The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PAPPA  -  pregnancy-associated plasma protein A,...

Homo sapiens

Synonyms: ASBABP2, DIPLA1, IGF-dependent IGFBP-4 protease, IGFBP-4ase, Insulin-like growth factor-dependent IGF-binding protein 4 protease, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PAPPA


High impact information on PAPPA


Chemical compound and disease context of PAPPA


Biological context of PAPPA


Anatomical context of PAPPA


Associations of PAPPA with chemical compounds


Physical interactions of PAPPA


Enzymatic interactions of PAPPA

  • PAPP-A specifically cleaves IGF-binding protein (IGFBP)-4, one of six antagonists of IGF action, which results in release of IGF bound to IGFBP-4 [25].
  • Herein, we first determined that PAPP-A cleaves IGFBP-4 at a single site (Met-135/Lys-136), and we analysed the influence of ionic strength, pH and zinc ion concentration on the cleavage reaction [26].

Co-localisations of PAPPA


Regulatory relationships of PAPPA

  • Proteolysis of radiolabeled IGFBP-4 in conditioned media from OSE(tsT) lines was IGF-dependent and blocked by anti-PAPP-A antisera [27].
  • On the other hand, interferon-gamma (IFN gamma) treatment markedly inhibited PAPP-A expression [17].
  • Purified PAPP-A protein directly up-regulated runt-related transcription factor 2 and Igf-I gene expression but not Osterix [28].
  • Interestingly, pretreatment of hCASMC with resveratrol, a polyphenol found in the skin of grapes and in red wine purported to underlie the "French paradox," inhibited TNF-alpha- and IL-1beta-induced PAPP-A expression and, hence, its IGFBP-4 proteolytic activity [4].
  • CONCLUSIONS: Elevated serum PAPP-A levels represent a potential marker of the degree of echogenicity of carotid atherosclerotic plaques in asymptomatic hyperlipidemic patients at high cardiovascular risk and equally of an enhanced local inflammatory state involving remodeling of subendothelial extracellular matrix [29].

Other interactions of PAPPA


Analytical, diagnostic and therapeutic context of PAPPA

  • Short-term ovarian tumor cell cultures expressed variable levels of PAPP-A and high levels of proMBP, and consequently secreted little or no IGFBP-4 protease activity [27].
  • Coculture of fibroblasts with cells transfected with pro-MBP cDNA resulted in inhibition of IGFBP-4 proteolytic activity without having any effect on PAPP-A synthesis [3].
  • Using flow cytometry, we first demonstrate that PAPP-A reversibly binds to the cell surface of several cell types analyzed [21].
  • PAPP-A mRNA levels were the same in control and Dex-treated cultures as evaluated by RT-PCR [32].
  • PAPP-A mRNA was quantified by real-time PCR, and PAPP-A protein expression was studied by immunocytochemistry and TRACE technology with specific monoclonal antibodies [33].


