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Gene Review

REG3A  -  regenerating islet-derived 3 alpha

Homo sapiens

Synonyms: HIP, HIP/PAP, Hepatointestinal pancreatic protein, Human proislet peptide, INGAP, ...
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Disease relevance of REG3A


Psychiatry related information on REG3A

  • The first is a 13-year-old Hispanic girl with severe RP, PAP, mental retardation and obesity (BMI >40) [5].
  • Increased serum pancreatitis associated protein (PAP) concentration after longterm alcohol consumption: further evidence for regular subclinical pancreatic damage after heavy drinking [6]?
  • Lithostathine and pancreatitis-associated protein are involved in the very early stages of Alzheimer's disease [7].
  • The measurement of transmural values allowed a reliable assessment of PAP changes occurring during apneas, and different degrees of such changes shown by different patients may be related to a host of factors relevant to wakefulness and sleep, including individual responsivity to hypoxic stimulus [8].
  • This review presents the possible involvement of 3'(2')-phosphoadenosine-5'-phosphate (PAP) phosphatase in the etiology of bipolar disorder and the mechanism of action of Li [9].

High impact information on REG3A


Chemical compound and disease context of REG3A


Biological context of REG3A


Anatomical context of REG3A

  • In Northern blot analysis the expression of the ovine PAP-like protein mRNA was restricted to the ileal and jejunal Peyer's patches [2].
  • PAP-like protein mRNA was detected in cells of the epithelial lining in most crypts and in some intestinal villi in the ileum and jejunum while in the colon and rectum, the PAP-like protein mRNA expression was only detected in the deep portion of a few crypts [2].
  • Taken overall, these results suggest that HIP/PAP protein may be of potential importance to liver cell differentiation/proliferation [3].
  • In addition, expression in pancreas of the genes encoding the human protein and rat PAP showed similar characteristics: both were expressed at very low levels in control tissue and overexpressed during the acute phase of pancreatitis, contrary to most secretory products [4].
  • The human PAP gene was mapped to chromosome 2p12 using rodent-human hybrid cells and in situ chromosomal hybridization [21].

Associations of REG3A with chemical compounds


Physical interactions of REG3A

  • PDX-1 binds directly to the INGAP promoter as determined in electromobility shift and antibody supershift assays [27].

