パンクレアスタチン
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2014/05/21 15:28:53」(JST)
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Chromogranin A (parathyroid secretory protein 1) |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
1LV4
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Identifiers |
Symbols |
CHGA ; CGA |
External IDs |
OMIM: 118910 MGI: 88394 HomoloGene: 976 GeneCards: CHGA Gene |
Gene ontology |
Molecular function |
• calcium ion binding
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Cellular component |
• extracellular region
• secretory granule
• transport vesicle membrane
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Biological process |
• regulation of blood pressure
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Sources: Amigo / QuickGO |
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RNA expression pattern |
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More reference expression data |
Orthologs |
Species |
Human |
Mouse |
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Entrez |
1113 |
12652 |
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Ensembl |
ENSG00000100604 |
ENSMUSG00000021194 |
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UniProt |
P10645 |
P26339 |
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RefSeq (mRNA) |
NM_001275 |
NM_007693 |
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RefSeq (protein) |
NP_001266 |
NP_031719 |
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Location (UCSC) |
Chr 14:
93.39 – 93.4 Mb |
Chr 12:
102.55 – 102.57 Mb |
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PubMed search |
[1] |
[2] |
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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. In humans, chromogranin A protein is encoded by the CHGA gene.[1]
Contents
- 1 Tissue distribution
- 2 Function
- 3 Clinical significance
- 4 References
- 5 Further reading
- 6 External links
Tissue distribution
Examples of cells producing chromogranin A are chromaffin cells of the adrenal medulla, paraganglia, enterochromaffin-like cells and beta cells of the pancreas.
Function
Chromogranin A is the precursor to several functional peptides including vasostatin, pancreastatin, catestatin and parastatin. These peptides negatively modulate the neuroendocrine function of the releasing cell (autocrine) or nearby cells (paracrine). Other peptides derived from chromogranin A with uncertain function include chromostatin, WE-14 and GE-25.
Chromogranin A might promote the generation of secretory granules.
Clinical significance
Micrograph of a paraganglioma stained with chromogranin A immunostain.
Chromogranin A is elevated in pheochromocytomas.[2]
It is used as an indicator for pancreas and prostate cancer[3] and in carcinoid syndrome.[4] It might play a role in early neoplasic progression. It is also elevated in diabetes[citation needed]. 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.[5]
References
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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
- chromogranin A antibody stains via Google Image [3]
Tumor markers
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Blood |
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Endocrine |
Thyroid cancer
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- Thyroglobulin
- Medullary thyroid cancer (Calcitonin
- Carcinoembryonic antigen)
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Pheochromocytoma
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- Normetanephrine
- Enolase 2
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Neuroendocrine tumors
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- Synaptophysin
- Chromogranin A
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Neuroblastoma
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Nervous system |
Brain tumor
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Astrocytoma
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- Glial fibrillary acidic protein
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NC/Melanoma
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- S-100 protein
- Melanoma inhibitory activity
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Cardiovascular/
respiratory |
Lung cancer
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- Carcinoembryonic antigen
- Enolase 2
- Autocrine motility factor
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Hemangiosarcoma (endothelium)
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Digestive |
Colorectal cancer
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- CA19-9
- Carcinoembryonic antigen
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Pancreatic cancer
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- CA19-9
- Carcinoembryonic antigen
- CA 242
- Tumor-associated glycoprotein 72
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Hepatocellular carcinoma
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Reproductive/
urinary/
breast |
Ovarian tumor
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- Surface epithelial-stromal tumor
- EC
- EST
- Choriocarcinoma
- Dysgerminoma
- Sertoli-Leydig cell tumour
- GCT
