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Gene Review

PDAP1  -  PDGFA associated protein 1

Homo sapiens

Synonyms: 28 kDa heat-and acid-stable phosphoprotein, HASPP28, PAP, PAP1, PDGF-associated protein, ...
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Disease relevance of PDAP1


Psychiatry related information on PDAP1

  • The PDAPP transgenic mouse, which overexpresses mutant human APP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallmarks of Alzheimer's disease in an age- and brain-region-dependent manner [5].
  • Age-independent and age-related deficits in visuospatial learning, sleep-wake states, thermoregulation and motor activity in PDAPP mice [6].
  • Aged PDAPP mice also showed an increase in the amount of time spent in W and a reduction in REM sleep during the dark period [6].
  • 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 [7].
  • 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 [8].

High impact information on PDAP1

  • Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse [5].
  • Monospecific rabbit antiserums to PAPP-A, PAPP-C and hCS all stained the trophoblast cytoplasm equivalently in a continuous layer, usggesting that the same trophoblast cells synthesize all three pregnancy proteins [9].
  • We first measured hippocampal acetylcholine (ACh) release in young, freely moving PDAPP mice, a well-characterized transgenic mouse model of AD, and found marked A beta-dependent alterations in both basal and evoked ACh release compared with WT controls [10].
  • Pulmonary alveolar proteinosis (PAP) is a heterogeneous disorder of genetic or acquired etiologies [11].
  • Overall, the apparent order of prognostic reliability for disease progression was found to be PA greater than PAP greater than BAP greater than AcP greater than TAP [12].

Chemical compound and disease context of PDAP1

  • We used this SCID mouse model of human pre-B ALL to evaluate and compare, in a total of 434 SCID mice, the antileukemic efficacy of B43 (anti-CD19)-pokeweed antiviral protein (PAP) immunotoxin and cyclophosphamide (CPA) as individual reagents and as combined immunochemotherapeutic regimens [13].
  • HIP/PAP transgenic mice were protected against acetaminophen-induced acute liver failure and were stimulated to regenerate post-hepatectomy [14].
  • Estrogen therapy fails to alter amyloid deposition in the PDAPP model of Alzheimer's disease [15].
  • While neither low nor high doses of DHAS and PAP exerted any significant influence on the incidence of ductal lesions including carcinomas, the high dose of DHAS (350 mg/kg body wt) and a both low (90 mg/kg) and high (180 mg/kg) doses of PAP reduced the mean numbers of pancreatic ductal adenocarcinomas [16].
  • We found some correlation between CPK-BB and androgen cytosolic receptors as well as between PAP content and androgen cytosolic receptors in patients with benign hyperplasia [17].

Biological context of PDAP1

  • PAP-2 contains two clip domains at its amino terminus and a catalytic domain at its carboxyl terminus, whereas PAP-1 has only one clip domain [18].
  • Pap1 and Pap2 are more similar to each other (84% amino acid sequence identity) than to Pap3 (46% and 44%, respectively) in the encoded mature proteins [19].
  • Here we showed that in cultured human vascular smooth muscle cells (SMC), the PKC stimulator phorbol 12-myristate 13-acetate (PMA) inhibited [(3)H]thymidine incorporation in response to the growth factor PDGF associated with downregulation of PDGFbeta (but not alpha) receptors, which was recovered to normal level after PKC was depleted [20].
  • The observed results are in agreement with the concentration-dependent kinetics of hPAP reactivation, assuming that the reconstitution of the active enzyme requires the association of subunits in dimeric form [21].
  • In an effort to understand the transcriptional regulation, we isolated a genomic clone of the PAP-1 gene, determined its nucleotide sequence, and elucidated its exon-intron organization [22].

Anatomical context of PDAP1


Associations of PDAP1 with chemical compounds

  • Manduca sexta PAP-1, the final component of a serine proteinase cascade, cleaves proPO to generate active PO [22].
  • Human prostatic acid phosphatase (hPAP) [EC], a homodimer of ca. 50 kDa subunit molecular weight, shows reversible denaturation in 6 M urea at pH 2 [21].
  • Treatment of PDAPP mice with the anti-A beta antibody m266 rapidly and completely restored hippocampal ACh release and high-affinity choline uptake while greatly reducing impaired habituation learning that is characteristic of these mice [10].
  • In contrast, correlations were noted between PS-positive erythrocytes and F1.2 (P <.0002), D-dimer (P <.000002), and PAP (P <.01) [26].
  • Estradiol reduced the levels of PAP in sera from untreated male mice regardless of the tumor weight [27].

