| Acsbg1 (acyl-CoA synthetase bubblegum family member 1) Rattus norvegicus |
The alternative exon 8 is essential for the fatty acyl-CoA synthetase activity of GR-LACS |
(Li et al., 2006) |
| AGRN (agrin) |
An eight amino acid insert at the B-side is necessary for the enzymatic activity |
(Scotton et al., 2006) |
| CES2 (carboxylesterase 2) |
Alternative splicing in exon 10 results in an enzymatically inactive protein |
(Schiel et al., 2007) |
| Ctsm (Cathepsin M) Mus musculus and Rattus norvegicus |
Aberrant splicing of exon 7 leads to catalytically inactive isoforms |
(Bode et al., 2005) |
| Entpd2 (ectonucleoside triphosphate diphosphohydrolase 2) Rattus norvegicus |
Different in cellular distribution, catalytic properties and regulation by protein kinases |
(Wang et al., 2005a) |
| FMR1 (fragile × mental retardation 1) |
Reduction in methylation activity |
(Dolzhanskaya et al., 2006) |
| Grk6 (G-protein-coupled receptor kinase 6) Mus musculus |
C-terminus is required for the catalytic activity and contains three auto-regulatory elements |
(Vatter et al., 2005) |
| hpse (heparanase) Xenopus laevis |
Skipping of cassette exon generates catalytic inactive form |
(Bertolesi et al., 2008) |
| IDE(insulin-degrading enzyme) |
Isoform with an exon 15b has inefficient proteolytic activity |
(Farris et al., 2005) |
| IRAK1 (interleukin-1 (IL-1) receptor-associated kinase 1) |
Alternative exon necessary for kinase activity |
(Rao et al., 2005) |
| LPIN1 (lipin 1) |
Alpha isoform has the highest turnover number, followed by the beta and gamma isoforms |
(Han and Carman, 2010) |
| mhc (Myosin heavy chain) Drosophila melanogaster |
Alternatively spliced exon 7 domain modulates myosin ATPase activity |
(Miller et al., 2005) |
| MTHFD1L (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like) |
Short isoform lacking exon 8 is soluble and enzymatically inactive |
(Prasannan and Appling, 2009) |
| NOS3 (nitric oxide synthase 3 (endothelial cell) |
Novel 3'splice sites within intron 13 given three splice variants of NOS3 resulting truncated proteins lacking enzyme activity |
(Lorenz et al., 2007) |
| PIP5K1A (phosphatidylinositol-4-phosphate 5-kinase, type I, alpha) |
Different kinase activity that regulates exocytosis |
(Wang et al., 2005c) |
| PIP5K1B (phosphatidylinositol-4-phosphate 5-kinase, type I, beta) |
Beta isoform has lower kinase activity and does not prime exocytosis |
(Wang et al., 2005c) |
| PTGS1 (prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase)) |
Isoform lacking the last 111 nucleotides of exon 9 cannot be detected as protein. The recombinant protein is catalytically inactive |
(Schneider et al., 2005) |
| SAT1 (spermidine/spermine N1-acetyltransferase 1) |
Hypoxia and iron-deficiency promote inclusion of 110 nucleotides of intron 3 leading to a truncated isoform lacking catalytic activity |
(Kim et al., 2005a) |
| TAZ (tafazzin) |
The isoform lacking exon 5 has transacylase activity |
(Xu et al., 2009) |
| TMLHE (trimethyllysine hydroxylase, epsilon) |
TMLHE-b isoform lacking the last 90 amino acids at the C-terminal end is inactive |
(Monfregola et al., 2005) |
| TPH2 (tryptophan hydroxylase 2) |
TPH2B variant has a higher activity than TPH2B in which part of intron 3 is retained |
(Grohmann et al., 2010) |
| Trhde (thyrotropin-releasing hormone degrading enzyme) Rattus norvegicus |
Alternatively spliced isoform lacking part of the C-terminal domain is enzymatically inactive |
(Chavez-Gutierrez et al., 2005) |
| Tssk6 (testis-specific serine kinase 5) Mus musculus |
Insertion of 10 amino acid residues in region VIb results in inactive splice variants |
(Wei et al., 2007) |
| B. Generation of constitutively active variants |
| Name |
Function |
Reference |
| Mst1r (macrophage stimulating 1 receptor (c-met-related tyrosine kinase) Mus musculus |
Exon deletion is responsible for constitutive kinase activation |
(Wei et al., 2005) |
| Pak3 (p21 protein (Cdc42/Rac)-activated kinase 3) Mus musculus |
Alternative exons are inserted into the catalytic domain and make the kinase constitutively active |
(Kreis et al., 2008) |
| C. Dominant negative effects |
| Name |
Function |
Reference |
| ENTPD3 (Nucleoside triphosphate diphosphohydrolase 3 (NTPDase3)) |
Alternative exon of NTPDase3 (nucleoside triphosphate diphosphohydrolase 3) is necessary for activity, the presence of the inactive variant downregulates the activity of the active variant |
(Crawford et al., 2007) |
| UGT1A (UDP glucuronosyltransferase 1 family, polypeptide A complex locus) |
The inactive isoform inhibits the UGT1A-mediated glucuronidation from acting as a dominant-negative repressor |
(Bellemare et al., 2010) |
| D. Miscellaneous |
| ACSL5 (acyl-CoA synthetase long-chain family member 5) |
Splice variant lacking exon 20 is inactive at highly alkaline pH |
(Gassler et al., 2007) |
| ACSL6 (acyl-CoA synthetase long-chain family member 6) |
Specific fatty acid gate-domain residues are essential for activity. Isoform lacking the domain is inactive, isoforms containing different motifs have different activity |
(Soupene et al., 2010) |
| CETP (cholesteryl ester transfer protein, plasma) |
Alternative exons create less efficiently secreted variants |
(Lira et al., 2008) |
| FYN (FYN oncogene related to SRC, FGR, YES) |
Inclusion of either exon 7A or 7B changes the SH3-dependent interaction and tyrosine phosphorylation of Sam68. It affects the auto-inhibition of FYN |
(Brignatz et al., 2009) |
| PRKDC (protein kinase, DNA-activated, catalytic polypeptide) |
Splice variant II and III are conserved and expressed predominantly in non-dividing cells |
(Convery et al., 2005) |
| PTGER3 (prostaglandin E receptor 3 (subtype EP3)) |
Prostaglandin-E2 mediated phosphorylation of ERK1/2 by PTGER3 isoform II and III involves activation of Galpha(i)/PI3K/PKC/Src and EGFR-dependent pathway, ERK ½ phosphorylation by isoform Ia is minimal and involves activation of Galpha(i)/Src and EGFR-dependent pathway |
(Israel and Regan, 2009) |
| RAC1 (ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)) |
Exon encodes a 19-a.a. insertion that leads to decreased GTPase activity and reduced affinity to GDP |
(Orlichenko et al.) |
| TNFRSF1B (tumor necrosis factor receptor superfamily, member 1B) |
Skipping of two alternative exons leads to a soluble TNFRS1B receptor associated with greater insulin sensitivity |
(Fernandez-Real et al., 2006) |