Regulatory relationships of REG3A


Other interactions of REG3A


Analytical, diagnostic and therapeutic context of REG3A


  1. Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primary liver tumors with beta-catenin mutations. Cavard, C., Terris, B., Grimber, G., Christa, L., Audard, V., Radenen-Bussiere, B., Simon, M.T., Renard, C.A., Buendia, M.A., Perret, C. Oncogene (2006) [Pubmed]
  2. 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]
  3. HIP/PAP is an adhesive protein expressed in hepatocarcinoma, normal Paneth, and pancreatic cells. Christa, L., Carnot, F., Simon, M.T., Levavasseur, F., Stinnakre, M.G., Lasserre, C., Thepot, D., Clement, B., Devinoy, E., Brechot, C. Am. J. Physiol. (1996) [Pubmed]
  4. Human pancreatitis-associated protein. Messenger RNA cloning and expression in pancreatic diseases. Orelle, B., Keim, V., Masciotra, L., Dagorn, J.C., Iovanna, J.L. J. Clin. Invest. (1992) [Pubmed]
  5. Mutations in MKKS cause Bardet-Biedl syndrome. Slavotinek, A.M., Stone, E.M., Mykytyn, K., Heckenlively, J.R., Green, J.S., Heon, E., Musarella, M.A., Parfrey, P.S., Sheffield, V.C., Biesecker, L.G. Nat. Genet. (2000) [Pubmed]
  6. Increased serum pancreatitis associated protein (PAP) concentration after longterm alcohol consumption: further evidence for regular subclinical pancreatic damage after heavy drinking? Nordback, I., Jaakkola, M., Iovanna, J.L., Dagorn, J.C. Gut (1995) [Pubmed]
  7. Lithostathine and pancreatitis-associated protein are involved in the very early stages of Alzheimer's disease. Duplan, L., Michel, B., Boucraut, J., Barthellémy, S., Desplat-Jego, S., Marin, V., Gambarelli, D., Bernard, D., Berthézène, P., Alescio-Lautier, B., Verdier, J.M. Neurobiol. Aging (2001) [Pubmed]
  8. Transmural pressure measurements. Importance in the assessment of pulmonary hypertension in obstructive sleep apneas. Marrone, O., Bellia, V., Ferrara, G., Milone, F., Romano, L., Salvaggio, A., Stallone, A., Bonsignore, G. Chest (1989) [Pubmed]
  9. Possible role of 3'(2')-phosphoadenosine-5'-phosphate phosphatase in the etiology and therapy of bipolar disorder. Agam, G., Shaltiel, G. Prog. Neuropsychopharmacol. Biol. Psychiatry (2003) [Pubmed]
  10. Placental localization of human pregnancy--associated plasma proteins. Lin, T.M., Halbert, S.P. Science (1976) [Pubmed]
  11. Pentamidine-associated fatal acute pancreatitis. Zuger, A., Wolf, B.Z., el-Sadr, W., Simberkoff, M.S., Rahal, J.J. JAMA (1986) [Pubmed]
  12. Pancreatitis-associated arthritis. Sequential study of synovial fluid abnormalities. Hammond, J., Tesar, J. JAMA (1980) [Pubmed]
  13. Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte/macrophage colony-stimulating factor. Kitamura, T., Tanaka, N., Watanabe, J., Uchida, n.u.l.l., Kanegasaki, S., Yamada, Y., Nakata, K. J. Exp. Med. (1999) [Pubmed]
  14. Fibronectin in relation to growth patterns of fibrohistiocytic tumours--an immunohistochemical study of benign and malignant fibrous histiocytomas. Stiller, D., Bahn, H. Acta Histochem. (1987) [Pubmed]
  15. Acute pancreatitis associated with high-concentration lipid emulsion during total parenteral nutrition therapy for Crohn's disease. Lashner, B.A., Kirsner, J.B., Hanauer, S.B. Gastroenterology (1986) [Pubmed]
  16. Pancreatitis associated with isotretinoin-induced hypertriglyceridemia. Flynn, W.J., Freeman, P.G., Wickboldt, L.G. Ann. Intern. Med. (1987) [Pubmed]
  17. Effective immunochemotherapy of CALLA+C mu+ human pre-B acute lymphoblastic leukemia in mice with severe combined immunodeficiency using B43 (anti-CD19) pokeweed antiviral protein immunotoxin plus cyclophosphamide. Uckun, F.M., Chelstrom, L.M., Finnegan, D., Tuel-Ahlgren, L., Manivel, C., Irvin, J.D., Myers, D.E., Gunther, R. Blood (1992) [Pubmed]
  18. Reg2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post-hepatectomy in mice. Lieu, H.T., Simon, M.T., Nguyen-Khoa, T., Kebede, M., Cortes, A., Tebar, L., Smith, A.J., Bayne, R., Hunt, S.P., Br??chot, C., Christa, L. Hepatology (2006) [Pubmed]
