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tRNA-splicing endonuclease subunit Sen2

 
Known also as: tRNA-intron endonuclease Sen2, HsSen2

Known abbreviations: TSEN2, SEN2

 

FUNCTION:
 
Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. Isoform 1 probably carries the active site for 5'-splice site cleavage. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events. Isoform 2 is responsible for processing a yet unknown RNA substrate. The complex containing isoform 2 is not able to cleave pre-tRNAs properly, although it retains endonucleolytic activity. 
 
CATALYTIC ACTIVITY:
 
Endonucleolytic cleavage of pre-tRNA, producing 5'-hydroxy and 2',3'-cyclic phosphate termini, and specifically removing the intron.
 
SUBUNIT STRUCTURE:
 
tRNA splicing endonuclease is a heterotetramer composed of isoform 1 of SEN2, SEN15, SEN34/LENG5 and SEN54. tRNA splicing endonuclease complex also contains proteins of the pre-mRNA 3'-end processing machinery such as CLP1, CPSF1, CPSF4 and CSTF2. Isoform 2 belongs to a different complex that contains SEN54 but low level of SEN15 and SEN34/LENG5.
 
CELLULAR LOCALIZATION:
 
Nucleus. Nucleus › nucleolus. Note: May be transiently localized in the nucleolus. 
 
TISSUE SPECIFICITY:
 
Isoform 1 and isoform 2 are widely expressed at very low level. 
 
POST-TRANSLATIONAL MODIFICATION:
 
Phosphorylated upon DNA damage, probably by ATM or ATR.
 
INVOLVEMENT IN DISEASE:
 
Defects in TSEN2 are the cause of pontocerebellar hypoplasia type 2B (PCH2B) [MIM:612389]. Pontocerebellar hypoplasia (PCH) is a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem. PCH type 2 is characterized by progressive microcephaly from birth combined with extrapyramidal dyskinesia and chorea, epilepsy, and normal spinal cord findings.



This protein can be a part of a given complexes: Activities in which tRNA-splicing endonuclease subunit Sen2 is involved: Pathways in which tRNA-splicing endonuclease subunit Sen2 is involved:

NCBI GI number(s): 223972632
223972631
223972634
223972633
13376882
223972629
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q8NCE0 Q8NCE0
BRENDA - -
KEGG hsa:8074 hsa:8074
PFAM: PF01974
PF02778
PF01974
PF02778
InterPro: IPR011856
IPR006677
IPR006678
IPR016589
IPR011856
IPR006677
IPR006678
IPR016589
CATH: - -
SCOP: - -


Protein sequence:
MAEAVFHAPKRKRRVYETYESPLPIPFGQDHGPLKEFKIFRAEMINNNVI
VRNAEDIEQLYGKGYFGKGILSRSRPSFTISDPKLVAKWKDMKTNMPIIT
SKRYQHSVEWAAELMRRQGQDESTVRRILKDYTKPLEHPPVKRNEEAQVH
DKLNSGMVSNMEGTAGGERPSVVNGDSGKSGGVGDPREPLGCLQEGSGCH
PTTESFEKSVREDASPLPHVCCCKQDALILQRGLHHEDGSQHIGLLHPGD
RGPDHEYVLVEEAECAMSEREAAPNEELVQRNRLICRRNPYRIFEYLQLS
LEEAFFLVYALGCLSIYYEKEPLTIVKLWKAFTVVQPTFRTTYMAYHYFR
SKGWVPKVGLKYGTDLLLYRKGPPFYHASYSVIIELVDDHFEGSLRRPLS
WKSLAALSRVSVNVSKELMLCYLIKPSTMTDKEMESPECMKRIKVQEVIL
SRWVSSRERSDQDDL

TRNA-splicing endonuclease subunit Sen2 (Homo sapiens) is product of expression of TSEN2 gene.

References:

Title Authors Journal Publication date (Issue) PubMed ID
tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. Budde BS, Namavar Y, Barth PG, Poll-The BT, Nurnberg G, Becker C, van Ruissen F, Weterman MA, Fluiter K, te Beek ET, Aronica E, van der Knaap MS, Hohne W, Toliat MR, Crow YJ, Steinling M, Voit T, Roelenso F, Brussel W, Brockmann K, Kyllerman M, Boltshauser E, Hammersen G, Willemsen M, Basel-Vanagaite L, Krageloh-Mann I, de Vries LS, Sztriha L, Muntoni F, Ferrie CD, Battini R, Hennekam RC, Grillo E, Beemer FA, Stoets LM, Wollnik B, Nurnberg P, Baas F Nat Genet 2008-09-01 (40) 18711368
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, K Genome Res 2004-10-01 (14) 15489334
Identification of a human endonuclease complex reveals a link between tRNA splicing and pre-mRNA 3' end formation. Paushkin SV, Patel M, Furia BS, Peltz SW, Trotta CR Cell 2004-04-01 (117) 15109492
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 Nat Genet 2004-02-01 (36) 14702039
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ Science 2007-05-25 (316) 17525332



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Last modification of this entry: Sept. 25, 2012.

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