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Gene Review

ELSPBP1  -  epididymal sperm binding protein 1

Homo sapiens

Synonyms: E12, EDDM12, EL149, Epididymal secretory protein 12, Epididymal sperm-binding protein 1, ...
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Disease relevance of ELSPBP1


Psychiatry related information on ELSPBP1

  • S5a interacts strongly with Id1, less strongly with the basic helix-loop-helix proteins MyoD and E12, and not at all with other Id proteins [5].

High impact information on ELSPBP1

  • The kappa E2 sequence binding proteins, E12 and E47, are generated by alternative splicing of the E2A gene, giving closely related basic and helix-loop-helix structures crucial for DNA binding and dimerization [6].
  • In this report we provide four lines of evidence indicating that E12/E47-like proteins interact in vivo with the myogenic HLH proteins MyoD and myogenin [7].
  • Thus, E47 binds to DNA both as a heterodimer with MyoD and as a homodimer, while E12 and MyoD bind to DNA efficiently only as heterodimers [6].
  • Second, mobility-shift assays of muscle cell nuclear extracts, "double shifted" with specific antisera, have identified complexes binding to the MEF1 site that contain either MyoD or myogenin in association with E12/E47-like proteins [7].
  • In contrast, the non-tissue-specific bHLH protein E12 can bind to the MyoD binding site but does not induce myogenesis [8].

Chemical compound and disease context of ELSPBP1

  • Another peptide, E12 (from glycoprotein (GP)350, the major EBV outer membrane GP) which shows a high degree of similarity with P14, also inhibited the proliferative response of Raji cells, suggesting that this segment on GP350 is involved in the interaction of EBV with CR2 [9].
  • The acetylcholine levels measured in E12 explants were 6.3 and 38.4 pm/ganglion/5 min at 3 and 7 days in culture, respectively, while in E18 explant cultures they were 10.7 and 15.5 pm/ganglion/5 min [10].
  • Apart from myoepithelial cells and some luminal-duct cells, the remaining epithelia in dacryoadenitis were negative with AB 34 beta E12 (CK 5) [11].
  • METHODS: 18 extra-adrenal paragangliomas and seven adrenal phaeochromocytomas were stained with CAM 5.2, AE1/3, and 34 beta E12 following microwave antigen retrieval of formalin fixed tissue [12].

Biological context of ELSPBP1

  • First, overexpression of ITF-1, and E12/E47-related protein that binds the microE5 motif, leads to transcriptional activation itself [13].
  • The DNA-binding protein E12 co-operates with XMyoD in the activation of muscle-specific gene expression in Xenopus embryos [14].
  • Although myogenin alone binds DNA inefficiently, in the presence of the widely expressed HLH proteins E12 and E47 (encoded by the E2A gene), it forms heterooligomers that bind with high affinity to a DNA sequence known as a kappa E-2 site [15].
  • To define the relative contributions of the basic regions of myogenin and E12 to DNA binding and muscle-specific gene activation, we created chimeras of the two proteins by swapping their basic regions [15].
  • These results demonstrate in vivo that E12 and E47 modulate both MyoD and Id1 degradation and may have implications for the physiological regulation of muscle development [16].

Anatomical context of ELSPBP1

  • The Yae antibody detected an E2A-containing microE2 enhancer element-binding complex (BCF-1) in pre-B- and mature B-cell lines in electrophoretic mobility shift assays which displayed a migration rate similar to that of in vitro-produced rat E12 and rat E47 [17].
  • E2A proteins of a predominant molecular mass of 72 kDa, which comigrated with in vitro-produced rat E12 and and rat E47, were detected in human pro-B, pre-B, mature B, and plasma cell lines [17].
  • Both E12 and E47 elicited EMT effects on tubular epithelial cells with E47 more potent in inducing the fibroblast-like phenotype [18].
  • Exposure of rat embryos to excess atRA at times ranging from E9.25 to E12 leads to altered NEDD9 expression in the developing hindbrain within 6 hr [19].
  • In previous studies of BAEBL from two clones, Dd2/Nm from Vietnam and E12 from Papua New Guinea (PNG), it was found that BAEBL bound different erythrocyte receptors [20].

Associations of ELSPBP1 with chemical compounds

  • HEN1 encodes a 20-kDa polypeptide (pp20HEN1) that is phosphorylated exclusively at serine residues and forms dimeric bHLH complexes either by self-association or by heterologous interaction with the E2A gene products (E12 or E47) [21].
  • Hemoglobin Great Lakes (beta 68 [E12] leucine replaced by histidine): a new high-affinity hemoglobin [4].
  • The leucyl residue at beta 68th position (E12) is in the middle of E-helix, which is part of the heme pocket and next to the valine (E11), which is the heme binding site [4].
  • As reported for other E-box-regulated promoters, ectopic expression of E47 and E12 basic helix-loop-helix (bHLH) proteins enhances RA-dependent expression of TrkB and p21(Cip1), whereas the inhibitory HLH Id2 exerts opposite effects [22].
  • MyoD-E12 heterodimers interact with MEF2 proteins to synergistically activate myogenesis, while homodimers of E12, which lack the conserved alanine and threonine residues in the basic domain, do not interact with MEF2 [23].

