Human beta-hexosaminidase alpha chain: coding sequence and homology with the beta chain

Proc Natl Acad Sci U S A. 1985 Dec;82(23):7830-4. doi: 10.1073/pnas.82.23.7830.

Abstract

We have isolated a cDNA clone, p beta H alpha-5, from an adult human liver library that contains the entire coding sequence of the alpha chain of beta-hexosaminidase. The cDNA insert of p beta H alpha-5 is 1944 base pairs long and contains a 168-base-pair 5' untranslated region, a 186-base-pair 3' untranslated region, and an open reading frame of 1587 base pairs corresponding to 529 amino acids (Mr, 60,697). The first 17-22 amino acids satisfy the requirements of a signal sequence. A striking sequence homology with a published partial amino acid sequence for the beta chain [O'Dowd, B. F., Quan, F., Willard, H. F., Lamhonwah, A. M., Korneluk, R. G., Lowden, J. A., Gravel, R. A. & Mahuran, D. J. (1985) Proc. Natl. Acad. Sci. USA 82, 1184-1188] suggests that both chains may have evolved from a common ancestor. A shorter alpha-chain cDNA was found to hybridize to the long arm of chromosome 15, the known location for the alpha-chain gene. In addition, we isolated another alpha-chain cDNA clone, p beta H alpha-4, from a simian virus 40-transformed human fibroblast library that contained an extra 453-base-pair piece at its 3' end. A probe consisting of this additional sequence hybridized exclusively to a single mRNA species (2.6 kilobases) in mRNA preparations from cultured human fibroblasts. In contrast, p beta H alpha-5 hybridized to both a 2.1-kilobase major and a 2.6-kilobase minor mRNA species in these same mRNA preparations, indicating the presence of two distinct alpha-chain mRNA species differing at the 3' end. Fibroblasts from an Ashkenazi Jewish patient with classic Tay-Sachs disease were deficient in both species of mRNA, confirming their genetic relationship.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, 13-15*
  • Genes
  • Hexosaminidases / genetics*
  • Humans
  • Macromolecular Substances
  • RNA, Messenger / genetics
  • Sequence Homology, Nucleic Acid
  • beta-N-Acetylhexosaminidases

Substances

  • Macromolecular Substances
  • RNA, Messenger
  • Hexosaminidases
  • beta-N-Acetylhexosaminidases

Associated data

  • GENBANK/J02704
  • GENBANK/M11572
  • GENBANK/M16411
  • GENBANK/M16412
  • GENBANK/M16413
  • GENBANK/M16414
  • GENBANK/M16415
  • GENBANK/M16416
  • GENBANK/M16417
  • GENBANK/M16418
  • GENBANK/M16419
  • GENBANK/M16420
  • GENBANK/M16421
  • GENBANK/M16422
  • GENBANK/M16423
  • GENBANK/M16424