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Gene Review

TMEM37  -  transmembrane protein 37

Homo sapiens

Synonyms: Neuronal voltage-gated calcium channel gamma-like subunit, PR, PR1, Transmembrane protein 37, Voltage-dependent calcium channel gamma-like subunit
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Disease relevance of TMEM37

  • Interestingly, suppression of OsMAPK5 expression and its kinase activity resulted in the constitutive expression of pathogenesis-related (PR) genes such as PR1 and PR10 in the dsRNAi transgenic plants and significantly enhanced resistance to fungal (Magnaporthe grisea) and bacterial (Burkholderia glumae) pathogens [1].
  • A recombinant toxin was then constructed that has the heavy chain variable region of monoclonal antibody PR1 connected to the light chain variable region by a flexible peptide linker to create a single-chain Fv; the Fv in turn is fused to a truncated form of Pseudomonas exotoxin [2].
  • Monoclonal antibody PR1 binds to the surface of normal prostate cells and to adenocarcinomas of the prostate [2].
  • We have found that increases in endogenous SA levels correlates with both resistance of tobacco to infection with tobacco mosaic virus and induction of defense-related genes such as that encoding pathogenesis-related protein 1 (PR-1) [3].
  • A recombinant immunotoxin that is active on prostate cancer cells and that is composed of the Fv region of monoclonal antibody PR1 and a truncated form of Pseudomonas exotoxin [2].

Psychiatry related information on TMEM37

  • In grapevine, the most frequently observed and best characterized defense mechanisms are the accumulation of phytoalexins and the synthesis of PR-proteins [4].

High impact information on TMEM37

  • There was a strong correlation between the presence of PR1-specific T cells and clinical responses after IFN-alpha and allogeneic BMT [5].
  • Although high-avidity PR1-specific T cells killed CML more effectively than low-avidity T cells, only high-avidity T cells underwent apoptosis when stimulated with high PR1 peptide concentration or when exposed to leukemia that overexpressed proteinase 3 [6].
  • Some patients with persistent disease also have circulating PR1-specific T cells, however, suggesting the likelihood of immune tolerance [6].
  • Circulating high-avidity PR1-specific T cells were identified in IFN-sensitive patients in cytogenetic remission, however [6].
  • The consensus binding site of SEBF, PyTGTCNC, is present in a number of PR genes and shows striking similarity to the auxin response element [7].

Chemical compound and disease context of TMEM37


Biological context of TMEM37

  • In vivo dimethyl sulfate footprinting was used to identify two putative sites of protein-DNA interaction in the promoter of one PR1 gene, located around positions -240 and -130 relative to the transcription start site [12].
  • Activation of PR gene expression in the leaves of the mutants infected with rice blast was delayed for 24 h relative to the wild type [13].
  • This cluster is conserved in all known plant PR proteins of class 1, indicating a common putative active site for GliPR and PR-1 proteins and thus a functional link between the human immune system and a plant defense system [14].
  • Thus, it appears that many compounds that induce PR gene expression and disease resistance in plants inactivate catalases directly or indirectly [3].
  • The resulting elevated levels of cellular H2O2 appeared to induce PR-1 gene expression, perhaps by acting as a second messenger [3].

Anatomical context of TMEM37

  • 1. Based on its high predicted binding, a 9-mer peptide, "PR-1," was synthesized and tested for binding to HLA-A2.1 using the T2 cell line [15].
  • One of 2 HLA-A*0201-negative individuals inhibited the colony formation of HLA-identical chronic myelogenous leukemia progenitor cells (73% inhibition at 50:1 effector-target [E/T] ratio), indicating that peptides other than PR1 can induce leukemia-reactive CTLs [16].
  • Patients treated in PR1 or PR2/CR2 had a significantly longer rate of OS and FFS than those treated in subsequent progression (P = .002 and P = .001, respectively), whereas age, response to salvage treatment, presence or absence of residual bone marrow involvement, or conditioning regimen had no influence on outcome [17].
  • In human leukocyte antigen A*0201(+) (HLA-A*0201(+)) individuals, response after interferon-alpha (IFN-alpha) was shown to be associated with the emergence of CML-specific cytotoxic T cells that recognize PR-1, a myeloblastin (MBN)-derived nonapeptide [18].
  • Lipofection of promoter-chloramphenicol acetyltransferase fusion constructs into C2C12 myogenic cells revealed that two of the three positive domains (PR1 and PR2) function in both myoblasts and myotubes, whereas the third positive domain (PR3) and the sole negative domain (NR1) seem to function only in myotubes [19].

