Q13148 (TADBP_HUMAN) 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

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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. 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. Ref.2 Ref.12
Subunit structure	Homodimer 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. Ref.15
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. Ref.2 Ref.11
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.
Post-translational modification	Hyperphosphorylated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. Ref.11 Ref.14 Ubiquitinated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. Ref.2 Ref.11 Cleaved to generate C-terminal fragments in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU.
Involvement in 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. Ref.15 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29
Sequence similarities	Contains 2 RRM (RNA recognition motif) domains.

Ontologies

Keywords
Biological process	Transcription Transcription regulation mRNA processing mRNA splicing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Amyotrophic lateral sclerosis Disease mutation Neurodegeneration
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 direct assay Ref.2. Source: BHF-UCL RNA splicing Inferred from direct assay Ref.12. Source: BHF-UCL cell death 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 direct assay Ref.1. Source: BHF-UCL transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc
Cellular component	nucleus Inferred from direct assay Ref.12Ref.2. Source: BHF-UCL
Molecular function	double-stranded DNA binding Inferred from direct assay Ref.1. Source: BHF-UCL mRNA 3'-UTR binding Inferred from direct assay Ref.2. Source: BHF-UCL nucleotide binding Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction Ref.15. Source: UniProtKB sequence-specific DNA binding transcription factor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13148-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q13148-2)

The sequence of this isoform differs from the canonical sequence as follows:
     414-414: M → MNH

Isoform 3 (identifier: Q13148-3)

The sequence of this isoform differs from the canonical sequence as follows:
     86-204: Missing.
     276-312: Missing.
     414-414: M → MNH

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_0000081972

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

91

1

Phosphoserine Ref.14

Modified residue

92

1

Phosphoserine Ref.14

Natural variations

Alternative sequence

86 – 204

119

Missing in isoform 3.

VSP_039989

Alternative sequence

276 – 312

37

Missing in isoform 3.

VSP_039990

Alternative sequence

414

1

M → MNH in isoform 2 and isoform 3.

VSP_039991

Natural variant

90

1

A → V. Ref.22 Ref.23

VAR_045656

Natural variant

169

1

D → G in ALS10. Ref.22

VAR_045657

Natural variant

267

1

N → S in ALS10; also in a patient with frontotemporal dementia. Ref.25 Ref.26

VAR_058611

Natural variant

287

1

G → S in ALS10. Ref.22 Ref.25

VAR_045658

Natural variant

290

1

G → A in ALS10. Ref.21

VAR_045659

Natural variant

294

1

G → A in ALS10. Ref.23 Ref.27

VAR_045660

Natural variant

294

1

G → V in ALS10; a patient with bulbar signs and dementia. Ref.25

VAR_058612

Natural variant

295

1

G → R in ALS10. Ref.25

VAR_058613

Natural variant

295

1

G → S in ALS10; also in patients with frontotemporal lobar degeneration with motor neuron disease. Ref.24 Ref.25

VAR_058614

Natural variant

298

1

G → S in ALS10. Ref.21

VAR_045661

Natural variant

315

1

A → T in ALS10. Ref.19 Ref.22

VAR_045662

Natural variant

331

1

Q → K in ALS10; impedes the development of normal limb and tail buds and increases the number of apoptotic nuclei when expressed in chick embryos; does not affect the interaction with ATNX2. Ref.15 Ref.23

VAR_045663

Natural variant

332

1

S → N in ALS10. Ref.25

VAR_058615

Natural variant

335

1

G → D in ALS10. Ref.25

VAR_058616

Natural variant

337

1

M → V in ALS10; impedes the development of normal limb and tail buds and increases the number of apoptotic nuclei when expressed in chick embryos. Ref.23 Ref.25

VAR_045664

Natural variant

343

1

Q → R in ALS10. Ref.20

VAR_062767

Natural variant

348

1

G → C in ALS10. Ref.22

VAR_045665

Natural variant

361

1

R → S in ALS10. Ref.22

VAR_045666

Natural variant

379

1

S → C in ALS10. Ref.25

VAR_058617

Natural variant

379

1

S → P in ALS10. Ref.25

VAR_058618

Natural variant

382

1

A → T in ALS10. Ref.22 Ref.25 Ref.28 Ref.29

VAR_045667

Natural variant

390

1

N → D in ALS10. Ref.22

VAR_045668

Natural variant

390

1

N → S in ALS10. Ref.22

VAR_045669

Natural variant

393

1

S → L in ALS10. Ref.25

VAR_058619

Experimental info

Mutagenesis

106 – 175

70

Missing: Completely abolishes RNA binding.

