Chromogranin-A

CHGA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1LV4
Identifiers
Aliases	CHGA , CGA, chromogranin A, Chromogranin A, PHES, PHE5
External IDs	OMIM: 118910; MGI: 88394; HomoloGene: 976; GeneCards: CHGA; OMA:CHGA - orthologs
Gene location (Human) Chr. Chromosome 14 (human) [1] Band 14q32.12 Start 92,923,150 bp [1] End 92,935,285 bp [1]
Gene location (Mouse) Chr. Chromosome 12 (mouse) [2] Band 12 E|12 51.66 cM Start 102,521,228 bp [2] End 102,531,287 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in islet of Langerhans primary visual cortex duodenum superior frontal gyrus pituitary gland dorsolateral prefrontal cortex prefrontal cortex Brodmann area 9 rectum anterior pituitary Top expressed in islet of Langerhans adrenal gland pituitary gland median eminence motor neuron olfactory epithelium neural layer of retina superior frontal gyrus superior cervical ganglion epithelium of stomach More reference expression data BioGPS More reference expression data
Orthologs Species Human Mouse Entrez 1113 12652 Ensembl ENSG00000276781 ENSG00000100604 ENSMUSG00000021194 UniProt P10645 P26339 RefSeq (mRNA) NM_001275 NM_001301690 NM_007693 RefSeq (protein) NP_001266 NP_001288619 NP_001288619.1 NP_031719 Location (UCSC) Chr 14: 92.92 – 92.94 Mb Chr 12: 102.52 – 102.53 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Chromogranin-A (CgA) or parathyroid secretory protein 1 is encoded in the human by the gene CHGA. Cga is a member of the granin family of neuroendocrine secretory proteins. As such, it is located in secretory vesicles of neurons and endocrine cells such as islet beta cell secretory granules in the pancreas. ^[5]

Tissue distribution

Examples of cells producing chromogranin-A (CgA) 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. chromogranin-A (CgA)+ Pulmonary neuroendocrine cells account for 0.41% of all epithelial cells in the conducting airway, but are absent from the alveoli.

Function

Chromogranin-A is the precursor to several functional peptides ^[6] 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.Chromogranin-A is also present in the secretory granules of chromaffin cells and is co-released with catecholamines, playing a role in regulating their release. ^[7]

Clinical significance

Micrograph of a paraganglioma stained with chromogranin-A immunostain.

Chromogranin-A is elevated in pheochromocytomas. ^[8] It has been identified as autoantigen in type 1 diabetes. ^[9] A peptide fragment of CgA 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. ^{[10] [11]}

It is used as an indicator for pancreas and prostate cancer ^[12] and in carcinoid syndrome. ^{[13] [14]} It might play a role in early neoplastic 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. ^[15]

Mass spec data shows that several peptides originating from CHGA (163-194; 194–214; 272–295;) are significantly lower in samples from ulcerative colitis patients compared to control biopsies. ^[16]

There are considerable differences in the amino acid composition between different species' chromogranin-A . Commercial assays for measuring human CgA can usually not be used for measuring CgA in samples from other animals. Some specific parts of the molecule have a higher degree of amino acid homology and methods where the antibodies are directed against specific epitopes can be used to measure samples from different animals. ^[17] Region-specific assays measuring defined parts of CgA, CGB and SG2 can be used for measurements in samples from cats and dogs. ^{[18] [19] [20] [21] [22]} In dogs, the catestatin concentration showed weak negative associations with left atrial and ventricular sizes and the catestatin concentration showed weak positive associations with blood pressure. ^[23]

Variants

Variants exist for pancreastatin in various populations of the world. The variant Glycine297Serine has been shown to be more potent in inhibiting insulin-induced glucose uptake, resulting in higher risk of insulin resistance and diabetes among carriers of this variant. A team of researchers led by the Indian Institute of Technology Madras has found that the Glycine297Serine variation was present in approximately 15 percent of Indian and other South Asian populations. ^{[24] [25]}

