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Gene Review

ECD  -  ecdysoneless homolog (Drosophila)

Homo sapiens

Synonyms: GCR2, HSGT1, Protein SGT1, Protein ecdysoneless homolog, SGT1, ...
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Disease relevance of ECD

  • A HER2-ECD cDNA encoding the truncated variant was overexpressed in MCF7 breast cancer cells [1].
  • To confirm these data, ribozymes were targeted to the 3'-untranslated region of the 2.3 kb HER2-ECD mRNA which is spontaneously expressed in MKN7 gastric cancer cells [1].
  • 99mTc-bicisate reliably images CBF in chronic brain diseases but fails to show reflow hyperemia in subacute stroke: report of a multicenter trial of 105 cases comparing 133Xe and 99mTc-bicisate (ECD, neurolite) measured by SPECT on same day [2].
  • In contrast, transfer of MBP-ECD in vivo primed unfractionated T cells resulted in thyroiditis in 9 of 13 BALB/c mice and 5 of 6 NOD mice; similarly, the equivalent CD4+-enriched population produced extensive thyroiditis in 2 of 3 BALB/c mice and all three NOD mice [3].
  • Clinical observations have shown discrepancies between ECD and HMPAO regional cerebral perfusion, particularly in brain tumors and during stroke recovery [4].

Psychiatry related information on ECD

  • There were significant positive correlations in the OCD group between the ECD uptake in the left lateral orbitofrontal cortex and ratings for obsessive-compulsive symptoms (OCS), and between the ECD uptake in the right medial orbitofrontal cortex and the ratings for both OCS and depressive symptoms [5].
  • We have studied brain perfusion with SPECT and the tracer ECD in 44 PD patients, 22 presenting with normal cognitive function and 22 with clinical and neuropsychological signs of dementia [6].

High impact information on ECD

  • In plants, SGT1 positively regulates disease resistance conferred by many Resistance (R) proteins and developmental responses to the phytohormone, auxin [7].
  • While the respective tetratricopeptide repeat (TPR) domains of SGT1a and SGT1b control protein accumulation, they are dispensable for intrinsic functions of SGT1 in resistance and auxin responses [7].
  • Here we report that although Calindol has little or no agonist activity in the absence of extracellular Ca(2+) for the ECD-containing wild type or carboxyl-terminal deleted receptors, it acts as a strong agonist of the T903-Rhoc [8].
  • The mean Euclidean distances between the ECD (equivalent current dipole) locations for the thumb and index finger in the secondary somatosensory cortex (SII) across the subjects were 8.5 +/- 2.1 mm in the close hand posture and 11.2 +/- 2.6 mm in the open hand posture [9].
  • Sgt1 has been identified as a subunit of both core kinetochore and SCF (Skp1-Cul1-F-box) ubiquitin ligase complexes and is also implicated in plant disease resistance [10].

Chemical compound and disease context of ECD


Biological context of ECD

  • To determine whether similar regulatory mechanisms control the expression of glycolytic genes in yeast and human cells, we screened a human brain cDNA library for clones which complement the growth defect of the gcr2 mutant of Saccharomyces cerevisiae, and isolated hSGT1 (human suppressor of GCR two) [15].
  • Although the predicted amino acid sequence of hSgt1p does not display significant similarity to Gcr2p, we speculate that their functions may be analogous [15].
  • A human gene, hSGT1, can substitute for GCR2, which encodes a general regulatory factor of glycolytic gene expression in Saccharomyces cerevisiae [15].
  • These results suggest that covalent, disulfide bond-mediated dimerization of the calcium-sensing receptor contributes to stabilization of the ECD and to acceleration of the transitions between inactive and active receptor conformations [16].
  • These data show that the HER2-ECD variant inhibits growth factor-mediated tumour cell proliferation suggesting an important role during the progression of human cancer [1].

