SF3B5

SF3B5 (SF3b10) is a small structural subunit of the heptameric SF3b complex within the U2 snRNP, where it contributes to the assembly architecture required for pre-mRNA splicing (PMID:27720643, PMID:32494006). Crystallographic and crosslinking analysis of the human SF3b core showed that SF3B5 makes multiple direct contacts with SF3B1 (SF3b155) and SF3b130, helping maintain the distinctive conformation of the SF3B1 HEAT domain (PMID:27720643); in the assembled 17S U2 snRNP, these contacts help hold the SF3B1 HEAT domain in the open conformation associated with branch point adenosine recognition (PMID:32494006). SF3B5 is an integral component of the drug-bound SF3b subcomplex (SF3B1–SF3B3–PHF5A–SF3B5) whose quaternary architecture facilitates binding of the splicing modulator E7107 in the branch point adenosine pocket (PMID:29491137). Its membership in an SF3b-like complex is evolutionarily conserved, with orthologs co-purifying with SF3b subunits in Trypanosoma and being required for fitness in Candida albicans (PMID:19450735, PMID:41105619). Beyond its role as a conformational scaffold within SF3b, no independent catalytic or regulatory activity for SF3B5 has been characterized in the available corpus.

1. 2009 Low

   Establishing that the SF3B5 homologue is a conserved member of an SF3b-like complex addressed whether its complex association predates vertebrates.

   Evidence TAP-tag co-purification of the DRBD1/SF3b10 homologue with p14, SAP130, SAP145, and SAP155 in Trypanosoma brucei, with nuclear localization and RNAi growth assay

   PMID:19450735

   Open questions at the time

   • Single method (TAP purification) in a distant organism with SF3b10 not directly studied
   • No structural or molecular role defined for the homologue itself
   • No mapping of direct binding partners within the complex
2. 2016 High

   Determining where SF3B5 sits in the SF3b complex answered whether it is a structural scaffold and which subunits it contacts.

   Evidence Crystal structure of the human SF3b core complex plus crosslinking mass spectrometry, with complementary integrative modeling guided by cryo-EM density

   PMID:27618338 PMID:27720643

   Open questions at the time

   • No mutagenesis test of which SF3B5 contacts are functionally required
   • Conformational role inferred structurally rather than by functional perturbation
   • Does not define SF3B5 contribution to splicing catalysis directly
3. 2018 High

   Resolving the drug-bound SF3b subcomplex established that SF3B5 is part of the architecture targeted by splicing modulators.

   Evidence Cryo-EM structure at 3.95 Å of the SF3B1–SF3B3–PHF5A–SF3B5 subcomplex bound to E7107, with chemical probe and resistance mutation analyses

   PMID:29491137

   Open questions at the time

   • SF3B5 is a structural participant but no SF3B5 residue is shown to directly contact E7107
   • Functional consequence of SF3B5 perturbation on drug response not tested
4. 2020 High

   Placing SF3B5 in the assembled 17S U2 snRNP confirmed its role in maintaining the open SF3B1 HEAT-domain conformation in the physiological particle.

   Evidence Cryo-EM structure of the human 17S U2 snRNP at 4.1 Å core resolution combined with protein crosslinking mass spectrometry

   PMID:32494006

   Open questions at the time

   • Conformational role inferred from static structure
   • No dynamics of the open-to-closed transition resolved with respect to SF3B5
5. 2025 Medium

   Loss-of-function screening tested whether the SF3B5 ortholog is required for organismal fitness, linking it to viability and thermal adaptation.

   Evidence Genome-wide GRACE library screen of YSF3 in Candida albicans across temperature conditions with a loss-of-function fitness assay

   PMID:41105619

   Open questions at the time

   • No molecular mechanism dissected for YSF3 specifically
   • Single study
   • Connection between fitness phenotype and splicing function not directly demonstrated

• Whether SF3B5 contributes activity beyond a static conformational scaffold — and how its perturbation alters splice site selection — remains unresolved.
• No functional perturbation of SF3B5 in human cells reported in the corpus
• No defined effect of SF3B5 loss on specific splicing events
• No regulatory or post-translational control of SF3B5 described