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Gene Review

CHGA  -  chromogranin A (parathyroid secretory...

Homo sapiens

Synonyms: CgA, Chromogranin-A, Pituitary secretory protein I, SP-I
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Disease relevance of CHGA


Psychiatry related information on CHGA

  • Human saliva chromogranin A (CgA) is clinically promising as a psychological stress marker [6].
  • The immunoreactive patterns of CgA and CgB were investigated in CJD and compared to those observed in Alzheimer's disease [7].
  • In cortical and hippocampal plaques in Alzheimer's disease (AD) beta APP colocalized with CgA in a neuritic population largely distinct from the subset of neurites labeled by tau [8].
  • CgA was detectable in each sample, but the results in dementia showed substantial overlap with and no significant (p = 0.55) difference from the results in healthy controls [9].
  • Several lines of evidence link chromogranin A (CgA), the major soluble protein in catecholamine storage vesicles, with the cholinergic nervous system, abnormalities of which may play a central role in memory deficits in Alzheimer dementia [9].

High impact information on CHGA

  • CgA is a 49 kilodalton protein that is present in the secretory granules of most endocrine and many neuroendocrine cells [10].
  • CgA is an important new tool for the endocrinologist in the diagnosis and management of patients with endocrine and neuroendocrine tumors [10].
  • The secretory prohormone chromogranin A (CHGA) is overexpressed in essential hypertension, a complex trait with genetic predisposition, while its catecholamine release-inhibitory fragment catestatin is diminished, and low catestatin predicts augmented adrenergic pressor responses [11].
  • These results suggest a coupled relationship between CHGA-mediated chromaffin granule biogenesis, necessary for catecholamine storage, and catestatin-induced inhibition of cholinergic-stimulated catecholamine release, which regulates autonomic control of blood pressure [12].
  • Transgenic expression of human Chga and exogenous injection of human catestatin, a CHGA-derived nicotinic cholinergic antagonist, restored normal blood pressure in these mice [12].

Chemical compound and disease context of CHGA


Biological context of CHGA

  • Functional variants include both common alleles that quantitatively alter gene expression and rare alleles that qualitatively change the encoded product to alter the signaling potency of CHGA-derived catecholamine release-inhibitory catestatin peptides [1].
  • We show that a full-length CgA/EAP chimera is sorted to chromaffin granules for exocytosis [18].
  • The single copy human CgA gene was isolated from a human fetal liver gene library [4].
  • Functional analysis of Sp1-, Egr-1-, or CREB-specific promoter mutations in transfection studies confirmed the tripartite organization of the CgA -92/-62 element [19].
  • The gene for human chromogranin A (CgA) is located on chromosome 14 [20].

Anatomical context of CHGA

  • Because the binding-prone property of CgA with secretory proteins may be essential for its targeting to secretory granules, we screened its binding partner proteins using a yeast two-hybrid system [21].
  • Localization analysis showed that CgA and SgIII were coexpressed in pituitary and pancreatic endocrine cell lines, whereas SgIII was not expressed in the adrenal glands and PC12 cells [21].
  • These results identify plasmin as a protease, present in the local environment of the chromaffin cell, that selectively cleaves CgA to generate a bioactive fragment, hCgA-(360-373), that inhibits nicotinic-mediated catecholamine release [2].
  • In the present study, we investigated the expression and localization of CgA in the human submandibular gland (HSG) using various methods [6].
  • However, expression of CgA is poorly understood in humans, although salivary gland localization of CgA in other mammals, such as rodents and horses, has been demonstrated [6].

Associations of CHGA with chemical compounds

  • RATIONALE: The chromogranin A (CHGA) fragment pancreastatin (human CHGA250-301) impairs glucose metabolism, but the role of human pancreastatin in vivo remains unexplored [22].
  • Proteolytic cleavage of chromogranin A (CgA) by plasmin. Selective liberation of a specific bioactive CgA fragment that regulates catecholamine release [2].
  • CgA and CgB were sporadically detected in normal cells of the ducts, acini, and luminal secretion [23].
  • Chromogranin A (CgA) is an acidic glycoprotein, which is widely expressed in endocrine and neuroendocrine cells [4].
  • The effect of bafilomycin A1 on CgA secretion depends on a sorting determinant located within the amino terminus (CgA-(1-115)) but not the C-terminal region of the granin [18].

Physical interactions of CHGA

  • We found that CgA bound to secretogranin III (SgIII) by specific interaction both in vitro and in endocrine cells [21].
  • Gastrin elevated cellular and nuclear Egr-1 levels in a time-dependent manner and also increased Egr-1 binding to the CgA -92/-73 region [19].

