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FLASH GENE

Symbol

EIF2S1

contributors: mct - updated : 28-12-2016

HGNC name	eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa
HGNC id	3265

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	14q24.1      Physical location : 67.827.033 - 67.853.232
Synonym name	eukaryotic translation initiation factor 2, subunit 1 (alpha, 35kD)
	EIF- 2alpha
Synonym symbol(s)	EIF-2alpha, EIF-2A, EIF2, EIF-2, EIF2A

DNA

TYPE	functioning gene
STRUCTURE	26.20 kb     8 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004094 8 - 4165 NP_004085 36 315 - 2007 17488873

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive pharynx       highly   stomach       highly Lymphoid/Immune lymph node       highly Respiratory respiratory tract larynx     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Connective bone     highly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

mono polymer

heteromer , trimer

HOMOLOGY

interspecies

homolog to murine Eif2a

Homologene

FAMILY

EIF-2-alpha family

CATEGORY

RNA associated

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytosolic,ribosome
	intracellular,nucleus

basic FUNCTION	functioning in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA
	playing a critical role in the mechanics and regulation of protein synthesis
	phosphorylation of EIF2S1 coordinately attenuates mRNA translation, prevents oxidative stress, and optimizes ER protein folding to support insulin production
	EIF2S1 phosphorylation is a key step in maintaining a balance between the life and death of a glucose-deficient cell
	EIF2S1 phosphorylation is a significant determinant of survival and adaptation of glucose-deficient cells with possible important implications in biological processes that interfere with glucose metabolism
	is a key translation regulator that plays an important role in cellular stress responses
	crosstalk between cellular metabolism (fatty acids), pro-inflammatory signaling (STAT3), innate immunity (EIF2AK2), and translational control (EIF2S1) that regulates autophagy
	ER stress-induced EIF2S1 phosphorylation underlies sensitivity of striatal neurons to pathogenic huntingtin
	EIF2AK3-EIF2S1 signaling, which is required to maintain ER homeostasis, is also indispensable for EMT cells to invade and metastasize

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

EIF2AK3/EIF2S1-P/ATF4 signaling acts as a brake in the decline of protein synthesis during chronic ER stress by positively regulating signaling downstream of the MTOR activity

a component

heterotrimer composed of an alpha, a beta and a gamma chain

INTERACTION

DNA

RNA

binding

small molecule

protein	OGFOD1 plays important proapoptotic roles in the regulation of translation and EIF2AK1-mediated phosphorylation of EIF2S1 in cells subjected to arsenite-induced stress
	docking of EIF2S1 on EIF2AK2 induces a conformational change that regulates the degree of Ser51 exposure and thus restricts phosphorylation to the proper kinases
	loss of EIF2AK4 ablated urea-induced phosphorylation of EIF2S1 and reduced the expression of ATF3
	novel role of PTEN in regulating stress response through modulating the PPP1R15B/EIF2S1 pathway
	PTPN1 is a physiologically-relevant modulator of ER stress in brown adipocytes and PTPN1 deficiency modulates EIF2AK3-EIF2S1 phosphorylation and protein synthesis
	induction of DDIT4 gene expression was shown to require the protein kinase EIF2AK3 and enhanced phosphorylation of its substrate EIF2S1
	CDC123 is critical for EIF2S1, EIF2S2, EIF2S3 activity, and CDC123 is a specific EIF2 assembly factor indispensable for the onset of protein synthesis
	EIF2AK4 activation and phosphorylation of EIF2S1 in response to MTOR inhibition are necessary for autophagy
	novel function of ERN1 in the regulation of EIF2S1 phosphorylation and the translational control
	PPP1R15A associates with the broadly acting serine/threonine protein phosphatase 1 (PP1) to dephosphorylate EIF2S1
	preferentially translated PPP1R15A and constitutively expressed PPP1R15B function to dephosphorylate EIF2S1-phosphorylated and restore protein synthesis
	novel redox signaling pathway, involving NOX4-PPP1R15A interaction and a targeted oxidative inactivation of the PP1 metal center, that sustains EIF2S1 phosphorylation to protect tissues under stress
	coordinate regulation of UPR by the PPP1R15A- and PPP1R15B-containing EIF2S1 phosphatases to control cell viability

cell & other

REGULATION

Phosphorylated by

EIF2AK3 phosphorylates EIF2S1, which blocks the initiation step of translation, reducing new protein synthesis

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --other   elevated phosphorylation of EIF2S1 has been observed in the brains of Alzheimer disease patients constitutional     --over   UPR activation and/or increased EIF2S1 levels are seen in patients with AD, PD and prion disease

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology infectious   promoting EIF2S1 dephosphorylation rescues vital translation rates and is thereby neuroprotective in prion disease

ANIMAL & CELL MODELS

reducing Eif2s1 levels in prion-diseased mice significantly increases survival