  1. Characterization of the common fragile site FRA9E and its potential role in ovarian cancer. Callahan, G., Denison, S.R., Phillips, L.A., Shridhar, V., Smith, D.I. Oncogene (2003) [Pubmed]
  2. Assignment of the human gene for pregnancy-associated plasma protein A (PAPPA) to 9q33.1 by fluorescence in situ hybridization to mitotic and meiotic chromosomes. Silahtaroglu, A.N., Tümer, Z., Kristensen, T., Sottrup-Jensen, L., Tommerup, N. Cytogenet. Cell Genet. (1993) [Pubmed]
  3. Molecular regulation of the IGF-binding protein-4 protease system in human fibroblasts: identification of a novel inducible inhibitor. Chen, B.K., Overgaard, M.T., Bale, L.K., Resch, Z.T., Christiansen, M., Oxvig, C., Conover, C.A. Endocrinology (2002) [Pubmed]
  4. Cytokine stimulation of pregnancy-associated plasma protein A expression in human coronary artery smooth muscle cells: inhibition by resveratrol. Conover, C.A., Bale, L.K., Harrington, S.C., Resch, Z.T., Overgaard, M.T., Oxvig, C. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  5. Genetic downregulation of pregnancy-associated plasma protein-A (PAPP-A) by bikunin reduces IGF-I-dependent Akt and ERK1/2 activation and subsequently reduces ovarian cancer cell growth, invasion and metastasis. Tanaka, Y., Kobayashi, H., Suzuki, M., Hirashima, Y., Kanayama, N., Terao, T. Int. J. Cancer (2004) [Pubmed]
  6. Integrated screening for Down's syndrome on the basis of tests performed during the first and second trimesters. Wald, N.J., Watt, H.C., Hackshaw, A.K. N. Engl. J. Med. (1999) [Pubmed]
  7. Placental localization of human pregnancy--associated plasma proteins. Lin, T.M., Halbert, S.P. Science (1976) [Pubmed]
  8. Elevated insulin receptor content in human breast cancer. Papa, V., Pezzino, V., Costantino, A., Belfiore, A., Giuffrida, D., Frittitta, L., Vannelli, G.B., Brand, R., Goldfine, I.D., Vigneri, R. J. Clin. Invest. (1990) [Pubmed]
  9. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Lawrence, J.B., Oxvig, C., Overgaard, M.T., Sottrup-Jensen, L., Gleich, G.J., Hays, L.G., Yates, J.R., Conover, C.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  10. Expression of haptoglobin-related protein and its potential role as a tumor antigen. Kuhajda, F.P., Katumuluwa, A.I., Pasternack, G.R. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  11. Pregnancy-associated plasma protein A in the human endometrium is dependent on the effect of progesterone. Sjöberg, J., Wahlström, T., Seppälä, M. J. Clin. Endocrinol. Metab. (1984) [Pubmed]
  12. The clinical course of multiple sclerosis during pregnancy and the puerperium. Birk, K., Ford, C., Smeltzer, S., Ryan, D., Miller, R., Rudick, R.A. Arch. Neurol. (1990) [Pubmed]
  13. Increased levels of pregnancy-associated plasma protein-A in patients with hypercholesterolemia: the effect of atorvastatin treatment. Stulc, T., Malbohan, I., Malík, J., Fialová, L., Soukupová, J., Ceska, R. Am. Heart J. (2003) [Pubmed]
  14. Placenta-associated plasma protein-A (PAPP-A, SP4) in trophoblastic tumours. Wahlström, T., Teisner, B., Lee, J.N., Grudzinskas, J.G., Seppälä, M., Folkersen, J. Acta pathologica et microbiologica Scandinavica. Section A, Pathology. (1981) [Pubmed]
  15. Pregnancy-associated plasma protein-A gene expression in human ovaries is restricted to healthy follicles and corpora lutea. Hourvitz, A., Widger, A.E., Filho, F.L., Chang, R.J., Adashi, E.Y., Erickson, G.F. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  16. Localization and regulation of pregnancy-associated plasma protein a expression in healing human skin. Chen, B.K., Leiferman, K.M., Pittelkow, M.R., Overgaard, M.T., Oxvig, C., Conover, C.A. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  17. Pregnancy-associated plasma protein a gene expression as a target of inflammatory cytokines. Resch, Z.T., Chen, B.K., Bale, L.K., Oxvig, C., Overgaard, M.T., Conover, C.A. Endocrinology (2004) [Pubmed]
  18. Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment. Overgaard, M.T., Sorensen, E.S., Stachowiak, D., Boldt, H.B., Kristensen, L., Sottrup-Jensen, L., Oxvig, C. J. Biol. Chem. (2003) [Pubmed]
