Human Gene TARDBP (uc001art.3)
  Description: Homo sapiens TAR DNA binding protein (TARDBP), mRNA.
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].
Transcript (Including UTRs)
   Position: hg19 chr1:11,072,679-11,085,549 Size: 12,871 Total Exon Count: 6 Strand: +
Coding Region
   Position: hg19 chr1:11,073,785-11,082,711 Size: 8,927 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsOther NamesGeneReviewsModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:11,072,679-11,085,549)mRNA (may differ from genome)Protein (414 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
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MGIneXtProtOMIMPubMedTreefamUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TARDBP
CDC HuGE Published Literature: TARDBP

-  MalaCards Disease Associations
  MalaCards Gene Search: TARDBP
Diseases sorted by gene-association score: amyotrophic lateral sclerosis 10, with or without ftd* (1200), tardbp-related amyotrophic lateral sclerosis* (500), amyotrophic lateral sclerosis 1* (454), motor neuron disease* (439), amyotrophic lateral sclerosis type 10* (416), lateral sclerosis* (324), frontotemporal dementia and/or amyotrophic lateral sclerosis 1* (260), tardbp-related frontotemporal dementia* (100), perry syndrome (17), postpoliomyelitis syndrome (15), pick disease (14), frontotemporal lobar degeneration with ubiquitin-positive inclusions (13), adult polyglucosan body disease (13), dementia, frontotemporal (11), inclusion body myopathy with paget disease of bone and frontotemporal dementia (10), speech and communication disorders (10), amyotrophic lateral sclerosis 6, with or without frontotemporal dementia (9), basal ganglia disease (9), semantic dementia (9), nominal aphasia (9), amyotrophic lateral sclerosis 18 (9), phonagnosia (9), amyotrophic lateral sclerosis-parkinsonism/dementia complex (8), expressive language disorder (7), associative agnosia (7), inclusion body myositis (7), postencephalitic parkinson disease (7), lethal congenital contracture syndrome 1 (6), arteriolosclerosis (6), agraphia (6), alexia (6), progressive muscular atrophy (6), corticobasal degeneration (6), ideomotor apraxia (5), amyotrophic lateral sclerosis type 14 (5), spinocerebellar ataxia 36 (5), motor peripheral neuropathy (5), amyotrophic lateral sclerosis 21 (5), amyotrophic lateral sclerosis 11 (5), dementia (4), spinocerebellar ataxia 11 (4), hypertrichotic osteochondrodysplasia cantu type (4), brown-vialetto-van laere syndrome (4), amyotrophic lateral sclerosis 9 (4), anterior horn cell disease (4), cystic fibrosis (4), amyotrophic lateral sclerosis 7 (4), hiv-1 (3), spinocerebellar ataxia 31 (3), alzheimer disease (2), nervous system disease (2), dementia, lewy body (2), central nervous system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 55.27 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 1915.71 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -58.90134-0.440 Picture PostScript Text
3' UTR -783.302838-0.276 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR012677 - Nucleotide-bd_a/b_plait
IPR000504 - RRM_dom

Pfam Domains:
PF00076 - RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain)

SCOP Domains:
54928 - RNA-binding domain, RBD

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1WF0 - NMR MuPIT 2CQG - NMR MuPIT


ModBase Predicted Comparative 3D Structure on Q13148
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details  Gene DetailsGene Details 
Gene Sorter  Gene SorterGene Sorter 
  EnsemblFlyBaseWormBase 
  Protein SequenceProtein SequenceProtein Sequence 
  AlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001205 transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0003690 double-stranded DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0003723 RNA binding
GO:0003730 mRNA 3'-UTR binding
GO:0005515 protein binding
GO:0042802 identical protein binding

Biological Process:
GO:0001933 negative regulation of protein phosphorylation
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0006397 mRNA processing
GO:0008380 RNA splicing
GO:0010629 negative regulation of gene expression
GO:0032024 positive regulation of insulin secretion
GO:0034976 response to endoplasmic reticulum stress
GO:0042981 regulation of apoptotic process
GO:0043922 negative regulation by host of viral transcription
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051726 regulation of cell cycle
GO:0070935 3'-UTR-mediated mRNA stabilization
GO:0071765 nuclear inner membrane organization

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005726 perichromatin fibrils
GO:0005737 cytoplasm
GO:0016607 nuclear speck
GO:0035061 interchromatin granule


