DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR.
Ubiquitously expressed. In particular, expression is high in pancreas, placenta, lung, genital tract and spleen.
Involvement in disease
Defects in TARDBP are the cause of amyotrophic lateral sclerosis type 10 (ALS10) [MIM:612069]. ALS is a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of ALS is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
Contains 2 RRM (RNA recognition motif) domains.
The RRM domains can bind to both DNA and RNA.
Hyperphosphorylated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. 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.
Nucleus. In patients with frontotemporal lobar degeneration and amyotrophic lateral sclerosis, it is absent from the nucleus of affected neurons but it is the primary component of cytoplasmic ubiquitin-positive inclusion bodies.
Western blot - Anti-TDP43 antibody [EPR5810] (ab109535)
Lane 1: Wild-type HAP1 cell lysate (40 µg) Lane 2: TDP43 knockout HAP1 cell lysate (40 µg) Lane 3: HeLa cell lysate (40 µg) Lane 4: Jurkat cell lysate (40 µg) Lanes 1 - 4: Merged signal (red and green). Green - ab109535 observed at 48 kDa. Red - loading control, ab8245, observed at 37 kDa.
ab109535 was shown to specifically react with TDP43 when TDP43 knockout samples were used. Wild-type and TDP43 knockout samples were subjected to SDS-PAGE. Ab109535 and ab8245 (loading control to GAPDH) were diluted at 1/1000 and 1:10,000 dilution respectively and incubated overnight at 4C. Blots were developed with IRDye® 800CW Goat anti-Rabbit IgG (H + L) and IRDye® 680 Goat anti-Mouse IgG (H + L) secondary antibodies at 1:10,000 dilution for 1 hour at room temperature before imaging.
ab109535 staining TDP43 in wild-type HAP1 cells (top panel) and TDP43 knockout HAP1 cells (bottom panel). The cells were fixed with 100% methanol (5min), permeabilized with 0.1% Triton X-100 for 5 minutes and then blocked with 1% BSA/10% normal goat serum/0.3M glycine in 0.1% PBS-Tween for 1h. The cells were then incubated with ab109535 at 1μg/ml concentration and ab195889 at 1/250 dilution (shown in pseudo colour red) overnight at +4°C, followed by a further incubation at room temperature for 1h with a goat secondary antibody to Rabbit IgG (Alexa Fluor® 488) (ab150081) at 2 μg/ml (shown in green). Nuclear DNA was labelled in blue with DAPI.
Flow Cytometry analysis of K562 (human chronic myelogenous leukemia) cells labeling TDP43 with purified ab109535 at 1/100 dilution(10ug/ml) (red). Cells were fixed with 4% paraformaldehyde and permeabilised with 90% methanol. A Goat anti rabbit IgG (Alexa Fluor® 488)(1/2000 dilution) was used as the secondary antibody. Rabbit monoclonal IgG (Black) was used as the isotype control, cells without incubation with primary antibody and secondary antibody (Blue) were used as the unlabeled control.
Western blot - Anti-TDP43 [EPR5810] antibody (ab109535)
All lanes : Anti-TDP43 antibody [EPR5810] (ab109535) at 1/1000 dilution
Lane 1 : HeLa cell lysate Lane 2 : 293T cell lysate Lane 3 : K562 cell lysate Lane 4 : A431 cell lysate
Lysates/proteins at 10 µg per lane.
Secondary All lanes : HRP-labelled goat anti-rabbit at 1/2000 dilution
Li W et al. Heat Shock-induced Phosphorylation of TAR DNA-binding Protein 43 (TDP-43) by MAPK/ERK Kinase Regulates TDP-43 Function. J Biol Chem292:5089-5100 (2017).
Read more (PubMed: 28167528) »
Llewellyn KJ et al. A Fine Balance of Dietary Lipids Improves Pathology of a Murine Model of VCP-Associated Multisystem Proteinopathy. PLoS One10:e0131995 (2015).
Read more (PubMed: 26134519) »