TABLE 1.

Key substrates or binding proteins of the UFM1 system.

Substrates	UFMylation sites	Involved biological processes	UFMylation functions
STING	Independent on UFMylation	HSV‐1 infection in macrophages	UFL1 stabilises STING by preventing its interaction with the E3 ubiquitin‐protein ligase TRIM29 to activate antiviral immunity
MAVS	K461	EBV replication in Burkitt lymphoma cell lines	BILF1 mediates MAVS UFMylation‐dependent immune evasion
PDL1	K75,89,105, 162, 280, 281	Breast cancer	Inhibition of PD‐L1 UFMylation stabilises PD‐L1 and undermines anti‐tumour immunity
PD1	K210,233	Colon cancer	UFMylation of PD1 inhibits PD‐1 ubiquitination and degradation and promotes T‐cell anti‐tumour activity
UFBP1	K267	B‐cell development and function	UFMylation of UFBP1 is necessary for the production of immunoglobulin and the expansion of ER in IRE1α‐deficient plasmablasts
14‐3‐3ε	Not available	SeV infection in 293T cells	14‐3‐3ε UFMylation is required for the interaction with activated RIG‐Ι to promote antiviral immunity
RPL26	K134,132, 134, 136, 142	ER proteostasis	RPL26 UFMylation controls protein synthesis, ER protein translocation, RQC and ER‐phagy
RPN1	Not available	ER‐phagy	UFMylation of RPN1 upon ribosome collision is involved in ER‐phagy with unknown mechanisms
CYB5R3	K214	ER‐phagy	CYB5R3 can be UFMylated to induce ER‐phagy, which is essential for brain development
H4	K31	DNA damage repair	H4 UFMylation is responsible for the activation of ATM pathway and maintenance of genomic stability
MRE11	K281, 282	DNA damage repair	MRE11 UFMylation is necessary for the assembly of MRN complex and activation of ATM
PTIP	K148	Replication stress	PTIP UFMylation promotes the degradation of replication fork in BRCA1‐deficient cells
PARP1	K548	Replication stress	UFMylation of PARP1 can enhance its catalytic activity during replication stress
P53	K351, 357, 370, 373	Colon cancer	UFMylation of tumour suppressor p53 can stabilise p53 by countering its ubiquitination and proteasome degradation
PLAC8	K103	TNBC	UFMylation of PLAC8 helps maintain its stability and upregulate PD‐L1 expression to promote TNBC cell proliferation
RPL10	Not available	Pancreatic cancer	UFMylation of RPL10 facilitates the proliferation and stemness in pancreatic cancer cells
ERα	K171, 180	Breast cancer	UFMylation of ERα can promote its stability and transactivity by inhibiting its ubiquitination and degradation, and facilitating breast cancer progression
ASC1	K324, 325, 334, 367	Breast cancer	ASC1 UFMylation can promote transcription factors binding to ERα and facilitates breast cancer development
SLC7A11	Not available	Ferroptosis	The anticancer effect of metformin was accomplished by the inhibition of SLC7A11 UFMylation
P4HB	K69, 114, 130	ER stress, mitochondrial function, and oxidative stress	UFMylation of P4HB helps maintain its stability and biological function in HepG2 cells