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FLASH GENE

Symbol

ATG5

contributors: mct/ - updated : 24-10-2018

HGNC name	ATG5 autophagy related 5 homolog (S. cerevisiae)
HGNC id	589

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)

cell lineage
cell lines	mammalian cell line
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a high number of acidic residues
	a potential glycosylation site
	potential casein kinase II, protein kinase C and tyrosine kinase sites

conjugated

Other

HOMOLOGY

interspecies	homolog to yeast S .cerevisiae Apg5p
	homolog to murine Apg5l
	homolog to Drosophila CG1643

Homologene

FAMILY

ATG5 family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
text	colocalizes with non-muscle actin

basic FUNCTION	involved in autophagy
	ATG12-ATG5 conjugate has a novel E3-like activity for protein lipidation in autophagy
	ATG5-ATG12 conjugate, a key regulator of the autophagic process, plays an important role in innate antiviral immune responses
	important for B cell survival during development and is differentially required at discrete stages of development in distinct, but closely related, cell lineages
	involved in normal adipocyte differentiation, suggesting an important role of autophagy in adipogenesis
	MAP1LC3B and ATG5 are not required for initiation of autophagy but mediate phagophore expansion and autophagosome formation
	required in antigen presentation by dendritic cells
	with ATG12, ATG2B, ATG9B, are autophagy-related genes, having mononucleotide repeats with seven or more nucleotides
	MAP1LC3B, ATG5 and ATG12 are involved in mitochondrial quality control after oxidative damage, and to cellular longevity
	regulates the formation of MYD88 condensed structures through association with MYD88 and eventually exerts a modulatory effect on MYD88-dependent signaling
	dual role for ATG5 in response to drug-induced DNA damage, where it acts in two signalling pathways in two distinct cellular compartments, the cytosol and the nucleus
	has a crucial role in cortical neurogenesis during early embryonic brain development, which may contribute to the understanding of neurodevelopmental disorders caused by autophagy dysregulation
	role of ATG5 in the dynamic regulation of ligation-induced cellular senescence and apoptosis
	ATG5-mediated autophagy in proximal epithelial cells is a critical host-defense mechanism that prevents renal fibrosis by blocking G2/M arrest
	important role of ATG5 and autophagy in maintaining the function of neutrophil extracellular traps (NETs) formation in response to infection and in regulating neutrophil death
	chronic morphine exposure caused ATG5 and ATG7-dependent and dopaminergic neuron-specific autophagy resulting in decreased neuron dendritic spines and the onset of addictive behaviors
	ATG5- and ATG7-dependent autophagy of dopaminergic neurons contributed to cellular and behavioral responses to morphine

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

text	highly expressed in apoptotic cells

PATHWAY

metabolism

signaling

involved in ATG5/ATG7-dependent conventional pathway for macroautophagy

a component	conjugation of the K-130 to the G-140 of APG12 is a covalent modification that is essential for autophagy
	is a key component of an E3-like ATG12-ATG5-ATG16L1 protein complex that catalyzes conjugation of the MAP1LC3 protein to lipids, thus controlling autophagic vesicle formation and expansion

INTERACTION

DNA

RNA

small molecule

protein	binding to ATG12
	ATG10 interacts with ATG7 to receive an ubiquitin-like protein ATG12, recognizes both ATG12 and ATG5 directly and catalyzes their conjugation reaction
	direct interaction between ATG5 and ATG16L1 is crucial to the performance of their roles in autophagy
	single known conjugation target of ATG12
	concerted interactions among TECPR1, ATG12-ATG5, and PtdIns(3)P provide the fusion specificity between autophagosomes and lysosomes and the assembly of this complex initiates the autophagosome maturation process
	autophagic E2 enzymes, ATG10, interacts with ATG7 to receive ATG12, a ubiquitin-like molecule, and is also involved in the ATG12-ATG5 conjugation reaction
	ATG5, a key regulatory protein of autophagy, inhibits the formation of MYD88 condensed structures
	ELAVL4 is an inducer of ATG5 expression and hence a critical regulator of autophagosome formation in pancreatic beta cells
	during process of induced autophagy, the ATG12-ATG5 conjugate requires 2 different binding partners, ATG16L1 for autophagosome elongation and TECPR1 for lysosomal fusion
	TECPR1 and ATG16L1 share the same binding site on ATG5 (swapping of interaction partners with ATG5 for autophagosome maturation)
	MUL1, a mitochondria-localized E3 ligase, regulates selenite-induced mitophagy in an ATG5 and ULK1-dependent manner
	RACK1 is a novel ATG5 interactor and an autophagy protein
	beneficial role of hypothalamic ATF4/ATG5 axis in the regulation of energy expenditure, obesity, and obesity-related metabolic disorders
	mechanistically, BSN was found to interact with ATG5, an E3-like ligase essential for autophagy, and to inhibit the induction of autophagy in heterologous cells
	ATG5 and ATG7 connect autophagy with ER stress through EIF2AK3 signaling

cell & other

binding to isolation membrane

REGULATION

induced by	apoptotic stimuli
		hypoxia

ASSOCIATED DISORDERS

corresponding disease(s)

SCAR25

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   deletion     led to increased mitochondrial mass in peripheral T cells constitutional     --over   in autoimmune demyelination and multiple sclerosis tumoral somatic mutation       in gastric and colorectal cancers with microsatellite instability

Susceptibility

to development of hepatocellular carcinoma (HCC)

Variant & Polymorphism other	ATG5 rs17067724 significantly associated with HCC risk

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed obesity     ATF4/ATG5 axis in the hypothalamus may be a new potential therapeutic target for treating obesity and obesity-related metabolic diseases

ANIMAL & CELL MODELS

	All Atg5-null mice died within 1 day of delivery, the survival time of starved Atg5-deficient neonates (approximately 12 hours) was much shorter than that of wildtype mice (approximately 21 hours). Atg5-deficient neonates exhibited reduced amino acid concentrations in plasma and tissues and displayed signs of energy depletion. Neonates adapt to immediate post-birth starvation by inducing autophagy
	mice deficient for Atg5 or Atg7 specifically in the dopaminergic neurons were less sensitive to developing a morphine reward response, behavioral sensitization, analgesic tolerance and physical dependence compared to wild-type mice
	Atg5-deficient mice displayed abnormal Tbx2 expression and defects in valve development and chamber septation