title: The human L-threonine 3-dehydrogenase gene is an expressed pseudogene.
abstract: BACKGROUND
  L-threonine is an indispensable amino acid. One of the major L-threonine degradation pathways is the conversion of L-threonine via 2-amino-3-ketobutyrate to glycine. L-threonine dehydrogenase (EC 1.1.1.103) is the first enzyme in the pathway and catalyses the reaction: L-threonine + NAD+ = 2-amino-3-ketobutyrate + NADH. The murine and porcine L-threonine dehydrogenase genes (TDH) have been identified previously, but the human gene has not been identified.
  
  
  RESULTS
  The human TDH gene is located at 8p23-22 and has 8 exons spanning 10 kb that would have been expected to encode a 369 residue ORF. However, 2 cDNA TDH transcripts encode truncated proteins of 157 and 230 residues. These truncated proteins are the result of 3 mutations within the gene. There is a SNP, A to G, present in the genomic DNA sequence of some individuals which results in the loss of the acceptor splice site preceding exon 4. The acceptor splice site preceding exon 6 was lost in all 23 individuals genotyped and there is an in-frame stop codon in exon 6 (CGA to TGA) resulting in arginine-214 being replaced by a stop codon. These truncated proteins would be non-functional since they have lost part of the NAD+ binding motif and the COOH terminal domain that is thought to be involved in binding L-threonine. TDH mRNA was present in all tissues examined.
  
  
  CONCLUSIONS
  The human L-threonine 3-dehydrogenase gene is an expressed pseudogene having lost the splice acceptor site preceding exon 6 and codon arginine-214 (CGA) is mutated to a stop codon (TGA).
mesh_terms: D000429:Alcohol Oxidoreductases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D002874:Chromosome Mapping; D018388:Codon, Terminator; D004262:DNA Restriction Enzymes; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D011544:Pseudogenes; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000096:biosynthesis; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014018:Tissue Distribution; D014158:Transcription, Genetic
chemical_list: D018388:Codon, Terminator; D022821:RNA Splice Sites; D012333:RNA, Messenger; D000429:Alcohol Oxidoreductases; C023159:L-threonine 3-dehydrogenase; D004262:DNA Restriction Enzymes