Chromogranin A

Chromogranin A
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CHGA ; CGA
External IDs OMIM: 118910 MGI: 88394 HomoloGene: 976 GeneCards: CHGA Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 1113 12652
Ensembl ENSG00000100604 ENSMUSG00000021194
UniProt P10645 P26339
RefSeq (mRNA) NM_001275 NM_007693
RefSeq (protein) NP_001266 NP_031719
Location (UCSC) Chr 14:
92.92 – 92.94 Mb		 Chr 12:
102.55 – 102.57 Mb
PubMed search

Chromogranin A or parathyroid secretory protein 1 (gene name CHGA) is a member of the granin family of neuroendocrine secretory proteins, i.e., it is located in secretory vesicles of neurons and endocrine cells such as islet beta cell secretory granules in pancreas. In humans, chromogranin A protein is encoded by the CHGA gene.[1]

Tissue distribution

Examples of cells producing chromogranin A (ChgA) are chromaffin cells of the adrenal medulla, paraganglia, enterochromaffin-like cells and beta cells of the pancreas. It is present in islet beta cell secretory granules.

Function

Chromogranin A is the precursor to several functional peptides including vasostatin-1, vasostatin-2, pancreastatin, catestatin and parastatin. These peptides negatively modulate the neuroendocrine function of the releasing cell (autocrine) or nearby cells (paracrine).

Chromogranin A induces and promotes the generation of secretory granules such as those containing insulin in pancreatic islet beta cells.

Clinical significance

Micrograph of a paraganglioma stained with chromogranin A immunostain.

Chromogranin A is elevated in pheochromocytomas.[2] It has been identified as autoantigen in type 1 diabetes.[3] A peptide fragment of ChgA located in the Vasostatin-1, namely ChgA29-42 has been identified as the antigenic epitope recognized by diabetogenic BDC2.5 T cells from type 1 diabetes prone NOD mice.[4][5]

It is used as an indicator for pancreas and prostate cancer[6] and in carcinoid syndrome.[7] It might play a role in early neoplasic progression. Chromogranin A is cleaved by an endogenous prohormone convertase to produce several peptide fragments. See chromogranin A GeneRIFs for references. In immunohistochemistry it can be used to identify a range of neuroendocrine tumours and is highly specific for both benign and malignant cells of this type.[8]

References

  1. ↑ Helman LJ, Ahn TG, Levine MA, Allison A, Cohen PS, Cooper MJ, Cohn DV, Israel MA (August 1988). "Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA". J. Biol. Chem. 263 (23): 11559–63. PMID 3403545.
  2. ↑ Cotesta D, Caliumi C, Alò P, Petramala L, Reale MG, Masciangelo R, Signore A, Cianci R, D'Erasmo E, Letizia C (2005). "High plasma levels of human chromogranin A and adrenomedullin in patients with pheochromocytoma". Tumori 91 (1): 53–8. PMID 15850005.
  3. ↑ Stadinski BD, Delong T, Reisdorph N, Reisdorph R, Powell RL, Armstrong M, Piganelli JD, Barbour G, Bradley B, Crawford F, Marrack P, Mahata SK, Kappler JW, Haskins K (2010). "Chromogranin A is an autoantigen in type 1 diabetes". Nat. Immunol. 11 (3): 225–31. doi:10.1038/ni.1844. PMC 3166626. PMID 20139986.
  4. ↑ Nikoopour E, Sandrock C, Huszarik K, Krougly O, Lee-Chan E, Masteller EL, Bluestone JA, Singh B (2011). "Cutting edge: vasostatin-1-derived peptide ChgA29-42 is an antigenic epitope of diabetogenic BDC2.5 T cells in nonobese diabetic mice". J. Immunol. 186 (7): 3831–5. doi:10.4049/jimmunol.1003617. PMID 21357258.
  5. ↑ Nikoopour E, Cheung R, Bellemore S, Krougly O, Lee-Chan E, Stridsberg M, Singh B (2014). "Vasostatin-1 antigenic epitope mapping for induction of cellular and humoral immune responses to chromogranin A autoantigen in NOD mice". Eur. J. Immunol. 44 (4): 1170–80. doi:10.1002/eji.201343986. PMID 24443235.
  6. ↑ Wu JT, Erickson AJ, Tsao KC, Wu TL, Sun CF (April 2000). "Elevated serum chromogranin A is detectable in patients with carcinomas at advanced disease stages". Ann. Clin. Lab. Sci. 30 (2): 175–8. PMID 10807161.
  7. ↑ Nikou GC, Lygidakis NJ, Toubanakis C, Pavlatos S, Tseleni-Balafouta S, Giannatou E, Mallas E, Safioleas M (2005). "Current diagnosis and treatment of gastrointestinal carcinoids in a series of 101 patients: the significance of serum chromogranin-A, somatostatin receptor scintigraphy and somatostatin analogues". Hepatogastroenterology 52 (63): 731–41. PMID 15966194.
  8. ↑ Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 159–160. ISBN 1-84110-100-1.

