ID EI2BE_RABIT Reviewed; 721 AA.
AC P47823;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 27-MAR-2024, entry version 126.
DE RecName: Full=Translation initiation factor eIF2B subunit epsilon;
DE AltName: Full=eIF2B GDP-GTP exchange factor subunit epsilon;
GN Name=EIF2B5; Synonyms=EIF2BE;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 359-371 AND 448-456.
RC STRAIN=New Zealand white; TISSUE=Reticulocyte;
RX PubMed=8688466; DOI=10.1016/0167-4781(96)00054-1;
RA Asuru A.I., Mellor H., Thomas N.S.B., Yu L., Chen J.-J., Crosby J.S.,
RA Hartson S.D., Kimball S.R., Jefferson L.S., Matts R.L.;
RT "Cloning and characterization of cDNAs encoding the epsilon-subunit of
RT eukaryotic initiation factor-2B from rabbit and human.";
RL Biochim. Biophys. Acta 1307:309-317(1996).
CC -!- FUNCTION: Acts as a component of the translation initiation factor 2B
CC (eIF2B) complex, which catalyzes the exchange of GDP for GTP on
CC eukaryotic initiation factor 2 (eIF2) gamma subunit. Its guanine
CC nucleotide exchange factor activity is repressed when bound to eIF2
CC complex phosphorylated on the alpha subunit, thereby limiting the
CC amount of methionyl-initiator methionine tRNA available to the ribosome
CC and consequently global translation is repressed.
CC {ECO:0000250|UniProtKB:Q13144}.
CC -!- ACTIVITY REGULATION: Activated by the chemical integrated stress
CC response (ISR) inhibitor ISRIB which stimulates guanine nucleotide
CC exchange factor activity for both phosphorylated and unphosphorylated
CC eIF2. {ECO:0000250|UniProtKB:Q13144}.
CC -!- SUBUNIT: Component of the translation initiation factor 2B (eIF2B)
CC complex which is a heterodecamer of two sets of five different
CC subunits: alpha, beta, gamma, delta and epsilon. Subunits alpha, beta
CC and delta comprise a regulatory subcomplex and subunits epsilon and
CC gamma comprise a catalytic subcomplex. Within the complex, the
CC hexameric regulatory complex resides at the center, with the two
CC heterodimeric catalytic subcomplexes bound on opposite sides.
CC {ECO:0000250|UniProtKB:Q13144}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P56287}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- PTM: Phosphorylated at Ser-544 by DYRK2; this is required for
CC subsequent phosphorylation by GSK3B. Phosphorylated on serine and
CC threonine residues by GSK3B; phosphorylation inhibits its function (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Polyubiquitinated, probably by NEDD4. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the eIF-2B gamma/epsilon subunits family.
CC {ECO:0000305}.
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DR EMBL; U23037; AAC48618.1; -; mRNA.
DR RefSeq; NP_001076143.1; NM_001082674.1.
DR AlphaFoldDB; P47823; -.
DR SMR; P47823; -.
DR STRING; 9986.ENSOCUP00000003919; -.
DR iPTMnet; P47823; -.
DR PaxDb; 9986-ENSOCUP00000003919; -.
DR GeneID; 100009393; -.
DR KEGG; ocu:100009393; -.
DR CTD; 8893; -.
DR eggNOG; KOG1461; Eukaryota.
DR HOGENOM; CLU_012507_2_0_1; -.
DR InParanoid; P47823; -.
DR OMA; LAQSCKI; -.
DR OrthoDB; 5474157at2759; -.
DR TreeFam; TF101509; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005851; C:eukaryotic translation initiation factor 2B complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IMP:UniProtKB.
DR GO; GO:0003743; F:translation initiation factor activity; IEA:UniProtKB-KW.
DR GO; GO:0031369; F:translation initiation factor binding; IEA:InterPro.
DR GO; GO:0014002; P:astrocyte development; ISS:UniProtKB.
DR GO; GO:0048708; P:astrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0002183; P:cytoplasmic translational initiation; ISS:UniProtKB.
DR GO; GO:0042552; P:myelination; ISS:UniProtKB.
DR GO; GO:0014003; P:oligodendrocyte development; ISS:UniProtKB.
DR GO; GO:0001541; P:ovarian follicle development; ISS:UniProtKB.