Mutagenesis

106 – 111

6

LIVLGL → DIDLGD: Completely abolishes RNA binding.

Mutagenesis

106 – 111

6

Missing: Completely abolishes RNA binding.

Mutagenesis

147 – 149

3

FGF → LGL: Highly reduces binding to RNA and DNA.

Mutagenesis

193 – 257

65

Missing: Alters but does not abolish RNA binding.

Sequence conflict

200

1

E → G in BAD96474. Ref.5

Sequence conflict

210

1

F → L in ABO32292. Ref.2

Sequence conflict

278

1

G → V in BAG35326. Ref.3

Secondary structure

1

.

.

.

.

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.

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414

Helix Strand Turn

Details...

Beta strand

106 – 110

5

Helix

117 – 124

8

Helix

125 – 127

3

Beta strand

130 – 137

8

Beta strand

139 – 141

3

Beta strand

143 – 154

12

Helix

155 – 163

9

Beta strand

166 – 168

3

Beta strand

171 – 176

6

Beta strand

193 – 197

5

Beta strand

200 – 202

3

Helix

204 – 210

7

Turn

212 – 214

3

Beta strand

219 – 221

3

Beta strand

231 – 233

3

Helix

237 – 242

6

Turn

243 – 245

3

Beta strand

247 – 250

4

Beta strand

253 – 258

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 8E09A1206FB4EF4A	FASTA	414	44,740
	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 KEYFSTFGEV LMVQVKKDLK TGHSKGFGFV RFTEYETQVK VMSQRHMIDG RWCDCKLPNS 190 200 210 220 230 240 KQSQDEPLRS RKVFVGRCTE DMTEDELREF FSQYGDVMDV FIPKPFRAFA FVTFADDQIA 250 260 270 280 290 300 QSLCGEDLII KGISVHISNA EPKHNSNRQL ERSGRFGGNP GGFGNQGGFG NSRGGGAGLG 310 320 330 340 350 360 NNQGSNMGGG MNFGAFSINP AMMAAAQAAL QSSWGMMGML ASQQNQSGPS GNNQNQGNMQ 370 380 390 400 410 REPNQAFGSG NNSYSGSNSG AAIGWGSASN AGSGSGFNGG FGSSMDSKSS GWGM
	Isoform 2 [UniParc]. Checksum: EA164E09A1206FB4	FASTA	416	44,991
	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 KEYFSTFGEV LMVQVKKDLK TGHSKGFGFV RFTEYETQVK VMSQRHMIDG RWCDCKLPNS 190 200 210 220 230 240 KQSQDEPLRS RKVFVGRCTE DMTEDELREF FSQYGDVMDV FIPKPFRAFA FVTFADDQIA 250 260 270 280 290 300 QSLCGEDLII KGISVHISNA EPKHNSNRQL ERSGRFGGNP GGFGNQGGFG NSRGGGAGLG 310 320 330 340 350 360 NNQGSNMGGG MNFGAFSINP AMMAAAQAAL QSSWGMMGML ASQQNQSGPS GNNQNQGNMQ 370 380 390 400 410 REPNQAFGSG NNSYSGSNSG AAIGWGSASN AGSGSGFNGG FGSSMDSKSS GWGMNH
	Isoform 3 [UniParc]. Checksum: A033BC3DE41C9D0C	FASTA	260	27,972
	10 20 30 40 50 60 MSEYIRVTED ENDEPIEIPS EDDGTVLLST VTAQFPGACG LRYRNPVSQC MRGVRLVEGI 70 80 90 100 110 120 LHAPDAGWGN LVYVVNYPKD NKRKMDELRE FFSQYGDVMD VFIPKPFRAF AFVTFADDQI 130 140 150 160 170 180 AQSLCGEDLI IKGISVHISN AEPKHNSNRQ LERSGRFGAF SINPAMMAAA QAALQSSWGM 190 200 210 220 230 240 MGMLASQQNQ SGPSGNNQNQ GNMQREPNQA FGSGNNSYSG SNSGAAIGWG SASNAGSGSG 250 260 FNGGFGSSMD SKSSGWGMNH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs." Ou S.-H.I., Wu F., Harrich D., Garcia-Martinez L.F., Gaynor R.B. J. Virol. 69:3584-3596(1995) [PubMed: 7745706] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: Cervix carcinoma.
[2]	"TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein." Strong M.J., Volkening K., Hammond R., Yang W., Strong W., Leystra-Lantz C., Shoesmith C. Mol. Cell. Neurosci. 35:320-327(2007) [PubMed: 17481916] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), SUBCELLULAR LOCATION, FUNCTION, UBIQUITINATION, ALTERNATIVE SPLICING.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Liver.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[7]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph and Testis.
