logo CaMPDB: Calpain for Modulatory Proteolysis Database

SB0140 : TAR DNA-binding protein 43, TDP-43

[ CaMP Format ]

* Basic Information

OrganismHomo sapiens (human)
Protein NamesTAR DNA-binding protein 43 [Homo sapiens]; TAR DNA-binding protein 43; TAR DNA-binding protein-43; TDP-43
Gene NamesTARDBP; TDP43; TAR DNA binding protein
Gene Locus1p36.22; chromosome 1
GO FunctionNot available
Entrez Protein Entrez Nucleotide Entrez Gene UniProt OMIM HGNC HPRD KEGG
NP_031401 NM_007375 23435 Q13148 605078 HGNC:11571 05466 hsa:23435

* Information From OMIM

Description: The TARDBP gene encodes the 43-kD TAR DNA-binding protein, which was originally identified as a transcriptional repressor that binds to TAR DNA of human immunodeficiency virus type 1. It is also involved in regulation of gene expression and splicing (summary by Benajiba et al., 2009).

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* Structure Information

1. Primary Information

Length: 414 aa

Average Mass: 44.739 kDa

Monoisotopic Mass: 44.711 kDa

2. Domain Information

Annotated Domains: interpro / pfam / smart / prosite

Computationally Assigned Domains (Pfam+HMMER):

domain namebeginendscoree-value
RNA recognition motif 1. 748829.00.0
DNA ligase IV 1. 11512520.00.2
DNA ligase IV 2. 19921317.00.1
--- cleavage 229 ---
--- cleavage 243 ---
--- cleavage 286 ---
--- cleavage 295 ---
--- cleavage 297 ---
--- cleavage 302 ---
--- cleavage 303 ---
--- cleavage 304 ---
--- cleavage 324 ---
RNA recognition motif (a.k.a. RRM, RBD, or RNP domain) 1. 32433847.00.0
--- cleavage 324 (inside RNA recognition motif (a.k.a. RRM, RBD, or RNP domain) 324..338) ---

3. Sequence Information

Fasta Sequence: SB0140.fasta

Amino Acid Sequence and Secondary Structures (PsiPred):

4. 3D Information

Known Structures in PDB: 1WF0 (NMR; -; A=193-267), 2CQG (NMR; -; A=96-185), 4BS2 (NMR; -; A=102-269), 4IUF (X-ray; 275 A; A=103-179)

* Cleavage Information

10 [sites] cleaved by Calpain 1

Source Reference: [PubMed ID: 23250437] Yamashita T, Hideyama T, Hachiga K, Teramoto S, Takano J, Iwata N, Saido TC, Kwak S, A role for calpain-dependent cleavage of TDP-43 in amyotrophic lateral sclerosis pathology. Nat Commun. 2012;3:1307. doi: 10.1038/ncomms2303.

Cleavage sites (±10aa)

[Site 1] VFIPKPFRAF229-AFVTFADDQI

Phe229 Ala

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Val220Phe221Ile222Pro223Lys224Pro225Phe226Arg227Ala228Phe229
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Ala230Phe231Val232Thr233Phe234Ala235Asp236Asp237Gln238Ile239

Sequence conservation (by blast)

[Site 2] FADDQIAQSL243-CGEDLIIKGI

Leu243 Cys

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Phe234Ala235Asp236Asp237Gln238Ile239Ala240Gln241Ser242Leu243
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Cys244Gly245Glu246Asp247Leu248Ile249Ile250Lys251Gly252Ile253

Sequence conservation (by blast)

[Site 3] GGNPGGFGNQ286-GGFGNSRGGG

Gln286 Gly

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Gly277Gly278Asn279Pro280Gly281Gly282Phe283Gly284Asn285Gln286
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Gly287Gly288Phe289Gly290Asn291Ser292Arg293Gly294Gly295Gly296

Sequence conservation (by blast)

[Site 4] QGGFGNSRGG295-GAGLGNNQGS

Gly295 Gly

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Gln286Gly287Gly288Phe289Gly290Asn291Ser292Arg293Gly294Gly295
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Gly296Ala297Gly298Leu299Gly300Asn301Asn302Gln303Gly304Ser305

Sequence conservation (by blast)

[Site 5] GFGNSRGGGA297-GLGNNQGSNM

Ala297 Gly

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Gly288Phe289Gly290Asn291Ser292Arg293Gly294Gly295Gly296Ala297
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Gly298Leu299Gly300Asn301Asn302Gln303Gly304Ser305Asn306Met307

Sequence conservation (by blast)

[Site 6] RGGGAGLGNN302-QGSNMGGGMN

Asn302 Gln

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Arg293Gly294Gly295Gly296Ala297Gly298Leu299Gly300Asn301Asn302
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Gln303Gly304Ser305Asn306Met307Gly308Gly309Gly310Met311Asn312

Sequence conservation (by blast)

[Site 7] GGGAGLGNNQ303-GSNMGGGMNF

Gln303 Gly

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Gly294Gly295Gly296Ala297Gly298Leu299Gly300Asn301Asn302Gln303
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Gly304Ser305Asn306Met307Gly308Gly309Gly310Met311Asn312Phe313

Sequence conservation (by blast)

[Site 8] GGAGLGNNQG304-SNMGGGMNFG

Gly304 Ser

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Gly295Gly296Ala297Gly298Leu299Gly300Asn301Asn302Gln303Gly304
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Ser305Asn306Met307Gly308Gly309Gly310Met311Asn312Phe313Gly314

Sequence conservation (by blast)

[Site 9] AFSINPAMMA324-AAQAALQSSW

Ala324 Ala

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Ala315Phe316Ser317Ile318Asn319Pro320Ala321Met322Met323Ala324
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Ala325Ala326Gln327Ala328Ala329Leu330Gln331Ser332Ser333Trp334

Sequence conservation (by blast)

[Site 10] MGMLASQQNQ346-SGPSGNNQNQ

Gln346 Ser

P10 P9 P8 P7 P6 P5 P4 P3 P2 P1
Met337Gly338Met339Leu340Ala341Ser342Gln343Gln344Asn345Gln346
P1' P2' P3' P4' P5' P6' P7' P8' P9' P10'
Ser347Gly348Pro349Ser350Gly351Asn352Asn353Gln354Asn355Gln356

Sequence conservation (by blast)

* References

[PubMed ID: 24440855] De Marco G, Lomartire A, Mandili G, Lupino E, Buccinna B, Ramondetti C, Moglia C, Novelli F, Piccinini M, Mostert M, Rinaudo MT, Chio A, Calvo A, Reduced cellular Ca(2+) availability enhances TDP-43 cleavage by apoptotic caspases. Biochim Biophys Acta. 2014 Apr;1843(4):725-34. doi: 10.1016/j.bbamcr.2014.01.010.

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