  19. HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice. Lieu, H.T., Batteux, F., Simon, M.T., Cortes, A., Nicco, C., Zavala, F., Pauloin, A., Tralhao, J.G., Soubrane, O., Weill, B., Bréchot, C., Christa, L. Hepatology (2005) [Pubmed]
  20. The human pancreatitis-associated protein (PAP)-encoding gene generates multiple transcripts through alternative use of 5' exons. Itoh, T., Sawabu, N., Motoo, Y., Funakoshi, A., Teraoka, H. Gene (1995) [Pubmed]
  21. Molecular cloning, genomic organization, and chromosomal localization of the human pancreatitis-associated protein (PAP) gene. Dusetti, N.J., Frigerio, J.M., Fox, M.F., Swallow, D.M., Dagorn, J.C., Iovanna, J.L. Genomics (1994) [Pubmed]
  22. HIP/PAP stimulates liver regeneration after partial hepatectomy and combines mitogenic and anti-apoptotic functions through the PKA signaling pathway. Simon, M.T., Pauloin, A., Normand, G., Lieu, H.T., Mouly, H., Pivert, G., Carnot, F., Tralhao, J.G., Brechot, C., Christa, L. FASEB J. (2003) [Pubmed]
  23. Pancreatitis associated protein I (PAP-I) alters adhesion and motility of human melanocytes and melanoma cells. Valery, C., Vasseur, S., Sabatier, F., Iovanna, J.L., Dagorn, J.C., Grob, J.J., Verrando, P. J. Invest. Dermatol. (2001) [Pubmed]
  24. Characterization of platelet agglutinating protein p37 purified from the plasma of a patient with thrombotic thrombocytopenic purpura. Siddiqui, F.A., Lian, E.C. Biochem. Mol. Biol. Int. (1993) [Pubmed]
  25. Pancreatitis associated with ondansetron. Alberti-Flor, J.J. J. Natl. Cancer Inst. (1995) [Pubmed]
  26. Failure of glucagon in the treatment of alcoholic pancreatitis. Olazabal, A., Fuller, R. Gastroenterology (1978) [Pubmed]
  27. PDX-1 can repress stimulus-induced activation of the INGAP promoter. Taylor-Fishwick, D.A., Shi, W., Pittenger, G.L., Vinik, A.I. J. Endocrinol. (2006) [Pubmed]
  28. Opposite roles of human pancreatitis-associated protein and REG1A expression in hepatocellular carcinoma: association of pancreatitis-associated protein expression with low-stage hepatocellular carcinoma, beta-catenin mutation, and favorable prognosis. Yuan, R.H., Jeng, Y.M., Chen, H.L., Hsieh, F.J., Yang, C.Y., Lee, P.H., Hsu, H.C. Clin. Cancer Res. (2005) [Pubmed]
  29. Development of an in vitro pancreatic tissue model to study regulation of islet neogenesis associated protein expression. Petropavlovskaia, M., Makhlin, J., Sampalis, J., Rosenberg, L. J. Endocrinol. (2006) [Pubmed]
  30. Protective effects of probucol treatment on pancreatic beta-cell function of SZ-induced diabetic APA hamsters. Takatori, A., Ohta, E., Inenaga, T., Horiuchi, K., Ishii, Y., Itagaki, S., Kyuwa, S., Yoshikawa, Y. Exp. Anim. (2003) [Pubmed]
  31. Chymotrypsin C (caldecrin) stimulates autoactivation of human cationic trypsinogen. Nemoda, Z., Sahin-Tóth, M. J. Biol. Chem. (2006) [Pubmed]
  32. Cystic fibrosis gene mutations and pancreatitis risk: relation to epithelial ion transport and trypsin inhibitor gene mutations. Noone, P.G., Zhou, Z., Silverman, L.M., Jowell, P.S., Knowles, M.R., Cohn, J.A. Gastroenterology (2001) [Pubmed]
  33. Interaction between trypsinogen isoforms in genetically determined pancreatitis: mutation E79K in cationic trypsin (PRSS1) causes increased transactivation of anionic trypsinogen (PRSS2). Teich, N., Le Maréchal, C., Kukor, Z., Caca, K., Witzigmann, H., Chen, J.M., Tóth, M., Mössner, J., Keim, V., Férec, C., Sahin-Tóth, M. Hum. Mutat. (2004) [Pubmed]
  34. Presence of cathepsin B in the human pancreatic secretory pathway and its role in trypsinogen activation during hereditary pancreatitis. Kukor, Z., Mayerle, J., Krüger, B., Tóth, M., Steed, P.M., Halangk, W., Lerch, M.M., Sahin-Tóth, M. J. Biol. Chem. (2002) [Pubmed]
  35. Human pregnancy-associated plasma proteins during the postpartum period. Lin, T.M., Halbert, S.P., Spellacy, W.N., Gall, S. Am. J. Obstet. Gynecol. (1976) [Pubmed]
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