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TARDBP

OverviewProducts

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). Regulates also 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:23398327, PubMed:19765185). Participates also 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.

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
  • Continuously travels in and out of the nucleus (PubMed:18957508). Localizes to stress granules in response to oxidative stress (PubMed:19765185).

Alternative names

  • TAR DNA-binding protein 43
  • TDP-43
  • TDP43
  • TARDBP

Database links

Target type

Proteins

Primary research area

Neuroscience

Molecular weight

44740Da