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Gene Review

REG1A  -  regenerating islet-derived 1 alpha

Homo sapiens

Synonyms: ICRF, Islet cells regeneration factor, Islet of Langerhans regenerating protein, Lithostathine-1-alpha, P19, ...
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Disease relevance of REG1A


Psychiatry related information on REG1A

  • Pancreatic thread protein (PTP) is a major exocrine secretory protein that in vitro forms filamentous bundles reminiscent of the paired helical filaments of Alzheimer's disease (AD) [6].
  • Postural instability successfully classified PSP from Pick's disease [7].
  • The motor skill task performance of the PD and PSP patients improved with training, but the improvement disappeared within a few months, whereas AD patients retained learned skills for 3-18 months [8].
  • In contrast to the two cases previously reported by others, in which the preoperative TEPs were normal, the two cases reported herein showed significant changes on the affected side: the sensory thresholds were greater and the peak latencies of P19 and N28 were longer on the affected side than those on the normal side [9].
  • We compared regional brain concentrations of CP and copper between subjects with Alzheimer's disease (AD, n = 12), Parkinson's disease (PD, n = 14), Huntington's disease (HD, n = 11), progressive supranuclear palsy (PSP, n = 11), young adult normal controls (YC, n = 6) and elderly normal controls (EC, n = 7) [10].

High impact information on REG1A

  • The architecture of the active site of members of the protein tyrosine phosphatase (PTP) superfamily renders these enzymes sensitive to reversible oxidation and inactivation [11].
  • Here, we present the set of 107 genes in the human genome that encode members of the four protein tyrosine phosphatase (PTP) families [12].
  • Using a positional cloning approach, we have identified at chromosome 6q24 a novel gene, EPM2A, that encodes a protein with consensus amino acid sequence indicative of a protein tyrosine phosphatase (PTP). mRNA transcripts representing alternatively spliced forms of EPM2A were found in every tissue examined, including brain [13].
  • One of these regulatory complexes, the 11S regulator (known as REG or PA28), stimulates proteasome peptidase activity and enhances the production of antigenic peptides for presentation by class I molecules of the major histocompatibility complex (MHC) [14].
  • The reliable construction of evolutionary trees from nucleotide sequences often depends on randomization tests such as the bootstrap and PTP (cladistic permutation tail probability) tests [15].

Chemical compound and disease context of REG1A


Biological context of REG1A


Anatomical context of REG1A


Associations of REG1A with chemical compounds

  • Effects of REG Ialpha protein on cell growth and H2O2-induced apoptosis in AGS cells were examined by 3,-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase nick-end labeling (TUNEL) assays, respectively [2].
  • A glycoprotein expressed in exocrine pancreas (where it has been called lithostathine) and endocrine pancreas (where it has been called the regeneration protein) is encoded by a gene (REG) which maps to 2p12 [26].
  • Among the eleven amino acids of the PSP S2-5 N-terminal extension Z-E-A-Q-T-E-L-P-Q-A-R, the first residue is an oxoproline and the fifth, a threonine, bears the single carbohydrate chain of the protein molecules [27].
  • Variations in the glycan chain composition account for the differences in the Mr of PSP S2-5 [27].
  • N-terminal sequence extension in the glycosylated forms of human pancreatic stone protein. The 5-oxoproline N-terminal chain is O-glycosylated on the 5th amino acid residue [27].

