PMID- 11286508
OWN - NLM
STAT- MEDLINE
DCOM- 20010621
LR  - 20131121
IS  - 1096-7192 (Print)
IS  - 1096-7192 (Linking)
VI  - 72
IP  - 4
DP  - 2001 Apr
TI  - Identification of the alpha-aminoadipic semialdehyde 
      dehydrogenase-phosphopantetheinyl transferase gene, the human ortholog of the 
      yeast LYS5 gene.
PG  - 336-42
AB  - In mammals, L-lysine is first catabolized to alpha-aminoadipate semialdehyde by 
      the bifunctional enzyme alpha-aminoadipate semialdehyde synthase (AASS), followed 
      by a conversion to alpha-aminoadipate by alpha-aminoadipate semialdehyde 
      dehydrogenase. In Saccharomyces cerevisiae, which synthesize rather than degrade 
      lysine, the latter activity requires two distinct genes. LYS2 encodes the 
      alpha-aminoadipate reductase activity, while LYS5 encodes a phosphopantetheinyl 
      transferase activity that is required to activate Lys2p. We have identified a 
      full-length human cDNA homologous to the yeast LYS5 gene. The cDNA contains an 
      open-reading frame of 930 bp predicted to encode 309 amino acids, and the human 
      protein is 26% identical and 44% similar to its yeast counterpart. In Northern 
      blot analysis the cDNA hybridizes to a single transcript of approximately 3 kb in 
      all tissues except testis, where there is an additional transcript of 1.5 kb. 
      Expression is highest in brain followed by heart and skeletal muscle, and to a 
      lesser extent in liver. We further identified three human genomic BAC clones 
      containing the human gene. Fluorescence in situ hybridization (FISH) analysis 
      using the BAC clones mapped the gene to chromosome 11q22 while alignment of the 
      cDNA and genomic sequences allowed partial identification of the intron-exon 
      boundaries. Finally, using one-step homologous recombination in S. cerevisiae we 
      generated a lys5 knockout strain. Complementation studies in the yeast knockout 
      demonstrate that the human homolog encodes alpha-aminoadipate dehydrogenase 
      phosphopantetheinyl transferase activity. We hypothesize that defects in this 
      gene may result in pipecolic acidemia.
CI  - Copyright 2001 Academic Press.
FAU - Praphanphoj, V
AU  - Praphanphoj V
AD  - Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland, USA.
FAU - Sacksteder, K A
AU  - Sacksteder KA
FAU - Gould, S J
AU  - Gould SJ
FAU - Thomas, G H
AU  - Thomas GH
FAU - Geraghty, M T
AU  - Geraghty MT
LA  - eng
GR  - HD24061/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 0 (Fungal Proteins)
RN  - EC 1.2.- (Aldehyde Oxidoreductases)
RN  - EC 1.2.1.31 (L-Aminoadipate-Semialdehyde Dehydrogenase)
RN  - EC 2.7.8.- (Transferases (Other Substituted Phosphate Groups))
RN  - EC 2.7.8.7 (holo-(acyl-carrier-protein) synthase)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Aldehyde Oxidoreductases/*genetics
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Cloning, Molecular
MH  - DNA Primers/chemistry
MH  - DNA, Complementary/analysis/isolation & purification
MH  - Fungal Proteins/chemistry/*genetics
MH  - Gene Expression
MH  - Genes, Fungal/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - L-Aminoadipate-Semialdehyde Dehydrogenase
MH  - Lysine/*genetics
MH  - Molecular Sequence Data
MH  - Molecular Weight
MH  - Polymerase Chain Reaction
MH  - Saccharomyces cerevisiae/enzymology/*genetics
MH  - Sequence Homology, Amino Acid
MH  - Transferases (Other Substituted Phosphate Groups)/*genetics
EDAT- 2001/04/05 10:00
MHDA- 2001/04/05 10:01
CRDT- 2001/04/05 10:00
PHST- 2001/04/05 10:00 [pubmed]
PHST- 2001/04/05 10:01 [medline]
PHST- 2001/04/05 10:00 [entrez]
AID - S1096-7192(00)93138-X [pii]
AID - 10.1006/mgme.2000.3138 [doi]
PST - ppublish
SO  - Mol Genet Metab. 2001 Apr;72(4):336-42. doi: 10.1006/mgme.2000.3138.