Disease relevance of TADA2L

• ADA2 is a major component of human plasma total ADA activity and ADA2 activity is significantly elevated in patients with various diseases such as HIV infection and chronic hepatitis [1].
• These findings suggest that serum ADA isoenzyme activities may be a new marker for liver disease, and that the increased serum ADA2 in chronic active hepatitis is unlikely to be the result of an increase in ADA2 production by activated peripheral blood mononuclear cells [2].
• A significant elevation in ADA2 activity was also seen in the sera of AIDS patients (P < 0.01) compared with that in the sera of HIV-1 antibody-positive individuals [3].
• In conclusion, we found that ADA2 is a dominant component of tuberculous pleural effusions and that ADA1 is a major component of lymphoid cells [4].
• In the case of patients with human immunodeficiency virus type 1 (HIV-1) infection, ADA1 and ADA2 activities in the sera of patients with AIDS and HIV-1 antibody-positive individuals were significantly (P < 0.001) higher than those in the sera of HIV-1 antibody-negative individuals [3].

High impact information on TADA2L

• In this paper, we have characterized the epitopes recognized by two clonotypically distinct, murine Tg autoreactive T cell hybridomas, CH9 and ADA2 [5].
• However, complementation of growth and transcriptional activation in gcn5- cells required not only the HAT domain of GCN5, but also interaction with ADA2 [6].
• CoREST contains two SANT (SW13/ADA2/NCoR/TFIIIB B) domains, a structural feature of the nuclear receptor and silencing mediator for retinoid and thyroid human receptors (SMRT)-extended corepressors that mediate inducible repression by steroid hormone receptors [7].
• Ada2 can be precipitated from nuclear extracts by a glutathione S-transferase-tau1 fusion protein coupled to agarose beads, and a direct interaction between Ada2 and tau1c can be shown by using purified proteins [8].
• Acute nonlymphoblastic leukemia (ANLL) with a monocytic component tended to have a greater percentage of ADA2 than ANLL without a monocytic component [9].

Chemical compound and disease context of TADA2L

• We investigated serum levels of adenosine deaminase 2 (ADA2) and neopterin (NP) in hemophiliacs with or without infection with human immunodeficiency virus type 1 (HIV-1) [10].
• Our results suggest that ADA2 may be active in sites of inflammation during hypoxia and in areas of tumour growth where the adenosine concentration is significantly elevated and the extracellular pH is acidic [11].

Biological context of TADA2L

• The human transcriptional adaptor genes TADA2L and GCN5L2 colocalize to chromosome 17q12-q21 and display a similar tissue expression pattern [12].
• This suggests that non-O ADA2 carrier genotypes may lose in the reproductive stage the selective advantage accumulated during the early stages of development [13].
• These results suggest that reduced serum total ADA activity reflects decrease in ADA2 activity, and which may be in part associated with depressed cell-mediated immunity during normal pregnancy [14].
• We measured serum activities of total ADA, ADA1 and ADA2 in normal pregnant women in the third trimester (n=24) and age-matched healthy nonpregnant women (n=24) [14].
• However, cell fusion experiments between A3-1A7 cells and mouse C1-1D cells established the existence of functional copies of both ADA 1 and ADA 2 allelic genes in the A3-1A7 cells [15].

Anatomical context of TADA2L

• In this study we succeeded in purifying human plasma ADA2 and demonstrate the extracellular secretion of ADA2 from human peripheral blood monocytes stimulated with phorbol 12-myristate 13-acetate and calcium ionophore [1].
• Adenosine deaminase (ADA) plays an important role in the immune system, and its activity is composed of two kinetically distinct isozymes, ADA1 and ADA2 [1].
• The ADA2 isoenzyme activity most likely reflects monocyte-macrophage turnover or activity, while ADA1 probably originates from lymphocytes or neutrophils [16].
• Total ADA, ADA-2 and 2'-deoxyadenosine deaminase activities were, respectively, 127.5 +/- 2.9, 103 +/- 29.5 and 42.8 +/- 14 U.L-1 in tuberculous exudates [17].
• Tumor ADA2 and total ADA activities were significantly (P < 0.05) correlated with lymph node involvement, histological grade and tumor size, whereas their levels in serum were significantly (P < 0.05) correlated with menopausal status and patient age [18].

Associations of TADA2L with chemical compounds

• Extracts of liver and spleen were used to isolate opossum adenosine deaminase isoenzymes (ADA1 and ADA2) and to determine their activities with adenosine and 2'-deoxyadenosine as substrates [19].
• Km values (microM) for adenosine and 2'-deoxyadenosine, respectively, as substrates for partially purified opossum liver adenosine deaminase isoenzymes were ADA1: 57 +/- 7 vs. 26 +/- 4 and ADA2: 285 +/- 25 vs. 580 +/- 92 [19].
• ADA2 activity was measured in the presence of a specific ADA1 inhibitor, EHNA [18].
• Normalization of the blood glucose level by the hospitalization was associated with the decrease in ADA2 (but not ADA1) activity in 6 of 8 IDDM or 11 of 12 NIDDM poorly controlled patients [20].
• Since the deamination of adenosine to inosine associated with ADA2-1 phenotype is slower than that associated with ADA1, the interaction of ADA on ACP1 activity may in fact be explained by a lower intracellular concentration of inosine in ADA2 carriers and, therefore, by a lower modulating effect of this on acid phosphatase activity [21].

Co-localisations of TADA2L

• Introduction of the nucleotide substitution into an ADA 1 cDNA and transfection into monkey kidney (Cos) cells confirmed that the mutation resulted in expression of an enzyme that comigrated with the naturally occurring ADA 2 allozyme [22].

Other interactions of TADA2L

• Northern blot analysis across a range of human tissues revealed that both the TADA2L and the GCN5L2 mRNAs are expressed to varying degrees in all tissue types [12].
• CONCLUSION: Serum tADA and ADA2 activity is closely associated with RA and these non-invasive investigations can be used as biochemical markers for inflammation [23].
• ADA2 (but not ADA1) activity in the poorly controlled NIDDM patients directly correlated with the hemoglobin A1c level (P < 0.002) [20].
• ABO-incompatible newborn infants showed a higher proportion of ADA2 carriers as compared to compatible newborns [13].
• Only the common ADA1 and ADA2 alleles were found, with the frequencies of the latter being 0.025, 0.103, 0.115 and 0.028 in the Semai, Semelai, Temuan, and Jakun groups, respectively [24].

Analytical, diagnostic and therapeutic context of TADA2L

• Chromosomal mapping by fluorescence in situ hybridization indicated that these genes reside near each other on chromosome 17; TADA2L mapped within bands 17q12-q21, while GCN5L2 mapped distally within band 17q21 [12].
• First, as shown for yADA2 and yGCN5, human ADA2 (hADA2) and human GCN5 (hGCN5) interacted in vivo in a yeast two-hybrid assay [25].
• Serum ADA was partially purified by CM-Sephadex, gel-filtration, and affinity chromatography into two types of isoenzymes, designated ADA1 (300 kDa) and ADA2 (120 kDa) [26].
• We prospectively measured serum ADA2 activity in 110 patients with pulmonary disease (65 cases with active PTB and 45 cases with other respiratory diseases) and 78 healthy volunteers (eight with tuberculin skin test positive) [27].
• The samples were used for blood culture, serological tests, leukocyte count and analysis of levels of C-reactive protein, procalcitonin, total adenosine deaminase (ADA) activity and its isoenzymes, ADA-1 and ADA-2 [28].

References