Structural highlights
Function
SPF45_HUMAN Splice factor that binds to the single stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites. Promotes the utilization of a cryptic splice site created by the beta-110 mutation in the HBB gene. The resulting frameshift leads to sickle cell anemia.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The U2AF-homology motif (UHM) mediates protein-protein interactions between factors involved in constitutive RNA splicing. Here we report that the splicing factor SPF45 regulates alternative splicing of the apoptosis regulatory gene FAS (also called CD95). The SPF45 UHM is necessary for this activity and binds UHM-ligand motifs (ULMs) present in the 3' splice site-recognizing factors U2AF65, SF1 and SF3b155. We describe a 2.1-A crystal structure of SPF45-UHM in complex with a ULM peptide from SF3b155. Features distinct from those of previously described UHM-ULM structures allowed the design of mutations in the SPF45 UHM that selectively impair binding to individual ULMs. Splicing assays using the ULM-selective SPF45 variants demonstrate that individual UHM-ULM interactions are required for FAS splicing regulation by SPF45 in vivo. Our data suggest that networks of UHM-ULM interactions are involved in regulating alternative splicing.
U2AF-homology motif interactions are required for alternative splicing regulation by SPF45.,Corsini L, Bonnal S, Basquin J, Hothorn M, Scheffzek K, Valcarcel J, Sattler M Nat Struct Mol Biol. 2007 Jul;14(7):620-9. Epub 2007 Jun 24. PMID:17589525[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lallena MJ, Chalmers KJ, Llamazares S, Lamond AI, Valcarcel J. Splicing regulation at the second catalytic step by Sex-lethal involves 3' splice site recognition by SPF45. Cell. 2002 May 3;109(3):285-96. PMID:12015979
- ↑ Corsini L, Bonnal S, Basquin J, Hothorn M, Scheffzek K, Valcarcel J, Sattler M. U2AF-homology motif interactions are required for alternative splicing regulation by SPF45. Nat Struct Mol Biol. 2007 Jul;14(7):620-9. Epub 2007 Jun 24. PMID:17589525 doi:10.1038/nsmb1260