Other interactions of PDAP1


Analytical, diagnostic and therapeutic context of PDAP1


  1. Antiproliferative effect of trapidil on PDGF-associated growth of human glioma cell lines in vitro. Tada, M., Aida, T., Hosokawa, M., Kobayashi, H., Sawamura, Y., Abe, H. Neurol. Med. Chir. (Tokyo) (1991) [Pubmed]
  2. 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]
  3. Radioimmunodetection of prostatic cancer. In vivo use of radioactive antibodies against prostatic acid phosphatase for diagnosis and detection of prostatic cancer by nuclear imaging. Goldenberg, D.M., DeLand, F.H., Bennett, S.J., Primus, F.J., Nelson, M.O., Flanigan, R.C., McRoberts, J.W., Bruce, A.W., Mahan, D.E. JAMA (1983) [Pubmed]
  4. 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]
  5. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Liao, Z., Lieberburg, I., Motter, R., Mutter, L., Soriano, F., Shopp, G., Vasquez, N., Vandevert, C., Walker, S., Wogulis, M., Yednock, T., Games, D., Seubert, P. Nature (1999) [Pubmed]
  6. Age-independent and age-related deficits in visuospatial learning, sleep-wake states, thermoregulation and motor activity in PDAPP mice. Huitrón-Reséndiz, S., Sánchez-Alavez, M., Gallegos, R., Berg, G., Crawford, E., Giacchino, J.L., Games, D., Henriksen, S.J., Criado, J.R. Brain Res. (2002) [Pubmed]
  7. 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]
  8. 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]
  9. Placental localization of human pregnancy--associated plasma proteins. Lin, T.M., Halbert, S.P. Science (1976) [Pubmed]
  10. Cholinergic dysfunction in a mouse model of Alzheimer disease is reversed by an anti-A beta antibody. Bales, K.R., Tzavara, E.T., Wu, S., Wade, M.R., Bymaster, F.P., Paul, S.M., Nomikos, G.G. J. Clin. Invest. (2006) [Pubmed]
  11. Human pulmonary alveolar proteinosis associated with a defect in GM-CSF/IL-3/IL-5 receptor common beta chain expression. Dirksen, U., Nishinakamura, R., Groneck, P., Hattenhorst, U., Nogee, L., Murray, R., Burdach, S. J. Clin. Invest. (1997) [Pubmed]
  12. Relative reliability of five serially measured markers for prognosis of progression in prostate cancer. Killian, C.S., Emrich, L.J., Vargas, F.P., Yang, N., Wang, M.C., Priore, R.L., Murphy, G.P., Chu, T.M. J. Natl. Cancer Inst. (1986) [Pubmed]
  13. 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]
  14. 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]
  15. Estrogen therapy fails to alter amyloid deposition in the PDAPP model of Alzheimer's disease. Green, P.S., Bales, K., Paul, S., Bu, G. Endocrinology (2005) [Pubmed]
  16. Inhibitory effects of sulfation inhibitors on initiation of pancreatic ductal carcinogenesis by N-nitrosobis(2-oxopropyl)amine in hamsters. Tsutsumi, M., Noguchi, O., Okita, S., Horiguchi, K., Kobayashi, E., Tamura, K., Tsujiuchi, T., Denda, A., Konishi, Y., Iimura, K. Carcinogenesis (1995) [Pubmed]
  17. Creatine phosphokinase isoenzymes in human prostatic tissues: a comparison between benign hyperplasia and adenocarcinoma. Truong, T., Carmel, M., Elhilali, M., Cloutier, D., Lehoux, J.G. Prostate (1985) [Pubmed]
  18. Prophenoloxidase-activating proteinase-2 from hemolymph of Manduca sexta. A bacteria-inducible serine proteinase containing two clip domains. Jiang, H., Wang, Y., Yu, X.Q., Kanost, M.R. J. Biol. Chem. (2003) [Pubmed]
