Description: Homo sapiens eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa (EIF2S1), mRNA. RefSeq Summary (NM_004094): The translation initiation factor EIF2 catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, EIF2, and GTP. EIF2 is composed of 3 nonidentical subunits, the 36-kD EIF2-alpha subunit (EIF2S1), the 38-kD EIF2-beta subunit (EIF2S2; MIM 603908), and the 52-kD EIF2-gamma subunit (EIF2S3; MIM 300161). The rate of formation of the ternary complex is modulated by the phosphorylation state of EIF2-alpha (Ernst et al., 1987 [PubMed 2948954]).[supplied by OMIM, Feb 2010]. Transcript (Including UTRs) Position: hg19 chr14:67,827,034-67,853,233 Size: 26,200 Total Exon Count: 8 Strand: + Coding Region Position: hg19 chr14:67,831,485-67,850,157 Size: 18,673 Coding Exon Count: 7
ID:IF2A_HUMAN DESCRIPTION: RecName: Full=Eukaryotic translation initiation factor 2 subunit 1; AltName: Full=Eukaryotic translation initiation factor 2 subunit alpha; Short=eIF-2-alpha; Short=eIF-2A; Short=eIF-2alpha; 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: 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. INTERACTION: O00571:DDX3X; NbExp=3; IntAct=EBI-1056162, EBI-353779; Q9Z2B5:Eif2ak3 (xeno); NbExp=4; IntAct=EBI-1056162, EBI-1226344; P20042:EIF2S2; NbExp=5; IntAct=EBI-1056162, EBI-711977; P41091:EIF2S3; NbExp=4; IntAct=EBI-1056162, EBI-1054228; 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). PTM: 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. SIMILARITY: Belongs to the eIF-2-alpha family. SIMILARITY: Contains 1 S1 motif domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P05198
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006412 translation GO:0006413 translational initiation GO:0006417 regulation of translation GO:0007568 aging GO:0032057 negative regulation of translational initiation in response to stress GO:0034063 stress granule assembly GO:0034198 cellular response to amino acid starvation GO:0034599 cellular response to oxidative stress GO:0034605 cellular response to heat GO:0034644 cellular response to UV GO:0034976 response to endoplasmic reticulum stress GO:0036499 PERK-mediated unfolded protein response GO:0043558 regulation of translational initiation in response to stress GO:0046777 protein autophosphorylation GO:0055085 transmembrane transport GO:1901216 positive regulation of neuron death GO:1905098 negative regulation of guanyl-nucleotide exchange factor activity GO:1990737 response to manganese-induced endoplasmic reticulum stress GO:2000676 positive regulation of type B pancreatic cell apoptotic process
AK312442 - Homo sapiens cDNA, FLJ92791, Homo sapiens eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa (EIF2S1), mRNA. BX161521 - human full-length cDNA clone CS0DL010YH08 of B cells (Ramos cell line) of Homo sapiens (human). AK297244 - Homo sapiens cDNA FLJ51242 complete cds, moderately similar to Eukaryotic translation initiation factor 2 subunit 1. D28379 - Homo sapiens mRNA for eukaryotic initiation factor-2alpha, 5'UTR region. BC002513 - Homo sapiens eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa, mRNA (cDNA clone MGC:1511 IMAGE:3139624), complete cds. JD485269 - Sequence 466293 from Patent EP1572962. JD385227 - Sequence 366251 from Patent EP1572962. J02645 - Human translational initiation factor (eIF-2), alpha subunit mRNA, complete cds. AB587562 - Synthetic construct DNA, clone: pF1KE1098, Homo sapiens EIF2S1 gene for eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa, without stop codon, in Flexi system. DQ895347 - Synthetic construct Homo sapiens clone IMAGE:100009807; FLH183488.01L; RZPDo839D02141D eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa (EIF2S1) gene, encodes complete protein. DQ892151 - Synthetic construct clone IMAGE:100004781; FLH183492.01X; RZPDo839D02142D eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa (EIF2S1) gene, encodes complete protein. JD066449 - Sequence 47473 from Patent EP1572962. JD258021 - Sequence 239045 from Patent EP1572962. JD192413 - Sequence 173437 from Patent EP1572962. JD476611 - Sequence 457635 from Patent EP1572962. U26032 - Human translation