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Testicular cancer
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- βhCG
- Alpha-fetoprotein/AFP-L3
- CD30
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Prostate cancer
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- Prostate specific antigen
- Prostatic acid phosphatase
- Glutamate carboxypeptidase II
- erbB-3 receptor
- Early prostate cancer antigen-2
- SPINK1
- GOLPH2
- PCA3
- TMPRSS2
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Germ cell tumor
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Bladder cancer
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Breast cancer
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- CA 15-3
- erbB-2 receptor
- erbB-3 receptor
- Cathepsin D
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General histology |
Sarcoma
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Carcinoma (epithelium)
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Musculoskeletal |
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Protein: nerve tissue protein
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Synuclein |
- Alpha-synuclein
- Beta-synuclein
- Gamma-synuclein
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Other |
- Agrin
- Chimerin
- Granin
- FMR1
- Gap-43 protein
- GLUT3
- Myelin
- Brain natriuretic peptide
- Nerve growth factor
- SCG5
- Neurogranin
- Neuronal calcium sensor
- Neuropeptide
- Olfactory marker protein
- S-100 protein
- Synapsin
- Synaptophysin
- Tubulin
- GPM6A
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anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp
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noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr
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proc, drug (N1A/2AB/C/3/4/7A/B/C/D)
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anat (h/r/t/c/b/l/s/a)/phys (r)/devp/prot/nttr/nttm/ntrp
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noco/auto/cong/tumr, sysi/epon, injr
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UpToDate Contents
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English Journal
- Naturally occurring variants of the dysglycemic peptide pancreastatin: differential potencies for multiple cellular functions and structure-function correlation.
- Allu PK, Chirasani VR, Ghosh D, Mani A, Bera AK, Maji SK, Senapati S, Mullasari AS, Mahapatra NR.Author information IIT Madras, India;AbstractPancreastatin (PST), a chromogranin A-derived peptide, is a potent physiological inhibitor of glucose-induced insulin secretion. PST also triggers glycogenolysis in liver and reduces glucose uptake in adipocytes and hepatocytes. Here, we probed for genetic variations in PST sequence and identified two variants within its functionally important carboxyl-terminus domain: Glu287Lys and Gly297Ser. To understand functional implications of these amino-acid substitutions, we tested the effects of wild-type (PST-WT), PST-287K and PST-297S peptides on various cellular processes/events. The rank order of efficacy to inhibit insulin-stimulated glucose-uptake was: PST-297S>PST-287K>PST-WT. The PST peptides also displayed the same order of efficacy for enhancing intracellular nitric oxide and Ca2+ levels in various cell types. In addition, PST peptides activated gluconeogenic genes in the following order: PST-297S≥PST-287K>PST-WT. Consistent with these in vitro results, the common PST variant allele 297Ser was associated with significantly higher (by ~17 mg/dl, as compared to the wild-type Gly297 allele) plasma glucose level in our study population (n=410). Molecular modelling and molecular dynamics simulations predicted the following rank order of alpha-helical content: PST-297S>PST-287K>PST-WT. Corroboratively, circular dichroism analysis of PST peptides revealed significant differences in global structures (e.g., the order of propensity to form alpha-helix was: PST-297S≈PST-287K>PST-WT). This study provides a molecular basis for enhanced potencies/efficacies of human PST variants (likely to occur in ~300 million people worldwide) and has quantitative implications for inter-individual variations in glucose/insulin homeostasis.
- The Journal of biological chemistry.J Biol Chem.2013 Dec 12. [Epub ahead of print]
- Pancreastatin (PST), a chromogranin A-derived peptide, is a potent physiological inhibitor of glucose-induced insulin secretion. PST also triggers glycogenolysis in liver and reduces glucose uptake in adipocytes and hepatocytes. Here, we probed for genetic variations in PST sequence and identified t
- PMID 24338022
- Increased N-terminal CgA in circulation associated with cardiac reperfusion in pigs.
- Frydland M, Kousholt B, Larsen JR, Burnettr JC Jr, Hilsted L, Hasenkam JM, Goetze JP.Author information Department of Cardiothoracic & Vascular Surgery, Aarhus University Hospital, Skejby, Denmark.AbstractAIM: Acute myocardial infarction causes neurohumoral activation characterized by increased sympathetic activity. CgA is a protein released during sympathoadrenal stress from neuroendocrine tissue. Recently, increased CgA concentrations in circulation have been reported and suggested to be an independent predictor of mortality after acute myocardial infarction.