DR GO; GO:0045948; P:positive regulation of translational initiation; IMP:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0009749; P:response to glucose; ISS:UniProtKB.
DR GO; GO:0009408; P:response to heat; ISS:UniProtKB.
DR GO; GO:0043434; P:response to peptide hormone; ISS:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006413; P:translational initiation; ISS:UniProtKB.
DR CDD; cd04197; eIF-2B_epsilon_N; 1.
DR CDD; cd11558; W2_eIF2B_epsilon; 1.
DR Gene3D; 1.25.40.180; -; 1.
DR Gene3D; 2.160.10.10; Hexapeptide repeat proteins; 2.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR035543; eIF-2B_epsilon_N.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR InterPro; IPR011004; Trimer_LpxA-like_sf.
DR InterPro; IPR003307; W2_domain.
DR InterPro; IPR044123; W2_eIF2B_epsilon.
DR PANTHER; PTHR45887; TRANSLATION INITIATION FACTOR EIF-2B SUBUNIT EPSILON; 1.
DR PANTHER; PTHR45887:SF1; TRANSLATION INITIATION FACTOR EIF-2B SUBUNIT EPSILON; 1.
DR Pfam; PF02020; W2; 1.
DR SMART; SM00515; eIF5C; 1.
DR SUPFAM; SSF48371; ARM repeat; 1.
DR SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1.
DR SUPFAM; SSF51161; Trimeric LpxA-like enzymes; 1.
DR PROSITE; PS51363; W2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Direct protein sequencing; Initiation factor;
KW Isopeptide bond; Methylation; Phosphoprotein; Protein biosynthesis;
KW Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13144"
FT CHAIN 2..721
FT /note="Translation initiation factor eIF2B subunit epsilon"
FT /id="PRO_0000156074"
FT DOMAIN 543..720
FT /note="W2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00695"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 446..478
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 517..545
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q13144"
FT MOD_RES 19
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHW4"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64350"
FT MOD_RES 322
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q64350"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13144"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13144"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13144"
FT MOD_RES 532
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64350"
FT MOD_RES 540
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64350"
FT MOD_RES 544
FT /note="Phosphoserine; by DYRK2"
FT /evidence="ECO:0000250|UniProtKB:Q13144"
FT MOD_RES 717
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13144"
FT CROSSLNK 61
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q64350"
FT CROSSLNK 103
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q64350"
FT CROSSLNK 141
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q64350"
FT CROSSLNK 217
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q64350"
FT CONFLICT 365..366
FT /note="GT -> FA (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 721 AA; 80167 MW; DDCBC7FEA3965061 CRC64;
MATTVVAPPG AVSDRANKRG GGPGGGGGGG GARGAEEESP PPLQAVLVAD SFNRRFFPIS
KDQPRVLLPL ANVALIDYTL EFLTATGVQE TFVFCCWKAA QIKEHLQKSK WCRPTSLNVV
RIITSELYRS LGDVLRDVDA KALVRSDFLL VYGDVVSNIN VTRALEEHRL RRKLEKNVSV
MTMIFKESSP SHPTRCHEDN VVVAVDSATN RILHFQKTQG LRRFSFPLSL FQGSGAGVEI
RYDLLDCHIS ICSPQVAQLF TDNFDYQTRD DFVRGLLVNE EILGNQIHMH VTTREYGARV
SNLHMYSAVC ADVIRRWVYP LTPEANFTDS TAQSCTHSRH NIYRGPEVSL GHGSILEENV
LLGSGTVIGS NCSITNSVIG PGCCIGDNVV LDRAYLWKGV QVASGAQIHQ SLLCDHAEVK
EQVTLKPHCV LTSQVVVGPN ITLPEGSVIS LHPPDAEEDE DDGQFSDDSG VNQAKEKAKL
KGYNPAEVGV AGKGYLWKAA DMNTEKEEEL RQSLWGLTIN EEEESETESE RSMDSEELDS
RAGSPQLDDI KVFQNEVLGT LQRGKEESIS CDNLILEINS LKYAYNISLK EVMQVLSHVV
LEFPLQQMDS PLEANRYCAL LLPLLKAWSP VFRNYIKRAA DHLEALAAIE EFFLEHEALG
TCIAKVLMGF YQLEILAEET ILSWFGQRDV TDKGRQLRKN QQLQRFIQWL KEAEEESSED
D
//
