EIF2S1 (eukaryotic translation initiation factor 2 subunit alpha)

Gene

• Entrez ID: 1965
• Gene name: Eukaryotic translation initiation factor 2 subunit alpha
• Gene symbol: EIF2S1
• Synonyms: EIF-2, EIF-2A, EIF-2alpha, EIF2, EIF2A
• Chromosome: 14
• Chromosome location: 14q23.3
• Summary: The translation initiation factor EIF2 catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, EIF2, and GTP. EIF2 is composed of 3 nonidentical subunits, the 36-kD EIF2-alpha subunit (EIF2S1), the 38-kD EIF2-beta subunit (EIF2S2; MIM 603908), and the 52-kD EIF2-gamma subunit (EIF2S3; MIM 300161). The rate of formation of the ternary complex is modulated by the phosphorylation state of EIF2-alpha (Ernst et al., 1987 [PubMed 2948954]).[supplied by OMIM, Feb 2010]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004813	hsa-miR-21-5p	Quantitative proteomic approach	19253296
MIRT019778	hsa-miR-375	Microarray	20215506
MIRT019778	hsa-miR-375	PAR-CLIP	21572407
MIRT019778	hsa-miR-375	HITS-CLIP	23824327
MIRT026383	hsa-miR-192-5p	Sequencing	20371350
MIRT046815	hsa-miR-222-3p	CLASH	23622248
MIRT070838	hsa-miR-17-5p	PAR-CLIP	21572407
MIRT070838	hsa-miR-17-5p	HITS-CLIP	23824327
MIRT070839	hsa-miR-20a-5p	PAR-CLIP	21572407
MIRT070839	hsa-miR-20a-5p	HITS-CLIP	23824327
MIRT070840	hsa-miR-93-5p	PAR-CLIP	21572407
MIRT070840	hsa-miR-93-5p	HITS-CLIP	23824327
MIRT070841	hsa-miR-106a-5p	PAR-CLIP	21572407
MIRT070841	hsa-miR-106a-5p	HITS-CLIP	23824327
MIRT070842	hsa-miR-106b-5p	PAR-CLIP	21572407
MIRT070842	hsa-miR-106b-5p	HITS-CLIP	23824327
MIRT070843	hsa-miR-302a-3p	PAR-CLIP	21572407
MIRT070843	hsa-miR-302a-3p	HITS-CLIP	23824327
MIRT070844	hsa-miR-302b-3p	PAR-CLIP	21572407
MIRT070844	hsa-miR-302b-3p	HITS-CLIP	23824327
MIRT070845	hsa-miR-302c-3p	PAR-CLIP	21572407
MIRT070845	hsa-miR-302c-3p	HITS-CLIP	23824327
MIRT070846	hsa-miR-302d-3p	PAR-CLIP	21572407
MIRT070846	hsa-miR-302d-3p	HITS-CLIP	23824327
MIRT070847	hsa-miR-376c-5p	HITS-CLIP	23824327
MIRT070848	hsa-miR-372-3p	PAR-CLIP	21572407
MIRT070848	hsa-miR-372-3p	HITS-CLIP	23824327
MIRT070849	hsa-miR-373-3p	PAR-CLIP	21572407
MIRT070849	hsa-miR-373-3p	HITS-CLIP	23824327
MIRT070850	hsa-miR-20b-5p	PAR-CLIP	21572407
MIRT070850	hsa-miR-20b-5p	HITS-CLIP	23824327
MIRT070851	hsa-miR-376b-5p	HITS-CLIP	23824327
MIRT070853	hsa-miR-520e	PAR-CLIP	21572407
MIRT070853	hsa-miR-520e	HITS-CLIP	23824327
MIRT070854	hsa-miR-520f-3p	PAR-CLIP	21572407
MIRT070854	hsa-miR-520f-3p	HITS-CLIP	23824327
MIRT070856	hsa-miR-520a-3p	PAR-CLIP	21572407
MIRT070856	hsa-miR-520a-3p	HITS-CLIP	23824327
MIRT070857	hsa-miR-526b-3p	PAR-CLIP	21572407
MIRT070857	hsa-miR-526b-3p	HITS-CLIP	23824327
MIRT070859	hsa-miR-520b	PAR-CLIP	21572407
MIRT070859	hsa-miR-520b	HITS-CLIP	23824327
MIRT070860	hsa-miR-520c-3p	PAR-CLIP	21572407
MIRT070860	hsa-miR-520c-3p	HITS-CLIP	23824327
MIRT070861	hsa-miR-519d-3p	PAR-CLIP	21572407
MIRT070861	hsa-miR-519d-3p	HITS-CLIP	23824327
MIRT070862	hsa-miR-520d-3p	PAR-CLIP	21572407
MIRT070862	hsa-miR-520d-3p	HITS-CLIP	23824327
MIRT070863	hsa-miR-520g-3p	PAR-CLIP	21572407
MIRT070863	hsa-miR-520g-3p	HITS-CLIP	23824327
MIRT070864	hsa-miR-520h	PAR-CLIP	21572407
MIRT070864	hsa-miR-520h	HITS-CLIP	23824327
MIRT070866	hsa-miR-548c-3p	PAR-CLIP	21572407
MIRT070866	hsa-miR-548c-3p	HITS-CLIP	23824327
MIRT070867	hsa-miR-875-5p	PAR-CLIP	21572407
MIRT070867	hsa-miR-875-5p	HITS-CLIP	23824327
MIRT070869	hsa-miR-302e	PAR-CLIP	21572407
MIRT070869	hsa-miR-302e	HITS-CLIP	23824327
MIRT070871	hsa-miR-4282	PAR-CLIP	21572407
MIRT070871	hsa-miR-4282	HITS-CLIP	23824327
MIRT070874	hsa-miR-4720-3p	PAR-CLIP	21572407
MIRT070874	hsa-miR-4720-3p	HITS-CLIP	23824327
MIRT070875	hsa-miR-4777-3p	PAR-CLIP	21572407
MIRT070875	hsa-miR-4777-3p	HITS-CLIP	23824327
MIRT279706	hsa-miR-2117	PAR-CLIP	21572407
MIRT279706	hsa-miR-2117	HITS-CLIP	23824327
MIRT279707	hsa-miR-4273	PAR-CLIP	21572407
MIRT279707	hsa-miR-4273	HITS-CLIP	23824327
MIRT279708	hsa-miR-4753-3p	PAR-CLIP	21572407
MIRT279708	hsa-miR-4753-3p	HITS-CLIP	23824327
MIRT279710	hsa-miR-6739-3p	PAR-CLIP	21572407
MIRT279710	hsa-miR-6739-3p	HITS-CLIP	23824327
MIRT279711	hsa-miR-6809-3p	PAR-CLIP	21572407
MIRT279711	hsa-miR-6809-3p	HITS-CLIP	23824327
MIRT279713	hsa-miR-7156-5p	PAR-CLIP	21572407
MIRT279713	hsa-miR-7156-5p	HITS-CLIP	23824327
MIRT405843	hsa-miR-302b-5p	HITS-CLIP	23824327
MIRT405844	hsa-miR-302d-5p	HITS-CLIP	23824327
MIRT558192	hsa-miR-4677-5p	PAR-CLIP	21572407
MIRT558192	hsa-miR-4677-5p	HITS-CLIP	23824327
MIRT558193	hsa-miR-4804-3p	PAR-CLIP	21572407
MIRT558193	hsa-miR-4804-3p	HITS-CLIP	23824327
MIRT558194	hsa-miR-130b-5p	PAR-CLIP	21572407
MIRT558194	hsa-miR-130b-5p	HITS-CLIP	23824327
MIRT558195	hsa-miR-3973	PAR-CLIP	21572407
MIRT558195	hsa-miR-3973	HITS-CLIP	23824327
MIRT731570	hsa-miR-30b-5p	Luciferase reporter assay	26898246
MIRT731571	hsa-miR-30c-5p	Luciferase reporter assay	26898246