References

1. ENSG00000100604 GRCh38: Ensembl release 89: ENSG00000276781, ENSG00000100604 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021194 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Helman LJ, Ahn TG, Levine MA, Allison A, Cohen PS, Cooper MJ, et al. (August 1988). "Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA". The Journal of Biological Chemistry. 263 (23): 11559–63. doi: 10.1016/S0021-9258(18)37995-X . PMID   3403545.
6. Troger, Josef; Theurl, Markus; Kirchmair, Rudolf; Pasqua, Teresa; Tota, Bruno; Angelone, Tommaso; Cerra, Maria C.; Nowosielski, Yvonne; Mätzler, Raphaela; Troger, Jasmin; Gayen, Jaur R.; Trudeau, Vance; Corti, Angelo; Helle, Karen B. (2017). "Granin-derived peptides". Progress in Neurobiology. 154: 37–61. doi:10.1016/j.pneurobio.2017.04.003. ISSN   1873-5118. PMID   28442394.
7. Jiang, Qijiao; Taupenot, Laurent; Mahata, Sushil K.; Mahata, Manjula; O'Connor, Daniel T.; Miles, Lindsey A.; Parmer, Robert J. (1 January 2001). "Proteolytic Cleavage of Chromogranin A (CgA) by Plasmin: SELECTIVE LIBERATION OF A SPECIFIC BIOACTIVE CgA FRAGMENT THAT REGULATES CATECHOLAMINE RELEASE*". Journal of Biological Chemistry. 276 (27): 25022–25029. doi: 10.1074/jbc.M101545200 . ISSN   0021-9258. PMID   11342539.
8. Cotesta D, Caliumi C, Alò P, Petramala L, Reale MG, Masciangelo R, et al. (2005). "High plasma levels of human chromogranin A and adrenomedullin in patients with pheochromocytoma". Tumori. 91 (1): 53–8. doi:10.1177/030089160509100110. PMID   15850005. S2CID   13142518.
9. Stadinski BD, Delong T, Reisdorph N, Reisdorph R, Powell RL, Armstrong M, et al. (March 2010). "Chromogranin A is an autoantigen in type 1 diabetes". Nature Immunology. 11 (3): 225–31. doi:10.1038/ni.1844. PMC   3166626 . PMID   20139986.
10. Nikoopour E, Sandrock C, Huszarik K, Krougly O, Lee-Chan E, Masteller EL, et al. (April 2011). "Cutting edge: vasostatin-1-derived peptide ChgA29-42 is an antigenic epitope of diabetogenic BDC2.5 T cells in nonobese diabetic mice". Journal of Immunology. 186 (7): 3831–5. doi: 10.4049/jimmunol.1003617 . PMID   21357258.
11. Nikoopour E, Cheung R, Bellemore S, Krougly O, Lee-Chan E, Stridsberg M, Singh B (April 2014). "Vasostatin-1 antigenic epitope mapping for induction of cellular and humoral immune responses to chromogranin A autoantigen in NOD mice". European Journal of Immunology. 44 (4): 1170–80. doi:10.1002/eji.201343986. PMID   24443235. S2CID   13414795.
12. 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". Annals of Clinical and Laboratory Science. 30 (2): 175–178. PMID   10807161.
13. Nikou GC, Lygidakis NJ, Toubanakis C, Pavlatos S, Tseleni-Balafouta S, Giannatou E, et al. (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". Hepato-Gastroenterology. 52 (63): 731–741. PMID   15966194.
14. Tomita T (August 2020). "Significance of chromogranin A and synaptophysin in pancreatic neuroendocrine tumors". Bosnian Journal of Basic Medical Sciences. 20 (3): 336–346. doi:10.17305/bjbms.2020.4632. PMC   7416176 . PMID   32020844.
