A gene on human chromosome 6 functions in assembly of tissue-specific adenosine deaminase isozymes

Abstract

In human tissues, adenosine deaminase (ADA) (adenosine aminohydrolase; EC 3.5.4.4) activity can be separated by gel electrophoresis into several isozymes. A structural gene (ADA) on chromosome 20 codes for the erythrocyte isozyme, ADA-1, which is also expressed in some nonerythroid tissues. Nonerythroid cells also differntially express 5 ADA tissue isozymes of a greater MW than ADA-1. Each ADA tissue isozyme has a characteristic electrophoretic mobility and tissue distribution. These ADA tissue isozymes may be composed of ADA-1 and other components. The expression of 1 of these tissue isozymes, ADA-d, is dependent on ADA on chromosome 20 and another gene on chromosome 6 which functions in the assembly of the ADA tissue isozymes. In human-mouse hybrids segregating human chromosomes, chromosome 6+,20+ hybrids express both ADA-1 and ADA-d; chromosome 6-,20+ hybrids express only ADA-1; while 6+,20- hybrids have no human ADA activity. ADA-d formation also occurs in vitro by self-assembly when an extract of human erythrocytes or chromosome 6-,20+ hybrids is mixed with a homogenate of chromosome 6+,20- hybrids. The gene on chromosome 6 was designated ADCP, coding for an adenosine deaminase complexing protein. The product of ADCP may combine with ADA-1 to form the ADA tissue isozymes. The hypothesis that the distribution of enzymatic activity between ADA-1 and the tissue isozymes depends on the expression of the gene for ADA complexing protein, is supported. Differences in the electrophoretic mobilities of the ADA isozymes, except ADA-1, may be generated by the degree of glycosylation of the complexing protein.