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003723	Function	RNA binding	HDA	22658674, 22681889
GO:0003743	Function	Translation initiation factor activity	IBA	21873635
GO:0003743	Function	Translation initiation factor activity	IDA	16289705
GO:0005515	Function	Protein binding	IPI	9431994, 11500362, 16288713, 16932749, 17894550, 18596238, 18971339, 22323517, 25393282, 28514442, 32296183
GO:0005634	Component	Nucleus	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005844	Component	Polysome	TAS	2948954
GO:0005850	Component	Eukaryotic translation initiation factor 2 complex	IBA	21873635
GO:0005850	Component	Eukaryotic translation initiation factor 2 complex	IDA	23063529
GO:0005851	Component	Eukaryotic translation initiation factor 2B complex	IBA	21873635
GO:0005851	Component	Eukaryotic translation initiation factor 2B complex	IDA	11323413
GO:0006413	Process	Translational initiation	TAS
GO:0007568	Process	Aging	IEA
GO:0010494	Component	Cytoplasmic stress granule	ISS
GO:0016020	Component	Membrane	HDA	19946888
GO:0032057	Process	Negative regulation of translational initiation in response to stress	ISS
GO:0033290	Component	Eukaryotic 48S preinitiation complex	IBA	21873635
GO:0034063	Process	Stress granule assembly	ISS
GO:0034198	Process	Cellular response to amino acid starvation	ISS
GO:0034599	Process	Cellular response to oxidative stress	ISS
GO:0034605	Process	Cellular response to heat	IEA
GO:0034644	Process	Cellular response to UV	ISS
GO:0034976	Process	Response to endoplasmic reticulum stress	IMP	18508033
GO:0034976	Process	Response to endoplasmic reticulum stress	ISS
GO:0036499	Process	PERK-mediated unfolded protein response	NAS	22934019
GO:0043022	Function	Ribosome binding	IBA	21873635
GO:0043022	Function	Ribosome binding	IDA	17894550
GO:0043614	Component	Multi-eIF complex	IBA	21873635
GO:0044207	Component	Translation initiation ternary complex	IEA
GO:0045202	Component	Synapse	IEA
GO:0046777	Process	Protein autophosphorylation	IEA
GO:0055085	Process	Transmembrane transport	TAS
GO:0070062	Component	Extracellular exosome	HDA	20458337
GO:0097451	Component	Glial limiting end-foot	IEA
GO:1901216	Process	Positive regulation of neuron death	IMP	18508033
GO:1905098	Process	Negative regulation of guanyl-nucleotide exchange factor activity	IEA
GO:1990737	Process	Response to manganese-induced endoplasmic reticulum stress	IEA
GO:2000676	Process	Positive regulation of type B pancreatic cell apoptotic process	IEA

