| Tchem | TAR DNA-binding protein 43 |
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.
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]
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]
Comments
| Disease | Target Count |
|---|---|
| AMYOTROPHIC LATERAL SCLEROSIS 10 (disorder) | 1 |
| Amyotrophic lateral sclerosis 10 | 1 |
| Disease | Target Count | P-value |
|---|---|---|
| lung carcinoma | 2844 | 3.08309872814246E-11 |
| juvenile dermatomyositis | 1189 | 1.10664861330659E-10 |
| osteosarcoma | 7933 | 2.77811426263061E-7 |
| dermatomyositis | 967 | 5.60686146077676E-4 |
| ovarian cancer | 8492 | 7.91913330300723E-4 |
| diabetes mellitus | 1663 | 0.0013150076623643 |
| Multiple myeloma | 1328 | 0.00456239862227497 |
| astrocytoma | 1493 | 0.00632089441093129 |
| acute myeloid leukemia | 785 | 0.0123903305995848 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Alopecia universalis | 10 | 0.0 | 2.0 |
| Bone cancer | 10 | 0.0 | 2.0 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Neurodegenerative disease | 383 | 0.0 | 4.0 |
| Disease | log2 FC | p |
|---|---|---|
| Multiple myeloma | 1.238 | 0.005 |
| osteosarcoma | -1.046 | 0.000 |
| astrocytoma | 1.300 | 0.006 |
| juvenile dermatomyositis | 1.048 | 0.000 |
| diabetes mellitus | 2.400 | 0.001 |
| lung carcinoma | 1.300 | 0.000 |
| acute myeloid leukemia | 2.500 | 0.012 |
| ovarian cancer | 1.500 | 0.001 |
| dermatomyositis | 1.800 | 0.001 |
| Species | Source |
|---|---|
| Chimp | OMA EggNOG |
| Macaque | OMA EggNOG Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA Inparanoid |
| Dog | OMA EggNOG Inparanoid |
| Cow | OMA EggNOG Inparanoid |
| Platypus | OMA EggNOG Inparanoid |
| Chicken | OMA EggNOG Inparanoid |
| Xenopus | OMA EggNOG Inparanoid |
| C. elegans | OMA EggNOG Inparanoid |
| PMID | Text |
|---|---|
| 27040765 | TDP-43 does have dynamic inter-domain interactions, which are coordinated by the intrinsically-disordered prion-like domain. |
| 26971127 | TDP-43 pathology in the basal forebrain is strongly associated with hippocampal sclerosis-aging. |
| 26902425 | Data suggest that TRIM16 and TDP43 are both good prognosis indicators; data shows that TRIM16 inhibits cancer cell viability by a novel mechanism involving interaction and stabilisation of TDP43 with consequent effects on E2F1 and pRb proteins. |
| 26769969 | Expression of truncated hyperactive form of CKIdelta causes mislocalization and aggregation of TDP-43 in cultured cells. |
| 26756435 | Data indicate that the structure of TAR DNA-binding protein-43 (TDP-43)consists of an alpha-helix and six beta-strands. |
| 26735904 | prion-like domain appears to have an energy landscape to allow the self-assembly of reversible and functional oligomers only under limited conditions |
| 26702100 | data indicate that impaired mTORC1 signaling and influenced ALP may contribute to TDP-43-mediated neurodegeneration. |
| 26605911 | Study identifies a common mechanism of transport into neurites of proteins linked to the pathology of Alzheimer's disease (i.e. sAPP) and ALS (i.e. FUS, TDP-43 and SOD1) |
| 26598621 | TDP-43 may be bidirectionally and vertically transmitted across synaptic terminals. |
| 26571498 | TDP-43 may play an important role in regulating the levels of NF-kappaB activity by controlling the nuclear translocation of p65. |
| More... |
MSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGN 1 - 70 LVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLK 71 - 140 TGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREF 141 - 210 FSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNP 211 - 280 GGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPS 281 - 350 GNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM 351 - 414 //
| PMID | Year | Title |
|---|---|---|
| 27040765 | 2016 | Inter-domain interactions of TDP-43 as decoded by NMR. |
| 26971127 | 2016 | Hippocampal Sclerosis but Not Normal Aging or Alzheimer Disease Is Associated With TDP-43 Pathology in the Basal Forebrain of Aged Persons. |
| 26902425 | 2016 | High TDP43 expression is required for TRIM16-induced inhibition of cancer cell growth and correlated with good prognosis of neuroblastoma and breast cancer patients. |
| 26769969 | 2016 | Phosphorylation of TAR DNA-binding Protein of 43 kDa (TDP-43) by Truncated Casein Kinase 1? Triggers Mislocalization and Accumulation of TDP-43. |
| 26756435 | 2016 | The TDP-43 N-terminal domain structure at high resolution. |
| 26735904 | 2016 | ALS-Causing Mutations Significantly Perturb the Self-Assembly and Interaction with Nucleic Acid of the Intrinsically Disordered Prion-Like Domain of TDP-43. |
| 26702100 | 2016 | TDP-43 loss of function increases TFEB activity and blocks autophagosome-lysosome fusion. |
| 26605911 | 2016 | Shared Molecular Mechanisms in Alzheimer's Disease and Amyotrophic Lateral Sclerosis: Neurofilament-Dependent Transport of sAPP, FUS, TDP-43 and SOD1, with Endoplasmic Reticulum-Like Tubules. |
| 26598621 | 2015 | TDP-43 is intercellularly transmitted across axon terminals. |
| 26571498 | 2015 | TDP-43 Inhibits NF-?B Activity by Blocking p65 Nuclear Translocation. |
| More... |
