TADBP_PONAB
ID TADBP_PONAB Reviewed; 414 AA.
AC Q5R5W2;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=TAR DNA-binding protein 43;
DE Short=TDP-43;
GN Name=TARDBP; Synonyms=TDP43;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: DNA- and RNA binding protein, involved in several nuclear
CC processes (By similarity). Binds the conventional octamer sequence in
CC double-stranded DNA (By similarity). Also binds single-stranded DNA and
CC RNA at a site independent of the duplex site (By similarity). Involved
CC in pre-mRNA splicing, probably as a heterodimer with SFPQ (By
CC similarity). Interacts with U5 snRNA, probably by binding to a purine-
CC rich sequence located on the 3' side of U5 snRNA stem 1b (By
CC similarity). Together with PSPC1, required for the formation of nuclear
CC paraspeckles (By similarity). The SFPQ-NONO heteromer associated with
CC MATR3 may play a role in nuclear retention of defective RNAs (By
CC similarity). The SFPQ-NONO heteromer may be involved in DNA unwinding
CC by modulating the function of topoisomerase I/TOP1 (By similarity). The
CC SFPQ-NONO heteromer may be involved in DNA non-homologous end joining
CC (NHEJ) required for double-strand break repair and V(D)J recombination
CC and may stabilize paired DNA ends (By similarity). In vitro, the
CC complex strongly stimulates DNA end joining, binds directly to the DNA
CC substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to
CC establish a functional preligation complex (By similarity). NONO is
CC involved in transcriptional regulation (By similarity). The SFPQ-NONO-
CC NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-
CC dependent transcriptional activity (By similarity). NONO binds to an
CC enhancer element in long terminal repeats of endogenous intracisternal
CC A particles (IAPs) and activates transcription (By similarity).
CC Regulates the circadian clock by repressing the transcriptional
CC activator activity of the CLOCK-ARNTL/BMAL1 heterodimer (By
CC similarity). Important for the functional organization of GABAergic
CC synapses (By similarity). Plays a specific and important role in the
CC regulation of synaptic RNAs and GPHN/gephyrin scaffold structure,
CC through the regulation of GABRA2 transcript (By similarity). Plays a
CC key role during neuronal differentiation by recruiting TET1 to genomic
CC loci and thereby regulating 5-hydroxymethylcytosine levels (By
CC similarity). Plays a role in the regulation of DNA virus-mediated
CC innate immune response by assembling into the HDP-RNP complex, a
CC complex that serves as a platform for IRF3 phosphorylation and
CC subsequent innate immune response activation through the cGAS-STING
CC pathway (By similarity). {ECO:0000250|UniProtKB:Q15233,
CC ECO:0000250|UniProtKB:Q5FVM4, ECO:0000250|UniProtKB:Q99K48}.
CC -!- SUBUNIT: Monomer and component of the SFPQ-NONO complex, which is
CC probably a heterotetramer of two 52 kDa (NONO) and two 100 kDa (SFPQ)
CC subunits. NONO is a component of spliceosome and U5.4/6 snRNP complexes
CC (By similarity). Interacts with CPNE4 (via VWFA domain) (By
CC similarity). Forms heterodimers with PSPC1; this involves formation of
CC a coiled coil domain by helices from both proteins. Part of complex
CC consisting of SFPQ, NONO and MATR3. Part of a complex consisting of
CC SFPQ, NONO and NR5A1. Part of a complex consisting of SFPQ, NONO and
CC TOP1. Interacts with SPI1. Interacts with RNF43 (By similarity).
