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Gene Review

ASAP2  -  ArfGAP with SH3 domain, ankyrin repeat and...

Homo sapiens

Synonyms: AMAP2, Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2, CENTB3, DDEF2, Development and differentiation-enhancing factor 2, ...
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Disease relevance of DDEF2


Psychiatry related information on DDEF2

  • 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 [5].
  • 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 [6].
  • Therefore, participation in physical activity programs (PAP) may reduce health care costs [7].
  • Physiological data (VO2peak, height, and weight), psychological data (physical self-perception profile subscale scores), information about physical activity participation (PAP, d x wk(-1)) and qualitative impressions (QI) of the program were collected pre- and post-intervention [8].

High impact information on DDEF2

  • 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 propose that PAG3 acts as a GAP for ARF6 and is hence involved in FcgammaR-mediated phagocytosis in mouse macrophages [10].
  • Overexpression of PAG3, but not its GAP-inactive mutant, attenuated the focal accumulation of F-actin and blocked phagocytosis, although surface levels of the FcgammaRs were not affected [10].
  • Northern blot analysis of various carcinomas and normal human tissues revealed an over expression of PAP in cancer tissues [4].
  • We also measured activation of thrombin: thrombin-antithrombin III (TAT), prothrombin fragment 1 + 2 (F1 + 2), and fibrinopeptide A (FPA) as well as markers of fibrinolysis: plasmin-alpha 2-antiplasmin (PAP) and D-dimer [11].

Chemical compound and disease context of DDEF2

  • 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 [12].
  • HIP/PAP transgenic mice were protected against acetaminophen-induced acute liver failure and were stimulated to regenerate post-hepatectomy [13].
  • 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 [14].
  • Using the PAP method, localization of the calcineurin in formalin-fixed, paraffin-embedded tissues were studied in 65 human intracranial neoplasms, and in 11 human extracranial neoplasms [15].
  • In 3 patients with acute myeloblastic leukemia, APL and pancreatic cancer, respectively, the PAP level remained high during heparin therapy although the TAT level was decreased [16].

Biological context of DDEF2


Anatomical context of DDEF2


Associations of DDEF2 with chemical compounds


Physical interactions of DDEF2

  • PAG3 bound to all paxillin isoforms and was induced during monocyte maturation, at which time paxillin expression is also increased and integrins are activated [17].

Other interactions of DDEF2

  • We also examined possible interaction of PAG3 with ARFs and showed evidence that at least one of them, ARF6, seems to be an intracellular substrate for GAP activity of PAG3 [17].
  • PAG3 was identical to KIAA0400/Papalpha, which was previously identified as a Pyk2-binding protein bearing a GAP activity toward several ARFs in vitro [17].
  • We have found that two ArfGAPs, namely AMAP1 and AMAP2, exhibit a novel biochemical property of directly and selectively binding to GTP-Arf6 without immediate GAPing activity, while they were previously shown to exhibit efficient catalytic GAPing activities to Arf isoforms except Arf6 in vitro [29].
  • Internalization of Tac, but not transferrin, was also significantly inhibited by AMAP2 silencing and overexpression [25].

Analytical, diagnostic and therapeutic context of DDEF2

  • Among the differentially expressed genes, SPA17 and DDEF2 were further validated using quantitative real time RT-PCR (qPCR) in a series of 25 prostate tumor samples [18].
  • Frozen sections of human placenta were examined for the presence of four human pregnancy proteins, pregnancy-associated plasma proteins A and C (PAPP-A and PAPP-C), human chorionic somatomammotropin (hCS), and pregnancy zone protein (PZP), by the indirect immunofluorescence technique [9].
  • The complex formation was demonstrated by the binding of fluid-phase IgG from normal adults and the same TTP patient after recovery to adsorbed PAP by using an enzyme-linked immunosorbent assay [30].
  • Further, antibody-PAP conjugate was separated from PAP by differential precipitation using polyethyleneglycol, and the PAP content of the fractions were analyzed by radioimmunoassay [31].
  • In order to gain insight into the possible role of HIP/PAP in vivo, we have investigated the pattern of HIP/PAP expression in the developing postimplantation mouse embryo by in situ hybridization [32].


