Disease relevance of ADD3

• Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL [1].
• In the European Project on Genes in Hypertension, we investigated whether polymorphisms in the genes encoding alpha-adducin (Gly460Trp), beta-adducin (C1797T) and gamma-adducin (A386G), alone or in combination, affected pulse pressure (PP), an index of vascular stiffness [2].

High impact information on ADD3

• ADD3 codes for the ubiquitous expressed subunit gamma of the adducin protein, and it seems to play an important role in the skeletal organization of the cell membrane [3].
• Cisplatin also caused an increased phosphorylation of alpha-adducin and gamma-adducin in the MARCKS domain that preceded alpha-adducin cleavage and was associated with loss of adducins from adherens junctions; this was not affected by z-VAD-fmk [4].
• Polymorphisms in the ADD2 and ADD3 genes taken alone were not associated with these variables [5].
• However, the differences in SBP and DBP between the two ADD1 genotypes were greatest in carriers of the ADD3 G allele (around + 8 mmHg) [5].
• Levels of ADD3 mRNA were higher than levels of ADD2 mRNA at early stages of erythropoiesis [6].

Biological context of ADD3

• CONCLUSIONS: The interaction of ADD1 and ADD3 gene variants in humans is statistically associated with variation in blood pressure, suggesting the presence of epistatic effects among these loci [5].
• Moreover, human ADD3 amino acid sequence presents 91.9% of identity compared to rat sequence [7].
• The human ADD3 gene spans over 20 kb and is composed of at least 13 introns and 14 exons covering the entire coding region [7].
• Adducin is a heterodymeric cytoskeleton protein, the 3 subunits of which are encoded by genes (ADD1, ADD2, ADD3) mapping to 3 different chromosomes [8].
• From a human fetal-brain cDNA library we isolated a novel human cDNA, termed human adducin-like 70 (gene symbol ADDL), whose predicted amino acid sequence showed a high degree of homology to adducins [9].

Anatomical context of ADD3

• The early expression of ADD3 suggests that it may have a role in erythroblasts but is replaced by ADD2 in later stages of erythropoiesis [6].
• Whereas ADD1 is ubiquitously distributed, ADD3 is more expressed in kidney medulla and cortex than in fetal kidney, while in adult liver it is less abundant than in fetal liver [10].
• Cloning, expression and chromosome mapping of adducin-like 70 (ADDL), a human cDNA highly homologous to human erythrocyte adducin [9].
• The presence of high affinity ADDL binding proteins in hippocampus and frontal cortex but not cerebellum parallels the regional specificity of AD pathology and suggests involvement of a toxin receptor-mediated mechanism [11].

Associations of ADD3 with chemical compounds

• Sesaminol glucoside (50-250microg/ml) also effectively decreased Abeta1-42 and ADDL form of Abeta1-42 as well as the combination of H2O2 with FeSO4-induced cell damages [12].

Analytical, diagnostic and therapeutic context of ADD3

• In this work we describe the development of a dot-blot immunoassay to measure ADDL at the femtomole level, its use in defining the time course of ADDL formation, and its use in determining the presence of ADDLs in the hAPP transgenic mouse brain [13].

References