Anatomical context of ECD

  • Curiously, mice immunized with the human EGFR-ECD (Her1-ECD) in VSSP though induced highly specific IgG antibodies with strong in vitro cytotoxic effect over EGFR+ human cell lines, showed low cross-reactivity with the mEGFR-ECD [17].
  • 99mTc-bicisate (ECD) was injected as a bolus into the internal carotid artery, and cerebral uptake and retention were recorded with fast-rotating single photon emission computed tomography (SPECT) equipment in four patients suffering from temporal lobe epilepsy [18].
  • Blood-brain barrier (BBB) passage of the flow tracer ethylenediylbis-L-cystein diethylester (bicisate, ECD) was measured repeatedly in five patients by means of the intravenous (i.v.) double-indicator technique using 24Na+ as an intravascular cotracer [19].
  • The method was validated for determination of 11 polychlorinated biphenyls (PCBs), 15 tetra- to heptachloro 3- and 4-MeSO2-PCBs, 3-MeSO2-DDE, and tris(4-chlorophenyl)-methanol spiked to herring gull egg, smelt, and polar bear liver and adipose tissue using gas chromatography with electron-capture detection (GC-ECD) [20].
  • METHODS: Time course incorporation of ECD was studied in a fast-growing human premonocytic line, U937, in a human astrocytic-derived cell line, U373, and a human hybridized endothelial cell line, EaHy926 [4].

Associations of ECD with chemical compounds

  • To identify the residue(s) involved in dimerization within the ECD, cysteine --> serine point mutations were made in residues that are conserved between hCaR and metabotropic glutamate receptors [16].
  • The integrin-binding motifs RGD and ECD, present in the pro- and in mature forms of cathepsin X, respectively, suggest that this enzyme might have a function in cell signaling and adhesion [21].
  • In univariate but not multivariate subset analyses, among patients treated with endocrine therapy (megestrol acetate), elevated initial ECD/HER-2 was associated with worse OS compared with nonelevated patients [22].
  • The safety, biodistribution and kinetics of a new perfusion imaging agent [99mTc-L,L]-ethyl cysteinate dimer (ECD) was evaluated in normal volunteers [23].
  • These alcohols are then reacted with pentafluorobenzoyl chloride and analyzed by GC-ECD [24].

Other interactions of ECD

  • HER-2/neu ECD and sEGFR levels at the onset of metastatic disease did not show a significant impact on overall survival [25].
  • Nevertheless, the optimized manual SPME method, encompassing GC/ECD or GC/MSD for the separation and detection of target analytes, offers a unique solution and showed acceptable performance characteristics: linear response in the range of 0.5-2 mg kg(-1) and repeatability expressed as R.S.D. between 14 and 23% at the spiking level of 2 mg kg(-1) [26].
  • The reactivity in GD patients was heterogeneous and spanned the entire TSHR-ECD [27].

Analytical, diagnostic and therapeutic context of ECD

  • Conclusions: Determination of HER-2/neu ECD levels in the serum measured by ELISA at the onset of metastatic disease could offer an alternative to immunohistochemistry of the primary tumor since serum levels are correlated with protein expression in primary tumors [25].
  • Fruit samples of ber, grapes and guava analysed for pesticide residues employing multiresidue analysis by gas liquid chromatography equipped with ECD and NPD detectors and capillary columns showed contamination with organochlorine, synthetic pyrethroid and organophosphate insecticides [28].
  • Brain perfusion was measured by (99m)Tc-labeled bicisate (ECD) brain SPECT and the images were compared using Statistical Parametric Mapping (SPM96) [29].
  • Vibrational circular dichroism (VCD) provides alternative views of protein and peptide conformation with advantages over electronic (UV) CD (ECD) or IR spectroscopy [30].
  • FTIR, electronic and vibrational CD (ECD and VCD) spectra for these small peptides are comparable to expected bandshapes for peptides of high beta-sheet content [31].


