Q921F2 (TADBP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TAR DNA-binding protein 43
Short name=TDP-43

Gene names

Name:	Tardbp
Synonyms:	Tdp43

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	414 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 By similarity.
Subunit structure	Homodimer. 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 BRDT. Ref.4 Ref.5
Subcellular location	Nucleus By similarity.
Domain	The RRM domains can bind to both DNA and RNA.
Post-translational modification	Hyperphosphorylated By similarity. Ubiquitinated By similarity.
Sequence similarities	Contains 2 RRM (RNA recognition motif) domains.

Ontologies

Keywords
Biological process	Transcription Transcription regulation mRNA processing mRNA splicing
Cellular component	Nucleus
Domain	Repeat
Ligand	DNA-binding RNA-binding
Molecular function	Repressor
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	3'-UTR-mediated mRNA stabilization Inferred from electronic annotation. Source: Compara RNA splicing Inferred from electronic annotation. Source: UniProtKB-KW mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW negative regulation by host of viral transcription Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	double-stranded DNA binding Inferred from electronic annotation. Source: Compara mRNA 3'-UTR binding Inferred from electronic annotation. Source: Compara nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 414

414

TAR DNA-binding protein 43

PRO_0000081973

Regions

Domain

104 – 200

97

RRM 1

Domain

191 – 262

72

RRM 2

Compositional bias

274 – 413

140

Gly-rich

Amino acid modifications

Modified residue

292

1

Phosphoserine By similarity

Experimental info

Sequence conflict

8

1

T → K in BAE32189. Ref.1

Sequence conflict

96

1

V → G in BAE32189. Ref.1

Sequence conflict

298

1

G → C in BAE21557. Ref.1

Secondary structure

1

.

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414

Helix Strand Turn

Details...

Beta strand

192 – 197

6

Helix

204 – 211

8

Turn

212 – 214

3

Beta strand

217 – 221

5

Beta strand

228 – 235

8

Helix

237 – 243

7

Beta strand

247 – 250

4

Beta strand

253 – 259

7

Sequences

	Sequence		Length	Mass (Da)
	Q921F2 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 2BE6A695EC2CA106	FASTA	414	44,548
	10 20 30 40 50 60 MSEYIRVTED ENDEPIEIPS EDDGTVLLST VTAQFPGACG LRYRNPVSQC MRGVRLVEGI 70 80 90 100 110 120 LHAPDAGWGN LVYVVNYPKD NKRKMDETDA SSAVKVKRAV QKTSDLIVLG LPWKTTEQDL 130 140 150 160 170 180 KDYFSTFGEV LMVQVKKDLK TGHSKGFGFV RFTEYETQVK VMSQRHMIDG RWCDCKLPNS 190 200 210 220 230 240 KQSPDEPLRS RKVFVGRCTE DMTAEELQQF FCQYGEVVDV FIPKPFRAFA FVTFADDKVA 250 260 270 280 290 300 QSLCGEDLII KGISVHISNA EPKHNSNRQL ERSGRFGGNP GGFGNQGGFG NSRGGGAGLG 310 320 330 340 350 360 NNQGGNMGGG MNFGAFSINP AMMAAAQAAL QSSWGMMGML ASQQNQSGPS GNNQSQGSMQ 370 380 390 400 410 REPNQAFGSG NNSYSGSNSG APLGWGSASN AGSGSGFNGG FGSSMDSKSS GWGM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Testis and Thymus.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary gland.
[3]	Lubec G., Klug S. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 276-293, MASS SPECTROMETRY. Tissue: Hippocampus.
[4]	"The testis-specific double bromodomain-containing protein BRDT forms a complex with multiple spliceosome components and is required for mRNA splicing and 3'-UTR truncation in round spermatids." Berkovits B.D., Wang L., Guarnieri P., Wolgemuth D.J. Nucleic Acids Res. 40:7162-7175(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BRDT.
[5]	"Structural insights into TDP-43 in nucleic-acid binding and domain interactions." Kuo P.H., Doudeva L.G., Wang Y.T., Shen C.K., Yuan H.S. Nucleic Acids Res. 37:1799-1808(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 192-265 IN COMPLEX WITH SINGLE-STRANDED DNA, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK133207 mRNA. Translation: BAE21557.1.
AK153803 mRNA. Translation: BAE32189.1.
BC012873 mRNA. Translation: AAH12873.1.
BC025544 mRNA. Translation: AAH25544.1.
BC027772 mRNA. Translation: AAH27772.1.
BC031126 mRNA. Translation: AAH31126.1.
BC033475 mRNA. Translation: AAH33475.1.

IPI

IPI00121758.

RefSeq

NP_663531.1. NM_145556.4.

UniGene

Mm.22453.
Mm.378962.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3D2W	X-ray	1.65	A	192-265	[»]

ProteinModelPortal

Q921F2.

SMR

Q921F2. Positions 90-261.

ModBase

Search...

Protein-protein interaction databases

STRING

10090.ENSMUSP00000081142.

PTM databases

PhosphoSite

Q921F2.

2D gel databases

REPRODUCTION-2DPAGE

Q921F2.

Proteomic databases

PaxDb

Q921F2.

PRIDE

Q921F2.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000084125; ENSMUSP00000081142; ENSMUSG00000041459.

GeneID

230908.

KEGG

mmu:230908.

Organism-specific databases

CTD

23435.

MGI

MGI:2387629. Tardbp.

Phylogenomic databases

eggNOG

NOG145464.

GeneTree

ENSGT00570000079202.

HOGENOM

HOG000254792.

HOVERGEN

HBG058671.

InParanoid

Q3V0E7.

OMA

QFFSQYG.

OrthoDB

EOG447FTT.

Gene expression databases

ArrayExpress

Q921F2.

Bgee

Q921F2.

CleanEx

MM_TARDBP.

Genevestigator

Q921F2.

GermOnline

ENSMUSG00000041459. Mus musculus.

Family and domain databases

Gene3D

3.30.70.330. 2 hits.

InterPro

IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]

Pfam

PF00076. RRM_1. 1 hit.
[Graphical view]

SMART

SM00360. RRM. 2 hits.
[Graphical view]

PROSITE

PS50102. RRM. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q921F2.

NextBio

380280.

SOURCE

Search...

Entry information

Entry name

TADBP_MOUSE

Accession

Primary (citable) accession number: Q921F2
Secondary accession number(s): Q3U591, Q3V0E7

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program