FEATURES

DESCRIPTION

Also known as TADBP_HUMAN, TARDBP, TDP43. 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). Regulates also 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:23398327, PubMed:19765185). Participates also 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). Homodimer (PubMed:20043239, PubMed:24464995). Homooligomer (via its N-terminal domain) (PubMed:28663553, PubMed:29438978). 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 ATXN2; the interaction is RNA-dependent (PubMed:20740007). Interacts with MATR3 (PubMed:24686783). Interacts with UBQLN2 (PubMed:23541532). Interacts with HNRNPA2B1 (PubMed:19429692). Interacts with ZNF106 (By similarity). Interacts with CNOT7/CAF1 (PubMed:30520513). Interacts with CRY2 (PubMed:27123980). Interacts with PPIA/CYPA; the interaction is dependent on RNA-binding activity of TARDBP and PPIase activity of PPIA/CYPA and acetylation of PPIA/CYPA at 'Lys-125' favors the interaction (PubMed:25678563).

EXTERNAL LINKS

TARDBP

Mutations

Mutation(s) distribution

Mutations table