The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

EIF2B5  -  eukaryotic translation initiation factor...

Homo sapiens

Synonyms: CACH, CLE, EIF-2B, EIF2BE, EIF2Bepsilon, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of EIF2B5

  • Childhood ataxia with central nervous system hypomyelination (CACH), or vanishing white matter leukoencephalopathy (VWM), is a fatal brain disorder caused by mutations in eukaryotic initiation factor 2B (eIF2B). eIF2B is essential for protein synthesis and regulates translation in response to cellular stresses [1].
  • Peripheral neuropathy in vanishing white matter disease with a novel EIF2B5 mutation [2].
  • In contrast, sepsis did not change either the total amount or the phosphorylation state of eIF2alpha or eIF2Bepsilon [3].
  • METHODS: Ninety-three individuals (78 families) with an undetermined leukodystrophy were selected on MRI-based criteria of childhood ataxia with central hypomyelination/vanishing white matter (CACH/VWM) for EIF2B genes analysis [4].
  • The human protein hCLE was previously identified by its interaction with the PA subunit of influenza virus polymerase [5].

Psychiatry related information on EIF2B5

  • VO2 and HR kinetics during CLE were significantly slower in HTR than in CTRL, whereas, unexpectedly, no significant differences were found for Delta[deoxy(Hb+Mb)] kinetics (mean response time: 21.3 +/- 1.1 vs 20.2 +/- 1.2 s) [6].
  • This study examined the relationships between observer ratings of interpersonal style (Chart of Interpersonal Reactions in Closed Living Environment [CIR-CLE]) and the personality disorder scales of the Millon Clinical Multiaxial Inventory (MCMI-I) in a sample of male forensic psychiatric inpatients (N = 104) [7].

High impact information on EIF2B5

  • We have identified mutations in EIF2B5 and EIF2B2, encoding the epsilon- and beta-subunits of the translation initiation factor eIF2B and located on chromosomes 3q27 and 14q24, respectively, as causing VWM [8].
  • EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy [9].
  • This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bepsilon in vivo [10].
  • The fifth site, which lies outside the catalytic domain of eIF2Bepsilon, can be phosphorylated by casein kinase 1 [10].
  • We performed mutagenesis to introduce changes equivalent to 12 human CACH/VWM mutations in three subunits of the equivalent factor from yeast (Saccharomyces cerevisiae) and analyzed effects on cell growth, translation, and gene expression in response to stresses [1].

Biological context of EIF2B5


Anatomical context of EIF2B5


Associations of EIF2B5 with chemical compounds

  • Identification of domains and residues within the epsilon subunit of eukaryotic translation initiation factor 2B (eIF2Bepsilon) required for guanine nucleotide exchange reveals a novel activation function promoted by eIF2B complex formation [17].
  • A hydroxyl 12-amino acid peptide derived from the conserved CLE motif of CLV3 promotes cell differentiation, whereas another CLE-derived peptide suppresses the differentiation [18].
  • Here we show that Ser(539) of eIF2Bepsilon, which is followed by proline, is phosphorylated specifically by two isoforms of dual-specificity tyrosine phosphorylated and regulated kinase (DYRK2 and DYRK1A), but only weakly or not at all by other 'proline-directed' protein kinases tested [19].
  • Cyclolinopeptides CLD and CLE, which contain methionine oxide, were detected in small quantities only [20].

Other interactions of EIF2B5


Analytical, diagnostic and therapeutic context of EIF2B5

  • Here we have established cell cultures from the brain of an individual with VWM carrying mutations in subunit 5 of eIF2B (encoded by EIF2B5) [9].
  • Accordingly, the expression profiling in hCLE-silenced cells studied by microarray analysis showed that, among the genes that exhibited a differential expression under hCLE silencing, more than 90% were down-regulated [5].
  • Here we show that hCLE and different phosphorylated forms of the RNA polymerase II (RNAP II) largest subunit, co-immunoprecipitate and colocalize by confocal microscopy analysis [5].
  • METHODS: Twenty male HTR (age 50.4 +/- 2.6 yr; mean +/- SE) and 17 healthy untrained age-matched controls (CTRL) performed an incremental exercise (IE) and a series of constant-load (CLE) moderate-intensity exercise tests on a cycloergometer [6].
  • We evaluated 21 normal subjects and 20 patients with LVWM abnormalities revealed by two-dimensional echocardiography [25].


