Human Gene TARDBP (ENST00000240185.8) from GENCODE V44
Description: Homo sapiens TAR DNA binding protein (TARDBP), mRNA. (from RefSeq NM_007375) RefSeq Summary (NM_007375): 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, Jul 2008]. Gencode Transcript: ENST00000240185.8 Gencode Gene: ENSG00000120948.19 Transcript (Including UTRs) Position: hg38 chr1:11,012,654-11,025,492 Size: 12,839 Total Exon Count: 6 Strand: + Coding Region Position: hg38 chr1:11,013,728-11,022,654 Size: 8,927 Coding Exon Count: 5
ID:TADBP_HUMAN DESCRIPTION: RecName: Full=TAR DNA-binding protein 43; Short=TDP-43; 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. SUBUNIT: Homodimer. Interacts with BRDT (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. INTERACTION: O43187:IRAK2; NbExp=2; IntAct=EBI-372899, EBI-447733; 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. 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 (By similarity). PTM: Hyperphosphorylated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. PTM: Ubiquitinated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. PTM: Cleaved to generate C-terminal fragments in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. 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. SIMILARITY: Contains 2 RRM (RNA recognition motif) domains.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13148
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.