Splicing factor U2AF 65 kDa subunit

Function

Plays a role in pre-mRNA splicing and 3'-end processing. By recruiting PRPF19 and the PRP19C/Prp19 complex/NTC/Nineteen complex to the RNA polymerase II C-terminal domain (CTD), and thereby pre-mRNA, may couple transcription to splicing. Induces cardiac troponin-T (TNNT2) pre-mRNA exon inclusion in muscle. Regulates the TNNT2 exon 5 inclusion through competition with MBNL1. Binds preferentially to a single-stranded structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Represses the splicing of MAPT/Tau exon 10. Positively regulates pre-mRNA 3'-end processing by recruiting the CFIm complex to cleavage and polyadenylation signals.

Classification

Family (Pfam)

PF00076 RRM_1

InterPro

Nucleotide-bd_a/b_plait_sf, RBD_domain_sf, RRM_dom, U2AF_lg

Functional cluster

Protein Serine/Threonine Kinases

Experimental structures · PDB · 40

• 1JMT X-ray 2.20A
• 1O0P NMR
• 1OPI NMR
• 1U2F NMR
• 2G4B X-ray 2.50A
• 2HZC X-ray 1.47A
• 2M0G NMR
• 2U2F NMR
• 2YH0 NMR
• 2YH1 NMR
• 3VAF X-ray 2.49A
• 3VAG X-ray 2.19A
• … and 28 more

A predicted model is available from AlphaFold.

Gene Ontology · 19

• GO:0000243 commitment complex
• GO:0016607 nuclear speck
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0005681 spliceosomal complex
• GO:0071004 U2-type prespliceosome
• GO:0089701 U2AF complex
• GO:0070742 C2H2 zinc finger domain binding
• GO:0019899 enzyme binding
• GO:0140678 molecular function inhibitor activity
• GO:0008187 poly-pyrimidine tract binding
• GO:0030628 pre-mRNA 3'-splice site binding
• GO:0003723 RNA binding
• GO:0006397 mRNA processing
• GO:0000398 mRNA splicing, via spliceosome
• GO:0048025 negative regulation of mRNA splicing, via spliceosome
• GO:0031397 negative regulation of protein ubiquitination
• GO:0033120 positive regulation of RNA splicing
• GO:0000245 spliceosomal complex assembly

Disease associations

• developmental delay, dysmorphic facies, and brain anomalies MONDO:0957810

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Splicing factor U2AF 65 kDa subunit 1.00
• Splicing factor U2AF 50 kDa subunit 0.98
• Splicing factor U2AF 65 kDa subunit 0.91
• Splicing factor U2AF 65 kDa subunit 0.90
• Splicing factor U2af large subunit B 0.88
• Splicing factor U2af large subunit B 0.86
• Splicing factor U2af large subunit A 0.85
• Splicing factor U2af large subunit A 0.84
• Splicing factor U2af large subunit A 0.84
• Splicing factor U2af large subunit B 0.83
• Splicing factor U2af large subunit B 0.81
• RNA-binding protein 39 0.78

Co-cited proteins · studied together in the literature

• Splicing factor 1 4 shared papers
• KH homology domain-containing protein 4 1 shared papers
• Splicing factor U2AF 35 kDa subunit 1 shared papers
• Muscleblind-like protein 1 1 shared papers
• Protein SCAF11 1 shared papers
• Putative RNA-binding protein Luc7-like 2 1 shared papers
• SNW domain-containing protein 1 1 shared papers
• Splicing factor 45 1 shared papers
• Pre-mRNA-processing factor 19 2 shared papers
• Cleavage and polyadenylation specificity factor subunit 7 1 shared papers
• Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 2 shared papers
• Serine/arginine-rich splicing factor 2 2 shared papers

Literature · 37 cited papers

• U2AF2 variant in a patient with developmental delay, dysmorphic features, and epilepsy. Am. J. Med. Genet. A · 2023
• A presumed missense variant in the U2AF2 gene causes exon skipping in neurodevelopmental diseases. J. Hum. Genet. · 2023
• Global developmental delay, systemic dysmorphism and epilepsy in a patient with a de novo U2AF2 variant. J. Hum. Genet. · 2021
• ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development. Nucleic Acids Res. · 2019
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Molecular architecture of SF3b and structural consequences of its cancer-related mutations. Mol. Cell · 2016
• Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. Mol. Cell. Proteomics · 2012
• The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65-Prp19 complex. Genes Dev. · 2011
• … and 25 more in the literature graph