Table 2.
Phosphorylation sites in troponin I
| Phosphorylation Site | Kinases | Function | Reference | ||
|---|---|---|---|---|---|
| cTnI | ssTnI | fsTnI | |||
| S5,S6 | NA | NA | Unknown | Unknown | (Zhang et al., 2012) |
| S23,S24 | NA | NA | PKA PKC-β PKC-ε PKD PKG |
Enhancing diastolic function | (Solaro et al., 2008) (Kobayashi et al., 2005) (Haworth et al., 2004 (Layland et al., 2002) |
| Y26 | NA | NA | Unknown | Enhancing diastolic function | (Zhang et al., 2012) (Salhi et al., 2014) |
| T31 | NA | NA | Mst1 | Increasing affinity for TnC; Decreasing affinity for TnT |
(You et al., 2009) |
| S39 | (P8) | (N8) | PKA | Decreasing affinity for TnC | (Ward et al., 2001) |
| S42,S44 | T11,S13 | (I11,A13) | PKC | Slowing cardiac relaxation | (Kooij et al., 2011) |
| T51 | S20 | S20 | Mst1 | Unknown | (You et al., 2009) |
| S77,T78 | (A46,E47) | (A46,E47) | Unknown | Unknown | (Zhang et al., 2012) |
| T129 | (K98) | (N97) | Mst1 | Unknown | (You et al., 2009) |
| T143 | (112P) | (111P) | PKC PKC-βII Mst1 |
Decreasing relaxation and contraction | (Westfall et al., 2005) (You et al., 2009) |
| S150 | S119 | S118 | Pak AMPK |
Slowing cardiac relaxation | (Buscemi et al., 2002) (Oliveira et al., 2012) (Sancho Solis et al., 2011) |
| S166 | S135 | (C134) | PKA | Decreasing affinity to TnC | (Ward et al., 2001) |
| T181 | T150 | T149 | Unknown | Unknown | (Zhang et al., 2012) |
| S199 | S169 | S169 | PKC | Decreasing affinity to actin-tropomyosin | (Wijnker et al., 2015) |
The amino acid residues in cTnI with known phosphorylation are listed. The residue numbers refer to that in human TnI isoforms with the first methionine included. NA, not applicable. Some of the residues are conserved between cardiac and skeletal muscle TnI, suggesting possible phosphorylations in skeletal muscle TnI. Some of the sites have been studied with engineered substitutions in cTnI with the counterpart amino acids in ssTnI or fsTnI (in brackets), suggesting that the phosphorylation modification of these sites in cTnI is a mechanism of tuning the function toward a skeletal muscle-like state. Phosphorylation of the sites in cTnI has been experimentally identified. Among the potential phosphorylation sites in ssTnI and fsTnI (in Italic font), only S118 in fsTnI was experimentally demonstrated.