D
IPR053822

SDE2-like domain

InterPro entry
Short nameSDE2-like_dom

Description

SDE2 (silencing defective 2) is a ubiquitin-fold-containing splicing regulator that supports splicing of selected pre-mRNAs in an intron-specific manner in Schizosaccharomyces pombe. This splicing regulator is conserved among intron-rich eukaryotes up to humans, but is absent in intron-poor organisms such as S. cerevisiae. SDE2 is important in pre-mRNA splicing in mammalian cells
[1, 4, 2]
. Human SDE2 is a regulatory component of the fork protection complex (FPC) at active and stalled replication forks
[5]
.

SDE2 is translated as an inactive precursor harbouring an ubiquitin-fold at its N-terminal that is processed by deubiquitinating enzymes (DUBs, Ubp5 and Ubp15 in S.pombe) in a conserved GG-K motif to form activated K-Sde2-C
[2]
, which is necessary to get incorporated into the spliceosome
[1, 4, 2, 3, 5]
. SDE2 is both an RNA-binding protein and also a trans-acting adaptor protein that functions to regulate RNA splicing and ribosome biogenesis.

This entry represents the SDE2 domain, a coiled-coil domain required for the interaction of SDE2 with TIMELESS (TIM), which promotes stable association of the FPC at active replication forks
[5]
.

References

1.Sde2 is an intron-specific pre-mRNA splicing regulator activated by ubiquitin-like processing. Thakran P, Pandit PA, Datta S, Kolathur KK, Pleiss JA, Mishra SK. EMBO J. 37, 89-101, (2018). View articlePMID: 28947618

2.Splicing of branchpoint-distant exons is promoted by Cactin, Tls1 and the ubiquitin-fold-activated Sde2. Anil AT, Choudhary K, Pandian R, Gupta P, Thakran P, Singh A, Sharma M, Mishra SK. Nucleic Acids Res 50, 10000-10014, (2022). PMID: 36095128

3.SDE2 is an essential gene required for ribosome biogenesis and the regulation of alternative splicing. Floro J, Dai A, Metzger A, Mora-Martin A, Ganem NJ, Cifuentes D, Wu CS, Dalal J, Lyons SM, Labadorf A, Flynn RL. Nucleic Acids Res 49, 9424-9443, (2021). PMID: 34365507

4.PCNA-Dependent Cleavage and Degradation of SDE2 Regulates Response to Replication Stress. Jo U, Cai W, Wang J, Kwon Y, D'Andrea AD, Kim H. PLoS Genet 12, e1006465, (2016). PMID: 27906959

5.Extended DNA-binding interfaces beyond the canonical SAP domain contribute to the function of replication stress regulator SDE2 at DNA replication forks. Weinheimer AS, Paung Y, Rageul J, Khan A, Lo N, Ho B, Tong M, Alphonse S, Seeliger MA, Kim H. J Biol Chem 298, 102268, (2022). View articlePMID: 35850305

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