[10]	Lubec G., Afjehi-Sadat L. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 122-136 AND 276-293, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[11]	"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis." Neumann M., Sampathu D.M., Kwong L.K., Truax A.C., Micsenyi M.C., Chou T.T., Bruce J., Schuck T., Grossman M., Clark C.M., McCluskey L.F., Miller B.L., Masliah E., Mackenzie I.R., Feldman H., Feiden W., Kretzschmar H.A., Trojanowski J.Q., Lee V.M.-Y. Science 314:130-133(2006) [PubMed: 17023659] [Abstract] Cited for: PROTEIN SEQUENCE OF 252-263; 276-293 AND 409-414, SUBCELLULAR LOCATION, PHOSPHORYLATION, UBIQUITINATION.
[12]	"Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping." Buratti E., Doerk T., Zuccato E., Pagani F., Romano M., Baralle F.E. EMBO J. 20:1774-1784(2001) [PubMed: 11285240] [Abstract] Cited for: FUNCTION.
[13]	"Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9." Buratti E., Baralle F.E. J. Biol. Chem. 276:36337-36343(2001) [PubMed: 11470789] [Abstract] Cited for: RNA-BINDING, MUTAGENESIS.
[14]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-91 AND SER-92, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS." Elden A.C., Kim H.J., Hart M.P., Chen-Plotkin A.S., Johnson B.S., Fang X., Armakola M., Geser F., Greene R., Lu M.M., Padmanabhan A., Clay-Falcone D., McCluskey L., Elman L., Juhr D., Gruber P.J., Rub U., Auburger G. , Trojanowski J.Q., Lee V.M., Van Deerlin V.M., Bonini N.M., Gitler A.D. Nature 466:1069-1075(2010) [PubMed: 20740007] [Abstract] Cited for: INTERACTION WITH ATNX2, CHARACTERIZATION OF VARIANT ALS10 LYS-331.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"Solution structure of the RNA binding domains of TAR DNA-binding protein-43." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 96-267.
[18]	"Solution structure of RRM domain in tar DNA-binding protein-43." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2009) to the PDB data bank Cited for: STRUCTURE BY NMR OF 193-267.
[19]	"TDP-43 A315T mutation in familial motor neuron disease." Gitcho M.A., Baloh R.H., Chakraverty S., Mayo K., Norton J.B., Levitch D., Hatanpaa K.J., White C.L. III, Bigio E.H., Caselli R., Baker M., Al-Lozi M.T., Morris J.C., Pestronk A., Rademakers R., Goate A.M., Cairns N.J. Ann. Neurol. 63:535-538(2008) [PubMed: 18288693] [Abstract] Cited for: VARIANT ALS10 THR-315.
[20]	"TDP-43 mutation in familial amyotrophic lateral sclerosis." Yokoseki A., Shiga A., Tan C.F., Tagawa A., Kaneko H., Koyama A., Eguchi H., Tsujino A., Ikeuchi T., Kakita A., Okamoto K., Nishizawa M., Takahashi H., Onodera O. Ann. Neurol. 63:538-542(2008) [PubMed: 18438952] [Abstract] Cited for: VARIANT ALS10 ARG-343.
[21]	"TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis." Van Deerlin V.M., Leverenz J.B., Bekris L.M., Bird T.D., Yuan W., Elman L.B., Clay D., Wood E.M., Chen-Plotkin A.S., Martinez-Lage M., Steinbart E., McCluskey L., Grossman M., Neumann M., Wu I.-L., Yang W.-S., Kalb R., Galasko D.R. , Montine T.J., Trojanowski J.Q., Lee V.M.-Y., Schellenberg G.D., Yu C.-E. Lancet Neurol. 7:409-416(2008) [PubMed: 18396105] [Abstract] Cited for: VARIANTS ALS10 ALA-290 AND SER-298.
[22]	"TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis." Kabashi E., Valdmanis P.N., Dion P., Spiegelman D., McConkey B.J., Vande Velde C., Bouchard J.-P., Lacomblez L., Pochigaeva K., Salachas F., Pradat P.-F., Camu W., Meininger V., Dupre N., Rouleau G.A. Nat. Genet. 40:572-574(2008) [PubMed: 18372902] [Abstract] Cited for: VARIANTS ALS10 GLY-169; SER-287; THR-315; CYS-348; SER-361; THR-382; ASP-390 AND SER-390, VARIANT VAL-90.