  1. Expression of a truncated 100 kDa HER2 splice variant acts as an endogenous inhibitor of tumour cell proliferation. Aigner, A., Juhl, H., Malerczyk, C., Tkybusch, A., Benz, C.C., Czubayko, F. Oncogene (2001) [Pubmed]
  2. 99mTc-bicisate reliably images CBF in chronic brain diseases but fails to show reflow hyperemia in subacute stroke: report of a multicenter trial of 105 cases comparing 133Xe and 99mTc-bicisate (ECD, neurolite) measured by SPECT on same day. Lassen, N.A., Sperling, B. J. Cereb. Blood Flow Metab. (1994) [Pubmed]
  3. Transfer of thyroiditis, with syngeneic spleen cells sensitized with the human thyrotropin receptor, to naive BALB/c and NOD mice. Costagliola, S., Many, M.C., Stalmans-Falys, M., Vassart, G., Ludgate, M. Endocrinology (1996) [Pubmed]
  4. Cellular basis of ECD brain retention. Jacquier-Sarlin, M.R., Polla, B.S., Slosman, D.O. J. Nucl. Med. (1996) [Pubmed]
  5. A voxel-based investigation of regional cerebral blood flow abnormalities in obsessive-compulsive disorder using single photon emission computed tomography (SPECT). Busatto, G.F., Zamignani, D.R., Buchpiguel, C.A., Garrido, G.E., Glabus, M.F., Rocha, E.T., Maia, A.F., Rosario-Campos, M.C., Campi Castro, C., Furuie, S.S., Gutierrez, M.A., McGuire, P.K., Miguel, E.C. Psychiatry research. (2000) [Pubmed]
  6. Perfusion ECD/SPECT in the characterization of cognitive deficits in Parkinson's disease. Antonini, A., De Notaris, R., Benti, R., De Gaspari, D., Pezzoli, G. Neurol. Sci. (2001) [Pubmed]
  7. Role of SGT1 in resistance protein accumulation in plant immunity. Azevedo, C., Betsuyaku, S., Peart, J., Takahashi, A., Noël, L., Sadanandom, A., Casais, C., Parker, J., Shirasu, K. EMBO J. (2006) [Pubmed]
  8. Calindol, a positive allosteric modulator of the human Ca(2+) receptor, activates an extracellular ligand-binding domain-deleted rhodopsin-like seven-transmembrane structure in the absence of Ca(2+). Ray, K., Tisdale, J., Dodd, R.H., Dauban, P., Ruat, M., Northup, J.K. J. Biol. Chem. (2005) [Pubmed]
  9. Hand posture modulates cortical finger representation in SII. Hamada, Y., Suzuki, R. Neuroimage (2005) [Pubmed]
  10. Human Sgt1 binds HSP90 through the CHORD-Sgt1 domain and not the tetratricopeptide repeat domain. Lee, Y.T., Jacob, J., Michowski, W., Nowotny, M., Kuznicki, J., Chazin, W.J. J. Biol. Chem. (2004) [Pubmed]
  11. Abnormal regional cerebral blood flow on 99mTc ECD brain SPECT in patients with primary Sjögren's syndrome and normal findings on brain magnetic resonance imaging. Chang, C.P., Shiau, Y.C., Wang, J.J., Ho, S.T., Kao, A. Ann. Rheum. Dis. (2002) [Pubmed]
  12. Statistical parametric mapping and statistical probabilistic anatomical mapping analyses of basal/acetazolamide Tc-99m ECD brain SPECT for efficacy assessment of endovascular stent placement for middle cerebral artery stenosis. Lee, T.H., Kim, S.J., Kim, I.J., Kim, Y.K., Kim, D.S., Park, K.P. Neuroradiology (2007) [Pubmed]
  13. TI-201 chloride and Tc-99m ECD brain SPECT in lymphoma with and without massive necrosis. Shih, W.J., McCormick, M.I., Wilson, D. Clinical nuclear medicine. (1997) [Pubmed]
  14. Correct localization of epileptogenic focus with I-123 iomazenil cerebral benzodiazepine receptor imaging: a case report of temporal lobe epilepsy with discordant ictal cerebral blood flow SPECT. Shuke, N., Hashizume, K., Kiriyama, K., Okizaki, A., Yamamoto, W., Zhao, C., Nakai, H., Tanaka, T., Aburano, T. Annals of nuclear medicine. (2004) [Pubmed]
  15. A human gene, hSGT1, can substitute for GCR2, which encodes a general regulatory factor of glycolytic gene expression in Saccharomyces cerevisiae. Sato, T., Jigami, Y., Suzuki, T., Uemura, H. Mol. Gen. Genet. (1999) [Pubmed]
