Splicing factor 3b subunit 2 (SF3B2)

Splicing factor 3b subunit 2 (SF3B2) is a highly conserved, protein-coding subunit of the SF3B complex, which itself is an essential part of the 17S U2 small nuclear ribonucleoprotein (U2 snRNP) in the major spliceosome[1][2][4]. SF3B2 anchors the SF3B complex to pre-mRNA upstream of the intron branch point, facilitating recognition of the correct site for intron excision during pre-mRNA splicing[1][2][4]. The protein is hydrophilic, with a proline-rich N-terminus and a glutamate-rich C-terminus[2][4]. SF3B2 is fundamental for the assembly of the spliceosome, the selection of the branch-site adenosine, and is involved in both U2-type and minor U12-type spliceosome reactions[1][2][4]. Dysregulation or mutation of SF3B2 has been implicated in developmental disorders and is likely to contribute to cancer pathogenesis due to its crucial role in gene expression regulation[1][3][4]. Drugs modulating the SF3B complex are being explored as cancer therapeutics, but substantial safety concerns remain due to the complex’s essential function in all cells[1][3].

Other names

SAP145SF3b145SAP 145SF3B145CFMCus1HFMSF3b1SF3b150Pre-mRNA-splicing factor SF3b 145 kDa subunitSpliceosome-associated protein 145splicing factor 3b, subunit 2, 145kDsplicing factor 3b, subunit 2, 145kDa

Small-molecule modulators (e.g., pladienolide B and related drugs) bind to and inhibit the SF3B complex (main target SF3B1, but likely impact the function of the entire complex including SF3B2), thereby preventing proper assembly/recognition of the branch point sequence and blocking splicing, which induces apoptosis in highly splicing-dependent cells (e.g., cancer cells)