  19. Pregnancy-associated plasma protein A proteolytic activity is associated with the human placental trophoblast cell membrane. Sun, I.Y., Overgaard, M.T., Oxvig, C., Giudice, L.C. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  20. Pregnancy-associated plasma protein-a is the insulin-like growth factor binding protein-4 protease secreted by human ovarian granulosa cells and is a marker of dominant follicle selection and the corpus luteum. Conover, C.A., Faessen, G.F., Ilg, K.E., Chandrasekher, Y.A., Christiansen, M., Overgaard, M.T., Oxvig, C., Giudice, L.C. Endocrinology (2001) [Pubmed]
  21. Cell surface targeting of pregnancy-associated plasma protein A proteolytic activity. Reversible adhesion is mediated by two neighboring short consensus repeats. Laursen, L.S., Overgaard, M.T., Weyer, K., Boldt, H.B., Ebbesen, P., Christiansen, M., Sottrup-Jensen, L., Giudice, L.C., Oxvig, C. J. Biol. Chem. (2002) [Pubmed]
  22. Evidence that the insulin-like growth factor binding protein-4 protease in human ovarian follicular fluid is pregnancy associated plasma protein-A. Conover, C.A., Oxvig, C., Overgaard, M.T., Christiansen, M., Giudice, L.C. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  23. Pregnancy-associated plasma protein-A accounts for the insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4) proteolytic activity in human pregnancy serum and enhances the mitogenic activity of IGF by degrading IGFBP-4 in vitro. Byun, D., Mohan, S., Yoo, M., Sexton, C., Baylink, D.J., Qin, X. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  24. Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis. Heeschen, C., Dimmeler, S., Hamm, C.W., Fichtlscherer, S., Simoons, M.L., Zeiher, A.M. J. Am. Coll. Cardiol. (2005) [Pubmed]
  25. Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor. Overgaard, M.T., Haaning, J., Boldt, H.B., Olsen, I.M., Laursen, L.S., Christiansen, M., Gleich, G.J., Sottrup-Jensen, L., Conover, C.A., Oxvig, C. J. Biol. Chem. (2000) [Pubmed]
  26. Substrate specificity of the metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) assessed by mutagenesis and analysis of synthetic peptides: substrate residues distant from the scissile bond are critical for proteolysis. Laursen, L.S., Overgaard, M.T., Nielsen, C.G., Boldt, H.B., Hopmann, K.H., Conover, C.A., Sottrup-Jensen, L., Giudice, L.C., Oxvig, C. Biochem. J. (2002) [Pubmed]
  27. Pregnancy-associated plasma protein-A (PAPP-A) expression and insulin-like growth factor binding protein-4 protease activity in normal and malignant ovarian surface epithelial cells. Kalli, K.R., Chen, B.K., Bale, L.K., Gernand, E., Overgaard, M.T., Oxvig, C., Cliby, W.A., Conover, C.A. Int. J. Cancer (2004) [Pubmed]
  28. Pregnancy-associated plasma protein-a is involved in matrix mineralization of human adult mesenchymal stem cells and angiogenesis in the chick chorioallontoic membrane. Jadlowiec, J., Dongell, D., Smith, J., Conover, C., Campbell, P. Endocrinology (2005) [Pubmed]
  29. Serum plasma pregnancy-associated protein A: a potential marker of echogenic carotid atherosclerotic plaques in asymptomatic hyperlipidemic subjects at high cardiovascular risk. Beaudeux, J.L., Burc, L., Imbert-Bismut, F., Giral, P., Bernard, M., Bruckert, E., Chapman, M.J. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  30. Insulin-like growth factor, insulin-like growth factor-binding protein-4, and pregnancy-associated plasma protein-A gene expression in human granulosa cell tumors. Alexiadis, M., Mamers, P., Chu, S., Fuller, P.J. Int. J. Gynecol. Cancer (2006) [Pubmed]
  31. Identification of two novel human genes, DIPLA1 and DIPAS, expressed in placenta tissue. García, J., Castrillo, J.L. Gene (2005) [Pubmed]
  32. Pregnancy-associated plasma protein-A proteolytic activity in rat vertebral cell cultures: stimulation by dexamethasone--a potential mechanism for glucocorticoid regulation of osteoprogenitor proliferation and differentiation. Jia, D., Heersche, J.N. J. Cell. Physiol. (2005) [Pubmed]
  33. Expression of pregnancy-associated plasma protein-A (PAPP-A) during human villous trophoblast differentiation in vitro. Guibourdenche, J., Frendo, J.L., Pidoux, G., Bertin, G., Luton, D., Muller, F., Porquet, D., Evain-Brion, D. Placenta (2003) [Pubmed]
WikiGenes - Universities