ID IF2A_BOVIN Reviewed; 315 AA.
AC P68102; P05199; Q3SWZ1;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 27-MAR-2024, entry version 135.
DE RecName: Full=Eukaryotic translation initiation factor 2 subunit 1;
DE AltName: Full=Eukaryotic translation initiation factor 2 subunit alpha;
DE Short=eIF-2-alpha;
DE Short=eIF-2A;
DE Short=eIF-2alpha;
DE Short=eIF2-alpha;
GN Name=EIF2S1; Synonyms=EIF2A;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymphosarcoma;
RX PubMed=1932125; DOI=10.1016/0167-4781(91)90119-7;
RA Green S.R., Fullekrug J., Sauer K., Tuite M.F.;
RT "Isolation and characterisation of a bovine cDNA encoding eukaryotic
RT initiation factor 2 alpha.";
RL Biochim. Biophys. Acta 1090:277-280(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Uterus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Member of the eIF2 complex that functions in the early steps
CC of protein synthesis by forming a ternary complex with GTP and
CC initiator tRNA. This complex binds to a 40S ribosomal subunit, followed
CC by mRNA binding to form a 43S pre-initiation complex. Junction of the
CC 60S ribosomal subunit to form the 80S initiation complex is preceded by
CC hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary
CC complex. In order for eIF2 to recycle and catalyze another round of
CC initiation, the GDP bound to eIF2 must exchange with GTP by way of a
CC reaction catalyzed by eIF2B. EIF2S1/eIF2-alpha is a key component of
CC the integrated stress response (ISR), required for adaptation to
CC various stress: phosphorylation by metabolic-stress sensing protein
CC kinases (EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2) in
CC response to stress converts EIF2S1/eIF2-alpha in a global protein
CC synthesis inhibitor, leading to a attenuation of cap-dependent
CC translation, while concomitantly initiating the preferential
CC translation of ISR-specific mRNAs, such as the transcriptional
CC activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-
CC mediated reprogramming. {ECO:0000250|UniProtKB:P05198}.
CC -!- ACTIVITY REGULATION: Activity is regulated by phosphorylation at Ser-49
CC and Ser-52, which stabilizes the eIF2/GDP/eIF2B complex and prevents
CC the eIF2B-mediated exchange of GDP for GTP, thereby preventing the
CC formation of the 43S pre-initiation complex (43S PIC). This results in
CC the global attenuation of 5' cap-dependent protein synthesis and
CC concomitant translation of ISR-specific mRNAs that contain a short
CC upstream open reading frame (uORF) in their 5' UTR, such as ATF4, ATF5,
CC DDIT3/CHOP and PPP1R15A/GADD34. {ECO:0000250|UniProtKB:P05198}.
CC -!- SUBUNIT: Eukaryotic translation initiation factor 2 eIF2 is a
CC heterotrimeric complex composed of an alpha (EIF2S1), a beta (EIF2S2)
CC and a gamma (EIF2S3) chain (By similarity). eIF2 is member of the 43S
CC pre-initiation complex (43S PIC). eIF2 forms a complex with at least
CC CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (By
CC similarity). Interaction with METAP2 protects EIF2S1 from inhibitory
CC phosphorylation (By similarity). Interacts with ABCF1 (By similarity).
CC Associates with ribosomes (By similarity). Interacts with DDX3X in an
CC RNA-independent manner (By similarity). {ECO:0000250|UniProtKB:P05198,
CC ECO:0000250|UniProtKB:P68101, ECO:0000250|UniProtKB:Q6ZWX6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:Q6ZWX6}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P56286}. Note=Colocalizes with NANOS3 in the
CC stress granules. {ECO:0000250|UniProtKB:Q6ZWX6}.
CC -!- PTM: Phosphorylation at Ser-49 and Ser-52 stabilizes the eIF-
CC 2/GDP/eIF2B complex and prevents GDP/GTP exchange reaction, thus
CC impairing the recycling of eIF-2 between successive rounds of
CC initiation and leading to global inhibition of translation, while
CC concomitantly initiating the preferential translation of integrated
CC stress response (ISR)-specific mRNAs (By similarity). Substrate for at
CC least 4 kinases: EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and
CC EIF2AK4/GCN2. Phosphorylated; phosphorylation on Ser-52 by the
CC EIF2AK4/GCN2 protein kinase occurs in response to amino acid starvation
CC and UV irradiation (By similarity). {ECO:0000250|UniProtKB:P05198,
CC ECO:0000250|UniProtKB:Q6ZWX6}.
CC -!- SIMILARITY: Belongs to the eIF-2-alpha family. {ECO:0000305}.
CC -!- CAUTION: This gene should not be confused with EIF2A, with which it
CC shares the alias EIF2A. Although both of these proteins function in
CC binding initiator tRNA to the 40S ribosomal subunit, the eIF2 complex
CC requires GTP, whereas the EIF2A protein does so in a codon-dependent
CC manner. {ECO:0000305}.
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DR EMBL; X53689; CAA37728.1; -; mRNA.
DR EMBL; BC104590; AAI04591.1; -; mRNA.
DR PIR; S18461; S18461.
DR RefSeq; NP_787007.1; NM_175813.2.
DR RefSeq; XP_005211998.1; XM_005211941.3.
DR AlphaFoldDB; P68102; -.
DR BMRB; P68102; -.
DR SMR; P68102; -.
DR STRING; 9913.ENSBTAP00000066638; -.