initiation factor eIF-2alpha mRNA, 3'UTR. JD539230 - Sequence 520254 from Patent EP1572962. JD065253 - Sequence 46277 from Patent EP1572962. JD285161 - Sequence 266185 from Patent EP1572962. JD494003 - Sequence 475027 from Patent EP1572962. JD071248 - Sequence 52272 from Patent EP1572962. JD204445 - Sequence 185469 from Patent EP1572962. LF209575 - JP 2014500723-A/17078: Polycomb-Associated Non-Coding RNAs. JD490777 - Sequence 471801 from Patent EP1572962. JD559106 - Sequence 540130 from Patent EP1572962. JD214839 - Sequence 195863 from Patent EP1572962. JD112030 - Sequence 93054 from Patent EP1572962. JD508654 - Sequence 489678 from Patent EP1572962. JD337880 - Sequence 318904 from Patent EP1572962. JD249745 - Sequence 230769 from Patent EP1572962. JD249746 - Sequence 230770 from Patent EP1572962. JD185752 - Sequence 166776 from Patent EP1572962. JD373188 - Sequence 354212 from Patent EP1572962. JD471562 - Sequence 452586 from Patent EP1572962. JD291632 - Sequence 272656 from Patent EP1572962. JD182702 - Sequence 163726 from Patent EP1572962. JD247339 - Sequence 228363 from Patent EP1572962. JD366838 - Sequence 347862 from Patent EP1572962. JD149760 - Sequence 130784 from Patent EP1572962. JD518817 - Sequence 499841 from Patent EP1572962. JD366998 - Sequence 348022 from Patent EP1572962. JD522559 - Sequence 503583 from Patent EP1572962. JD522560 - Sequence 503584 from Patent EP1572962. JD106055 - Sequence 87079 from Patent EP1572962. JD106056 - Sequence 87080 from Patent EP1572962. JD518011 - Sequence 499035 from Patent EP1572962. JD220055 - Sequence 201079 from Patent EP1572962. JD255794 - Sequence 236818 from Patent EP1572962. JD212246 - Sequence 193270 from Patent EP1572962. LF329737 - JP 2014500723-A/137240: Polycomb-Associated Non-Coding RNAs. JD022359 - Sequence 3383 from Patent EP1572962. JD035056 - Sequence 16080 from Patent EP1572962. JD035580 - Sequence 16604 from Patent EP1572962. LF329738 - JP 2014500723-A/137241: Polycomb-Associated Non-Coding RNAs. MA565314 - JP 2018138019-A/137240: Polycomb-Associated Non-Coding RNAs. MA565315 - JP 2018138019-A/137241: Polycomb-Associated Non-Coding RNAs. MA445152 - JP 2018138019-A/17078: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_chemicalPathway - Apoptotic Signaling in Response to DNA Damage h_igf1mtorpathway - Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway h_eifPathway - Eukaryotic protein translation h_rnaPathway - Double Stranded RNA Induced Gene Expression h_vegfPathway - VEGF, Hypoxia, and Angiogenesis h_eif2Pathway - Regulation of eIF2
Reactome (by CSHL, EBI, and GO)
Protein P05198 (Reactome details) participates in the following event(s):
R-HSA-381111 Phosphorylation of eIF2-alpha by PERK R-HSA-72663 De novo formation of eIF2:GTP R-HSA-72697 Start codon recognition R-HSA-5227009 ABCF1 binds EIF2 R-HSA-72722 eIF2 activation R-HSA-72670 Formation of eIF2:GDP:eIF2B intermediate R-HSA-72619 eIF2:GTP is hydrolyzed, eIFs are released R-HSA-72669 Met-tRNAi binds to eIF2:GTP to form the ternary complex R-HSA-72691 Formation of the 43S pre-initiation complex R-HSA-156808 Formation of translation initiation complexes yielding circularized Ceruloplasmin mRNA in a 'closed-loop' conformation R-HSA-157849 Formation of translation initiation complexes containing mRNA that does not circularize R-HSA-72621 Ribosomal scanning R-HSA-156823 Association of phospho-L13a with GAIT element of Ceruloplasmin mRNA R-HSA-381042 PERK regulates gene expression R-HSA-72695 Formation of the ternary complex, and subsequently, the 43S complex R-HSA-72702 Ribosomal scanning and start codon recognition R-HSA-382556 ABC-family proteins mediated transport R-HSA-381119 Unfolded Protein Response (UPR) R-HSA-72731 Recycling of eIF2:GDP R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit R-HSA-72737 Cap-dependent Translation Initiation R-HSA-382551 Transport of small molecules R-HSA-392499 Metabolism of proteins R-HSA-72613 Eukaryotic Translation Initiation R-HSA-72649 Translation initiation complex formation R-HSA-72766 Translation R-HSA-156827 L13a-mediated translation R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
US Server