Regulatory relationships of CHGA


Other interactions of CHGA

  • Immunoelectron microscopy demonstrated that CgA and SgIII were specifically colocalized in large secretory granules in male rat gonadotropes, which possess large-type and small-type granules [21].
  • These results suggest that the plasminogen/plasmin system through its interaction with CgA may play a major role in catecholaminergic function and suggest a specific mechanism as well as a discrete CgA peptide through which this effect is mediated [2].
  • In neonatal islets, CgA was localized in the periphery of immature alpha- and beta-cell granules and throughout the matrix of delta-cell granules; CgB was distributed throughout the matrix of these granules [26].
  • Thirty-seven carcinoids of the gastrointestinal tract were studied with immunohistochemical staining for chromogranin A (CgA) and Leu-7 (CD57) [27].
  • Ectopic Egr-1 overexpression potently stimulated the CgA promoter, whereas coexpression of Egr-1 with Sp1 and/or CREB resulted in additive effects [19].

Analytical, diagnostic and therapeutic context of CHGA


  1. Both rare and common polymorphisms contribute functional variation at CHGA, a regulator of catecholamine physiology. Wen, G., Mahata, S.K., Cadman, P., Mahata, M., Ghosh, S., Mahapatra, N.R., Rao, F., Stridsberg, M., Smith, D.W., Mahboubi, P., Schork, N.J., O'Connor, D.T., Hamilton, B.A. Am. J. Hum. Genet. (2004) [Pubmed]
  2. Proteolytic cleavage of chromogranin A (CgA) by plasmin. Selective liberation of a specific bioactive CgA fragment that regulates catecholamine release. Jiang, Q., Taupenot, L., Mahata, S.K., Mahata, M., O'Connor, D.T., Miles, L.A., Parmer, R.J. J. Biol. Chem. (2001) [Pubmed]
  3. Secretagogin is a new neuroendocrine marker in the human prostate. Adolf, K., Wagner, L., Bergh, A., Stattin, P., Ottosen, P., Borre, M., Birkenkamp-Demtröder, K., Orntoft, T.F., Tørring, N. Prostate (2007) [Pubmed]
  4. Human chromogranin A gene. Molecular cloning, structural analysis, and neuroendocrine cell-specific expression. Mouland, A.J., Bevan, S., White, J.H., Hendy, G.N. J. Biol. Chem. (1994) [Pubmed]
  5. Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease. Berruti, A., Mosca, A., Tucci, M., Terrone, C., Torta, M., Tarabuzzi, R., Russo, L., Cracco, C., Bollito, E., Scarpa, R.M., Angeli, A., Dogliotti, L. Endocr. Relat. Cancer (2005) [Pubmed]
  6. Expression and localization of chromogranin A gene and protein in human submandibular gland. Saruta, J., Tsukinoki, K., Sasaguri, K., Ishii, H., Yasuda, M., Osamura, Y.R., Watanabe, Y., Sato, S. Cells Tissues Organs (Print) (2005) [Pubmed]
  7. Different chromogranin immunoreactivity between prion and a-beta amyloid plaque. Rangon, C.M., Haïk, S., Faucheux, B.A., Metz-Boutigue, M.H., Fierville, F., Fuchs, J.P., Hauw, J.J., Aunis, D. Neuroreport (2003) [Pubmed]
  8. Qualitative and quantitative differences in senile plaque dystrophic neurites of Alzheimer's disease and normal aged brain. Wang, D., Munoz, D.G. J. Neuropathol. Exp. Neurol. (1995) [Pubmed]
  9. Cerebrospinal fluid chromogranin A is unchanged in Alzheimer dementia. O'Connor, D.T., Kailasam, M.T., Thal, L.J. Neurobiol. Aging (1993) [Pubmed]
  10. Chromogranin A: its role in endocrine function and as an endocrine and neuroendocrine tumor marker. Deftos, L.J. Endocr. Rev. (1991) [Pubmed]
  11. Hypertension from targeted ablation of chromogranin A can be rescued by the human ortholog. Mahapatra, N.R., O'Connor, D.T., Vaingankar, S.M., Hikim, A.P., Mahata, M., Ray, S., Staite, E., Wu, H., Gu, Y., Dalton, N., Kennedy, B.P., Ziegler, M.G., Ross, J., Mahata, S.K. J. Clin. Invest. (2005) [Pubmed]
  12. Chromogranin A: a surprising link between granule biogenesis and hypertension. Kim, T., Loh, Y.P. J. Clin. Invest. (2005) [Pubmed]