[23]	"TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis." Sreedharan J., Blair I.P., Tripathi V.B., Hu X., Vance C., Rogelj B., Ackerley S., Durnall J.C., Williams K.L., Buratti E., Baralle F., de Belleroche J., Mitchell J.D., Leigh P.N., Al-Chalabi A., Miller C.C., Nicholson G., Shaw C.E. Science 319:1668-1672(2008) [PubMed: 18309045] [Abstract] Cited for: VARIANTS ALS10 ALA-294; LYS-331 AND VAL-337, VARIANT VAL-90, CHARACTERIZATION OF VARIANTS ALS10 LYS-331 AND VAL-337.
[24]	"TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration." French clinical and genetic research network on frontotemporal lobar degeneration/frontotemporal lobar degeneration with motoneuron disease Benajiba L., Le Ber I., Camuzat A., Lacoste M., Thomas-Anterion C., Couratier P., Legallic S., Salachas F., Hannequin D., Decousus M., Lacomblez L., Guedj E., Golfier V., Camu W., Dubois B., Campion D., Meininger V., Brice A. Ann. Neurol. 65:470-473(2009) [PubMed: 19350673] [Abstract] Cited for: INVOLVEMENT OF VARIANT ALS10 SER-295 IN FRONTOTEMPORAL LOBAR DEGENERATION WITH MOTOR NEURON DISEASE.
[25]	"High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis." Corrado L., Ratti A., Gellera C., Buratti E., Castellotti B., Carlomagno Y., Ticozzi N., Mazzini L., Testa L., Taroni F., Baralle F.E., Silani V., D'Alfonso S. Hum. Mutat. 30:688-694(2009) [PubMed: 19224587] [Abstract] Cited for: VARIANTS ALS10 SER-267; SER-287; VAL-294; SER-295; ARG-295; ASN-332; ASP-335; VAL-337; PRO-379; CYS-379; THR-382 AND LEU-393.
[26]	"Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease." Borroni B., Bonvicini C., Alberici A., Buratti E., Agosti C., Archetti S., Papetti A., Stuani C., Di Luca M., Gennarelli M., Padovani A. Hum. Mutat. 30:E974-E983(2009) [PubMed: 19655382] [Abstract] Cited for: INVOLVEMENT OF VARIANT ALS10 SER-267 IN FRONTOTEMPORAL DEMENTIA.
[27]	"Genetic variants in the promoter of TARDBP in sporadic amyotrophic lateral sclerosis." Luquin N., Yu B., Saunderson R.B., Trent R.J., Pamphlett R. Neuromuscul. Disord. 19:696-700(2009) [PubMed: 19695877] [Abstract] Cited for: VARIANT ALS10 ALA-294.
[28]	"Large Proportion of Amyotrophic Lateral Sclerosis Cases in Sardinia Due to a Single Founder Mutation of the TARDBP Gene." Chio A., Borghero G., Pugliatti M., Ticca A., Calvo A., Moglia C., Mutani R., Brunetti M., Ossola I., Marrosu M.G., Murru M.R., Floris G., Cannas A., Parish L.D., Cossu P., Abramzon Y., Johnson J.O., Nalls M.A. , Arepalli S., Chong S., Hernandez D.G., Traynor B.J., Restagno G. Arch. Neurol. 68:594-598(2011) [PubMed: 21220647] [Abstract] Cited for: VARIANT ALS10 THR-382.
[29]	"High frequency of the TARDBP p.Ala382Thr mutation in Sardinian patients with amyotrophic lateral sclerosis." Orru S., Manolakos E., Orru N., Kokotas H., Mascia V., Carcassi C., Petersen M.B. Clin. Genet. 0:0-0(2011) [PubMed: 21418058] [Abstract] Cited for: VARIANT ALS10 THR-382.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U23731 mRNA. Translation: AAA70033.1.
EF434181 mRNA. Translation: ABO32290.1.
EF434182 mRNA. Translation: ABO32291.1.
EF434183 mRNA. Translation: ABO32292.1.
AK312416 mRNA. Translation: BAG35326.1.
CR533534 mRNA. Translation: CAG38565.1.
AK222754 mRNA. Translation: BAD96474.1.
AL050265 mRNA. Translation: CAB43367.1.
AL109811 Genomic DNA. Translation: CAI22098.1.
CH471130 Genomic DNA. Translation: EAW71670.1.
BC071657 mRNA. Translation: AAH71657.1.
BC095435 mRNA. Translation: AAH95435.1.

