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Gene Review

Reg3b  -  regenerating islet-derived 3 beta

Mus musculus

Synonyms: HIP, PAP1, Pancreatitis-associated protein 1, Pap, Pap1, ...
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Disease relevance of Pap


High impact information on Pap


Chemical compound and disease context of Pap


Biological context of Pap

  • 6. The data presented suggest regulation of pancreatitis-associated protein gene expression by both oxygen tension and iron status [2].
  • We provide evidence for the localization of HIP/PAP on chromosome 2, suggesting previous duplication of HIP/PAP and the related reg I alpha and reg I beta genes from the same ancestral gene [3].
  • Furthermore, the analysis of HIP/PAP gene indicates that the HIP/PAP CRD is encoded by four exons, a pattern shared with all members of this group of proteins [3].
  • The nucleotide sequences of cDNAs encoding human and mouse homologous for rat pancreatitis-associated protein (PAP) (J. Iovanna et al. (1991) J. Biol. Chem. 266, 24664-24669) were determined [13].
  • Similarly, pancreatitis-associated lung injury, as characterized by intrapulmonary sequestration of neutrophils and increased pulmonary microvascular permeability, was reduced in NK1R-/- animals [9].

Anatomical context of Pap


Associations of Pap with chemical compounds

  • The oxidative stress response is conserved through evolution, as green fluorescent protein-fused proteins bearing the Pap1 NES expressed in mammalian cells responded to diethyl maleate [10].
  • In support of this view, BEL-induced apoptosis is accompanied by a very strong inhibition of PAP-1-regulated events, such as incorporation of [3H]choline into phospholipids and de novo incorporation of [3H]arachidonic acid into triacylglycerol [14].
  • Deletion of the C-terminal cysteine-rich domain (CRD) resulted in nuclear accumulation of Pap1, while a glutathione S-transferase-green fluorescent protein-CRD fusion protein was localized in the cytoplasm in a Crm1-dependent manner [10].
  • However, propranolol, a PAP-1 inhibitor, is able to reproduce these effects, suggesting that it is the inhibition of PAP-1 and not of iPLA2 that is involved in BEL-induced cell death [14].
  • Blood glucose and insulin levels were measured, and a histologic and morphometric analysis of the pancreas was performed to determine the effect of INGAP peptide on the endocrine pancreas [11].

