KH domain-containing, RNA-binding, signal transduction-associated protein 3 (Sam68-like mammalian protein 2, SLM-2, Sam68-like phosphotyrosine protein, RNA-binding protein T-Star, KHDRBS3, SALP, SLM2)

Function

• RNA-binding protein
• role in regulation of alternative splicing
• influences mRNA splice site selection & exon inclusion
  • splice site selection of VEGF
  • induces an increased concentration-dependent incorporation of exon in CD44 pre-mRNA by direct binding to purine-rich exonic enhancer
• role as a negative regulator of cell growth (putative)
• inhibits cell proliferation
• RNA-binding abilities are down-regulated by tyrosine kinase PTK6
• interacts with splicing regulatory proteins SFRS9, SAFB & YTHDC1
• interacts with HNRPL & SLM1/KHDRBS2
• interacts with KHDRBS1, RBMX, RBMY1A1
• interacts with SH3 domain of PI-3-kinase p85 subunit via proline-rich domain
• interaction with SIAH1 promotes targeting for degradation
• phosphorylated on tyrosine residues

Structure

• self-associates to form homo-oligomers
• isoform 1 C-terminal region is Tyr-rich
• isoform 2 lacks this C-terminal region, but is also Tyr-phosphorylated
• contains 1 KH domain

Compartment

• nucleus
• localized in a compartment adjacent to nucleolus

Alternative splicing

named isoforms=2

Expression

• ubiquitous
• higher expression in testis, skeletal muscle, brain
• expressed in kidney only in podocytes, glomerular epithelial cells of the kidney
• strongly expressed after meiosis

Pathology

• role in post-transcriptional regulation of HIV-1 gene expression
• induced in proteinuric diseases
• down-regulated in immortalized fibroblasts isolated after a proliferative crisis accompanied with massive cell death

More general terms

• RNA-binding protein
• phosphoprotein
• nuclear protein

Database

• UniProt: http://www.uniprot.org/uniprot/O75525.html