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FLASH GENE

Symbol

EIF4G1

contributors: mct - updated : 19-02-2019

HGNC name	eukaryotic translation initiation factor 4 gamma, 1
HGNC id	3296

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	PARK18 Parkinson disease 18
Location	3q27.1      Physical location : 184.032.282 - 184.053.145
Synonym symbol(s)	p220, EIF4G, EIF4F, EIF-4G1, EIF4GI, PARK18

DNA

TYPE	like-sequence
STRUCTURE	20.86 kb     33 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	three identified promoters, generating alternately spliced mRNAs, yielding a total of five EIF4G1 protein isoforms (PMID: 16982693)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_182917 32 - 5636 NP_886553 - 1600 - 2006 16982693 NM_198241 33 - 5538 NP_937884 - 1599 - 2006 16982693 EIF4G1 I2 NM_004953 26 - 5050 NP_004944 - 1404 - 2006 16982693 NM_198242 30 - 5123 NP_937885 - 1435 - 2006 16982693 EIF4G1 I4 NM_001194946 34 - 5559 NP_001181875 - 1606 - 2006 16982693 NM_001194947 33 - 5502 NP_001181876 - 1606 - 2006 16982693 NM_198244 30 - 5300 NP_937887 - 1512 - 2006 16982693 NM_001291157 34 - 5581 NP_001278086 - 1559 - 2006 16982693

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 Reproductive female system uterus cervix   highly   female system breast mammary gland   highly Respiratory respiratory tract larynx     highly Skin/Tegument skin       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a RNA binding domain,a large middle alpha helical domain, RNA binding
	the second binding site of EIF4G1 is important to understand the functional difference between EIF4G1 and EIF4BP1 for EIF4E translation
	a C terminal eIF-5 domain maybe involved in interactions with eIF-2, and two atypical HEAT-repeat domains, supporting translational regulation by recruiting eIF4A, an RNA helicase, and MKNk1

HOMOLOGY

Homologene

FAMILY

eukaryotic translation initiation factor EIF4 family

CATEGORY

chaperone/stress , RNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic,ribosome
	intracellular,nucleus

basic FUNCTION	mRNA cap recognition, ATP-dependent unwinding of 5' terminal secondary structure (helicase activity) and recruitment of mRNA to ribosome
	involved in the binding of mRNA cap structure to ribosome
	increasing the poly (A)-binding protein (PABPx) RNA binding activity
	plays a critical role in mRNA recruitment to the ribosomes
	serves as a central adapter in cap-binding complex assembly
	is potentially necessary for maintenance of neuronal viability
	association of the translation factors polyadenylate-binding protein-1 (PABPC1) and EIF4G1 is essential for high-level expression of polyadenylated mRNAs
	increased expression of EIF4G1 facilitates resistance to both apoptosis and autophagy following IR-mediated genotoxic DNA damage
	EIF4G1 clearly has specific functions that do not overlap that of EIF4G2
	plays a crucial role in translation initiation, serving as a scaffolding protein binding several other initiation factors, other proteins, and RNA
	is related to tumorigenesis and tumor progression
	EIF4G1 functions as an oncoprotein during non-small cell lung cancers (NSCLC) development
	is required for cap-dependent mRNA translation, a process necessary for tumor growth and survival
	EIF4G1, EIF4E, EIF4A1, and EIF4B, facilitate the recruitment of mRNA onto the preassembled 43S pre-initiation complex (PIC), thus leading to the formation of the 48S PIC

CELLULAR PROCESS

protein, translation/synthesis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

scaffold protein for the assembly of eIF4A, eIF4B, eIF4E, MKNK1, EIF4EBPs, PABPC1 to form the eukaryotic translation initiation complex eIF4F

INTERACTION

DNA

RNA

small molecule

protein	binding to other EIFs
	interacting with the poly (A)-binding protein (PABPx)
	interacting with EIF4E3
	NCBP1, NCBP2 independently interact with EIF4G1 (EIF4G1 potentially serves to connect NCBP1/NCBP2 with other initiation factors during the pioneer round of translation)
	EIF4G1-PABPC1 interaction has been implicated in enhancing the formation of 48 S and 80 S initiation complexes and ribosome recycling through mRNA circularization
	original role of NQO1 in the regulation of mRNA translation via the control of EIF4GI stability by the proteasome
	MKNK1/MKNK2-EIF4G1 interaction is important for EIF4E phosphorylation
	PRKCA activation elicits a cascade of orchestrated phosphorylation events that may modulate EIF4G1 structure and control interaction with the EIF4E kinase, MKNK1
	EIF4E serves as a master switch that controls mRNA translation through the promotive binding to EIF4G1 and the regulative binding with the endogenous inhibitor EIF4EBP1
	plays a unique role, not shared by its closest paralog MKNK1, in limiting protein translation through its negative effect on eIF4G Ser¹¹&
	8304;&
	8312; phosphorylation and RPS6KB1 activation
	EIF4G1 interacts with the RRM2 domain of PABPC1
	EIF4GI participates in the miRNA-mediated post-transcriptional gene silencing by promoting the association of AGO2 with the cap-binding complex
	EIF4G1 protein binds to EIF3C, EIF3D, and EIF3D to promote mRNA recruitment to the ribosome
	interaction of EIF4E with the initiation factor EIF4G1 recruits the 40S ribosomal particle to the 5prime end of mRNAs, facilitates scanning to the AUG start codon, and is crucial for eukaryotic translation of nearly all genes
	low-frequency alterations such as EIF4G1 might participate in RET-associated tumorigenesis, possibly by regulating the activity of the RET pathway
	interactions between VPS35, EIF4G1, and SNCA
	EIF1-EIF4G1 cooperation involved in start codon selection
	USP10 can directly interacts with EIF4G1, while acting as a negative regulator for EIF4G1-mediated functions
	EIF4G1 plays a central role in translation initiation through its interactions with the cap-binding protein EIF4E
	EIF4G2 and EIF4G1 share many binding proteins, such as the eukaryotic translation initiation factors EIF3A and EIF4A1 and ribosomal proteins

cell & other

REGULATION

Other	calpain-mediated degradation of EIF4G1, is a cause of both persistent persistent protein synthesis inhibition and neuronal death
	regulation of EIF4GI stability by the proteasome may be prominent under oxidative stress

ASSOCIATED DISORDERS

corresponding disease(s)

PARK18

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   squamous cell lung carcinoma tumoral     --low   depletion impairs cell proliferation, bioenergetics, and mitochondrial activity, thereby promoting autophagy tumoral     --over   in many breast cancers might act to specifically increase proliferation, prevent autophagy, and release tumor cells from control by nutrient sensing tumoral     --over   strongly increased in breast cancers tumoral     --over   in prostate carcinoma and is associated with tumor progression and metastasis

Susceptibility

to dementia with Lewy bodies

Variant & Polymorphism other	variants in EIF4G1 can be associated with pathology that has a high likelihood of association with clinical features of dementia with Lewy bodies

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer lung   promising therapeutic target in lung cancer cancer hemopathy   targeting EIF4G1 translation initiation factor affords an attractive therapeutic strategy in multiple myeloma cancer reproductive prostate may serve as a novel target for intervention in PCa and castration-resistant prostate cancer (CRPC)

ANIMAL & CELL MODELS