Associations of TMEM37 with chemical compounds

  • The results suggest that EDS1 functions upstream of salicylic acid-dependent PR1 mRNA accumulation and is not required for jasmonic acid-induced PDF1.2 mRNA expression [20].
  • H(2)O(2) production and PR gene expression induced by sphingolipid elicitors (SE) were strongly suppressed in d1 cell cultures [13].
  • Therefore, in MDA-MB231 cells containing no progesterone and estrogen receptors, we transiently transfected progesterone receptor expression vectors coding for form B (hPR1 or hPR0) or form A (hPR2) along with the estrogen receptor expression vector HEO [21].
  • However, activation of the VP16/PR chimera by antagonists on a progesterone response element-controlled reporter gene (DHRE-E1b-CAT) was only a fraction (4-13%) of that stimulated by agonist R5020 [22].
  • The synthetic progestin R5020 chronically down-regulates A- and B-receptors; the proteins are profoundly suppressed for at least 48 h, while PR mRNAs fall to less than 15% of control [8].

Analytical, diagnostic and therapeutic context of TMEM37

  • Here we studied 38 CML patients treated with allogeneic BMT, IFN- alpha2b or chemotherapy to look for PR1-specific T cells using PR1/HLA-A*0201 tetrameric complexes [5].
  • The cDNAs coding for the heavy and light chain variable regions of monoclonal antibody PR1 were cloned by PCR techniques [2].
  • Using HLA-A2-PR1 tetramer analysis, we found that the frequency of T cells recognizing the PR1 epitope of proteinase 3 was not significantly different in allodepleted and unmanipulated PBMCs from patients with chronic myeloid leukemia (CML) undergoing transplantation [23].
  • The amino-acid sequence, determined by microsequencing and molecular cloning, revealed a significant homology with the superfamily of PR-1 proteins [24].
  • One possibility for the failure to detect an induction in the two-hybrid assay is antagonist-induced repression of the activity of the VP16/PR fusion protein rather than a failure of antagonists to stimulate interaction between the hybrid proteins [22].


