P05198 (IF2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eukaryotic translation initiation factor 2 subunit 1

Alternative name(s):
Eukaryotic translation initiation factor 2 subunit alpha
Short name=eIF-2-alpha
Short name=eIF-2A
Short name=eIF-2alpha

Gene names

Name:	EIF2S1
Synonyms:	EIF2A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	315 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S preinitiation complex. 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. 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.
Subunit structure	Heterotrimer composed of an alpha, a beta and a gamma chain. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Interaction with METAP2 protects EIF2S1 from inhibitory phosphorylation By similarity. Interacts with ABCF1 isoform 2. Associates with ribosomes. Ref.4
Subcellular location	Cytoplasmic granule By similarity. Note: The cytoplasmic granules are stress granules which are a dense aggregation in the cytosol composed of proteins and RNAs that appear when the cell is under stress. Co-localizes with NANOS3 in the stress granules By similarity.
Post-translational modification	Substrate for at least 4 kinases: EIF2AK3/PERK, GCN2, HRI and PKR. Phosphorylation stabilizes the eIF-2/GDP/eIF-2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF-2 between successive rounds of initiation and leading to global inhibition of translation. In case of infection by vaccinia virus or rotavirus A, eIF2S1 phosphorylation state is modulated.
Sequence similarities	Belongs to the eIF-2-alpha family. Contains 1 S1 motif domain.

Ontologies

Keywords
Biological process	Protein biosynthesis Translation regulation
Ligand	RNA-binding
Molecular function	Initiation factor
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of signaling protein activity involved in unfolded protein response Traceable author statement. Source: Reactome protein autophosphorylation Inferred from electronic annotation. Source: Compara regulation of translational initiation in response to stress Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasmic stress granule Inferred from sequence or structural similarity. Source: UniProtKB cytosol Traceable author statement. Source: Reactome eukaryotic translation initiation factor 2 complex Inferred from electronic annotation. Source: InterPro nucleus Inferred from electronic annotation. Source: Compara polysome Traceable author statement Ref.1. Source: ProtInc
Molecular_function	ribosome binding Inferred from direct assay Ref.4. Source: UniProtKB translation initiation factor activity Inferred from direct assay PubMed 16289705. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DDX3X	O00571	3	EBI-1056162,EBI-353779
Eif2ak3	Q9Z2B5	4	EBI-1056162,EBI-1226344	From a different organism.
EIF2S2	P20042	5	EBI-1056162,EBI-711977
EIF2S3	P41091	4	EBI-1056162,EBI-1054228

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 315

315

Eukaryotic translation initiation factor 2 subunit 1

PRO_0000137382

Regions

Domain

17 – 88

72

S1 motif

Amino acid modifications

Modified residue

49

1

Phosphoserine; by HRI By similarity

Modified residue

52

1

Phosphoserine Ref.6

Modified residue

141

1

N6-acetyllysine Ref.7

Secondary structure

1

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315

Helix Strand Turn

Details...

Beta strand

8 – 13

6

Beta strand

19 – 27

9

Beta strand

29 – 36

8

Turn

37 – 41

5

Beta strand

43 – 47

5

Helix

48 – 50

3

Turn

60 – 62

3

Beta strand

64 – 66

3

Beta strand

68 – 77

10

Turn

78 – 81

4

Beta strand

82 – 87

6

Helix

92 – 118

27

Helix

124 – 133

10

Helix

135 – 142

8

Helix

147 – 158

12

Helix

160 – 163

4

Helix

170 – 182

13

Beta strand

190 – 193

4

Turn

202 – 204

3

Helix

205 – 217

13

Beta strand

218 – 220

3

Beta strand

225 – 231

7

Beta strand

234 – 240

7

Helix

244 – 263

20

Helix

282 – 289

8

Helix

293 – 295

3

Sequences

	Sequence		Length	Mass (Da)
	P05198 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: FF3E75E3816E6B1E	FASTA	315	36,112
	10 20 30 40 50 60 MPGLSCRFYQ HKFPEVEDVV MVNVRSIAEM GAYVSLLEYN NIEGMILLSE LSRRRIRSIN 70 80 90 100 110 120 KLIRIGRNEC VVVIRVDKEK GYIDLSKRRV SPEEAIKCED KFTKSKTVYS ILRHVAEVLE 130 140 150 160 170 180 YTKDEQLESL FQRTAWVFDD KYKRPGYGAY DAFKHAVSDP SILDSLDLNE DEREVLINNI 190 200 210 220 230 240 NRRLTPQAVK IRADIEVACY GYEGIDAVKE ALRAGLNCST ENMPIKINLI APPRYVMTTT 250 260 270 280 290 300 TLERTEGLSV LSQAMAVIKE KIEEKRGVFN VQMEPKVVTD TDETELARQM ERLERENAEV 310 DGDDDAEEME AKAED

