Table 2.
Differential regulation of the phosphorylation pattern in gastrocnemius skeletal muscle of Stk25 transgenic and wild-type mice fed a high-fat diet
| Accession number | Symbol | Name | Phospho-rylation site | p value | Transgenic-to-wild-type ratio | Gene function |
|---|---|---|---|---|---|---|
| A2ASS6 | Ttn | Titin | S13904a | 0.003 | 2.45 | Titin is a giant muscle protein that spans from Z-disk to M-disk and plays a key role in muscle assembly, force transmission at the Z-disk, and maintenance of resting tension in the I-band region |
| S814a | 0.02 | −1.46 | ||||
| S22390a | 0.05 | 1.36 | ||||
| P97457 | Mylpf (alias Mlc2) | Myosin light chain, phosphorylatable, fast skeletal muscle | S15a | 0.001 | 2.29 | MYLPF is controlled by phosphorylation and modulates muscle contraction properties |
| Q7TQ48 | Srl | Sarcalumenin | S464a | 0.04 | 1.88 | Sarcalumenin is a Ca2+ binding protein localised to the sarcoplasmic reticulum that is considered to be important in the excitation–contraction–relaxation cycle in skeletal muscle cells |
| P07310 | Ckm (alias M-ck) | Creatine kinase, muscle (EC 2.7.3.2) | T166a | 0.02 | 1.81 | Creatine kinase catalyses the reversible transfer of a phosphate from phosphocreatine to ADP, maintaining intracellular ATP levels |
| T327a | 0.02 | 1.31 | ||||
| P05064 | Aldoa | Aldolase A, fructose-bisphosphate (EC 4.1.2.13) | S276a | 0.05 | 1.73 | ALDOA is a glycolytic enzyme that catalyses the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate |
| Q8CI12 | Smtnl2 | Smoothelin-like 2 | S98a | 0.04 | −1.67 | SMTNL2 is a functionally uncharacterised protein from the SMTN family with notably high expression in skeletal muscle |
| S339a | 0.03 | −1.34 | ||||
| P58771 | Tpm1 | Tropomyosin 1, alpha | S283a | 0.005 | 1.67 | Tropomyosin 1 represents a critical myofilament protein in the Ca2+ regulation of actin–myosin interaction, striated muscle contraction, and relaxation. TPM1 is the predominant isoform in the mammalian heart and fast skeletal muscle |
| P21550 | Eno3 | Enolase 3, beta muscle (EC 4.2.1.11) | S40a | 0.001 | 1.64 | Muscle-specific ENO3 is a glycolytic enzyme that resides at the M-disk and converts the glycolytic intermediate 2-phospho-d-glycerate to phosphoenolpyruvate |
| Q9JJW5 | Myoz2 (alias Cs-1) | Myozenin 2 (alias calsarcin-1) | S116a | 0.00005 | 1.61 | Myozenins are calcineurin-interacting proteins that also bind to ACTN2 and LDB3 at the Z-disk, suggesting a role in modulating calcium–calcineurin-dependent signalling |
| Q70KF4 | Cmya5 | Cardiomyopathy associated 5 (alias myospryn) | S769a | 0.02 | 1.61 | CMYA5 is a multifunctional desmin-binding protein that also associates with PKA. CMYA5 is suggested to participate in the subcellular targeting of PKA activity in striated muscle |
| Q62407 | Speg | SPEG complex locus | S1177a | 0.03 | −1.55 | SPEG is a protein localised to the sarcoplasmic reticulum that interacts with myotubularin; SPEG deficiency causes CNM in humans |
| Q8JZQ9 | Eif3b | Eukaryotic translation initiation factor 3, subunit B | S75a | 0.05 | −1.33 | EIF3B is part of the EIF3 complex |
| Q9JKB3 | Ybx3 (alias Csda) | Y box protein 3 (alias cold-shock domain protein A) | S328a | 0.03 | −1.55 | YBX3 is a transcriptional repressor, which is highly expressed in skeletal muscle, where it specifically regulates myogenin expression |
| Q9JK37 | Myoz1 (alias Cs-2) | Myozenin 1 (alias calsarcin-2) | S111 | 0.004 | −1.48 | Myozenins are calcineurin-interacting proteins that also bind to ACTN2 and LDB3 at the Z-disk, suggesting a role in modulating calcium–calcineurin-dependent signalling |
| O88990 | Actn3 | Actinin alpha 3 | S601a | 0.001 | −1.38 | ACTN3 is localised to the Z-disk, where it helps to anchor the actin filaments and regulates contractile properties of the muscle |
| Q5SX39 | Myh4 (alias MhcIIb) | Myosin, heavy polypeptide 4, skeletal muscle (alias myosin heavy chain IIb) | T258a | 0.05 | −1.32 | Skeletal muscle fibres are classified by speed of contraction, where expression of MYH4 defines the fast-twitch glycolytic type IIb fibres |
| S1339 | 0.02 | −1.24 | ||||
| P16858 | Gapdh | Glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) | T209a | 0.02 | −1.27 | GAPDH catalyses an important energy-yielding step in carbohydrate metabolism, the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate in the presence of inorganic phosphate and NAD |
| O08539 | Bin1 (alias Amph2) | Bridging integrator 1 (alias amphiphysin II) | T308a | 0.001 | −1.25 | BIN1 is localised in skeletal muscle at deep sarcolemmal invaginations, the T-tubules, implicated in excitation–contraction coupling; mutations in BIN1 have been described in CNM in humans |
| Q3MI48 | Jsrp1 | Junctional sarcoplasmic reticulum protein 1 | S228a | 0.03 | −1.23 | JSRP1 is an integral protein constituent of the skeletal muscle sarcoplasmic reticulum membrane, involved in the development and maintenance of skeletal muscle strength |
| P70670 | Naca | Nascent polypeptide-associated complex alpha polypeptide | S1489a | 0.02 | −1.21 | NACA, exclusively found in skeletal and heart muscle, is suggested to be involved in skeletal muscle development, homeostasis and regeneration, although the underlying mechanisms remain unclear |
| Q9JKS4 | Ldb3 (alias Zasp) | LIM domain binding 3 (alias Z-band alternatively spliced PDZ motif-containing protein) | S98a | 0.02 | 1.20 | LDB3 is a PDZ-LIM domain binding factor that plays an important role in maintaining the structural integrity of the striated muscle Z-disk. LDB3 binds to myozenin and ACTN2 |
A ratio of 1.15-fold serves as the threshold for differential regulation. The functions of the differentially phosphorylated proteins were annotated according to Gene Ontology database [50], NCBI OMIM and/or PubMed
aPhosphosites annotated in PhosphoSitePlus [32]
ACTN2, actinin alpha 2; CNM, centronuclear myopathy; NAD, nicotinamide adenine dinucleotide; PKA, cAMP dependent protein kinase