  1. 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]
  2. 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]
  3. 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]
  4. Binding of factor VIIa to tissue factor induces alterations in gene expression in human fibroblast cells: up-regulation of poly(A) polymerase. Pendurthi, U.R., Alok, D., Rao, L.V. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  5. 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]
  6. 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]
  7. Exercise intervention of 65+-year-old men and women: functional ability and health care costs. Vestergaard, S., Kronborg Andersen, C., Korsholm, L., Puggaard, L. Aging clinical and experimental research. (2006) [Pubmed]
  8. Daughters and mothers exercising together (DAMET): a 12-week pilot project designed to improve physical self-perception and increase recreational physical activity. Ransdell, L.B., Dratt, J., Kennedy, C., O'Neill, S., DeVoe, D. Women & health. (2001) [Pubmed]
  9. Placental localization of human pregnancy--associated plasma proteins. Lin, T.M., Halbert, S.P. Science (1976) [Pubmed]
  10. PAG3/Papalpha/KIAA0400, a GTPase-activating protein for ADP-ribosylation factor (ARF), regulates ARF6 in Fcgamma receptor-mediated phagocytosis of macrophages. Uchida, H., Kondo, A., Yoshimura, Y., Mazaki, Y., Sabe, H. J. Exp. Med. (2001) [Pubmed]
  11. Increased activation of the coagulation and fibrinolytic systems leads to hemorrhagic complications during left ventricular assist implantation. Livingston, E.R., Fisher, C.A., Bibidakis, E.J., Pathak, A.S., Todd, B.A., Furukawa, S., McClurken, J.B., Addonizio, V.P., Jeevanandam, V. Circulation (1996) [Pubmed]
  12. 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]
  13. 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]
  14. 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]
  15. Calcineurin as a neuronal marker of human brain tumors. Goto, S., Matsukado, Y., Mihara, Y., Inoue, N., Miyamoto, E. Brain Res. (1986) [Pubmed]
  16. Imbalance between thrombin and plasmin activity in disseminated intravascular coagulation. Assessment by the thrombin-antithrombin-III complex/plasmin-alpha-2-antiplasmin complex ratio. Kario, K., Matsuo, T., Kodama, K., Matsuo, M., Yamamoto, K., Kobayashi, H. Haemostasis (1992) [Pubmed]
  17. A new paxillin-binding protein, PAG3/Papalpha/KIAA0400, bearing an ADP-ribosylation factor GTPase-activating protein activity, is involved in paxillin recruitment to focal adhesions and cell migration. Kondo, A., Hashimoto, S., Yano, H., Nagayama, K., Mazaki, Y., Sabe, H. Mol. Biol. Cell (2000) [Pubmed]
  18. Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Coutinho-Camillo, C.M., Salaorni, S., Sarkis, A.S., Nagai, M.A. Cancer Genet. Cytogenet. (2006) [Pubmed]
  19. Interaction of poly(A) polymerase with the 25-kDa subunit of cleavage factor I. Kim, H., Lee, Y. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  20. The pressure-flow response of the pulmonary circulation in patients with heart failure and pulmonary vascular disease. Janicki, J.S., Weber, K.T., Likoff, M.J., Fishman, A.P. Circulation (1985) [Pubmed]
  21. Polynucleotide phosphorylase functions as both an exonuclease and a poly(A) polymerase in spinach chloroplasts. Yehudai-Resheff, S., Hirsh, M., Schuster, G. Mol. Cell. Biol. (2001) [Pubmed]
  22. Hereditary mucoepithelial dysplasia: a disease apparently of desmosome and gap junction formation. Witkop, C.J., White, J.G., King, R.A., Dahl, M.V., Young, W.G., Sauk, J.J. Am. J. Hum. Genet. (1979) [Pubmed]
  23. High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of patients with idiopathic pulmonary alveolar proteinosis. Uchida, K., Nakata, K., Trapnell, B.C., Terakawa, T., Hamano, E., Mikami, A., Matsushita, I., Seymour, J.F., Oh-Eda, M., Ishige, I., Eishi, Y., Kitamura, T., Yamada, Y., Hanaoka, K., Keicho, N. Blood (2004) [Pubmed]
  24. Defective expression of granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 receptor common beta chain in children with acute myeloid leukemia associated with respiratory failure. Dirksen, U., Hattenhorst, U., Schneider, P., Schroten, H., Göbel, U., Böcking, A., Müller, K.M., Murray, R., Burdach, S. Blood (1998) [Pubmed]
  25. A novel mode of action of an ArfGAP, AMAP2/PAG3/Papa lpha, in Arf6 function. Hashimoto, S., Hashimoto, A., Yamada, A., Kojima, C., Yamamoto, H., Tsutsumi, T., Higashi, M., Mizoguchi, A., Yagi, R., Sabe, H. J. Biol. Chem. (2004) [Pubmed]
  26. Thrombophilia in sickle cell disease: the red cell connection. Setty, B.N., Rao, A.K., Stuart, M.J. Blood (2001) [Pubmed]
  27. Crystal structure of the human estrogen sulfotransferase-PAPS complex: evidence for catalytic role of Ser137 in the sulfuryl transfer reaction. Pedersen, L.C., Petrotchenko, E., Shevtsov, S., Negishi, M. J. Biol. Chem. (2002) [Pubmed]
  28. A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. López-Coronado, J.M., Bellés, J.M., Lesage, F., Serrano, R., Rodríguez, P.L. J. Biol. Chem. (1999) [Pubmed]
  29. Assays and properties of the ArfGAPs, AMAP1 and AMAP2, in Arf6 function. Hashimoto, S., Hashimoto, A., Yamada, A., Onodera, Y., Sabe, H. Meth. Enzymol. (2005) [Pubmed]
  30. Platelet-agglutinating protein P37 from a thrombotic thrombocytopenic purpura plasma forms a complex with human immunoglobulin G. Siddiqui, F.A., Lian, E.C. Blood (1988) [Pubmed]
  31. Immunological and biological stability of immunotoxins in vivo as studied by the clearance of disulfide-linked pokeweed antiviral protein-antibody conjugates from blood. Ramakrishnan, S., Houston, L.L. Cancer Res. (1985) [Pubmed]
  32. HIP/PAP gene, encoding a C-type lectin overexpressed in primary liver cancer, is expressed in nervous system as well as in intestine and pancreas of the postimplantation mouse embryo. Lasserre, C., Colnot, C., Bréchot, C., Poirier, F. Am. J. Pathol. (1999) [Pubmed]
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