  1. Mutations causing childhood ataxia with central nervous system hypomyelination reduce eukaryotic initiation factor 2B complex formation and activity. Richardson, J.P., Mohammad, S.S., Pavitt, G.D. Mol. Cell. Biol. (2004) [Pubmed]
  2. Peripheral neuropathy in vanishing white matter disease with a novel EIF2B5 mutation. Federico, A., Scali, O., Stromillo, M.L., Di Perri, C., Bianchi, S., Sicurelli, F., De Stefano, N., Malandrini, A., Dotti, M.T. Neurology (2006) [Pubmed]
  3. Sepsis-induced suppression of skeletal muscle translation initiation mediated by tumor necrosis factor alpha. Lang, C.H., Frost, R.A. Metab. Clin. Exp. (2007) [Pubmed]
  4. The effect of genotype on the natural history of eIF2B-related leukodystrophies. Fogli, A., Schiffmann, R., Bertini, E., Ughetto, S., Combes, P., Eymard-Pierre, E., Kaneski, C.R., Pineda, M., Troncoso, M., Uziel, G., Surtees, R., Pugin, D., Chaunu, M.P., Rodriguez, D., Boespflug-Tanguy, O. Neurology (2004) [Pubmed]
  5. hCLE/CGI-99, a Human Protein that Interacts with the Influenza Virus Polymerase, Is a mRNA Transcription Modulator. Pérez-González, A., Rodriguez, A., Huarte, M., Salanueva, I.J., Nieto, A. J. Mol. Biol. (2006) [Pubmed]
  6. Noninvasive evaluation of skeletal muscle oxidative metabolism after heart transplant. Lanfranconi, F., Borrelli, E., Ferri, A., Porcelli, S., Maccherini, M., Chiavarelli, M., Grassi, B. Medicine and science in sports and exercise. (2006) [Pubmed]
  7. Relationship of personality disorders to observer ratings of interpersonal style in forensic psychiatric patients. Blackburn, R. J. Personal. Disord. (1998) [Pubmed]
  8. Subunits of the translation initiation factor eIF2B are mutant in leukoencephalopathy with vanishing white matter. Leegwater, P.A., Vermeulen, G., Könst, A.A., Naidu, S., Mulders, J., Visser, A., Kersbergen, P., Mobach, D., Fonds, D., van Berkel, C.G., Lemmers, R.J., Frants, R.R., Oudejans, C.B., Schutgens, R.B., Pronk, J.C., van der Knaap, M.S. Nat. Genet. (2001) [Pubmed]
  9. EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy. Dietrich, J., Lacagnina, M., Gass, D., Richfield, E., Mayer-Pröschel, M., Noble, M., Torres, C., Pröschel, C. Nat. Med. (2005) [Pubmed]
  10. Eukaryotic initiation factor 2B: identification of multiple phosphorylation sites in the epsilon-subunit and their functions in vivo. Wang, X., Paulin, F.E., Campbell, L.E., Gomez, E., O'Brien, K., Morrice, N., Proud, C.G. EMBO J. (2001) [Pubmed]
  11. Vanishing white matter disease: a review with focus on its genetics. Pronk, J.C., van Kollenburg, B., Scheper, G.C., van der Knaap, M.S. Mental retardation and developmental disabilities research reviews. (2006) [Pubmed]
  12. A severe variant of childhood ataxia with central hypomyelination/vanishing white matter leukoencephalopathy related to EIF21B5 mutation. Fogli, A., Dionisi-Vici, C., Deodato, F., Bartuli, A., Boespflug-Tanguy, O., Bertini, E. Neurology (2002) [Pubmed]
  13. Mutations linked to leukoencephalopathy with vanishing white matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways. Li, W., Wang, X., Van Der Knaap, M.S., Proud, C.G. Mol. Cell. Biol. (2004) [Pubmed]
  14. Keratinocyte apoptosis and p53 expression in cutaneous lupus and dermatomyositis. Pablos, J.L., Santiago, B., Galindo, M., Carreira, P.E., Ballestin, C., Gomez-Reino, J.J. J. Pathol. (1999) [Pubmed]
  15. Heightened stress response in primary fibroblasts expressing mutant eIF2B genes from CACH/VWM leukodystrophy patients. Kantor, L., Harding, H.P., Ron, D., Schiffmann, R., Kaneski, C.R., Kimball, S.R., Elroy-Stein, O. Hum. Genet. (2005) [Pubmed]
  16. In vitro spontaneous and UVB-induced lymphocyte apoptosis are not specific to SLE. Abe, M., Ishikawa, O., Miyachi, Y., Kanai, Y. Photodermatology, photoimmunology & photomedicine. (1997) [Pubmed]
  17. Identification of domains and residues within the epsilon subunit of eukaryotic translation initiation factor 2B (eIF2Bepsilon) required for guanine nucleotide exchange reveals a novel activation function promoted by eIF2B complex formation. Gomez, E., Pavitt, G.D. Mol. Cell. Biol. (2000) [Pubmed]
  18. CLE peptide ligands and their roles in establishing meristems. Fiers, M., Ku, K.L., Liu, C.M. Curr. Opin. Plant Biol. (2007) [Pubmed]
  19. The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase. Woods, Y.L., Cohen, P., Becker, W., Jakes, R., Goedert, M., Wang, X., Proud, C.G. Biochem. J. (2001) [Pubmed]
  20. Detection and sequencing of new cyclic peptides from linseed by electrospray ionization mass spectrometry. Stefanowicz, P. Acta Biochim. Pol. (2001) [Pubmed]
  21. Leukoencephalopathy with vanishing white matter: from magnetic resonance imaging pattern to five genes. Leegwater, P.A., Pronk, J.C., van der Knaap, M.S. J. Child Neurol. (2003) [Pubmed]
  22. The translation initiation factor eIF2beta is an interactor of protein phosphatase-1. Wakula, P., Beullens, M., van Eynde, A., Ceulemans, H., Stalmans, W., Bollen, M. Biochem. J. (2006) [Pubmed]
  23. Leukoencephalopathy with vanishing white matter due to homozygous EIF2B2 gene mutation. First Polish cases. Mierzewska, H., van der Knaap, M.S., Scheper, G.C., Jurkiewicz, E., Schmidt-Sidor, B., Szymańska, K. Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences. (2006) [Pubmed]
  24. TNF-binding protein ameliorates inhibition of skeletal muscle protein synthesis during sepsis. Cooney, R., Kimball, S.R., Eckman, R., Maish, G., Shumate, M., Vary, T.C. Am. J. Physiol. (1999) [Pubmed]
  25. Automated grading of left ventricular segmental wall motion by an artificial neural network using color kinesis images. Murta, L.O., Ruiz, E.E., Pazin-Filho, A., Schmidt, A., Almeida-Filho, O.C., Simões, M.V., Marin-Neto, J.A., Maciel, B.C. Braz. J. Med. Biol. Res. (2006) [Pubmed]
WikiGenes - Universities