  16. Dimerization of the calcium-sensing receptor occurs within the extracellular domain and is eliminated by Cys --> Ser mutations at Cys101 and Cys236. Pace, A.J., Gama, L., Breitwieser, G.E. J. Biol. Chem. (1999) [Pubmed]
  17. Active antimetastatic immunotherapy in Lewis lung carcinoma with self EGFR extracellular domain protein in VSSP adjuvant. Ramírez, B.S., Pestana, E.S., Hidalgo, G.G., García, T.H., Rodríguez, R.P., Ullrich, A., Férnandez, L.E. Int. J. Cancer (2006) [Pubmed]
  18. Retention of 99mTc-bicisate in the human brain after intracarotid injection. Friberg, L., Andersen, A.R., Lassen, N.A., Holm, S., Dam, M. J. Cereb. Blood Flow Metab. (1994) [Pubmed]
  19. Brain extraction and distribution of 99mTc-bicisate in humans and in rats. Knudsen, G.M., Andersen, A.R., Somnier, F.E., Videbaek, C., Hasselbalch, S., Paulson, O.B. J. Cereb. Blood Flow Metab. (1994) [Pubmed]
  20. An integrated analytical method for determination of polychlorinated aryl methyl sulfone metabolites and polychlorinated hydrocarbon contaminants in biological matrices. Letcher, R.J., Norstrom, R.J., Bergman, A. Anal. Chem. (1995) [Pubmed]
  21. Carboxypeptidase cathepsin X mediates beta2-integrin-dependent adhesion of differentiated U-937 cells. Obermajer, N., Premzl, A., Zavasnik Bergant, T., Turk, B., Kos, J. Exp. Cell Res. (2006) [Pubmed]
  22. Circulating HER-2/erbB-2/c-neu (HER-2) extracellular domain as a prognostic factor in patients with metastatic breast cancer: Cancer and Leukemia Group B Study 8662. Hayes, D.F., Yamauchi, H., Broadwater, G., Cirrincione, C.T., Rodrigue, S.P., Berry, D.A., Younger, J., Panasci, L.L., Millard, F., Duggan, D.B., Norton, L., Henderson, I.C. Clin. Cancer Res. (2001) [Pubmed]
  23. Characterization of technetium-99m-L,L-ECD for brain perfusion imaging, Part 2: Biodistribution and brain imaging in humans. Léveillé, J., Demonceau, G., De Roo, M., Rigo, P., Taillefer, R., Morgan, R.A., Kupranick, D., Walovitch, R.C. J. Nucl. Med. (1989) [Pubmed]
  24. Analysis of styrene oxide-globin adducts based upon reaction with Raney nickel. Ting, D., Smith, M.T., Doane-Setzer, P., Rappaport, S.M. Carcinogenesis (1990) [Pubmed]
  25. Clinical utility of determination of HER-2/neu and EGFR fragments in serum of patients with metastatic breast cancer. Witzel, I., Thomssen, C., Krenkel, S., Wilczak, W., Bubenheim, M., Pantel, K., Neumann, R., Janicke, F., Muller, V. Int. J. Biol. Markers (2006) [Pubmed]
  26. Headspace solid-phase microextraction of phthalic acid esters from vegetable oil employing solvent based matrix modification. Holadová, K., Prokůpková, G., Hajslová, J., Poustka, J. Anal. Chim. Acta (2007) [Pubmed]
  27. T-cells recognize multiple epitopes in the human thyrotropin receptor extracellular domain. Soliman, M., Kaplan, E., Yanagawa, T., Hidaka, Y., Fisfalen, M.E., DeGroot, L.J. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  28. Monitoring of pesticide residues in fruits. Kumari, B., Madan, V.K., Kathpal, T.S. Environmental monitoring and assessment (2006) [Pubmed]
  29. Perfusion brain SPECT and statistical parametric mapping analysis indicate that apathy is a cingulate syndrome: a study in Alzheimer's disease and nondemented patients. Migneco, O., Benoit, M., Koulibaly, P.M., Dygai, I., Bertogliati, C., Desvignes, P., Robert, P.H., Malandain, G., Bussiere, F., Darcourt, J. Neuroimage (2001) [Pubmed]
  30. Protein and peptide secondary structure and conformational determination with vibrational circular dichroism. Keiderling, T.A. Current opinion in chemical biology. (2002) [Pubmed]
  31. Optical spectroscopic investigations of model beta-sheet hairpins in aqueous solution. Hilario, J., Kubelka, J., Keiderling, T.A. J. Am. Chem. Soc. (2003) [Pubmed]
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