TARDBP Antibody – Rabbit Polyclonal

HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. The protein encoded by this gene is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. A similar pseudogene is present on chromosome 20. [provided by RefSeq]

Function: 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. Ref.2 Ref.12

Subunit structure: Homodimer

By similarity. Binds specifically to pyrimidine-rich motifs of TAR DNA and to single stranded TG repeated sequences. Binds to RNA, specifically to UG repeated sequences with a minimun of six contiguous repeats. Interacts with ATNX2; the interaction is RNA-dependent. Ref.15

Subcellular location: Nucleus. Note: 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. Ref.2 Ref.11

Tissue specificity: Ubiquitously expressed. In particular, expression is high in pancreas, placenta, lung, genital tract and spleen.

Domain: The RRM domains can bind to both DNA and RNA

Post-translational modification: Hyperphosphorylated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. Ref.11 Ref.14Ubiquitinated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. Ref.2 Ref.11Cleaved to generate C-terminal fragments in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU.

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. Ref.15 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29

Sequence similarities: Contains 2 RRM (RNA recognition motif) domains.