Jp. Kraus et al., THE HUMAN CYSTATHIONINE BETA-SYNTHASE (CBS) GENE - COMPLETE SEQUENCE,ALTERNATIVE SPLICING, AND POLYMORPHISMS, Genomics (San Diego, Calif.), 52(3), 1998, pp. 312-324
Cystathionine P-synthase [CBS; L-serine hydro-lyase (adding homocystei
ne), EC 4.2.1.22] catalyzes the first committed step of transsulfurati
on and is the enzyme deficient in classical homocystinuria, In this re
port, we describe the molecular cloning and the complete nucleotide se
quence of the human CBS gene. We report a total of 28,046 nucleotides
of sequence, which, in addition to the CBS gene, contains similar to 5
kb of the 5' flanking region. The human CBS gene contains 23 exons ra
nging from 42 to 209 bp. The 5' UTR is formed by 1 of 5 alternatively
used exons and 1 invariably present exon, while the 3' UTR is encoded
by exons 16 and 17. We also describe the identification of two alterna
tively used promoter regions that are GC rich (similar to 80%) and con
tain numerous putative binding sites for Sp1, Ap1, Ap2, and c-myb, but
lack the classical TATA box. The CBS locus contains an unusually high
number of Alu repeats, which may predispose this gene to deleterious
rearrangements. Additionally, we report on a number of DNA sequence re
peats that are polymorphic in North American and European Caucasians,
(C) 1998 Academic Press.