TARDBP
GeneName
TARDBP
Summary
TARDBP, also known as TDP-43 or TAR DNA binding protein 43, is a 45kDa protein predominantly localised in the nucleus and cytoplasm, including structures such as stress granules and nucleoplasmic regions. It is involved in various RNA-related processes, including RNA binding, mRNA processing, and regulation of gene expression. TDP-43 plays a role in the regulation of mRNA stability through its interactions with 3'-UTR regions, and is implicated in the formation of amyloid fibrils. Its diverse functions extend to cellular stress responses and the regulation of apoptotic processes, highlighting its significance in maintaining cellular homeostasis.
Importance
TARDBP is relevant to: - Neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, due to its aggregation and mislocalisation in pathological conditions. - The regulation of gene expression and RNA metabolism, impacting cellular responses to stress and apoptosis. - Viral infections, as it negatively regulates viral transcription, influencing host-pathogen interactions. - Insulin secretion and metabolic processes, linking it to conditions such as diabetes through its regulatory roles.
Top Products
For researchers investigating TARDBP, we highly recommend the top-selling recombinant antibody, Anti-TDP43 antibody [EPR5810] (ab109535). This antibody has been validated in knockout models, ensuring its reliability in various applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and flow cytometry (FC). With 24 citations, it is well-regarded in the research community, making it an excellent choice for those studying TDP-43. Its recombinant nature guarantees batch-to-batch consistency, providing confidence in your experimental results. The Human TDP43 ELISA Kit (TARDBP) (ab282880) is an excellent option for researchers looking to measure TDP43 levels in their samples.
Abcam Product Citation Summary
The data indicates that TARDBP antibodies from Abcam have been extensively used in various applications, primarily Western blotting and immunofluorescence, in human motor neuron and HAP1 cell models. The studies focus on protein aggregation and TDP-43 antibody screening, highlighting the relevance of TARDBP in neurodegenerative research.
Abcam Product Citation Table
Domain
Consists of an N-terminal domain (NTD) and two tandem RNA recognition motifs, RRM1 and RRM2, followed by a C-terminal glycine-rich region.
Contains a nuclear localization sequence and is mostly nuclear; however, its nuclear export sequence permits it to transport mRNAs to the cytoplasm and even to synapses as part of neuronal granules.
Function
RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Also regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:19765185, PubMed:23398327). Also participates in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563).
Involvement in disease
Amyotrophic lateral sclerosis 10
ALS10
A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
None
The disease is caused by variants affecting the gene represented in this entry. Neurodegeneration is caused by activation of the cGAS-STING pathway: defects in TARDBP trigger mitochondrial DNA release into the cytosol via the permeability transition pore (PubMed:33031745). Released mitochondrial DNA is then detected by CGAS, leading to activation of the cGAS-STING pathway, triggering type-I interferon production and autoinflammation (PubMed:33031745).
Post-translational modifications
Hyperphosphorylated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. Phosphorylated upon cellular stress.
Ubiquitinated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU.
Cleaved to generate C-terminal fragments in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU.
Tissue Specificity
Ubiquitously expressed. In particular, expression is high in pancreas, placenta, lung, genital tract and spleen.
Cellular localization
- Nucleus
- Cytoplasm
- Cytoplasm
- Stress granule
- Mitochondrion
- Continuously travels in and out of the nucleus (PubMed:18957508). Localizes to stress granules in response to oxidative stress (PubMed:19765185). A small subset localizes in mitochondria (PubMed:28794432).
Alternative names
TDP43, TARDBP, TAR DNA-binding protein 43, TDP-43