CC Interacts with PER1 and PER2 (By similarity). Part of the HDP-RNP
CC complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle
CC proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA. Interacts
CC (via second RRM domain) with WASL; the interaction is direct. Component
CC of a multiprotein complex with WASL and SFPQ (By similarity). Interacts
CC with ERCC6 (By similarity). Interacts (via DNA-binding domain) with
CC TET1 (By similarity). {ECO:0000250|UniProtKB:Q15233,
CC ECO:0000250|UniProtKB:Q5FVM4, ECO:0000250|UniProtKB:Q99K48}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q99K48}. Nucleus,
CC nucleolus {ECO:0000250|UniProtKB:Q99K48}. Nucleus speckle
CC {ECO:0000250|UniProtKB:Q99K48}. Chromosome
CC {ECO:0000250|UniProtKB:Q99K48}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q13148}. Note=Continuously travels in and out of
CC the nucleus. Localizes to stress granules in response to oxidative
CC stress. A small subset localizes in mitochondria.
CC {ECO:0000250|UniProtKB:Q13148}.
CC -!- DOMAIN: The RRM domains can bind to both DNA and RNA. {ECO:0000250}.
CC -!- PTM: Hyperphosphorylated. {ECO:0000250|UniProtKB:Q99K48}.
CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q99K48}.
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DR EMBL; CR860740; CAH92854.1; -; mRNA.
DR RefSeq; NP_001127597.1; NM_001134125.1.
DR AlphaFoldDB; Q5R5W2; -.
DR BMRB; Q5R5W2; -.
DR SMR; Q5R5W2; -.
DR STRING; 9601.ENSPPYP00000002194; -.
DR GeneID; 100174676; -.
DR KEGG; pon:100174676; -.
DR CTD; 23435; -.
DR eggNOG; ENOG502QPQ8; Eukaryota.
DR InParanoid; Q5R5W2; -.
DR OrthoDB; 1425837at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR InterPro; IPR041105; TDP43_N.
DR Pfam; PF00076; RRM_1; 2.
DR Pfam; PF18694; TDP43_N; 1.
DR SMART; SM00360; RRM; 2.
DR SUPFAM; SSF54928; SSF54928; 2.
DR PROSITE; PS50102; RRM; 2.
PE 2: Evidence at transcript level;
KW Chromosome; DNA-binding; Isopeptide bond; Methylation; Mitochondrion;
KW mRNA processing; mRNA splicing; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Repressor; RNA-binding; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..414
FT /note="TAR DNA-binding protein 43"
FT /id="PRO_0000317415"
FT DOMAIN 104..200
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 191..262
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 216..414
FT /note="Interaction with UBQLN2"
FT /evidence="ECO:0000250|UniProtKB:Q13148"
FT REGION 261..303
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 341..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13148"
FT MOD_RES 292
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13148"
FT MOD_RES 293
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q13148"
FT CROSSLNK 79
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13148"
FT CROSSLNK 84
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13148"
FT CROSSLNK 95
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13148"
FT CROSSLNK 102
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13148"
FT CROSSLNK 181
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13148"
FT CROSSLNK 263
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13148"
SQ SEQUENCE 414 AA; 44713 MW; A0D48506BDF6177E CRC64;
MSEYIRVTED ESDEPIEIPS EDDGTVLLST VTAQFPGACG LRYRNPVSQC MRGVRLVEGI
LHAPDAGWGN LVYVVNYPKD NKRKMDETDA SSAVKVKRAV QKTSDLIVLG LPWKTTEQDL
KEYFSTFGEV LMVQVKKDLK TGHSKGFGFV RFTEYETQVK VMSQRHMIDG RWCDCKLPNS
KQSQDEPLRS RKVFVGRCTE DMTEDELREF FSQYGDVMDV FIPKPFRAFA FVTFADDQIA
QSLCGEDLII KGISVHISNA EPKHNSNRQL ERSGRFGGNP GGFGNQGGFG NSRGGGAGLG
NNQGSNMGGG MNFGAFSINP AMMAAAQAAL QSSWGMMGML ASQQNQSGPS GNNQNQGNMQ
REPNQAFGSG NNSYSGSNSG AAIGWGSASN AGSGSGFNGG FGSSMDSKSS GWGM
