Table 1.

Diseases associated with crotonylation.

Diseases	Protein crotonylation	Regulatory mechanism	References
Colorectal cancer	ENO1	ENO1 K420 crotonylation promoted the growth, migration, and invasion of colorectal cancer cells (CRC) in vitro by enhancing the activity of ENO1 and regulating the expression of tumor-associated genes.	[27]
Non-small-cell lung cancer cells	BEX2	The crotonylation of BEX2 at the K59 site is found to be critical for mediating mitophagy in lung cancer cells.	[51]
Hepatocellular carcinoma	SEPT2	Crotonylation facilitates cell invasion through the crotonylated SEPT2-K74-P85α-AKT pathway	[52]
Pancreatic cancer	MTHFD	The activation of MTHFD1 by decrotonylation at Lys354 and Lys553 promotes pancreatic cancer the development of by increasing resistance to ferroptosis	[53]
Acute kidney injury	–	Cell stress increases affecting the TWEAK, it then decreased PGC1a and Sirt-3 expression and with increased CCL2 expression.	[60,61]
Autosomal dominant polycystic kidney disease	H3K18	CDYL increases the level of Kcr, and overexpression of CDYL decreased histone Kcr, inhibited the expression of cyst-related genes, and slowed the growth of cysts.	[64]
Depression	H3K27	Increased H3K27 content and decreased the level of Kcr to inhibit the transcription of a group of genes such as neuronal VGF, then it leads to promote depression.	[85,86]
Alzheimer's disease	H3K27	NEAT1 inhibition influences H3K27 acetylation (H3K27Ac) and H3K27 crotonylation (H3K27Cro) located nearby to the transcription start site of many genes, including endocytosis-related genes.	[81]
Hypertrophic cardiomyopathy	H3K18 and H2BK12	Short-chain enoyl-CoA hydratase (ECHS1) downregulation was accompanied with the upregulation of H3K18cr and H2BK12cr in human hearts with hypertrophic cardiomyopathy.	[30]
HIV latency	H3K4	Viral infection or addition of crotonyl-CoA induces the expression of the fatty acid metabolic enzyme ACSS2, and ACSS2 increased H3K4 crotonylation which leads to regulation of HIV latency/transcription.	[89]
Ischemic heart disease	IDH3a	IDH3a K199 and TPM1 L28/29 crotonyalation could not only protect cardiomyocytes but also preserve myocardial function after injury.	[72]
Immunoglobulin A nephropathy	–	Identified 353 crotonylated proteins	[68,119]
Chronic renal failure	–	Identified 1109 lysine modification sites	[69,120]
Hemodialysis	–	Identified total 1109 lysine crotonylation sites on 347 proteins	[57]
COPD Combined with Type II RF	–	Identified 32 sites of 23 proteins were upregulated and 914 sites of 295 proteins were downregulated	[121]