Other IDs

• MIM: 603907
• HGNC: 3265
• e!Ensembl: ENSG00000134001

Protein

• UniProt ID: P05198
• Protein name: Eukaryotic translation initiation factor 2 subunit 1 (Eukaryotic translation initiation factor 2 subunit alpha) (eIF-2-alpha) (eIF-2A) (eIF-2alpha)
• Protein function: Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (PubMed:16289705). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (PubMed:16289705). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex (PubMed:16289705). In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (PubMed:16289705). EIF2S1/eIF-2-alpha is a key component of the integrated stress response (ISR), required for adaptation to various stress: phosphorylation by metabolic-stress sensing protein kinases (EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2) in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to an attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:19131336, PubMed:33384352).
• PDB: 1KL9, 1Q8K, 6K71, 6K72, 6O81, 6O85, 6O9Z, 6YBV, 6ZMW, 6ZP4, 7A09, 7D43, 7D44, 7D45
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00575	S1	14 → 88	S1 RNA binding domain	Domain
  PF07541	EIF_2_alpha	130 → 244	Eukaryotic translation initiation factor 2 alpha subunit	Family

• Sequence:

  MPGLSCRFYQHKFPEVEDVVMVNVRSIAEMGAYVSLLEYNNIEGMILLSELSRRRIRSIN
  KLIRIGRNECVVVIRVDKEKGYIDLSKRRVSPEEAIKCEDKFTKSKTVYSILRHVAEVLE
  YTKDEQLESLFQRTAWVFDDKYKRPGYGAYDAFKHAVSDPSILDSLDLNEDEREVLINNI
  NRRLTPQAVKIRADIEVACYGYEGIDAVKEALRAGLNCSTENMPIKINLIAPPRYVMTTT
  TLERTEGLSVLSQAMAVIKEKIEEKRGVFNVQMEPKVVTDTDETELARQMERLERENAEV
  DGDDDAEEMEAKAED

• Sequence length: 315