15. Leong AS, Cooper K, Leong FJ (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 159–160. ISBN   1-84110-100-1.
16. Kirov S, Sasson A, Zhang C, Chasalow S, Dongre A, Steen H, et al. (February 2019). "Degradation of the extracellular matrix is part of the pathology of ulcerative colitis". Molecular Omics. 15 (1): 67–76. doi: 10.1039/c8mo00239h . PMID   30702115.
17. Stridsberg M, Angeletti RH, Helle KB (June 2000). "Characterisation of N-terminal chromogranin A and chromogranin B in mammals by region-specific radioimmunoassays and chromatographic separation methods". The Journal of Endocrinology. 165 (3): 703–14. doi: 10.1677/joe.0.1650703 . PMID   10828855.
18. Stridsberg M, Pettersson A, Hagman R, Westin C, Höglund O (June 2014). "Chromogranins can be measured in samples from cats and dogs". BMC Research Notes. 7 (1): 336. doi: 10.1186/1756-0500-7-336 . PMC   4055239 . PMID   24899097.
19. Höglund OV, Hagman R, Stridsberg M (27 March 2015). "Chromogranin A and cortisol at intraoperative repeated noxious stimuli: Surgical stress in a dog model". SAGE Open Medicine. 3: 2050312115576432. doi:10.1177/2050312115576432. PMC   4679230 . PMID   26770773.
20. Srithunyarat T, Höglund OV, Hagman R, Olsson U, Stridsberg M, Lagerstedt AS, Pettersson A (August 2016). "Catestatin, vasostatin, cortisol, temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale and visual analog scale for stress and pain behavior in dogs before and after ovariohysterectomy". BMC Research Notes. 9 (1): 381. doi: 10.1186/s13104-016-2193-1 . PMC   4969733 . PMID   27484122.
21. Srithunyarat T, Hagman R, Höglund OV, Olsson U, Stridsberg M, Jitpean S, et al. (January 2017). "Catestatin and vasostatin concentrations in healthy dogs". Acta Veterinaria Scandinavica. 59 (1): 1. doi: 10.1186/s13028-016-0274-8 . PMC   5210291 . PMID   28049540.
22. Srithunyarat T, Hagman R, Höglund OV, Stridsberg M, Hanson J, Lagerstedt AS, Pettersson A (April 2018). "Catestatin, vasostatin, cortisol, and visual analog scale scoring for stress assessment in healthy dogs". Research in Veterinary Science. 117: 74–80. doi: 10.1016/j.rvsc.2017.11.015 . PMID   29195227.
23. Höglund K, Häggström J, Höglund OV, Stridsberg M, Tidholm A, Ljungvall I (August 2020). "The chromogranin A-derived peptides catestatin and vasostatin in dogs with myxomatous mitral valve disease". Acta Veterinaria Scandinavica. 62 (1): 43. doi: 10.1186/s13028-020-00541-3 . PMC   7405357 . PMID   32758260.
24. "IIT Madras-led International Research Team Identifies gene/protein variation in Indians & other South Asians that increases risk of metabolic diseases". India Education Diary. Chennai. 31 January 2022. Retrieved 2 February 2022.
25. Allu PK, Kiranmayi M, Mukherjee SD, Chirasani VR, Garg R, Vishnuprabu D, et al. (December 2021). "Functional Gly297Ser Variant of the Physiological Dysglycemic Peptide Pancreastatin is a Novel Risk Factor for Cardiometabolic Disorders". Diabetes. 71 (3): 538–553. doi: 10.2337/db21-0289 . PMID   34862200. S2CID   244871964. (apparently the abstract has been released in advance of the full publication of the paper).

