Cloning of human cDNAs encoding mitochondrial and cytosolic serine hydroxymethyltransferases and chromosomal localization.
Human cDNAs for cytosolic and mitochondrial serine hydroxymethyltransferase (SHMT) were cloned by functional complementation of an Escherichia coli glyA mutant with a human cDNA library. The cDNA for the cytosolic enzyme encodes a 483-residue protein of M(r) 53,020. The cDNA for the mitochondrial enzyme encodes a mature protein of 474 residues of M(r) 52,400. The deduced protein sequences share a high degree of sequence identity to each other (63%), and the individual isozymes are highly homologous to the analogous rabbit liver cytosolic (92% identity) and mitochondrial (97% identity) SHMT isozymes (Martini, F., Angelaccio, S., Pascarella, S., Barra, D., Bossa, F., and Schirch, V. (1987) J. Biol. Chem. 262, 5499-5509; Martini, F., Maras, B., Tanci, P., Angelaccio, S., Pascarella, S., Barra, D., Bossa, F., and Schirch, V. (1989) J. Biol. Chem. 264, 8509-8519). SHMT is a highly conserved protein with the human isozymes retaining about 43% sequence identity with the E. coli protein. The human cytosolic and mitochondrial SHMT genes were localized to chromosome regions 17p11.2 and 12q13, respectively. The high degree of nucleotide sequence identity between the two isozymes, and the presence of keratin genes in both chromosomal regions, is consistent with these regions of chromosome 12 and 17 arising by a duplication event.
Garrow
T A
TA
Department of Nutritional Sciences, University of California, Berkeley 94720.
Brenner
A A
AA
Whitehead
V M
VM
Chen
X N
XN
Duncan
R G
RG
Korenberg
J R
JR
Shane
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D001483:Base Sequence; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D003600:Cytosol / Q000201:enzymology; D004247:DNA / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008928:Mitochondria / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals / Q000235:genetics; D011817:Rabbits; D017386:Sequence Homology, Amino Acid
D007527:Isoenzymes; D021382:Protein Sorting Signals; D004247:DNA; D012696:Glycine Hydroxymethyltransferase