Physical interactions of ELSPBP1


Regulatory relationships of ELSPBP1

  • Finally, cotransfection of rPM-Scl and E47 specifically increased the promoter activity of a luciferase reporter construct containing an E box and did not affect the basal activity of the reporter construct. rPM-Scl appears to be a novel non-HLH-interacting partner of E12/E47 that regulates E2A protein transcription [24].

Other interactions of ELSPBP1

  • This motif mediates HEF1 homodimerization and HEF1 heterodimerization with a recognition specificity similar to that of the transcriptional regulatory HLH proteins Id2, E12, and E47 [25].
  • In contrast, two members of the E2A gene family were identified in Takifugu; one of these shows the alternative processing of transcripts that identifies it as the ortholog of the E12/E47-encoding mammalian E2A gene, whereas the second Takifugu E2A gene has no predicted alternative splice products [26].
  • TAL1 does not self-associate to form homodimeric complexes, implying that the in vivo functions of TAL1 depend on heterologous interaction with other bHLH proteins such as E12 and E47 [27].
  • INSAF was also shown to associate in vitro with the bHLH protein E12 [28].
  • In addition, HEB was shown to form hetero-oligomers with the E12 and ITF2 proteins [29].

Analytical, diagnostic and therapeutic context of ELSPBP1


  1. Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Nourse, J., Mellentin, J.D., Galili, N., Wilkinson, J., Stanbridge, E., Smith, S.D., Cleary, M.L. Cell (1990) [Pubmed]
  2. The gene for enhancer binding proteins E12/E47 lies at the t(1;19) breakpoint in acute leukemias. Mellentin, J.D., Murre, C., Donlon, T.A., McCaw, P.S., Smith, S.D., Carroll, A.J., McDonald, M.E., Baltimore, D., Cleary, M.L. Science (1989) [Pubmed]
  3. Bridge-1, a novel PDZ-domain coactivator of E2A-mediated regulation of insulin gene transcription. Thomas, M.K., Yao, K.M., Tenser, M.S., Wong, G.G., Habener, J.F. Mol. Cell. Biol. (1999) [Pubmed]
  4. Hemoglobin Great Lakes (beta 68 [E12] leucine replaced by histidine): a new high-affinity hemoglobin. Rahbar, S., Winkler, K., Louis, J., Rea, C., Blume, K., Beutler, E. Blood (1981) [Pubmed]
  5. Novel regulation of the helix-loop-helix protein Id1 by S5a, a subunit of the 26 S proteasome. Anand, G., Yin, X., Shahidi, A.K., Grove, L., Prochownik, E.V. J. Biol. Chem. (1997) [Pubmed]
  6. An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers. Sun, X.H., Baltimore, D. Cell (1991) [Pubmed]
  7. Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Lassar, A.B., Davis, R.L., Wright, W.E., Kadesch, T., Murre, C., Voronova, A., Baltimore, D., Weintraub, H. Cell (1991) [Pubmed]
  8. Acquisition of myogenic specificity by replacement of three amino acid residues from MyoD into E12. Davis, R.L., Weintraub, H. Science (1992) [Pubmed]
  9. C3 synthetic peptides support growth of human CR2-positive lymphoblastoid B cells. Servis, C., Lambris, J.D. J. Immunol. (1989) [Pubmed]
  10. Detection of basal and potassium-evoked acetylcholine release from embryonic DRG explants. Bernardini, N., Tomassy, G.S., Tata, A.M., Augusti-Tocco, G., Biagioni, S. J. Neurochem. (2004) [Pubmed]
  11. Immunohistochemical characterization of epithelial cells in human lacrimal glands. II. Inflammatory and neoplastic lesions of lacrimal glands. Wilk, C.M., Vigneswaran, N., Heese, A., Hornstein, O.P., Naumann, G.O. Graefes Arch. Clin. Exp. Ophthalmol. (1990) [Pubmed]
  12. Cytokeratin expression in adrenal phaeochromocytomas and extra-adrenal paragangliomas. Chetty, R., Pillay, P., Jaichand, V. J. Clin. Pathol. (1998) [Pubmed]
  13. Modulation of the IgH enhancer's cell type specificity through a genetic switch. Ruezinsky, D., Beckmann, H., Kadesch, T. Genes Dev. (1991) [Pubmed]
  14. The DNA-binding protein E12 co-operates with XMyoD in the activation of muscle-specific gene expression in Xenopus embryos. Rashbass, J., Taylor, M.V., Gurdon, J.B. EMBO J. (1992) [Pubmed]
  15. Inefficient homooligomerization contributes to the dependence of myogenin on E2A products for efficient DNA binding. Chakraborty, T., Brennan, T.J., Li, L., Edmondson, D., Olson, E.N. Mol. Cell. Biol. (1991) [Pubmed]
