TARDBP
entrez
23435
canonical
uniprot
Q13148
canonical
ensembl
ENSG00000120948
resolver
ensp
ENSP00000240185
resolver
genesymbol
TARDBP
resolver
genesymbol_syn
TDP43
resolver
hgnc
HGNC:11571
resolver
uniprot
A4GUK4
resolver
uniprot
A4GUK5
resolver
uniprot
A4GUK6
resolver
uniprot
B2R629
resolver
uniprot
B4DJ45
resolver
uniprot
E2PU12
resolver
uniprot
Q53H27
resolver
uniprot
Q6FI92
resolver
uniprot
Q96DJ0
resolver
uniprot
Q9H256
resolver
uniprot_entry
Q9H256_HUMAN
resolver
uniprot_entry
TADBP_HUMAN
resolver
uniprot_sec
A4GUK4
resolver
uniprot_sec
A4GUK5
resolver
uniprot_sec
A4GUK6
resolver
uniprot_sec
B2R629
resolver
uniprot_sec
B4DJ45
resolver
uniprot_sec
E2PU12
resolver
uniprot_sec
Q53H27
resolver
uniprot_sec
Q6FI92
resolver
uniprot_sec
Q96DJ0
resolver
amino_acid_sequence
MSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
uniprot
proteins
disease_involvement
DISEASE: Amyotrophic lateral sclerosis 10 (ALS10) [MIM:612069]: 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. {ECO:0000269|PubMed:18288693, ECO:0000269|PubMed:18309045, ECO:0000269|PubMed:18372902, ECO:0000269|PubMed:18396105, ECO:0000269|PubMed:18438952, ECO:0000269|PubMed:19224587, ECO:0000269|PubMed:19350673, ECO:0000269|PubMed:19655382, ECO:0000269|PubMed:19695877, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:20740007, ECO:0000269|PubMed:21220647, ECO:0000269|PubMed:21418058, ECO:0000269|PubMed:22456481, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:33031745}. Note=The disease is caused by variants affecting the gene represented in this entry. Neurodegeneration is caused by activation of the cGAS-STING pathway: defects in TARDBP trigger mitochondrial DNA release into the cytosol via the permeability transition pore (PubMed:33031745). Released mitochondrial DNA is then detected by CGAS, leading to activation of the cGAS-STING pathway, triggering type-I interferon production and autoinflammation (PubMed:33031745). {ECO:0000269|PubMed:33031745}.
uniprot
proteins
function
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). Also regulates 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:19765185, PubMed:23398327). Also participates 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). {ECO:0000269|PubMed:11285240, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:21358640, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:23519609, ECO:0000269|PubMed:24240615, ECO:0000269|PubMed:24464995, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28794432, ECO:0000269|PubMed:29438978, ECO:0000269|PubMed:30464263, ECO:0000269|PubMed:30520513}.
uniprot
proteins
mass_dalton
44740
uniprot
proteins
mutagenesis
MUTAGEN 48; /note="S->E: Complete loss of self-oligomerization."; /evidence="ECO:0000269|PubMed:29438978"; MUTAGEN 103..183; /note="Missing: Loss of RNA-binding and reduced interaction with PPIA/CYPA."; /evidence="ECO:0000269|PubMed:25678563"; MUTAGEN 106..175; /note="Missing: Completely abolishes RNA binding."; /evidence="ECO:0000269|PubMed:11470789"; MUTAGEN 106..111; /note="LIVLGL->DIDLGD: Completely abolishes RNA binding."; /evidence="ECO:0000269|PubMed:11470789"; MUTAGEN 106..111; /note="Missing: Completely abolishes RNA binding."; /evidence="ECO:0000269|PubMed:11470789"; MUTAGEN 147..149; /note="FGF->LGL: Highly reduces binding to RNA and DNA."; /evidence="ECO:0000269|PubMed:11470789"; MUTAGEN 193..257; /note="Missing: Alters but does not abolish RNA binding."; /evidence="ECO:0000269|PubMed:11470789
uniprot
proteins
post_translational_modification
PTM: Hyperphosphorylated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. Phosphorylated upon cellular stress. {ECO:0000269|PubMed:23398327}.; PTM: Ubiquitinated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. {ECO:0000269|PubMed:17023659, ECO:0000269|PubMed:17481916}.; PTM: Cleaved to generate C-terminal fragments in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU.
uniprot
proteins
pubmed
11285240
uniprot
proteins
pubmed
11470789
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17023659
uniprot
proteins
pubmed
17481916
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18288693
uniprot
proteins
pubmed
18309045
uniprot
proteins
pubmed
18372902
uniprot
proteins
pubmed
18396105
uniprot
proteins
pubmed
18438952
uniprot
proteins
pubmed
18957508
uniprot
proteins
pubmed
19224587
uniprot
proteins
pubmed
19350673
uniprot
proteins
pubmed
19429692
uniprot
proteins
pubmed
19655382
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19695877
uniprot
proteins
pubmed
19760257
uniprot
proteins
pubmed
19765185
uniprot
proteins
pubmed
20043239
uniprot
proteins
pubmed
20740007
uniprot
proteins
pubmed
21220647
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21358640
uniprot
proteins
pubmed
21418058
uniprot
proteins
pubmed
22456481
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23398327
uniprot
proteins
pubmed
23519609
uniprot
proteins
pubmed
23541532
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24240615
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24464995
uniprot
proteins
pubmed
24686783
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25678563
uniprot
proteins
pubmed
25772364
uniprot
proteins
pubmed
27123980
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28663553
uniprot
proteins
pubmed
28794432
uniprot
proteins
pubmed
29438978
uniprot
proteins
pubmed
29531287
uniprot
proteins
pubmed
30464263
uniprot
proteins
pubmed
30520513
uniprot
proteins
pubmed
33031745
uniprot
proteins
pubmed
7745706
uniprot
proteins
sequence_length
414
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17023659, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:18957508, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:28663553, ECO:0000269|PubMed:29438978}. Cytoplasm {ECO:0000269|PubMed:18957508, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:30464263}. Cytoplasm, Stress granule {ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:23398327}. Mitochondrion {ECO:0000269|PubMed:28794432, ECO:0000269|PubMed:33031745}. Note=Continuously travels in and out of the nucleus (PubMed:18957508). Localizes to stress granules in response to oxidative stress (PubMed:19765185). A small subset localizes in mitochondria (PubMed:28794432). {ECO:0000269|PubMed:18957508, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:28794432}.
uniprot
proteins