-  Descriptions from all associated GenBank mRNAs
  JA482047 - Sequence 30 from Patent WO2011072091.
JE980339 - Sequence 30 from Patent EP2862929.
AK299454 - Homo sapiens cDNA FLJ57180 complete cds, highly similar to TAR DNA-binding protein 43.
AK312416 - Homo sapiens cDNA, FLJ92755, highly similar to Homo sapiens TAR DNA binding protein (TARDBP), mRNA.
BC001487 - Homo sapiens TAR DNA binding protein, mRNA (cDNA clone IMAGE:3506121).
BC095435 - Homo sapiens TAR DNA binding protein, mRNA (cDNA clone MGC:111119 IMAGE:30389805), complete cds.
BC071657 - Homo sapiens TAR DNA binding protein, mRNA (cDNA clone MGC:87845 IMAGE:5498250), complete cds.
AL050265 - Homo sapiens mRNA; cDNA DKFZp564O1716 (from clone DKFZp564O1716).
AK295920 - Homo sapiens cDNA FLJ58188 complete cds, highly similar to TAR DNA-binding protein 43.
AK222754 - Homo sapiens mRNA for TAR DNA binding protein variant, clone: HEP00195.
JD465653 - Sequence 446677 from Patent EP1572962.
KJ904691 - Synthetic construct Homo sapiens clone ccsbBroadEn_14085 TARDBP gene, encodes complete protein.
AB463300 - Synthetic construct DNA, clone: pF1KB3512, Homo sapiens TARDBP gene for TAR DNA binding protein, without stop codon, in Flexi system.
AM392916 - Synthetic construct Homo sapiens clone IMAGE:100001755 for hypothetical protein (TARDBP gene).
EF434181 - Homo sapiens TDP43 mRNA, complete cds, alternatively spliced.
EF434183 - Homo sapiens TDP43 splice variant 2 mRNA, complete cds, alternatively spliced.
EU446942 - Synthetic construct Homo sapiens clone IMAGE:100070226; IMAGE:100012151; FLH258208.01L TAR DNA binding protein (TARDBP) gene, encodes complete protein.
EF434182 - Homo sapiens TDP43 splice variant 1 mRNA, complete cds, alternatively spliced.
HQ628633 - Homo sapiens TDP43 isoform F (TDP43) mRNA, complete cds, alternatively spliced.
HQ628634 - Homo sapiens TDP43 isoform G (TDP43) mRNA, complete cds, alternatively spliced.
HQ628637 - Homo sapiens TDP43 isoform J (TDP43) mRNA, complete cds, alternatively spliced.
U23731 - Human TAR DNA-binding protein-43 mRNA, complete cds.
CR533534 - Homo sapiens full open reading frame cDNA clone RZPDo834F0419D for gene TARDBP, TAR DNA binding protein; complete cds, incl. stopcodon.
HQ628635 - Homo sapiens TDP43 isoform H (TDP43) mRNA, complete cds, alternatively spliced.
HQ628636 - Homo sapiens TDP43 isoform I (TDP43) mRNA, complete cds, alternatively spliced.
LF205807 - JP 2014500723-A/13310: Polycomb-Associated Non-Coding RNAs.
DQ580109 - Homo sapiens piRNA piR-48221, complete sequence.
LF348433 - JP 2014500723-A/155936: Polycomb-Associated Non-Coding RNAs.
JD499029 - Sequence 480053 from Patent EP1572962.
LF348434 - JP 2014500723-A/155937: Polycomb-Associated Non-Coding RNAs.
JD093354 - Sequence 74378 from Patent EP1572962.
LF348435 - JP 2014500723-A/155938: Polycomb-Associated Non-Coding RNAs.
LF348436 - JP 2014500723-A/155939: Polycomb-Associated Non-Coding RNAs.
LF348437 - JP 2014500723-A/155940: Polycomb-Associated Non-Coding RNAs.
LF348438 - JP 2014500723-A/155941: Polycomb-Associated Non-Coding RNAs.
JD426069 - Sequence 407093 from Patent EP1572962.
LF348439 - JP 2014500723-A/155942: Polycomb-Associated Non-Coding RNAs.
JD236253 - Sequence 217277 from Patent EP1572962.
LF348440 - JP 2014500723-A/155943: Polycomb-Associated Non-Coding RNAs.
LF348441 - JP 2014500723-A/155944: Polycomb-Associated Non-Coding RNAs.
JD393058 - Sequence 374082 from Patent EP1572962.
LF348442 - JP 2014500723-A/155945: Polycomb-Associated Non-Coding RNAs.
JD241595 - Sequence 222619 from Patent EP1572962.
JD250187 - Sequence 231211 from Patent EP1572962.
JD089605 - Sequence 70629 from Patent EP1572962.
LF348443 - JP 2014500723-A/155946: Polycomb-Associated Non-Coding RNAs.
