IF2A_PONAB
ID IF2A_PONAB Reviewed; 315 AA.
AC Q5R493;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 86.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-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 (EIF2AK1/HRI, EIF2AK2/PKR,
CC EIF2AK3/PERK and EIF2AK4/GCN2) 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, and hence allowing
CC ATF4- and QRICH1-mediated reprogramming.
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, such as ATF4, ATF5,
CC DDIT3/CHOP and PPP1R15A/GADD34. {ECO:0000250|UniProtKB:P05198}.
CC -!- SUBUNIT: Heterotrimer composed of an alpha, a beta and a gamma chain
CC (By similarity). Component of an EIF2 complex at least composed of
CC CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5.
CC Interaction with METAP2 protects EIF2S1 from inhibitory phosphorylation
CC (By similarity). Interacts with ABCF1 isoform 2. Associates with
CC ribosomes. Interacts with DDX3X in an RNA-independent manner (By
CC 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}. 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-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 (By similarity). Substrate for at least 4 kinases: EIF2AK1/HRI,
CC EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2. Phosphorylated;
CC phosphorylation on Ser-52 by the EIF2AK4/GCN2 protein kinase occurs in
CC response to amino acid starvation and UV irradiation (By similarity).
CC {ECO:0000250|UniProtKB:P05198, 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; CR861363; CAH93423.1; -; mRNA.
DR RefSeq; NP_001127006.1; NM_001133534.1.
DR AlphaFoldDB; Q5R493; -.
DR BMRB; Q5R493; -.
DR SMR; Q5R493; -.
DR STRING; 9601.ENSPPYP00000006729; -.
DR GeneID; 100174029; -.
DR KEGG; pon:100174029; -.
DR CTD; 1965; -.
DR eggNOG; KOG2916; Eukaryota.
DR InParanoid; Q5R493; -.
DR OrthoDB; 1093186at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:AgBase.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
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 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_0000331510"
FT DOMAIN 17..88
FT /note="S1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00180"
FT REGION 293..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; 36165 MW; AF35C5E381696DC5 CRC64;
MPGLSCRFYQ HKFPEVEDVV MVNVRSIAEM GAYVSLLEYN NIEGMILLSE LSRRRIRSIN
KLIRIGRNER VVVIRVDKEK GYIDLSKRRV SPEEAIKCED KFTKSKTVYS ILRHVAEVLE
YTKDEQLESL FQRTAWVFDD KYKRPGYGAY DAFKHAVSDP SILDSLDLNE DEREVLINNI
NRRLTPQAVK IRADIEVACY GYEGIDAVKE ALRAGLNCST ENMPIKINLI APPRYVMTTT
TLERTEGLSV LSQAMAVIKE KIEEKRGVFN VQMEPKVVTD TDETELARQM ERLERENAEV
DGDDDAEEME AKAED
