IF2A_XENTR
ID IF2A_XENTR Reviewed; 315 AA.
AC Q6GL89;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 101.
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;
GN Name=eif2s1; Synonyms=eif2a; ORFNames=TGas059e16.1;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Gastrula;
RG Sanger Xenopus tropicalis EST/cDNA project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Functions in the early steps of protein synthesis by forming
CC a ternary complex with GTP and initiator tRNA. This complex binds to a
CC 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-
CC initiation complex. Junction of the 60S ribosomal subunit to form the
CC 80S initiation complex is preceded by hydrolysis of the GTP bound to
CC eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to
CC recycle and catalyze another round of initiation, the GDP bound to eIF-
CC 2 must exchange with GTP by way of a reaction catalyzed by eIF-2B.
CC EIF2S1/eIF-2-alpha is a key component of the integrated stress response
CC (ISR), required for adaptation to various stress: phosphorylation by
CC metabolic-stress sensing protein kinases in response to stress converts
CC EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to
CC a attenuation of cap-dependent translation, while concomitantly
CC initiating the preferential translation of ISR-specific mRNAs, such as
CC the transcriptional activators ATF4 and QRICH1.
CC {ECO:0000250|UniProtKB:P05198}.
CC -!- ACTIVITY REGULATION: Activity is regulated by phosphorylation at Ser-49
CC and Ser-52, which stabilizes the eIF-2/GDP/eIF-2B complex and prevents
CC the eIF-2B-mediated exchange of GDP for GTP, thereby preventing the
CC formation of the 43S pre-initiation complex (PIC). This results in the
CC 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.
CC {ECO:0000250|UniProtKB:P05198}.
CC -!- SUBUNIT: Heterotrimer composed of an alpha, a beta and a gamma chain.
CC {ECO:0000250|UniProtKB:P05198}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:Q6ZWX6}.
CC -!- PTM: Phosphorylation at Ser-49 and Ser-52 stabilizes the eIF-2/GDP/eIF-
CC 2B complex and prevents GDP/GTP exchange reaction, thus impairing the
CC recycling of eIF-2 between successive rounds of initiation and leading
CC to global inhibition of translation, while concomitantly initiating the
CC preferential translation of integrated stress response (ISR)-specific
CC mRNAs. {ECO:0000250|UniProtKB:P05198}.
CC -!- SIMILARITY: Belongs to the eIF-2-alpha family. {ECO:0000305}.
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DR EMBL; CR761726; CAJ83389.1; -; mRNA.
DR EMBL; BC074615; AAH74615.1; -; mRNA.
DR RefSeq; NP_001005630.1; NM_001005630.1.
DR AlphaFoldDB; Q6GL89; -.
DR SMR; Q6GL89; -.
DR STRING; 8364.ENSXETP00000061363; -.
DR DNASU; 448087; -.
DR Ensembl; ENSXETT00000024514; ENSXETP00000024514; ENSXETG00000011221.
DR GeneID; 448087; -.
DR KEGG; xtr:448087; -.
DR CTD; 1965; -.
DR Xenbase; XB-GENE-989630; eif2s1.
DR eggNOG; KOG2916; Eukaryota.
DR InParanoid; Q6GL89; -.
DR OrthoDB; 1093186at2759; -.
DR Reactome; R-XTR-156827; L13a-mediated translational silencing of Ceruloplasmin expression.
DR Reactome; R-XTR-72649; Translation initiation complex formation.
DR Reactome; R-XTR-72702; Ribosomal scanning and start codon recognition.
DR Proteomes; UP000008143; Chromosome 8.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000011221; Expressed in neurula embryo and 19 other tissues.
DR ExpressionAtlas; Q6GL89; baseline.
DR GO; GO:0005737; C:cytoplasm; ISS:AgBase.
DR GO; GO:0010494; C:cytoplasmic stress granule; 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; IBA:GO_Central.
DR GO; GO:0005851; C:eukaryotic translation initiation factor 2B complex; IBA:GO_Central.
DR GO; GO:0043614; C:multi-eIF complex; IBA:GO_Central.
DR GO; GO:0043022; F:ribosome binding; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003743; F:translation initiation factor activity; IBA:GO_Central.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB.
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:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR CDD; cd04452; S1_IF2_alpha; 1.
DR Gene3D; 1.10.150.190; -; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.30.70.1130; -; 1.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR022967; S1_dom.
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; PTHR10602; 1.
DR Pfam; PF07541; EIF_2_alpha; 1.
DR Pfam; PF00575; S1; 1.
DR SMART; SM00316; S1; 1.
DR SUPFAM; SSF110993; SSF110993; 1.
DR SUPFAM; SSF116742; SSF116742; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR PROSITE; PS50126; S1; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Initiation factor; Phosphoprotein; Protein biosynthesis;
KW Reference proteome; RNA-binding; Translation regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250"
FT CHAIN 2..315
FT /note="Eukaryotic translation initiation factor 2 subunit
FT 1"
FT /id="PRO_0000331512"
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"
FT /evidence="ECO:0000250|UniProtKB:P83268"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6ZWX6"
SQ SEQUENCE 315 AA; 36126 MW; 99BB6AA1756EDB95 CRC64;
MPALSCRFYQ HKFPEVDDVV MVNVRSIAEM GAYVSLLEYN NIEGMILLSE LSRRRIRSIN
KLIRIGRNEC VVVIRVDKDK GYIDLSKRRV SPEEALKCED KFTKSKTVYS ILRHVAEVLE
YTKDEQLESL YQRTAWVFDE KYKKPGYGAY DAFKHAVSDP DVLDGLDLNE DERRVLIDNI
NRRLTPQAVK IRADIEVACY GYEGIDAVKD ALRAGLSCST ENMPIKINLI APPRYVMTTT
TLERTEGLSV LNQAMSVIKE RIEEKRGVFN VQMEPKVVTD TDETELARQL ERLEKENAEV
DGDDDAEEME AKTED
