the activity of TPGC with all eight subunits. TBC1D19 and KIAA1841 were essential for assembly and activity, and loss of TBC1D19 strongly compromised multiple tubulin modifications, including axonemal poly-glutamylation. TBC1D19 loss abolished transport of Arl13b and other ciliary membrane proteins, abrogating primary cilium assembly. Structural modeling revealed an essential role for TBC1D19 and KIAA1841 in complex assembly, microtubule binding, and preferential poly-glutamylation of α-tubulin. We found that TBC1D19 loss abrogated the ciliary localization of phosphatidyl inositol phosphatase, INPP5E, triggering cilium instability. Ciliogenesis in TBC1D19 null cells could be restored through inhibition of a specific phosphatidyl inositol phosphate (PIP) kinase, PIP5K1c, suggesting that TBC1D19 is required to instigate and maintain PIP homeostasis during ciliogenesis. Collectively, our data show that TPGC is a multi-functional enzyme essential for cilium assembly and maintenance. - Source: PubMed
Publication date: 2025/03/04
Badarudeen BinshadChiang Hung-JuCollado LorenWang LeiSanchez IrmaDynlacht Brian David - Numerous variants associated with increased risk for SCZ have undergone positive selection and were associated with human brain development, but which brain regions and developmental stages were influenced by the positive selection for SCZ risk alleles are unclear. We analyzed SCZ using summary statistics from a genome-wide association study (GWAS) from the Psychiatric Genomics Consortium (PGC). Machine-learning scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele has reached fixation) and incomplete selection (loci where a selected allele has not yet reached fixation). Based on the p value of single nucleotide polymorphisms (SNPs) with selection scores in the top 5%, we formed five subgroups: p < 0.0001, 0.001, 0.01, 0.05, or 0.1. We found that 48 and 29 genes (p < 0.0001) in complete and incomplete selection, respectively, were enrichedfor the transcriptionalco-expressionprofilein theprenatal dorsolateral prefrontal cortex (DFC), inferior parietal cortex (IPC), and ventrolateral prefrontal cortex (VFC). Core genes (GNA13, TBC1D19, and ZMYM4) involved in regulating early brain development were identified in these three brain regions. RNA sequencing for primary cortical neurons that were transfected Gna13 overexpressed lentivirus demonstrated that 135 gene expression levels changed in the Gna13 overexpressed groups compared with the controls. Gene-set analysis identified important associations among common variants of these 13 genes, which were associated with neurodevelopment and putamen volume [p = 0.031; family-wise error correction (FWEC)], SCZ (p = 0.022; FWEC). The study indicate that certain SCZ risk alleles were likely to undergo positive selection during human evolution due to their involvement in the development of prenatal DFC, IPC and VFC, and suggest that SCZ is related to abnormal neurodevelopment. - Source: PubMed
Publication date: 2019/10/30
Xiang BoYang JuanjuanZhang JinYu MinglanHuang ChaohuaHe WenyingLei WeiChen JingLiu Kezhi - Tricho-dento-osseous (TDO) syndrome is an autosomal dominant disorder characterized by abnormalities in the thickness and density of bones and teeth. A 4-bp deletion mutation in the Distal-Less 3 (DLX3) gene is etiologic for most cases of TDO. To investigate the in vivo role of mutant DLX3 (MT-DLX3) on dentin development, we generated transgenic (TG) mice expressing MT-DLX3 driven by a mouse 2.3 Col1A1 promoter. Dentin defects were radiographically evident in all teeth and the size of the nonmineralized pulp was enlarged in TG mice, consistent with clinical characteristics in patients with TDO. High-resolution radiography, microcomputed tomography, and SEM revealed a reduced zone of mineralized dentin with anomalies in the number and organization of dentinal tubules in MT-DLX3 TG mice. Histological and immunohistochemical studies demonstrated that the decreased dentin was accompanied by altered odontoblast cytology that included disruption of odontoblast polarization and reduced numbers of odontoblasts. TUNEL assays indicated enhanced odontoblast apoptosis. Expression levels of the apoptotic marker caspase-3 were increased in odontoblasts in TG mice as well as in odontoblastic-like MDPC-23 cells transfected with MT-DLX3 cDNA. Expression of Runx2, Wnt 10A, and TBC1D19 colocalized with DLX3 expression in odontoblasts, and MT-DLX3 significantly reduced expression of all three genes. TBC1D19 functions in cell polarity and decreased TBC1D19 expression may contribute to the observed disruption of odontoblast polarity and apoptosis. These data indicate that MT-DLX3 acts to disrupt odontoblast cytodifferentiation leading to odontoblast apoptosis, and aberrations of dentin tubule formation and dentin matrix production, resulting in decreased dentin and taurodontism. In summary, this TG model demonstrates that MT-DLX3 has differential effects on matrix production and mineralization in dentin and bone and provides a novel tool for the investigation of odontoblast biology. - Source: PubMed
Publication date: 2010/05/25
Choi S JSong I SFeng J QGao THaruyama NGautam PRobey P GHart Thomas C