  1. Disease resistance and abiotic stress tolerance in rice are inversely modulated by an abscisic acid-inducible mitogen-activated protein kinase. Xiong, L., Yang, Y. Plant Cell (2003) [Pubmed]
  2. A recombinant immunotoxin that is active on prostate cancer cells and that is composed of the Fv region of monoclonal antibody PR1 and a truncated form of Pseudomonas exotoxin. Brinkmann, U., Gallo, M., Brinkmann, E., Kunwar, S., Pastan, I. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  3. Induction, modification, and transduction of the salicylic acid signal in plant defense responses. Chen, Z., Malamy, J., Henning, J., Conrath, U., Sánchez-Casas, P., Silva, H., Ricigliano, J., Klessig, D.K. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  4. Phytoalexins from the Vitaceae: biosynthesis, phytoalexin gene expression in transgenic plants, antifungal activity, and metabolism. Jeandet, P., Douillet-Breuil, A.C., Bessis, R., Debord, S., Sbaghi, M., Adrian, M. J. Agric. Food Chem. (2002) [Pubmed]
  5. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Molldrem, J.J., Lee, P.P., Wang, C., Felio, K., Kantarjian, H.M., Champlin, R.E., Davis, M.M. Nat. Med. (2000) [Pubmed]
  6. Chronic myelogenous leukemia shapes host immunity by selective deletion of high-avidity leukemia-specific T cells. Molldrem, J.J., Lee, P.P., Kant, S., Wieder, E., Jiang, W., Lu, S., Wang, C., Davis, M.M. J. Clin. Invest. (2003) [Pubmed]
  7. Repression of the defense gene PR-10a by the single-stranded DNA binding protein SEBF. Boyle, B., Brisson, N. Plant Cell (2001) [Pubmed]
  8. Multiple human progesterone receptor messenger ribonucleic acids and their autoregulation by progestin agonists and antagonists in breast cancer cells. Wei, L.L., Krett, N.L., Francis, M.D., Gordon, D.F., Wood, W.M., O'Malley, B.W., Horwitz, K.B. Mol. Endocrinol. (1988) [Pubmed]
  9. CD34+-selected peripheral blood progenitor cell transplantation in patients with multiple myeloma: tumour cell contamination and outcome. Gupta, D., Bybee, A., Cooke, F., Giles, C., Davis, J.G., McDonald, C., Armitage, S.E., McGuigan, D., Lyttelton, M.P., Kanfer, E.J., Apperley, J.F., Samson, D. Br. J. Haematol. (1999) [Pubmed]
  10. Fluid resuscitation after an otherwise fatal hemorrhage: I. Crystalloid solutions. Traverso, L.W., Lee, W.P., Langford, M.J. The Journal of trauma. (1986) [Pubmed]
  11. Detection of breast tumor progesterone receptor isoforms with the PR-enzyme immunoassay kit (Abbott). Effect of heat shock proteins on epitope recognition. Goussard, J., Lemoisson, E., Cren, H. Ann. Biol. Clin. (Paris) (1995) [Pubmed]
  12. Elicitor-inducible and constitutive in vivo DNA footprints indicate novel cis-acting elements in the promoter of a parsley gene encoding pathogenesis-related protein 1. Meier, I., Hahlbrock, K., Somssich, I.E. Plant Cell (1991) [Pubmed]
  13. The heterotrimeric G protein alpha subunit acts upstream of the small GTPase Rac in disease resistance of rice. Suharsono, U., Fujisawa, Y., Kawasaki, T., Iwasaki, Y., Satoh, H., Shimamoto, K. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  14. Structure comparison of human glioma pathogenesis-related protein GliPR and the plant pathogenesis-related protein P14a indicates a functional link between the human immune system and a plant defense system. Szyperski, T., Fernández, C., Mumenthaler, C., Wüthrich, K. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  15. Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells. Molldrem, J., Dermime, S., Parker, K., Jiang, Y.Z., Mavroudis, D., Hensel, N., Fukushima, P., Barrett, A.J. Blood (1996) [Pubmed]
  16. Identification and in vitro expansion of CD4+ and CD8+ T cells specific for human neutrophil elastase. Fujiwara, H., El Ouriaghli, F., Grube, M., Price, D.A., Rezvani, K., Gostick, E., Sconocchia, G., Melenhorst, J., Hensel, N., Douek, D.C., Barrett, A.J. Blood (2004) [Pubmed]
  17. Intensive therapy with peripheral blood progenitor cell transplantation in 60 patients with poor-prognosis follicular lymphoma. Bastion, Y., Brice, P., Haioun, C., Sonet, A., Salles, G., Marolleau, J.P., Espinouse, D., Reyes, F., Gisselbrecht, C., Coiffier, B. Blood (1995) [Pubmed]
  18. Interferon-alpha, but not the ABL-kinase inhibitor imatinib (STI571), induces expression of myeloblastin and a specific T-cell response in chronic myeloid leukemia. Burchert, A., Wölfl, S., Schmidt, M., Brendel, C., Denecke, B., Cai, D., Odyvanova, L., Lahaye, T., Müller, M.C., Berg, T., Gschaidmeier, H., Wittig, B., Hehlmann, R., Hochhaus, A., Neubauer, A. Blood (2003) [Pubmed]
  19. OXBOX and REBOX, overlapping promoter elements of the mitochondrial F0F1-ATP synthase beta subunit gene. OXBOX/REBOX in the ATPsyn beta promoter. Haraguchi, Y., Chung, A.B., Neill, S., Wallace, D.C. J. Biol. Chem. (1994) [Pubmed]
  20. EDS1, an essential component of R gene-mediated disease resistance in Arabidopsis has homology to eukaryotic lipases. Falk, A., Feys, B.J., Frost, L.N., Jones, J.D., Daniels, M.J., Parker, J.E. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  21. Differential effect of forms A and B of human progesterone receptor on estradiol-dependent transcription. Chalbos, D., Galtier, F. J. Biol. Chem. (1994) [Pubmed]
  22. Agonist and antagonists induce homodimerization and mixed ligand heterodimerization of human progesterone receptors in vivo by a mammalian two-hybrid assay. Leonhardt, S.A., Altmann, M., Edwards, D.P. Mol. Endocrinol. (1998) [Pubmed]
  23. Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses. Amrolia, P.J., Muccioli-Casadei, G., Yvon, E., Huls, H., Sili, U., Wieder, E.D., Bollard, C., Michalek, J., Ghetie, V., Heslop, H.E., Molldrem, J.J., Rooney, C.M., Schlinder, J., Vitetta, E., Brenner, M.K. Blood (2003) [Pubmed]
  24. Identification and characterization of a novel human plant pathogenesis-related protein that localizes to lipid-enriched microdomains in the Golgi complex. Eberle, H.B., Serrano, R.L., Füllekrug, J., Schlosser, A., Lehmann, W.D., Lottspeich, F., Kaloyanova, D., Wieland, F.T., Helms, J.B. J. Cell. Sci. (2002) [Pubmed]
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