Rm. Cook et al., HUMAN AMINOACYLASE-1 - CLONING, SEQUENCE, AND EXPRESSION ANALYSIS OF A CHROMOSOME-3P21 GENE INACTIVATED IN SMALL-CELL LUNG-CANCER, The Journal of biological chemistry, 268(23), 1993, pp. 17010-17017
Human aminoacylase-1 (N-acyl-L-amino-acid amidohydrolase, EC 3.5.1.14;
ACY1) is a homodimeric zinc-binding enzyme that catalyzes the hydroly
sis of N(alpha)-acylated amino acids. ACY1 has been assigned to chromo
some 3p21.1, a region reduced to homozygosity in small cell lung cance
r (SCLC), and has been reported to exhibit reduced or absent expressio
n in SCLC cell lines and tumors. Two human cDNA libraries and one huma
n genomic DNA library were screened with a previously isolated partial
ACY1 cDNA to isolate a full-length transcript. Sequence analysis of c
lones from each of these libraries resulted in an ACY1 cDNA of 1438 ba
se pairs with an open reading frame of 1224-base pairs coding for a pu
tative protein of 408 amino acids with a predicted molecular mass of 4
5,882 Da. Sequence analysis revealed no homologies to previously repor
ted cDNA or protein sequences and establishes ACY1 as the first member
of a new family of zinc-binding enzymes to be so characterized. The s
ubcellular location of ACY1 has been established as cytosolic by flow
cytometry. Southern and northern analyses of ACY1 in SCLC cell lines f
ailed to demonstrate any gross abnormalities of the ACY1 structural ge
ne or instances of absent or aberrantly sized mRNA, respectively.