DR PaxDb; 9913-ENSBTAP00000040899; -.
DR PeptideAtlas; P68102; -.
DR Ensembl; ENSBTAT00000043322.2; ENSBTAP00000040899.1; ENSBTAG00000016311.5.
DR Ensembl; ENSBTAT00000071779.1; ENSBTAP00000066638.1; ENSBTAG00000016311.5.
DR GeneID; 327694; -.
DR KEGG; bta:327694; -.
DR CTD; 1965; -.
DR VEuPathDB; HostDB:ENSBTAG00000016311; -.
DR VGNC; VGNC:28390; EIF2S1.
DR eggNOG; KOG2916; Eukaryota.
DR GeneTree; ENSGT00390000007015; -.
DR HOGENOM; CLU_033458_0_0_1; -.
DR InParanoid; P68102; -.
DR OMA; DVNEHQR; -.
DR OrthoDB; 4371132at2759; -.
DR TreeFam; TF101502; -.
DR Reactome; R-BTA-156827; L13a-mediated translational silencing of Ceruloplasmin expression.
DR Reactome; R-BTA-381042; PERK regulates gene expression.
DR Reactome; R-BTA-382556; ABC-family proteins mediated transport.
DR Reactome; R-BTA-72649; Translation initiation complex formation.
DR Reactome; R-BTA-72695; Formation of the ternary complex, and subsequently, the 43S complex.
DR Reactome; R-BTA-72702; Ribosomal scanning and start codon recognition.
DR Reactome; R-BTA-72731; Recycling of eIF2:GDP.
DR Proteomes; UP000009136; Chromosome 10.
DR Bgee; ENSBTAG00000016311; Expressed in conceptus and 107 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:AgBase.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0033290; C:eukaryotic 48S preinitiation complex; IBA:GO_Central.
DR GO; GO:0005850; C:eukaryotic translation initiation factor 2 complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:AgBase.
DR GO; GO:0031090; C:organelle membrane; IEA:UniProt.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0043022; F:ribosome binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003743; F:translation initiation factor activity; ISS:AgBase.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl.
DR GO; GO:0034644; P:cellular response to UV; ISS:UniProtKB.
DR GO; GO:0032057; P:negative regulation of translational initiation in response to stress; ISS:UniProtKB.
DR GO; GO:0036499; P:PERK-mediated unfolded protein response; ISS:UniProtKB.
DR GO; GO:0036490; P:regulation of translation in response to endoplasmic reticulum stress; IEA:Ensembl.
DR GO; GO:0043558; P:regulation of translational initiation in response to stress; ISS:AgBase.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; IEA:Ensembl.
DR GO; GO:0006412; P:translation; ISS:AgBase.
DR GO; GO:0006413; P:translational initiation; IBA:GO_Central.
DR CDD; cd04452; S1_IF2_alpha; 1.
DR Gene3D; 3.30.70.1130; EIF_2_alpha; 1.
DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR003029; S1_domain.
DR InterPro; IPR044126; S1_IF2_alpha.
DR InterPro; IPR024055; TIF2_asu_C.
DR InterPro; IPR024054; TIF2_asu_middle_sf.
DR InterPro; IPR011488; TIF_2_asu.
DR PANTHER; PTHR10602; EUKARYOTIC TRANSLATION INITIATION FACTOR 2 SUBUNIT 1; 1.
DR PANTHER; PTHR10602:SF0; EUKARYOTIC TRANSLATION INITIATION FACTOR 2 SUBUNIT 1; 1.
DR Pfam; PF07541; EIF_2_alpha; 1.
DR Pfam; PF00575; S1; 1.
DR SMART; SM00316; S1; 1.
DR SUPFAM; SSF110993; eIF-2-alpha, C-terminal domain; 1.
DR SUPFAM; SSF116742; eIF2alpha middle domain-like; 1.
DR SUPFAM; SSF50249; Nucleic acid-binding proteins; 1.
DR PROSITE; PS50126; S1; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Initiation factor; Phosphoprotein;
KW Protein biosynthesis; Reference proteome; RNA-binding;
KW Translation regulation.
FT CHAIN 1..315
FT /note="Eukaryotic translation initiation factor 2 subunit
FT 1"
FT /id="PRO_0000137381"
FT DOMAIN 17..88
FT /note="S1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00180"
FT REGION 292..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 300..315
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 49
FT /note="Phosphoserine; by HRI"
FT /evidence="ECO:0000250|UniProtKB:P83268"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05198"
FT MOD_RES 141
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P05198"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05198"
FT MOD_RES 279
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P05198"
FT MOD_RES 281
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P05198"
SQ SEQUENCE 315 AA; 36108 MW; 018480B89175D118 CRC64;
MPGLSCRFYQ HKFPEVEDVV MVNVRSIAEM GAYVSLLEYN NIEGMILLSE LSRRRIRSIN
KLIRIGRNEC VVVIRVDKEK GYIDLSKRRV SPEEAIKCED KFTKSKTVYS ILRHVAEVLE
YTKDEQLESL FQRTAWVFDD KYKRPGYGAY DAFKHAVSDP SILDSLDLNE DEREVLINNI
NRRLTPQAVK IRADIEVACY GYEGIDAVKE ALRAGLNCST ETMPIKINLI APPRYVMTTT
TLERTEGLSV LNQAMAVIKE KIEEKRGVFN VQMEPKVVTD TDETELARQL ERLERENAEV
DGDDDAEEME AKAED
//