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of complementary DNAs encoding the alpha-subunit of translational initiation factor eIF-2. Characterization of the protein and its messenger RNA." Ernst H., Duncan R.F., Hershey J.W.B. J. Biol. Chem. 262:1206-1212(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fibroblast.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[3]	"Inhibition of PKR by vaccinia virus: role of the N- and C-terminal domains of E3L." Langland J.O., Jacobs B.L. Virology 324:419-429(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION STATE REGULATION BY VACCINIA VIRUS PROTEIN E3.
[4]	"The N-terminal region of ABC50 interacts with eukaryotic initiation factor eIF2 and is a target for regulatory phosphorylation by CK2." Paytubi S., Morrice N.A., Boudeau J., Proud C.G. Biochem. J. 409:223-231(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ABCF1, ASSOCIATION WITH RIBOSOMES.
[5]	"Rotavirus infection induces the phosphorylation of eIF2alpha but prevents the formation of stress granules." Montero H., Rojas M., Arias C.F., Lopez S. J. Virol. 82:1496-1504(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION STATE REGULATION BY ROTAVIRUS A.
[6]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[7]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-141, MASS SPECTROMETRY.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Crystal structure of the N-terminal segment of human eukaryotic translation initiation factor 2alpha." Nonato M.C., Widom J., Clardy J. J. Biol. Chem. 277:17057-17061(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-183.
[10]	"Solution structure of human initiation factor eIF2alpha reveals homology to the elongation factor eEF1B." Ito T., Marintchev A., Wagner G. Structure 12:1693-1704(2004) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 5-303.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02645 mRNA. Translation: AAA52373.1.
BC002513 mRNA. Translation: AAH02513.1.

IPI

IPI00219678.

RefSeq

NP_004085.1. NM_004094.4.

UniGene

Hs.151777.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KL9	X-ray	1.90	A	2-183	[»]
1Q8K	NMR	-	A	5-303	[»]

ProteinModelPortal

P05198.

ModBase

Search...

Protein-protein interaction databases

IntAct

P05198. 13 interactions.

MINT

MINT-2983901.

STRING

9606.ENSP00000256383.

PTM databases

PhosphoSite

P05198.

Polymorphism databases

DMDM

124200.

2D gel databases

OGP

P05198.

REPRODUCTION-2DPAGE

IPI00219678.

Proteomic databases

PaxDb

P05198.

PeptideAtlas

P05198.

PRIDE

P05198.

Protocols and materials databases

DNASU

1965.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000256383; ENSP00000256383; ENSG00000134001.
ENST00000466499; ENSP00000425299; ENSG00000134001.

GeneID

1965.

KEGG

hsa:1965.

UCSC

uc001xjg.3. human.

Organism-specific databases

CTD

1965.

GeneCards

GC14P067826.

HGNC

HGNC:3265. EIF2S1.

HPA

CAB011663.

MIM

603907. gene.

neXtProt

NX_P05198.

PharmGKB

PA27695.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1093.

HOGENOM

HOG000199476.

HOVERGEN

HBG001910.

InParanoid

P05198.

KO

K03237.

OMA

EKCTERF.

OrthoDB

EOG4BZN35.

PhylomeDB

P05198.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.
REACT_17015. Metabolism of proteins.
REACT_1762. 3' -UTR-mediated translational regulation.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P05198.

Bgee

P05198.

CleanEx

HS_EIF2A.
HS_EIF2S1.

Genevestigator

P05198.

GermOnline

ENSG00000134001. Homo sapiens.

Family and domain databases

Gene3D

1.10.150.190. 1 hit.
2.40.50.140. 1 hit.
3.30.70.1130. 1 hit.

InterPro

IPR012340. NA-bd_OB-fold.
IPR003029. Rbsml_prot_S1_RNA-bd_dom.
IPR022967. RNA-binding_domain_S1.
IPR024055. TIF2_asu_C.
IPR024054. TIF2_asu_middle.
IPR011488. TIF_2_asu.
[Graphical view]

Pfam

PF07541. EIF_2_alpha. 1 hit.
PF00575. S1. 1 hit.
[Graphical view]

SMART

SM00316. S1. 1 hit.
[Graphical view]

SUPFAM

SSF50249. Nucleic_acid_OB. 1 hit.
SSF110993. SSF110993. 1 hit.
SSF116742. SSF116742. 1 hit.

PROSITE

PS50126. S1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL1255131.

ChiTaRS

EIF2S1. human.

EvolutionaryTrace

P05198.

GenomeRNAi

1965.

NextBio

7971.

PMAP-CutDB

P05198.

SOURCE

Search...

Entry information

Entry name

IF2A_HUMAN

Accession

Primary (citable) accession number: P05198

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 142 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.