JD436986 - Sequence 418010 from Patent EP1572962.
LF348444 - JP 2014500723-A/155947: Polycomb-Associated Non-Coding RNAs.
JD171277 - Sequence 152301 from Patent EP1572962.
JD282918 - Sequence 263942 from Patent EP1572962.
JD178009 - Sequence 159033 from Patent EP1572962.
JD175051 - Sequence 156075 from Patent EP1572962.
JD375632 - Sequence 356656 from Patent EP1572962.
JD344373 - Sequence 325397 from Patent EP1572962.
JD272469 - Sequence 253493 from Patent EP1572962.
JD022446 - Sequence 3470 from Patent EP1572962.
JD034520 - Sequence 15544 from Patent EP1572962.
BC059955 - Homo sapiens TAR DNA binding protein, mRNA (cDNA clone IMAGE:4372646), partial cds.
JD025031 - Sequence 6055 from Patent EP1572962.
JD028735 - Sequence 9759 from Patent EP1572962.
AF311304 - Homo sapiens unknown mRNA.
JD236117 - Sequence 217141 from Patent EP1572962.
JD432809 - Sequence 413833 from Patent EP1572962.
JD295973 - Sequence 276997 from Patent EP1572962.
JD205924 - Sequence 186948 from Patent EP1572962.
JD268965 - Sequence 249989 from Patent EP1572962.
JD280323 - Sequence 261347 from Patent EP1572962.
JD244439 - Sequence 225463 from Patent EP1572962.
JD188067 - Sequence 169091 from Patent EP1572962.
JD324074 - Sequence 305098 from Patent EP1572962.
MA823565 - WO 2019013141-A/3: Antisense oligonucleotide for regulating TDP-43 expression level and use thereof.
MA823564 - WO 2019013141-A/2: Antisense oligonucleotide for regulating TDP-43 expression level and use thereof.
MA823563 - WO 2019013141-A/1: Antisense oligonucleotide for regulating TDP-43 expression level and use thereof.
MA823566 - WO 2019013141-A/4: Antisense oligonucleotide for regulating TDP-43 expression level and use thereof.
MA823626 - WO 2019013141-A/64: Antisense oligonucleotide for regulating TDP-43 expression level and use thereof.
MA823627 - WO 2019013141-A/65: Antisense oligonucleotide for regulating TDP-43 expression level and use thereof.
MA823567 - WO 2019013141-A/5: Antisense oligonucleotide for regulating TDP-43 expression level and use thereof.
MA584010 - JP 2018138019-A/155936: Polycomb-Associated Non-Coding RNAs.
MA584011 - JP 2018138019-A/155937: Polycomb-Associated Non-Coding RNAs.
MA584012 - JP 2018138019-A/155938: Polycomb-Associated Non-Coding RNAs.
MA584013 - JP 2018138019-A/155939: Polycomb-Associated Non-Coding RNAs.
MA584014 - JP 2018138019-A/155940: Polycomb-Associated Non-Coding RNAs.
MA584015 - JP 2018138019-A/155941: Polycomb-Associated Non-Coding RNAs.
MA584016 - JP 2018138019-A/155942: Polycomb-Associated Non-Coding RNAs.
MA584017 - JP 2018138019-A/155943: Polycomb-Associated Non-Coding RNAs.
MA584018 - JP 2018138019-A/155944: Polycomb-Associated Non-Coding RNAs.
MA584019 - JP 2018138019-A/155945: Polycomb-Associated Non-Coding RNAs.
MA584020 - JP 2018138019-A/155946: Polycomb-Associated Non-Coding RNAs.
MA584021 - JP 2018138019-A/155947: Polycomb-Associated Non-Coding RNAs.
MA441384 - JP 2018138019-A/13310: Polycomb-Associated Non-Coding RNAs.

-  Other Names for This Gene
  Alternate Gene Symbols: A4GUK4, A4GUK5, A4GUK6, B2R629, E2PU12, NM_007375, NP_031401, Q13148, Q53H27, Q6FI92, Q96DJ0, TADBP_HUMAN, TDP43
UCSC ID: uc001art.3
RefSeq Accession: NM_007375
Protein: Q13148 (aka TADBP_HUMAN or TDBP_HUMAN)
CCDS: CCDS122.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene TARDBP:
tardbp-als (TARDBP-Related Amyotrophic Lateral Sclerosis-Frontotemporal Dementia)
als-overview (Amyotrophic Lateral Sclerosis Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_007375.3
exon count: 6CDS single in 3' UTR: no RNA size: 4236
ORF size: 1245CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2690.00frame shift in genome: no % Coverage: 99.55
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.