Further reading

  • Hendy GN, Bevan S, Mattei MG, Mouland AJ (1995). "Chromogranin A.". Clinical and investigative medicine. Médecine clinique et experimentale 18 (1): 47–65. PMID 7768066. 
  • Iacangelo AL, Eiden LE (1996). "Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway.". Regul. Pept. 58 (3): 65–88. doi:10.1016/0167-0115(95)00069-N. PMID 8577930. 
  • Curry WJ, Barkatullah SC, Johansson AN, Quinn JG, Norlen P, Connolly CK, McCollum AP, McVicar CM (2002). "WE-14, a chromogranin a-derived neuropeptide.". Ann. N. Y. Acad. Sci. 971: 311–6. doi:10.1111/j.1749-6632.2002.tb04485.x. PMID 12438141. 
  • Curry WJ, Shaw C, Johnston CF, Thim L, Buchanan KD (1992). "Isolation and primary structure of a novel chromogranin A-derived peptide, WE-14, from a human midgut carcinoid tumour.". FEBS Lett. 301 (3): 319–21. doi:10.1016/0014-5793(92)80266-J. PMID 1577173. 
  • Tamamura H, Ohta M, Yoshizawa K, Ono Y, Funakoshi A, Miyasaka K, Tateishi K, Jimi A, Yajima H, Fujii N (1990). "Isolation and characterization of a tumor-derived human protein related to chromogranin A and its in vitro conversion to human pancreastatin-48.". Eur. J. Biochem. 191 (1): 33–9. doi:10.1111/j.1432-1033.1990.tb19090.x. PMID 2165909. 
  • Konecki DS, Benedum UM, Gerdes HH, Huttner WB (1988). "The primary structure of human chromogranin A and pancreastatin.". J. Biol. Chem. 262 (35): 17026–30. PMID 2445752. 
  • Sekiya K, Ghatei MA, Minamino N, Bretherton-Watt D, Matsuo H, Bloom SR (1988). "Isolation of human pancreastatin fragment containing the active sequence from a glucagonoma.". FEBS Lett. 228 (1): 153–6. doi:10.1016/0014-5793(88)80606-9. PMID 2830133. 
  • Helman LJ, Ahn TG, Levine MA, Allison A, Cohen PS, Cooper MJ, Cohn DV, Israel MA (1988). "Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA.". J. Biol. Chem. 263 (23): 11559–63. PMID 3403545. 
  • Wilson BS, Phan SH, Lloyd RV (1986). "Chromogranin from normal human adrenal glands: purification by monoclonal antibody affinity chromatography and partial N-terminal amino acid sequence.". Regul. Pept. 13 (3–4): 207–23. doi:10.1016/0167-0115(86)90040-6. PMID 3704195. 
  • Deftos LJ, Murray SS, Burton DW, Parmer RJ, O'Connor DT, Delegeane AM, Mellon PL (1986). "A cloned chromogranin A (CgA) cDNA detects a 2.3Kb mRNA in diverse neuroendocrine tissues". Biochem. Biophys. Res. Commun. 137 (1): 418–23. doi:10.1016/0006-291X(86)91226-X. PMID 3718511. 
  • Hagn C, Schmid KW, Fischer-Colbrie R, Winkler H (1986). "Chromogranin A, B, and C in human adrenal medulla and endocrine tissues". Lab. Invest. 55 (4): 405–11. PMID 3762065. 
  • Murray SS, Deaven LL, Burton DW, O'Connor DI, Mellon PL, Deftos LJ (1987). "The gene for human chromogranin A (CgA) is located on chromosome 14". Biochem. Biophys. Res. Commun. 142 (1): 141–6. doi:10.1016/0006-291X(87)90462-1. PMID 3814131. 
  • Cetin Y, Aunis D, Bader MF, Galindo E, Jörns A, Bargsten G, Grube D (1993). "Chromostatin, a chromogranin A-derived bioactive peptide, is present in human pancreatic insulin (beta) cells". Proc. Natl. Acad. Sci. U.S.A. 90 (6): 2360–4. doi:10.1073/pnas.90.6.2360. PMC 46086. PMID 8096340. 
  • Mouland AJ, Bevan S, White JH, Hendy GN (1994). "Human chromogranin A gene. Molecular cloning, structural analysis, and neuroendocrine cell-specific expression". J. Biol. Chem. 269 (9): 6918–26. PMID 8120054. 
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
  • Simon-Chazottes D, Wu H, Parmer RJ, Rozansky DJ, Szpirer J, Levan G, Kurtz TW, Szpirer C, Guenet JL, O'Connor DT (1993). "Assignment of the chromogranin A (Chga) locus to homologous regions on mouse chromosome 12 and rat chromosome 6". Genomics 17 (1): 252–5. doi:10.1006/geno.1993.1316. PMID 8406464. 
  • Mahata SK, Kozak CA, Szpirer J, Szpirer C, Modi WS, Gerdes HH, Huttner WB, O'Connor DT (1996). "Dispersion of chromogranin/secretogranin secretory protein family loci in mammalian genomes". Genomics 33 (1): 135–9. doi:10.1006/geno.1996.0171. PMID 8617499. 
  • Strub JM, Goumon Y, Lugardon K, Capon C, Lopez M, Moniatte M, Van Dorsselaer A, Aunis D, Metz-Boutigue MH (1996). "Antibacterial activity of glycosylated and phosphorylated chromogranin A-derived peptide 173-194 from bovine adrenal medullary chromaffin granules". J. Biol. Chem. 271 (45): 28533–40. doi:10.1074/jbc.271.45.28533. PMID 8910482. 

External links

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