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Gene Review

SCG2  -  secretogranin II

Homo sapiens

Synonyms: CHGC, Chromogranin-C, EM66, SN, Secretogranin II, ...
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Disease relevance of SCG2


Psychiatry related information on SCG2


High impact information on SCG2


Chemical compound and disease context of SCG2

  • The finding of strongly reduced mRNA levels in upd(15)mat cells of the gene encoding secretogranin II (SCG2), which is a precursor of the dopamine releasing factor secretoneurin, raises the question whether hyperphagia in patients with PWS might be due to a defect in dopamine-modulated food reward circuits [12].
  • Chromogranin A and B and secretogranin II in prostatic adenocarcinomas: neuroendocrine expression in patients untreated and treated with androgen deprivation therapy [13].

Biological context of SCG2


Anatomical context of SCG2

  • The SCG2 transcript was 2.9 kb in all tissues with an additional 4.2 kb transcript also being present in the pancreas and thymus [14].
  • The primary structure of human secretogranin II, a widespread tyrosine-sulfated secretory granule protein that exhibits low pH- and calcium-induced aggregation [18].
  • Taken together, these data demonstrate that posttranslational processing of SgII actually generates EM66 in the adrenal gland [19].
  • To investigate the functional significance of this motif, intracellular cAMP levels were increased in a neuronal cell line derived from the septal region of the brain and the level of secretogranin II gene expression was analysed [3].
  • In the majority of differentiated cells, a clearly punctate SgII immunolabeling indicative of the presence of secretory organelles was present in the Golgi region, at the cell periphery, along the neurites and in growth cones [20].

Associations of SCG2 with chemical compounds

  • In vivo, ammonium chloride, which is known to neutralize the pH of acidic intracellular compartments, inhibited the packaging of newly synthesized secretogranin II into secretory granules [18].
  • Analysis of a 2.35-kilobase cDNA clone isolated from a human pituitary library and identified as secretogranin II by various criteria showed that human presecretogranin II is a 617-residue polypeptide containing an NH2-terminal located signal peptide [18].
  • Secretoneurin (SN), a 33-amino acid neuropeptide, is derived from secretogranin II that is released from sensory afferent C-fibers by capsaicin [21].
  • The transfer of SgII from the sulfation site to this distal compartment of the TGN involves BFA-sensitive membrane dynamics [22].
  • In this study, we have investigated the subcellular compartment in which the cleavage of SgII is initiated by taking advantage of its tyrosine sulfation in the trans-Golgi network (TGN) [22].

Other interactions of SCG2


Analytical, diagnostic and therapeutic context of SCG2

  • Molecular cloning of secretogranin II (SgII) in phylogenetically distant species has recently revealed the existence of a highly conserved 66-amino acid peptide flanked by preserved pairs of basic residues [19].
  • In the present report, a specific hSgII antiserum was used in immunohistochemistry experiments to determine the distribution of SgII in normal anterior pituitaries and pituitary adenomas (5 gonadotroph, 3 non-functioning and 5 mammotroph tumors) [4].
  • Northern blot analyses demonstrated the same 2.5 kb SgII mRNA species in all types of tumors as in normal anterior pituitaries [4].
  • Western blotting experiments revealed that both the 46 K and 31 K polypeptides arose from the second half (C-terminal) of the molecule, thus suggesting that SgII may be processed by cleavage of short N-terminal polypeptides not detected in our conditions [4].
  • Sequence analysis revealed the existence of numerous putative cis-regulatory elements in the SgII gene promoter, including a consensus cyclic AMP-responsive element (CRE) [17].


