IF2A_XENLA
ID IF2A_XENLA Reviewed; 315 AA.
AC Q7ZTK4;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 90.
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;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (FEB-2003) 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; BC046576; AAH46576.1; -; mRNA.
DR RefSeq; NP_001080752.1; NM_001087283.1.
DR AlphaFoldDB; Q7ZTK4; -.
DR SMR; Q7ZTK4; -.
DR BioGRID; 98686; 2.
DR IntAct; Q7ZTK4; 1.
DR PRIDE; Q7ZTK4; -.
DR DNASU; 380444; -.
DR GeneID; 380444; -.
DR KEGG; xla:380444; -.
DR CTD; 380444; -.
DR Xenbase; XB-GENE-989636; eif2s1.S.
DR OrthoDB; 1093186at2759; -.
DR Proteomes; UP000186698; Chromosome 8S.
DR Bgee; 380444; Expressed in internal ear and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:AgBase.
DR GO; GO:0010494; C:cytoplasmic stress granule; IEA:UniProtKB-SubCell.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003743; F:translation initiation factor activity; IEA:UniProtKB-KW.
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_0000331511"
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; 36045 MW; D2D602E717F5F20F CRC64;
MPGLNCRFYQ HKFPEVDDVV MVNVRSIAEM GAYVSLLEYN NIEGMILLSE LSRRRIRSIN
KLIRIGRNEC VVVIRVDKDK GYIDLSKRRV SPEEALKCED KFTKSKTVYS ILRHVAEVLD
YTKDEQLDSL FQRTAWVFDE KYKKPGYGAY DAFKNAVSDP DILDGLDLSE DERRVLIDNI
NRRLTPQAVK IRADIEVACY GYEGIDAVKD ALRAGLSCST ENMPIKINLI APPRYVMTTT
TLERTEGLSV LNQAMSVIKE RIEEKRGVFN VQMEPKVVTD TDETELARQL ERLEKENAEV
DGDDDADEME AKTED