IPI

IPI00025815.
IPI00844544.
IPI00971018.

PIR

I38977.

RefSeq

NP_031401.1. NM_007375.3.

UniGene

Hs.300624.
Hs.635053.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WF0	NMR	-	A	193-267	[»]
2CQG	NMR	-	A	96-185	[»]

ProteinModelPortal

Q13148.

SMR

Q13148. Positions 90-267.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31167N.

IntAct

Q13148. 16 interactions.

STRING

Q13148.

PTM databases

PhosphoSite

Q13148.

Polymorphism databases

DMDM

20140568.

Proteomic databases

PRIDE

Q13148.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000240185; ENSP00000240185; ENSG00000120948.

GeneID

23435.

KEGG

hsa:23435.

UCSC

uc001art.1. human.

Organism-specific databases

CTD

23435.

GeneCards

GC01P011006.

H-InvDB

HIX0000120.
HIX0030280.

HGNC

HGNC:11571. TARDBP.

HPA

CAB003703.
HPA017284.

MIM

605078. gene.
612069. phenotype.

neXtProt

NX_Q13148.

Orphanet

803. Amyotrophic lateral sclerosis.
98929. Frontotemporal dementia with motor neuron-disease type inclusions.

PharmGKB

PA36336.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG058671.

InParanoid

Q13148.

OMA

KHNSSRQ.

OrthoDB

EOG447FTT.

PhylomeDB

Q13148.

Gene expression databases

ArrayExpress

Q13148.

Bgee

Q13148.

CleanEx

HS_TARDBP.

Genevestigator

Q13148.

GermOnline

ENSG00000120948. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.30.70.330. a_b_plait_nuc_bd. 2 hits.

Pfam

PF00076. RRM_1. 2 hits.
[Graphical view]

SMART

SM00360. RRM. 2 hits.
[Graphical view]

PROSITE

PS50102. RRM. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

45695.

SOURCE

Search...

Entry information

Entry name

TADBP_HUMAN

Accession

Primary (citable) accession number: Q13148
Secondary accession number(s): A4GUK4 , A4GUK5, A4GUK6, B2R629, E2PU12, Q53H27, Q6FI92, Q96DJ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 127 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.