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

Proc Natl Acad Sci U S A. 1978 Aug;75(8):3876-80. doi: 10.1073/pnas.75.8.3876.


In human tissues, adenosine deaminase (ADA) (adenosine aminohydrolase; EC 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 differentially express five ADA "tissue isozymes" of a greater molecular weight than ADA-1. Each ADA tissue isozyme has a characteristic electrophoretic mobility and tissue distribution. It has been suggested that these ADA tissue isozymes are composed of ADA-1 and other components. We report that the expression of one of these tissue isozymes, ADA-d, is dependent upon 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, designated ADCP, codes for an adenosine deaminase complexing protein. The product of ADCP presumably combines with ADA-1 to form the ADA tissue isozymes. The data are consistent with 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, while the differences in the electrophoretic mobilities of the ADA isozymes, except ADA-1, are generated, as suggested by others, by the degree of glycosylation of the complexing protein.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Deaminase / genetics*
  • Animals
  • Carrier Proteins / genetics
  • Chromosomes, Human, 6-12 and X*
  • Electrophoresis, Starch Gel
  • Humans
  • Hybrid Cells
  • Isoenzymes / genetics*
  • Mice
  • Molecular Weight
  • Nucleoside Deaminases / genetics*


  • Carrier Proteins
  • Isoenzymes
  • Nucleoside Deaminases
  • Adenosine Deaminase