- Biomarkers in medicine.Biomark Med.2013 Dec;7(6):959-67. doi: 10.2217/bmm.13.92.
- AIM: Acute myocardial infarction causes neurohumoral activation characterized by increased sympathetic activity. CgA is a protein released during sympathoadrenal stress from neuroendocrine tissue. Recently, increased CgA concentrations in circulation have been reported and suggested to be an indepen
- PMID 24266831
- Pancreastatin is an endogenous peptide that regulates glucose homeostasis.
- Valicherla GR, Hossain Z, Mahata SK, Gayen JR.Author information Pharmacokinetics and Metabolism Division, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow, India;AbstractPancreastatin (PST) is a regulatory peptide containing 49 amino acids, first isolated from porcine pancreas. Intracellular and extracellular processing of the prohormone Chromogranin A (Chga) results various bioactive peptides of which PST has dysglycemic activity. PST regulates glucose, lipid, and protein metabolism in liver and adipose tissues. It also regulates the secretion of leptin and expression of leptin and uncoupling protein 2 in adipose tissue. In Chga knockout mice, PST induces gluconeogenesis in the liver. PST reduces glucose uptake in mice hepatocytes and adipocytes. In rat hepatocytes, PST induces glycogenolysis and glycolysis and inhibits glycogen synthesis. In rat adipocytes, PST inhibits lactate production and lipogenesis. These metabolic effects are confirmed in humans. In the dual signaling mechanism of PST receptor, mostly PST activates Gαq/11 protein leads to the activation of phospholipase C β3-isoform, therefore increasing cytoplasmic free calcium and stimulating protein kinase C. PST inhibits the cell growth in rat HTC hepatoma cells, mediated by nitric oxide and cyclic GMP production. Elevated levels of PST correlating with catecholamines have been found in gestational diabetes and essential hypertension. Rise in the blood PST level in Type 2 diabetes suggests that PST is a negative regulator of insulin sensitivity and glucose homeostasis.
- Physiological genomics.Physiol Genomics.2013 Nov 15;45(22):1060-71. doi: 10.1152/physiolgenomics.00131.2013. Epub 2013 Sep 24.
- Pancreastatin (PST) is a regulatory peptide containing 49 amino acids, first isolated from porcine pancreas. Intracellular and extracellular processing of the prohormone Chromogranin A (Chga) results various bioactive peptides of which PST has dysglycemic activity. PST regulates glucose, lipid, and
- PMID 24064537
Japanese Journal
- OP-125-5 膵内分泌腫瘍におけるpancreastatin(PST)の免疫組織化学的検討(膵内分泌腫瘍,一般口演,第110回日本外科学会定期学術集会)
- 堤 宏介,大塚 隆生,仲田 興平,森 泰寿,安井 隆晴,貞苅 良彦,大内田 研宙,高畑 俊一,水元 一博,田中 雅夫
- 日本外科学会雑誌 111(臨時増刊号_2), 486, 2010-03-05
- NAID 110007716705
- Pancreastatin, a chromogranin A-derived peptide, inhibits leptin and enhances UCP-2 expression in isolated rat adipocytes
- O-450 Rat胃ECL細胞のpancreastatin分泌について
- 木村 恵三,CHEN DUAN.,LINDSTR0M ERIK.,ZHA CHUN-MEI.,HAKANSON ROLF.,金井 道夫,青木 照明,二村 雄次
- 日本外科学会雑誌 100(臨時増刊), 220, 1999-02-10
- NAID 110003937778
Related Links
- References for "Pancreastatin" online, at universities and in literature... cyclopaedia.net ... Chromogranins: Functional and Clinical Aspects (Advances in Experimental Medicine and Biology) 2013 Proceedings of Session VII of the ...
- chromogranin A A major protein in catecholamine storage vesicles (chromaffin granules) of the adrenal medulla, which is co-released therefrom with catecholamines ... CGA([left arrow] 301 AMIDE) ASSAY Immunoreactive pancreastatin ...
Related Pictures