Further reading

• Hendy GN, Bevan S, Mattei MG, Mouland AJ (February 1995). "Chromogranin A". Clinical and Investigative Medicine. 18 (1): 47–65. PMID   7768066.
• Iacangelo AL, Eiden LE (August 1995). "Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway". Regulatory Peptides. 58 (3): 65–88. doi:10.1016/0167-0115(95)00069-N. PMID   8577930. S2CID   23202363.
• Curry WJ, Barkatullah SC, Johansson AN, Quinn JG, Norlen P, Connolly CK, et al. (October 2002). "WE-14, a chromogranin a-derived neuropeptide". Annals of the New York Academy of Sciences. 971 (1): 311–6. Bibcode:2002NYASA.971..311C. doi:10.1111/j.1749-6632.2002.tb04485.x. PMID   12438141. S2CID   22565635.
• Curry WJ, Shaw C, Johnston CF, Thim L, Buchanan KD (April 1992). "Isolation and primary structure of a novel chromogranin A-derived peptide, WE-14, from a human midgut carcinoid tumour". FEBS Letters. 301 (3): 319–21. Bibcode:1992FEBSL.301..319C. doi: 10.1016/0014-5793(92)80266-J . PMID   1577173. S2CID   11191027.
• Tamamura H, Ohta M, Yoshizawa K, Ono Y, Funakoshi A, Miyasaka K, et al. (July 1990). "Isolation and characterization of a tumor-derived human protein related to chromogranin A and its in vitro conversion to human pancreastatin-48". European Journal of Biochemistry. 191 (1): 33–9. doi: 10.1111/j.1432-1033.1990.tb19090.x . PMID   2165909.
• Konecki DS, Benedum UM, Gerdes HH, Huttner WB (December 1987). "The primary structure of human chromogranin A and pancreastatin". The Journal of Biological Chemistry. 262 (35): 17026–30. doi: 10.1016/S0021-9258(18)45486-5 . PMID   2445752.
• Sekiya K, Ghatei MA, Minamino N, Bretherton-Watt D, Matsuo H, Bloom SR (February 1988). "Isolation of human pancreastatin fragment containing the active sequence from a glucagonoma". FEBS Letters. 228 (1): 153–6. Bibcode:1988FEBSL.228..153S. doi: 10.1016/0014-5793(88)80606-9 . PMID   2830133. S2CID   36547482.
• Helman LJ, Ahn TG, Levine MA, Allison A, Cohen PS, Cooper MJ, et al. (August 1988). "Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA". The Journal of Biological Chemistry. 263 (23): 11559–63. doi: 10.1016/S0021-9258(18)37995-X . PMID   3403545.
• Wilson BS, Phan SH, Lloyd RV (February 1986). "Chromogranin from normal human adrenal glands: purification by monoclonal antibody affinity chromatography and partial N-terminal amino acid sequence" (PDF). Regulatory Peptides. 13 (3–4): 207–23. doi:10.1016/0167-0115(86)90040-6. hdl: 2027.42/26277 . PMID   3704195. S2CID   36060758.
• Deftos LJ, Murray SS, Burton DW, Parmer RJ, O'Connor DT, Delegeane AM, Mellon PL (May 1986). "A cloned chromogranin A (CgA) cDNA detects a 2.3Kb mRNA in diverse neuroendocrine tissues". Biochemical and Biophysical Research Communications. 137 (1): 418–23. doi:10.1016/0006-291X(86)91226-X. PMID   3718511.
• Hagn C, Schmid KW, Fischer-Colbrie R, Winkler H (October 1986). "Chromogranin A, B, and C in human adrenal medulla and endocrine tissues". Laboratory Investigation; A Journal of Technical Methods and Pathology. 55 (4): 405–11. PMID   3762065.
• Murray SS, Deaven LL, Burton DW, O'Connor DI, Mellon PL, Deftos LJ (January 1987). "The gene for human chromogranin A (CgA) is located on chromosome 14". Biochemical and Biophysical Research Communications. 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 (March 1993). "Chromostatin, a chromogranin A-derived bioactive peptide, is present in human pancreatic insulin (beta) cells". Proceedings of the National Academy of Sciences of the United States of America. 90 (6): 2360–4. Bibcode:1993PNAS...90.2360C. doi: 10.1073/pnas.90.6.2360 . PMC   46086 . PMID   8096340.
• Mouland AJ, Bevan S, White JH, Hendy GN (March 1994). "Human chromogranin A gene. Molecular cloning, structural analysis, and neuroendocrine cell-specific expression". The Journal of Biological Chemistry. 269 (9): 6918–26. doi: 10.1016/S0021-9258(17)37462-8 . PMID   8120054.
• Maruyama K, Sugano S (January 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, et al. (July 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, et al. (April 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, et al. (November 1996). "Antibacterial activity of glycosylated and phosphorylated chromogranin A-derived peptide 173-194 from bovine adrenal medullary chromaffin granules". The Journal of Biological Chemistry. 271 (45): 28533–40. doi: 10.1074/jbc.271.45.28533 . PMID   8910482.

External links

• chromogranin A antibody stains via Google Image
• Overview of all the structural information available in the PDB for UniProt : P10645 (Chromogranin-A) at the PDBe-KB .
• Overview of all the structural information available in the PDB for UniProt : P26339 (Mouse Chromogranin-A) at the PDBe-KB .