  16. E12 and E47 modulate cellular localization and proteasome-mediated degradation of MyoD and Id1. Lingbeck, J.M., Trausch-Azar, J.S., Ciechanover, A., Schwartz, A.L. Oncogene (2005) [Pubmed]
  17. E2A expression, nuclear localization, and in vivo formation of DNA- and non-DNA-binding species during B-cell development. Jacobs, Y., Vierra, C., Nelson, C. Mol. Cell. Biol. (1993) [Pubmed]
  18. Overexpression of E2A proteins induces epithelial-mesenchymal transition in human renal proximal tubular epithelial cells suggesting a potential role in renal fibrosis. Slattery, C., McMorrow, T., Ryan, M.P. FEBS Lett. (2006) [Pubmed]
  19. Crk-associated substrate (Cas) family member, NEDD9, is regulated in human neuroblastoma cells and in the embryonic hindbrain by all-trans retinoic acid. Merrill, R.A., See, A.W., Wertheim, M.L., Clagett-Dame, M. Dev. Dyn. (2004) [Pubmed]
  20. Polymorphism in a Plasmodium falciparum erythrocyte-binding ligand changes its receptor specificity. Mayer, D.C., Mu, J.B., Feng, X., Su, X.Z., Miller, L.H. J. Exp. Med. (2002) [Pubmed]
  21. HEN1 encodes a 20-kilodalton phosphoprotein that binds an extended E-box motif as a homodimer. Brown, L., Baer, R. Mol. Cell. Biol. (1994) [Pubmed]
  22. Basic helix-loop-helix proteins bind to TrkB and p21(Cip1) promoters linking differentiation and cell cycle arrest in neuroblastoma cells. Liu, Y., Encinas, M., Comella, J.X., Aldea, M., Gallego, C. Mol. Cell. Biol. (2004) [Pubmed]
  23. Multiple roles for the MyoD basic region in transmission of transcriptional activation signals and interaction with MEF2. Black, B.L., Molkentin, J.D., Olson, E.N. Mol. Cell. Biol. (1998) [Pubmed]
  24. The polymyositis-scleroderma autoantigen interacts with the helix-loop-helix proteins E12 and E47. Kho, C.J., Huggins, G.S., Endege, W.O., Patterson, C., Jain, M.K., Lee, M.E., Haber, E. J. Biol. Chem. (1997) [Pubmed]
  25. Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain. Law, S.F., Zhang, Y.Z., Fashena, S.J., Toby, G., Estojak, J., Golemis, E.A. Exp. Cell Res. (1999) [Pubmed]
  26. Evolution of vertebrate E protein transcription factors: comparative analysis of the E protein gene family in Takifugu rubripes and humans. Hikima, J., Lennard, M.L., Wilson, M.R., Miller, N.W., Clem, L.W., Warr, G.W. Physiol. Genomics (2005) [Pubmed]
  27. Formation of in vivo complexes between the TAL1 and E2A polypeptides of leukemic T cells. Hsu, H.L., Wadman, I., Baer, R. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  28. Isolation and characterization of a novel transcription factor that binds to and activates insulin control element-mediated expression. Robinson, G.L., Cordle, S.R., Henderson, E., Weil, P.A., Teitelman, G., Stein, R. Mol. Cell. Biol. (1994) [Pubmed]
  29. HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors. Hu, J.S., Olson, E.N., Kingston, R.E. Mol. Cell. Biol. (1992) [Pubmed]
  30. Molecular investigation of 19p13 in standard and variant translocations: the E12 probe recognizes the 19p13 breakpoint in cases with t(1;19) and acute leukemia other than pre-B immunophenotype. Yamada, T., Craig, J.M., Hawkins, J.M., Janossy, G., Secker-Walker, L.M. Leukemia (1991) [Pubmed]
  31. Alternative multimeric structures affect myogenin DNA binding activity. Farmer, K., Catala, F., Wright, W.E. J. Biol. Chem. (1992) [Pubmed]
  32. Identification of MRF4, myogenin, and E12 oligomer complexes by chemical cross-linking and two-dimensional gel electrophoresis. Lin, H., Konieczny, S.F. J. Biol. Chem. (1992) [Pubmed]
  33. Protein retention in the endoplasmic reticulum, blockade of programmed cell death and autophagy selectively occur in spinal cord motoneurons after glutamate receptor-mediated injury. Tarabal, O., Calderó, J., Casas, C., Oppenheim, R.W., Esquerda, J.E. Mol. Cell. Neurosci. (2005) [Pubmed]
  34. Reconstitution of an epithelial chloride channel. Conservation of the channel from mudpuppy to man. Tsai, L.M., Dillard, M., Rosenberg, R.L., Falk, R.J., Gaido, M.L., Finn, A.L. J. Gen. Physiol. (1991) [Pubmed]
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