Other interactions of REG1A


Analytical, diagnostic and therapeutic context of REG1A


  1. Exocrine meets endocrine: pancreatic stone protein and regenerating protein--two sides of the same coin. Graf, R., Schiesser, M., Reding, T., Appenzeller, P., Sun, L.K., Fortunato, F., Perren, A., Bimmler, D. J. Surg. Res. (2006) [Pubmed]
  2. REG Ialpha protein may function as a trophic and/or anti-apoptotic factor in the development of gastric cancer. Sekikawa, A., Fukui, H., Fujii, S., Takeda, J., Nanakin, A., Hisatsune, H., Seno, H., Takasawa, S., Okamoto, H., Fujimori, T., Chiba, T. Gastroenterology (2005) [Pubmed]
  3. Death from early colorectal cancer is predicted by the presence of transcripts of the REG gene family. Macadam, R.C., Sarela, A.I., Farmery, S.M., Robinson, P.A., Markham, A.F., Guillou, P.J. Br. J. Cancer (2000) [Pubmed]
  4. Activated pancreatic enzyme and pancreatic stone protein (PSP/reg) in bile of patients with pancreaticobiliary maljunction/ choledochal cysts. Ochiai, K., Kaneko, K., Kitagawa, M., Ando, H., Hayakawa, T. Dig. Dis. Sci. (2004) [Pubmed]
  5. Combined 123I-FP-CIT and 123I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients. Plotkin, M., Amthauer, H., Klaffke, S., Kühn, A., Lüdemann, L., Arnold, G., Wernecke, K.D., Kupsch, A., Felix, R., Venz, S. Journal of neural transmission (Vienna, Austria : 1996) (2005) [Pubmed]
  6. Enhanced expression of an exocrine pancreatic protein in Alzheimer's disease and the developing human brain. de la Monte, S.M., Ozturk, M., Wands, J.R. J. Clin. Invest. (1990) [Pubmed]
  7. Which clinical features differentiate progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) from related disorders? A clinicopathological study. Litvan, I., Campbell, G., Mangone, C.A., Verny, M., McKee, A., Chaudhuri, K.R., Jellinger, K., Pearce, R.K., D'Olhaberriague, L. Brain (1997) [Pubmed]
  8. Deficits in long-term retention of learned motor skills in patients with cortical or subcortical degeneration. Mochizuki-Kawai, H., Kawamura, M., Hasegawa, Y., Mochizuki, S., Oeda, R., Yamanaka, K., Tagaya, H. Neuropsychologia. (2004) [Pubmed]
  9. Trigeminal sensory evoked potentials in patients with trigeminal neurinoma: report of two cases. Takayasu, M., Shibuya, M., Suzuki, Y., Harada, T., Kanamori, M., Kageyama, N. Neurosurgery (1987) [Pubmed]
  10. Increased regional brain concentrations of ceruloplasmin in neurodegenerative disorders. Loeffler, D.A., LeWitt, P.A., Juneau, P.L., Sima, A.A., Nguyen, H.U., DeMaggio, A.J., Brickman, C.M., Brewer, G.J., Dick, R.D., Troyer, M.D., Kanaley, L. Brain Res. (1996) [Pubmed]
  11. Redox redux: revisiting PTPs and the control of cell signaling. Tonks, N.K. Cell (2005) [Pubmed]
  12. Protein tyrosine phosphatases in the human genome. Alonso, A., Sasin, J., Bottini, N., Friedberg, I., Friedberg, I., Osterman, A., Godzik, A., Hunter, T., Dixon, J., Mustelin, T. Cell (2004) [Pubmed]
  13. Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy. Minassian, B.A., Lee, J.R., Herbrick, J.A., Huizenga, J., Soder, S., Mungall, A.J., Dunham, I., Gardner, R., Fong, C.Y., Carpenter, S., Jardim, L., Satishchandra, P., Andermann, E., Snead, O.C., Lopes-Cendes, I., Tsui, L.C., Delgado-Escueta, A.V., Rouleau, G.A., Scherer, S.W. Nat. Genet. (1998) [Pubmed]
  14. Structure of the proteasome activator REGalpha (PA28alpha). Knowlton, J.R., Johnston, S.C., Whitby, F.G., Realini, C., Zhang, Z., Rechsteiner, M., Hill, C.P. Nature (1997) [Pubmed]
  15. Confidence in evolutionary trees from biological sequence data. Steel, M.A., Lockhart, P.J., Penny, D. Nature (1993) [Pubmed]
  16. Retinoic acid stimulates erythropoietin gene transcription in embryonal carcinoma cells through the direct repeat of a steroid/thyroid hormone receptor response element half-site in the hypoxia-response enhancer. Kambe, T., Tada-Kambe, J., Kuge, Y., Yamaguchi-Iwai, Y., Nagao, M., Sasaki, R. Blood (2000) [Pubmed]