  19. Brassica rapa has three genes that encode proteins associated with different neutral lipids in plastids of specific tissues. Kim, H.U., Wu, S.S., Ratnayake, C., Huang, A.H. Plant Physiol. (2001) [Pubmed]
  20. Phorbol ester downregulates PDGFbeta receptor via PKCbeta1 in vascular smooth muscle cells. Yang, Z., Huerlimann, D.A., Viswambharan, H., Luescher, T.F. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  21. The folding intermediate of reversibly denatured human prostatic acid phosphatase. Kuciel, R., Mazurkiewicz, A., Ostrowski, W.S. Int. J. Biol. Macromol. (1996) [Pubmed]
  22. Manduca sexta prophenoloxidase activating proteinase-1 (PAP-1) gene: organization, expression, and regulation by immune and hormonal signals. Zou, Z., Wang, Y., Jiang, H. Insect Biochem. Mol. Biol. (2005) [Pubmed]
  23. Prophenoloxidase-activating proteinase-3 (PAP-3) from Manduca sexta hemolymph: a clip-domain serine proteinase regulated by serpin-1J and serine proteinase homologs. Jiang, H., Wang, Y., Yu, X.Q., Zhu, Y., Kanost, M. Insect Biochem. Mol. Biol. (2003) [Pubmed]
  24. Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Beeton, C., Wulff, H., Standifer, N.E., Azam, P., Mullen, K.M., Pennington, M.W., Kolski-Andreaco, A., Wei, E., Grino, A., Counts, D.R., Wang, P.H., Leehealey, C.J., S Andrews, B., Sankaranarayanan, A., Homerick, D., Roeck, W.W., Tehranzadeh, J., Stanhope, K.L., Zimin, P., Havel, P.J., Griffey, S., Knaus, H.G., Nepom, G.T., Gutman, G.A., Calabresi, P.A., Chandy, K.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  25. Amyloid deposition in the hippocampus and entorhinal cortex: quantitative analysis of a transgenic mouse model. Reilly, J.F., Games, D., Rydel, R.E., Freedman, S., Schenk, D., Young, W.G., Morrison, J.H., Bloom, F.E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  26. Thrombophilia in sickle cell disease: the red cell connection. Setty, B.N., Rao, A.K., Stuart, M.J. Blood (2001) [Pubmed]
  27. Hormone dependency of a serially transplantable human prostatic cancer (HONDA) in nude mice. Ito, Y.Z., Mashimo, S., Nakazato, Y., Takikawa, H. Cancer Res. (1985) [Pubmed]
  28. Identification of processing events in the synthesis of platelet-derived growth factor-like proteins by human osteosarcoma cells. Graves, D.T., Owen, A.J., Williams, S.R., Antoniades, H.N. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  29. Negative regulation of prophenoloxidase (proPO) activation by a clip-domain serine proteinase homolog (SPH) from endoparasitoid venom. Zhang, G., Lu, Z.Q., Jiang, H., Asgari, S. Insect Biochem. Mol. Biol. (2004) [Pubmed]
  30. Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease. Johnson-Wood, K., Lee, M., Motter, R., Hu, K., Gordon, G., Barbour, R., Khan, K., Gordon, M., Tan, H., Games, D., Lieberburg, I., Schenk, D., Seubert, P., McConlogue, L. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  31. Neuropathology and pathogenesis of encephalitis following amyloid-beta immunization in Alzheimer's disease. Ferrer, I., Boada Rovira, M., Sánchez Guerra, M.L., Rey, M.J., Costa-Jussá, F. Brain Pathol. (2004) [Pubmed]
  32. LRP and senile plaques in Alzheimer's disease: colocalization with apolipoprotein E and with activated astrocytes. Arélin, K., Kinoshita, A., Whelan, C.M., Irizarry, M.C., Rebeck, G.W., Strickland, D.K., Hyman, B.T. Brain Res. Mol. Brain Res. (2002) [Pubmed]
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