  13. Plasma and tissue chromogranin in patients with adrenocortical adenomas. Bernini, G.P., Moretti, A., Borgioli, M., Bardini, M., Miccoli, P., Berti, P., Basolo, F., Faviana, P., Birindelli, R., Salvetti, A. J. Endocrinol. Invest. (2004) [Pubmed]
  14. Retinoic acid and cAMP differentially regulate human chromogranin A promoter activity during differentiation of neuroblastoma cells. Gaetano, C., Manni, I., Bossi, G., Piaggio, G., Soddu, S., Farina, A., Helman, L.J., Sacchi, A. Eur. J. Cancer (1995) [Pubmed]
  15. Pancreastatin secretion by pituitary adenomas and regulation of chromogranin B mRNA expression. Jin, L., Scheithauer, B.W., Young, W.F., Davis, D.H., Klee, G.G., Lloyd, R.V. Am. J. Pathol. (1996) [Pubmed]
  16. 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]
  17. Is physiologic sympathoadrenal catecholamine release exocytotic in humans? Takiyyuddin, M.A., Cervenka, J.H., Sullivan, P.A., Pandian, M.R., Parmer, R.J., Barbosa, J.A., O'Connor, D.T. Circulation (1990) [Pubmed]
  18. Role of H+-ATPase-mediated acidification in sorting and release of the regulated secretory protein chromogranin A: evidence for a vesiculogenic function. Taupenot, L., Harper, K.L., O'Connor, D.T. J. Biol. Chem. (2005) [Pubmed]
  19. Interaction of early growth response protein 1 (Egr-1), specificity protein 1 (Sp1), and cyclic adenosine 3'5'-monophosphate response element binding protein (CREB) at a proximal response element is critical for gastrin-dependent activation of the chromogranin A promoter. Raychowdhury, R., Schäfer, G., Fleming, J., Rosewicz, S., Wiedenmann, B., Wang, T.C., Höcker, M. Mol. Endocrinol. (2002) [Pubmed]
  20. The gene for human chromogranin A (CgA) is located on chromosome 14. Murray, S.S., Deaven, L.L., Burton, D.W., O'Connor, D.I., Mellon, P.L., Deftos, L.J. Biochem. Biophys. Res. Commun. (1987) [Pubmed]
  21. Identification of a chromogranin A domain that mediates binding to secretogranin III and targeting to secretory granules in pituitary cells and pancreatic beta-cells. Hosaka, M., Watanabe, T., Sakai, Y., Uchiyama, Y., Takeuchi, T. Mol. Biol. Cell (2002) [Pubmed]
  22. Pancreastatin: multiple actions on human intermediary metabolism in vivo, variation in disease, and naturally occurring functional genetic polymorphism. O'Connor, D.T., Cadman, P.E., Smiley, C., Salem, R.M., Rao, F., Smith, J., Funk, S.D., Mahata, S.K., Mahata, M., Wen, G., Taupenot, L., Gonzalez-Yanes, C., Harper, K.L., Henry, R.R., Sanchez-Margalet, V. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  23. Chromogranin A and chromogranin B in noninvasive and invasive breast carcinoma. Kimura, N., Yoshida, R., Shiraishi, S., Pilichowska, M., Ohuchi, N. Endocr. Pathol. (2002) [Pubmed]
  24. Chromogranin A protects vessels against tumor necrosis factor alpha-induced vascular leakage. Ferrero, E., Scabini, S., Magni, E., Foglieni, C., Belloni, D., Colombo, B., Curnis, F., Villa, A., Ferrero, M.E., Corti, A. FASEB J. (2004) [Pubmed]
  25. Clinicopathological study of chromogranin A, B and BRCA1 expression in node-negative breast carcinoma. Yoshida, R., Ohuchi, N., Kimura, N. Oncol. Rep. (2002) [Pubmed]
  26. Cellular expression and specific intragranular localization of chromogranin A, chromogranin B, and synaptophysin during ontogeny of pancreatic islet cells: an ultrastructural study. Lukinius, A., Stridsberg, M., Wilander, E. Pancreas (2003) [Pubmed]
  27. Different patterns of chromogranin A and Leu-7 (CD57) expression in gastrointestinal carcinoids: immunohistochemical and confocal laser scanning microscopy study. Jirásek, T., Hozák, P., Mandys, V. Neoplasma (2003) [Pubmed]
  28. A cloned chromogranin A (CgA) cDNA detects a 2.3Kb mRNA in diverse neuroendocrine tissues. Deftos, L.J., Murray, S.S., Burton, D.W., Parmer, R.J., O'Connor, D.T., Delegeane, A.M., Mellon, P.L. Biochem. Biophys. Res. Commun. (1986) [Pubmed]
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