Table 1:

Listed are the numerous identified PTMs for cTnI. For most their function or if they are linked to cardiac diseases is still unknown. PTM localizations obtained from animal studies are listed based on their orthologous locations within the human cTnI sequence.

AA	PTM	Domain	targeting enzyme	Information	Disease	Ref.
2	N-acetylalanine					[123,124]
5	Serine-O-linked b- N-acetyl-D- glucosamine (O-GlcNAc)	Acidic region of N-terminal extension	O-GlcNAc Transferase		Potentially associated with Diabetes	[125]
5	Phosphoserine	Acidic region of N-terminal extension			HF.	[19]
6	Phosphoserine				HF.	[19]
6	O-GlcNAc	Acidic region of N-terminal extension	O-GlcNAc Transferase		Potentially associated with Diabetes	[125]
23	Phosphoserine	N-terminal extension	PKA [126], PKC [127], PKD [128], PKG [129], AMPK [120], PP1 [130], PP2A[68,69]	decreases Ca2+ affinity of TnC, reduces Ca2+ sensitivity, increases relaxation velocity & contractile power [5,126,127,131,132]	HCM [68,69]. AMPK activity is inhibited in humans with progressed HF [99].	[19,68,69, 99,120, 124,126, 127,128, 129,130, 133]
24	Phosphoserine		PKA [126], PKC [127], PKD [128], PKG [129], AMPK [120]
26	Phosphotyrosine	N-terminal extension			HF.	[19]
31	Phosphothreonine		TK4/MST1			[134]
36	Acetyllysine					[78]
42/44*	O-GlcNAc	IT arm	O-GlcNAc Transferase		Potentially associated with Diabetes	[125]
42	Phosphoserine	IT arm	PKC/PRKCE	Increases myofilament Ca2+ sensitivity; slows kinetics & stabilizes inhibition of thin filament activation [107]; in vivo pseudo-phosphorylation leads to decreased contractility & relaxation [135]	HF. Phosphorylation contributes to cardiac dysfunction.	[19,103– 105]
44	Phosphoserine		PKC/ PRKCE			[19,103– 105]
51	Phosphothreonine	IT arm	STK4/ MST1		HF.	[19,134]
76	O-GlcNAc	IT arm region	O-GlcNAc Transferase		Potentially associated with Diabetes	[125]
77	Phosphoserine	IT arm region			HF.	[19]
78	Phosphothreonine				HF.	[19]
106	Acetyllysine					[78]
117	Acetyllysine					[78]
129	Phosphothreonine		STK4/MST1			[134]
131	Acetyllysine					[78]
143	Phosphothreonine	Inhibitory region	PKC/STK4/MST1		HF.	[19,134]
150	Phosphoserine		PAK3 [136]/AMPK [85,119,120]	Phosphorylation increases myofilament Ca2+ sensitivity [85,119,120]. Blockade of AMPK mediated phosphorylation reduces cell shortening & electrical conduction abnormalities [121].	AMPK activity is inhibited in humans with progressed HF [99].	[85,99, 119–121, 136]
150	O-GlcNAc		O-GlcNAc Transferase	Potentially decreasing Ca2+ sensitivity	HF	[74]
166	Phosphoserine	Switch peptide between 2 actin binding regions	PKA [137]		HCM [68,69], HF	[19]
167	O-GlcNAc	Switch peptide between 2 actin binding regions	O-GlcNAc Transferase		Potentially associated with Diabetes	[125]
174	Acetyllysine					[78]
177	Acetyllysine					[78]
181	Phosphothreonine	C-terminal region			HF	[19]
193	Acetyllysine					[78]
199	O-GlcNAc	C-terminal region	PKCα [138]	Pseudo-phosphorylation increases myofilament Ca2+ sensitivity for force development most likely by reduced actin & actin-TM binding [118].	Increased phosphorylation in end stage HF [19]. Mutation found in HCM & is associated with arrhythmias & sudden death [139].	[19,118, 138,139]
	O-GlcNAc	Potentially cTnI	O-GlcNAc Transferase	Compensatory/ adaptive in HF	O-GlcNAc is critical in HF; Hypertrophy	[75,73]

^*Asterisk denotes ambiguity in PTM site mapping.