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FLASH GENE

Symbol

EIF2AK4

contributors: mct - updated : 31-08-2012

HGNC name	eukaryotic translation initiation factor 2 alpha kinase 4
HGNC id	19687

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

Homologene

FAMILY

ser/thr family of protein kinases

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION

intracellular,cytoplasm,cytosolic,ribosome

basic FUNCTION	translation regulation
	role in regulating lipid metabolism during leucine deprivation in addition to regulating amino acid metabolism
	both EIF2AK3 and EIF2AK4 mediate the cell adaptation to hypoxic stress
	importance of EIF2AK4 for the immune system to adapt to amino acid starvation by ASNase
	EIF2AK3, and EIF2AK4 also have a functional role on regulating translation under non-stressed conditions, apart from their long established roles as stress kinases
	EIF2AK4 pathway was involved in the regulation of NUPR1 through an AARE in the context of amino acid limitation
	protein kinase considered to be an important sensor for amino acids availability and a potential regulator of redox homeostasis
	with its downstream signaling pathway, have an important role in the protection against oxidative injuries induced by an amino acid-imbalanced diet, and it can play a critical role in the prevention of oxidative damage

CELLULAR PROCESS

protein, translation regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

	EIF2AK4-ATF4 pathway is critical for maintaining metabolic homeostasis in tumour cells, making it a novel and attractive target for anti-tumour approaches
	EIF2AK4/ATF4 pathway is involved in this regulation through the presence of an AARE in NUPR1 promoter

a component

INTERACTION

DNA

RNA

small molecule

protein	loss of EIF2AK4 ablated urea-induced phosphorylation of EIF2S1 and reduced the expression of ATF3
	EIF2AK4 activation and phosphorylation of EIF2S1 in response to MTOR inhibition are necessary for autophagy

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     abrogation of EIF2AK4 expression significantly inhibited tumour growth neurology neurodegenerative alzheimer EIF2AK3, EIF2AK4 are potential therapeutic targets for treatment of individuals with Alzheimer disease

ANIMAL & CELL MODELS

	Gcn2-/- mice exhibited an increase in protein carbonylation, a marker of oxidative stress, in response to a long-term (24 weeks) leucine-imbalanced diet (ED&
	916;Leu)