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Gene Review

ITM2A  -  integral membrane protein 2A

Homo sapiens

Synonyms: BRICD2A, E25A, Integral membrane protein 2A, Protein E25, UNQ603/PRO1189
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Disease relevance of ITM2A


High impact information on ITM2A

  • We report here our studies of one gene, ITM2A, whose expression is dramatically higher in T cells in the selecting thymus [5].
  • In addition, ITM2A expression is higher in the thymus than in either the spleen or lymph nodes, but can be upregulated in peripheral T cells upon activation [5].
  • ITM2A is induced during thymocyte selection and T cell activation and causes downregulation of CD8 when overexpressed in CD4(+)CD8(+) double positive thymocytes [5].
  • The expression pattern of ITM2A in thymocyte subsets correlates with upregulation during positive selection [5].
  • Homology searches of DNA databanks showed that E25 belongs to a novel multigene family, containing three members both in man and mouse [6].

Biological context of ITM2A

  • The human homolog, ITM2A, was mapped to chromosome position Xq13.3-Xq21.2 [7].
  • Finally, overexpression of ITM2A under control of the lck proximal promoter in mice results in partial downregulation of CD8 in CD4(+)CD8(+) double positive (DP) thymocytes, and a corresponding increase in the number of CD4(+)CD8(lo) thymocytes [5].
  • Differential screening of a cDNA library constructed from in vitro cultured condyles allowed the isolation of a novel gene, named E25 [6].
  • Sustained hypoxia-ischemia at 70% (E22) and 79% (E25) caused stillbirths and multiple deficits in the postnatal survivors [8].
  • Gene expression analysis demonstrated that muscle creatin kinase was upregulated in the presence of exogenous Itm2A [9].

Anatomical context of ITM2A

  • In situ hybridization experiments show that E25 is expressed in the outer perichondrial rim of the postnatal mandibular condyle, which contains the proliferating progenitor cells, but not in the deeper layers of the condyle containing the more differentiated chondroblasts and chondrocytes [6].
  • One group, called the large-celled perireticular zone (LPR), enters the internal capsule very early in development (from E25; Mitrofanis, J., Eur. J. Neurosci., 6, 253-263, 1994) and is not labelled from the lateral geniculate nucleus at any developmental stage [10].
  • A monoclonal antibody (mAb), E25, is described that binds to the surface of cultured human endothelial cells [11].
  • Itm2A is also highly expressed in skeletal muscle [9].
  • In order to understand the role of Itm2A in muscle development, we constitutively overexpressed exogenous Itm2A in C2C12 myoblast cells [9].

Associations of ITM2A with chemical compounds

  • Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response [12].
  • Selective liposome targeting to the surface of the cells is performed using a biotinylated E25 antibody and an avidin-biotin system [11].
  • Serotonin uptake, as indicated by 5,7-dihydroxytryptamine-induced fluorescence, first occurred between stages E18 and E25 [13].
  • After E25 patch application individual serum oestradiol levels were variable and peaked between 13 and 36 h with a median value of 83.8 pmol L-1 [14].
  • In stage E25 embryos, optimal doses of the NO donors SNAP and SNP increased the rate of embryonic rotation by twofold, in contrast to the fourfold increase caused by 100 micro mol l(-1) serotonin [15].

Analytical, diagnostic and therapeutic context of ITM2A

  • We report here the solution characteristics of immune complexes formed by a humanized anti-IgE monoclonal antibody (rhuMAb E25) and IgE using sedimentation analysis and size exclusion chromatography [16].
  • We studied the binding of purified human IgE and cynomolgus monkey IgE to E25 and the human high affinity IgE receptor alpha-chain-IgG fusion molecule (Fc epsilon RI-IgG) by surface plasmon resonance [17].