  17. Embryonal carcinoma P19 cells produce erythropoietin constitutively but express lactate dehydrogenase in an oxygen-dependent manner. Kambe, T., Tada, J., Chikuma, M., Masuda, S., Nagao, M., Tsuchiya, T., Ratcliffe, P.J., Sasaki, R. Blood (1998) [Pubmed]
  18. Expression of multiple heparin-binding growth factor species by murine embryonal carcinoma and embryonic stem cells. Heath, J.K., Paterno, G.D., Lindon, A.C., Edwards, D.R. Development (1989) [Pubmed]
  19. Human REG I gene is up-regulated in intrahepatic cholangiocarcinoma and its precursor lesions. Harada, K., Zen, Y., Kanemori, Y., Chen, T.C., Chen, M.F., Yeh, T.S., Jan, Y.Y., Masuda, S., Nimura, Y., Takasawa, S., Okamoto, H., Nakanuma, Y. Hepatology (2001) [Pubmed]
  20. Hyperglycemia potentiates collagen-induced platelet activation through mitochondrial superoxide overproduction. Yamagishi, S.I., Edelstein, D., Du, X.L., Brownlee, M. Diabetes (2001) [Pubmed]
  21. Cloning and expression analysis of an ovine PAP-like protein cDNA, a gene differentially expressed in scrapie. Skretting, G., Austbø, L., Olsaker, I., Espenes, A. Gene (2006) [Pubmed]
  22. Molecular cloning, expression and chromosomal localization of a novel human REG family gene, REG III. Nata, K., Liu, Y., Xu, L., Ikeda, T., Akiyama, T., Noguchi, N., Kawaguchi, S., Yamauchi, A., Takahashi, I., Shervani, N.J., Onogawa, T., Takasawa, S., Okamoto, H. Gene (2004) [Pubmed]
  23. Human regeneration protein/lithostathine genes map to chromosome 2p12. Gharib, B., Fox, M.F., Bartoli, C., Giorgi, D., Sansonetti, A., Swallow, D.M., Dagorn, J.C., Berge-lefranc, J.L. Ann. Hum. Genet. (1993) [Pubmed]
  24. Secretory pancreatic stone protein messenger RNA. Nucleotide sequence and expression in chronic calcifying pancreatitis. Giorgi, D., Bernard, J.P., Rouquier, S., Iovanna, J., Sarles, H., Dagorn, J.C. J. Clin. Invest. (1989) [Pubmed]
  25. Isolation, characterization, and distribution of an unusual pancreatic human secretory protein. Gross, J., Carlson, R.I., Brauer, A.W., Margolies, M.N., Warshaw, A.L., Wands, J.R. J. Clin. Invest. (1985) [Pubmed]
  26. A limited genomic region contains the human REG and REG-related genes. Bartoli, C., Dagorn, J.C., Fontes, M., Bergé-Lefranc, J.L. Eur. J. Hum. Genet. (1995) [Pubmed]
  27. N-terminal sequence extension in the glycosylated forms of human pancreatic stone protein. The 5-oxoproline N-terminal chain is O-glycosylated on the 5th amino acid residue. De Caro, A.M., Adrich, Z., Fournet, B., Capon, C., Bonicel, J.J., De Caro, J.D., Rovery, M. Biochim. Biophys. Acta (1989) [Pubmed]
  28. Two-dimensional protein database of human pancreas. Hu, L., Evers, S., Lu, Z.H., Shen, Y., Chen, J. Electrophoresis (2004) [Pubmed]
  29. Elevated levels of an exocrine pancreatic secretory protein in Alzheimer disease brain. Ozturk, M., de la Monte, S.M., Gross, J., Wands, J.R. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  30. The primary structure of coagulation factor IX/factor X-binding protein isolated from the venom of Trimeresurus flavoviridis. Homology with asialoglycoprotein receptors, proteoglycan core protein, tetranectin, and lymphocyte Fc epsilon receptor for immunoglobulin E. Atoda, H., Hyuga, M., Morita, T. J. Biol. Chem. (1991) [Pubmed]
  31. The amino-terminal domain of thrombomodulin and pancreatic stone protein are homologous with lectins. Petersen, T.E. FEBS Lett. (1988) [Pubmed]
  32. REG gene expression is associated with the infiltrating growth of gastric carcinoma. Yonemura, Y., Sakurai, S., Yamamoto, H., Endou, Y., Kawamura, T., Bandou, E., Elnemr, A., Sugiyama, K., Sasaki, T., Akiyama, T., Takasawa, S., Okamoto, H. Cancer (2003) [Pubmed]
  33. Expression of regenerating gene I in gastric adenocarcinomas: correlation with tumor differentiation status and patient survival. Dhar, D.K., Udagawa, J., Ishihara, S., Otani, H., Kinoshita, Y., Takasawa, S., Okamoto, H., Kubota, H., Fujii, T., Tachibana, M., Nagasue, N. Cancer (2004) [Pubmed]
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