Disease relevance of DDEF2

• Both the proband and her affected brother had RP, PAP, mild mental retardation, morbid obesity (BMI >50 and 37, respectively), lobulated kidneys with prominent calyces and diabetes mellitus (diagnosed at ages 33 and 30, respectively) [1].
• The first is a 13-year-old Hispanic girl with severe RP, PAP, mental retardation and obesity (BMI >40) [1].
• The antibody was found to be present in all specimens of bronchoalveolar lavage fluid obtained from 11 I-PAP patients but not in samples from 2 secondary PAP patients, 53 normal subjects, and 14 patients with other lung diseases [2].
• Pulmonary alveolar proteinosis (PAP) is a heterogeneous disorder of genetic or acquired etiologies [3].
• Enhanced expression of PAP upon VIIa binding to tumor cell TF may potentially play an important role in tumor metastasis [4].

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

• Moreover, overexpression of PAG3, but not its GAP-inactive mutant, inhibited paxillin recruitment to focal contacts and hampered cell migratory activities, whereas cell adhesion activities were almost unaffected [17].
• The DDEF2 gene is involved in adhesion and cell migration of monocytes, and the SPA17 gene might be involved in cellular signal transduction [18].
• Mammalian poly(A) polymerase (PAP), a key enzyme in the pre-mRNA 3'-end processing reaction, carries the catalytic domain in the N-terminal region, an RNA binding domain, two nuclear localization signals, and a serine/threonine-rich regulatory domain in the C-terminal region [19].
• We measured pulmonary arterial (PAP) and occlusive wedge pressures and cardiac output at rest (i.e., standing) and during progressive upright treadmill exercise in 51 patients [20].
• While trying to purify the chloroplast PAP by following in vitro polyadenylation activity, it was found to copurify with PNPase and indeed could not be separated from it [21].

Anatomical context of DDEF2

• PAG3 was diffusely distributed in the cytoplasm in premature monocytes but became localized at cell periphery in mature monocytes, a fraction of which then colocalized with paxillin [17].
• PAG3, on the other hand, did not accumulate at focal adhesion plaques, suggesting that PAG3 is not an integrin assembly protein [17].
• Mucosal PAP smears show lack of epithelial maturation, cytoplasmic vacuoles and inclusions, and individual cell dyskeratosis [22].
• Deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mice results in pulmonary alveolar proteinosis (PAP) from impaired surfactant catabolism by alveolar macrophages (AMs) [23].
• In mice, the PAP phenotype was generated by targeted deletion of the gene for betac and can be treated by transplantation of wild-type bone marrow into betac -/- mice [24].

Associations of DDEF2 with chemical compounds

• AMAP2 was moreover found to bind to amphiphysin IIm, a component of the endocytic machinery, via its proline-rich domain [25].
• The glutathione S-transferase pull-down assay and the immunoprecipitation experiment revealed that PAP directly interacts with CFI-25 and that the C-terminal 69 residues of PAP and the N-terminal 60 residues of CFI-25 are sufficient for the interaction between CFI-25 and PAP [19].
• In contrast, correlations were noted between PS-positive erythrocytes and F1.2 (P <.0002), D-dimer (P <.000002), and PAP (P <.01) [26].
• Superimposing this structure with the crystal structure of hEST in complex with the donor product 3'-phosphoadenosine 5'-phosphate (PAP) and the acceptor substrate 17beta-estradiol, the ternary structure with the PAPS and estradiol molecule, is modeled [27].
• We report the molecular cloning in Rattus norvegicus of a novel mammalian enzyme (RnPIP), which shows both 3'-phosphoadenosine 5'-phosphate (PAP) phosphatase and inositol-polyphosphate 1-phosphatase activities [28].

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].

References