Regulatory relationships of Pap


Other interactions of Pap


Analytical, diagnostic and therapeutic context of Pap


  1. p8 improves pancreatic response to acute pancreatitis by enhancing the expression of the anti-inflammatory protein pancreatitis-associated protein I. Vasseur, S., Folch-Puy, E., Hlouschek, V., Garcia, S., Fiedler, F., Lerch, M.M., Dagorn, J.C., Closa, D., Iovanna, J.L. J. Biol. Chem. (2004) [Pubmed]
  2. Regulation of pancreatitis-associated protein (HIP/PAP) mRNA levels in mouse pancreas and small intestine. McKie, A.T., Simpson, R.J., Ghosh, S., Peters, T.J., Farzaneh, F. Clin. Sci. (1996) [Pubmed]
  3. Structural organization and chromosomal localization of a human gene (HIP/PAP) encoding a C-type lectin overexpressed in primary liver cancer. Lasserre, C., Simon, M.T., Ishikawa, H., Diriong, S., Nguyen, V.C., Christa, L., Vernier, P., Brechot, C. Eur. J. Biochem. (1994) [Pubmed]
  4. The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice. van Westerloo, D.J., Giebelen, I.A., Florquin, S., Bruno, M.J., Larosa, G.J., Ulloa, L., Tracey, K.J., van der Poll, T. Gastroenterology (2006) [Pubmed]
  5. Molecular cloning of a glibenclamide-sensitive, voltage-gated potassium channel expressed in rabbit kidney. Yao, X., Chang, A.Y., Boulpaep, E.L., Segal, A.S., Desir, G.V. J. Clin. Invest. (1996) [Pubmed]
  6. Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury. Ethridge, R.T., Chung, D.H., Slogoff, M., Ehlers, R.A., Hellmich, M.R., Rajaraman, S., Saito, H., Uchida, T., Evers, B.M. Gastroenterology (2002) [Pubmed]
  7. Cd40 ligand-deficient mice are protected against cerulein-induced acute pancreatitis and pancreatitis-associated lung injury. Frossard, J.L., Kwak, B., Chanson, M., Morel, P., Hadengue, A., Mach, F. Gastroenterology (2001) [Pubmed]
  8. The role of intercellular adhesion molecule 1 and neutrophils in acute pancreatitis and pancreatitis-associated lung injury. Frossard, J.L., Saluja, A., Bhagat, L., Lee, H.S., Bhatia, M., Hofbauer, B., Steer, M.L. Gastroenterology (1999) [Pubmed]
  9. Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury. Bhatia, M., Saluja, A.K., Hofbauer, B., Frossard, J.L., Lee, H.S., Castagliuolo, I., Wang, C.C., Gerard, N., Pothoulakis, C., Steer, M.L. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  10. A novel nuclear export signal sensitive to oxidative stress in the fission yeast transcription factor Pap1. Kudo, N., Taoka, H., Toda, T., Yoshida, M., Horinouchi, S. J. Biol. Chem. (1999) [Pubmed]
  11. A pentadecapeptide fragment of islet neogenesis-associated protein increases beta-cell mass and reverses diabetes in C57BL/6J mice. Rosenberg, L., Lipsett, M., Yoon, J.W., Prentki, M., Wang, R., Jun, H.S., Pittenger, G.L., Taylor-Fishwick, D., Vinik, A.I. Ann. Surg. (2004) [Pubmed]
  12. Complement factor C5a exerts an anti-inflammatory effect in acute pancreatitis and associated lung injury. Bhatia, M., Saluja, A.K., Singh, V.P., Frossard, J.L., Lee, H.S., Bhagat, L., Gerard, C., Steer, M.L. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  13. Cloning and tissue-specific expression of cDNAs for the human and mouse homologues of rat pancreatitis-associated protein (PAP). Itoh, T., Teraoka, H. Biochim. Biophys. Acta (1993) [Pubmed]
  14. Bromoenol lactone promotes cell death by a mechanism involving phosphatidate phosphohydrolase-1 rather than calcium-independent phospholipase A2. Fuentes, L., Pérez, R., Nieto, M.L., Balsinde, J., Balboa, M.A. J. Biol. Chem. (2003) [Pubmed]
  15. Neurite outgrowth in dorsal root ganglia induced by islet neogenesis-associated protein peptide involves protein kinase A activation. Tam, J., Rosenberg, L., Maysinger, D. Neuroreport (2006) [Pubmed]
  16. Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome. Jaffray, C., Yang, J., Carter, G., Mendez, C., Norman, J. Surgery (2000) [Pubmed]
  17. Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury. Bhatia, M., Slavin, J., Cao, Y., Basbaum, A.I., Neoptolemos, J.P. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  18. Treatment with antileukinate, a CXCR2 chemokine receptor antagonist, protects mice against acute pancreatitis and associated lung injury. Bhatia, M., Hegde, A. Regul. Pept. (2007) [Pubmed]
  19. Neutral endopeptidase determines the severity of pancreatitis-associated lung injury. Day, A.L., Wick, E., Jordan, T.H., Jaffray, C.E., Bunnett, N.W., Grady, E.F., Kirkwood, K.S. J. Surg. Res. (2005) [Pubmed]
  20. Inhibition of poly(ADP-ribose) polymerase attenuates the severity of acute pancreatitis and associated lung injury. Mota, R.A., Sánchez-Bueno, F., Saenz, L., Hernández-Espinosa, D., Jimeno, J., Tornel, P.L., Martínez-Torrano, A., Ramírez, P., Parrilla, P., Yélamos, J. Lab. Invest. (2005) [Pubmed]
  21. Blockade of interleukin 6 accelerates acinar cell apoptosis and attenuates experimental acute pancreatitis in vivo. Chao, K.C., Chao, K.F., Chuang, C.C., Liu, S.H. The British journal of surgery. (2006) [Pubmed]
  22. Pancreatic changes in TNBS-induced colitis in mice. Barthet, M., Dubucquoy, L., Garcia, S., Gasmi, M., Desreumaux, P., Colombel, J.F., Grimaud, J.C., Iovanna, J., Dagorn, J.C. Gastroenterol. Clin. Biol. (2003) [Pubmed]
  23. The effects of neutrophil depletion on a completely noninvasive model of acute pancreatitis-associated lung injury. Bhatia, M., Saluja, A.K., Hofbauer, B., Lee, H.S., Frossard, J.L., Steer, M.L. Int. J. Pancreatol. (1998) [Pubmed]
  24. Preclinical evaluation of the ribosome-inactivating proteins PAP-1, PAP-S and RTA in mice. Benigni, F., Canevari, S., Gadina, M., Adobati, E., Ferreri, A.J., Di Celle, E.F., Comolli, R., Colnaghi, M.I. Int. J. Immunopharmacol. (1995) [Pubmed]
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