  1. Site-directed mutagenesis of the virion host shutoff gene (UL41) of herpes simplex virus (HSV): analysis of functional differences between HSV type 1 (HSV-1) and HSV-2 alleles. Everly, D.N., Read, G.S. J. Virol. (1999) [Pubmed]
  2. Neonatal enterovirus infections reported to the national enterovirus surveillance system in the United States, 1983-2003. Khetsuriani, N., Lamonte, A., Oberste, M.S., Pallansch, M. Pediatr. Infect. Dis. J. (2006) [Pubmed]
  3. Improved diagnosis on a daily basis of enterovirus meningitis using a one-step real-time RT-PCR assay. Archimbaud, C., Mirand, A., Chambon, M., Regagnon, C., Bailly, J.L., Peigue-Lafeuille, H., Henquell, C. J. Med. Virol. (2004) [Pubmed]
  4. Low dose 25 mg oestradiol implants and 1 mg norethisterone as continuous combined hormone therapy: a prospective study. Panay, N., Zamblera, D., Sands, R., Jones, J., Alaghband-Zadeh, J., Studd, J.W. BJOG : an international journal of obstetrics and gynaecology. (2002) [Pubmed]
  5. ITM2A is induced during thymocyte selection and T cell activation and causes downregulation of CD8 when overexpressed in CD4(+)CD8(+) double positive thymocytes. Kirchner, J., Bevan, M.J. J. Exp. Med. (1999) [Pubmed]
  6. Isolation of markers for chondro-osteogenic differentiation using cDNA library subtraction. Molecular cloning and characterization of a gene belonging to a novel multigene family of integral membrane proteins. Deleersnijder, W., Hong, G., Cortvrindt, R., Poirier, C., Tylzanowski, P., Pittois, K., Van Marck, E., Merregaert, J. J. Biol. Chem. (1996) [Pubmed]
  7. Genomic organization and chromosomal localization of the Itm2a gene. Pittois, K., Wauters, J., Bossuyt, P., Deleersnijder, W., Merregaert, J. Mamm. Genome (1999) [Pubmed]
  8. A model of cerebral palsy from fetal hypoxia-ischemia. Derrick, M., Drobyshevsky, A., Ji, X., Tan, S. Stroke (2007) [Pubmed]
  9. Constitutive overexpression of the integral membrane protein Itm2A enhances myogenic differentiation of C2C12 cells. Van den Plas, D., Merregaert, J. Cell Biol. Int. (2004) [Pubmed]
  10. Development of the pathway from the reticular and perireticular nuclei to the thalamus in ferrets: a Dil study. Mitrofanis, J. Eur. J. Neurosci. (1994) [Pubmed]
  11. Monoclonal antibody to human endothelial cell surface internalization and liposome delivery in cell culture. Trubetskaya, O.V., Trubetskoy, V.S., Domogatsky, S.P., Rudin, A.V., Popov, N.V., Danilov, S.M., Nikolayeva, M.N., Klibanov, A.L., Torchilin, V.P. FEBS Lett. (1988) [Pubmed]
  12. Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Boulet, L.P., Chapman, K.R., Côté, J., Kalra, S., Bhagat, R., Swystun, V.A., Laviolette, M., Cleland, L.D., Deschesnes, F., Su, J.Q., DeVault, A., Fick, R.B., Cockcroft, D.W. Am. J. Respir. Crit. Care Med. (1997) [Pubmed]
  13. Early development of an identified serotonergic neuron in Helisoma trivolvis embryos: serotonin expression, de-expression, and uptake. Diefenbach, T.J., Koss, R., Goldberg, J.I. J. Neurobiol. (1998) [Pubmed]
  14. Effects of low- and conventional-dose transcutaneous HRT over 2 years on bone metabolism in younger and older postmenopausal women. Sharp, C.A., Evans, S.F., Risteli, L., Risteli, J., Worsfold, M., Davie, M.W. Eur. J. Clin. Invest. (1996) [Pubmed]
  15. Regulation of early embryonic behavior by nitric oxide in the pond snail Helisoma trivolvis. Cole, A.G., Mashkournia, A., Parries, S.C., Goldberg, J.I. J. Exp. Biol. (2002) [Pubmed]
  16. Characterization of complex formation by humanized anti-IgE monoclonal antibody and monoclonal human IgE. Liu, J., Lester, P., Builder, S., Shire, S.J. Biochemistry (1995) [Pubmed]
  17. Binding of cynomolgus monkey IgE to a humanized anti-human IgE antibody and human high affinity IgE receptor. Meng, Y.G., Singh, N., Wong, W.L. Mol. Immunol. (1996) [Pubmed]
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