  1. Identification of the secretogranin II-derived peptide EM66 in pheochromocytomas as a potential marker for discriminating benign versus malignant tumors. Yon, L., Guillemot, J., Montero-Hadjadje, M., Grumolato, L., Leprince, J., Lefebvre, H., Contesse, V., Plouin, P.F., Vaudry, H., Anouar, Y. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  2. Differentiation of human pituitary adenomas determines the pattern of chromogranin/secretogranin messenger ribonucleic acid expression. Jin, L., Chandler, W.F., Smart, J.B., England, B.G., Lloyd, R.V. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  3. Identification of a functional cAMP response element in the secretogranin II gene. Cibelli, G., Jüngling, S., Schoch, S., Gerdes, H.H., Thiel, G. Eur. J. Biochem. (1996) [Pubmed]
  4. Secretogranin II (SgII) distribution and processing studies in human normal and adenomatous anterior pituitaries using new polyclonal antibodies. Vallet, V.S., Li, J.Y., Duval, J. Regul. Pept. (1997) [Pubmed]
  5. Secretogranin II: a key AP-1-regulated protein that mediates neuronal differentiation and protection from nitric oxide-induced apoptosis of neuroblastoma cells. Li, L., Hung, A.C., Porter, A.G. Cell Death Differ. (2008) [Pubmed]
  6. Biochemical characterisation and immunohistochemical localisation of the secretogranin II-derived peptide EM66 in the hypothalamus of the jerboa (Jaculus orientalis): modulation by food deprivation. Boutahricht, M., Guillemot, J., Montero-Hadjadje, M., Bellafqih, S., El Ouezzani, S., Alaoui, A., Yon, L., Vaudry, H., Anouar, Y., Magoul, R. J. Neuroendocrinol. (2005) [Pubmed]
  7. Cell-free protein sorting to the regulated and constitutive secretory pathways. Tooze, S.A., Huttner, W.B. Cell (1990) [Pubmed]
  8. Identification of gastroenteropancreatic neuroendocrine cells in normal and neoplastic human tissue with antibodies against synaptophysin, chromogranin A, secretogranin I (chromogranin B), and secretogranin II. Wiedenmann, B., Waldherr, R., Buhr, H., Hille, A., Rosa, P., Huttner, W.B. Gastroenterology (1988) [Pubmed]
  9. Synaptotagmin IV is necessary for the maturation of secretory granules in PC12 cells. Ahras, M., Otto, G.P., Tooze, S.A. J. Cell Biol. (2006) [Pubmed]
  10. Reduction of the disulfide bond of chromogranin B (secretogranin I) in the trans-Golgi network causes its missorting to the constitutive secretory pathways. Chanat, E., Weiss, U., Huttner, W.B., Tooze, S.A. EMBO J. (1993) [Pubmed]
  11. Characterization of the immature secretory granule, an intermediate in granule biogenesis. Tooze, S.A., Flatmark, T., Tooze, J., Huttner, W.B. J. Cell Biol. (1991) [Pubmed]
  12. Somatic mosaicism for maternal uniparental disomy 15 in a girl with Prader-Willi syndrome: confirmation by cell cloning and identification of candidate downstream genes. Horsthemke, B., Nazlican, H., Hüsing, J., Klein-Hitpass, L., Claussen, U., Michel, S., Lich, C., Gillessen-Kaesbach, G., Buiting, K. Hum. Mol. Genet. (2003) [Pubmed]
  13. Chromogranin A and B and secretogranin II in prostatic adenocarcinomas: neuroendocrine expression in patients untreated and treated with androgen deprivation therapy. Pruneri, G., Galli, S., Rossi, R.S., Roncalli, M., Coggi, G., Ferrari, A., Simonato, A., Siccardi, A.G., Carboni, N., Buffa, R. Prostate (1998) [Pubmed]
  14. Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1. Lemmens, I., Van de Ven, W.J., Kas, K., Zhang, C.X., Giraud, S., Wautot, V., Buisson, N., De Witte, K., Salandre, J., Lenoir, G., Pugeat, M., Calender, A., Parente, F., Quincey, D., Gaudray, P., De Wit, M.J., Lips, C.J., Höppener, J.W., Khodaei, S., Grant, A.L., Weber, G., Kytölä, S., Teh, B.T., Farnebo, F., Thakker, R.V. Hum. Mol. Genet. (1997) [Pubmed]
  15. Role of basic region leucine zipper transcription factors cyclic AMP response element binding protein (CREB), CREB2, activating transcription factor 2 and CAAT/enhancer binding protein alpha in cyclic AMP response element-mediated transcription. Thiel, G., Al Sarraj, J., Vinson, C., Stefano, L., Bach, K. J. Neurochem. (2005) [Pubmed]
  16. Modular structure of cAMP response element binding protein 2 (CREB2). Schoch, S., Cibelli, G., Magin, A., Steinmüller, L., Thiel, G. Neurochem. Int. (2001) [Pubmed]
  17. Synergistic action of upstream elements and a promoter-proximal CRE is required for neuroendocrine cell-specific expression and second-messenger regulation of the gene encoding the human secretory protein secretogranin II. Desmoucelles, C., Vaudry, H., Eiden, L.E., Anouar, Y. Mol. Cell. Endocrinol. (1999) [Pubmed]
  18. The primary structure of human secretogranin II, a widespread tyrosine-sulfated secretory granule protein that exhibits low pH- and calcium-induced aggregation. Gerdes, H.H., Rosa, P., Phillips, E., Baeuerle, P.A., Frank, R., Argos, P., Huttner, W.B. J. Biol. Chem. (1989) [Pubmed]
  19. Identification of a novel secretogranin II-derived peptide (SgII(187-252)) in adult and fetal human adrenal glands using antibodies raised against the human recombinant peptide. Anouar, Y., Desmoucelles, C., Yon, L., Leprince, J., Breault, L., Gallo-Payet, N., Vaudry, H. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  20. Immunolocalization of secretogranin II, chromogranin A, and chromogranin B in differentiating human neuroblastoma cells. Giudici, A.M., Sher, E., Pelagi, M., Clementi, F., Zanini, A. Eur. J. Cell Biol. (1992) [Pubmed]
  21. Secretoneurin, a novel neuropeptide, is a potent chemoattractant for human eosinophils. Dunzendorfer, S., Schratzberger, P., Reinisch, N., Kähler, C.M., Wiedermann, C.J. Blood (1998) [Pubmed]
  22. Proteolytic processing of sulfated secretogranin II in the trans-Golgi network of GH3B6 prolactin cells. Muller, L., Barret, A., Picart, R., Tougard, C. J. Biol. Chem. (1997) [Pubmed]
  23. Argyrophilia and granin (chromogranin/secretogranin) expression in female breast carcinomas. Their relationship to survival and other disease parameters. Scopsi, L., Andreola, S., Pilotti, S., Testori, A., Baldini, M.T., Leoni, F., Lombardi, L., Hutton, J.C., Shimizu, F., Rosa, P. Am. J. Surg. Pathol. (1992) [Pubmed]
  24. Quantitation of somatostatin receptor type 2 gene expression in neuroblastoma cell lines and primary tumors using competitive reverse transcription-polymerase chain reaction. Sestini, R., Orlando, C., Peri, A., Tricarico, C., Pazzagli, M., Serio, M., Pagani, A., Bussolati, G., Granchi, S., Maggi, M. Clin. Cancer Res. (1996) [Pubmed]
  25. Occurrence of two types of secretory vesicles in the human neuroblastoma SH-SY5Y. Goodall, A.R., Danks, K., Walker, J.H., Ball, S.G., Vaughan, P.F. J. Neurochem. (1997) [Pubmed]
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