TY - JOUR
T1 - cDNA and genomic cloning of human palmitoyl-protein thioesterase (PPT), the enzyme defective in infantile neuronal ceroid lipofuscinosis
AU - Schriner, Julie E.
AU - Yi, Won
AU - Hofmann, Sandra L.
N1 - Funding Information:
Homology searching was performed at the NCBI using the BLAST network service. The authors thank Tommy Hyatt, Jeff Cormier, Bill Doerrler, and Steve Madden for technical assistance, Shari Cundiff and the Simmons Cancer Center Core Facility for oligonucleotides, and Helen Hobbs and David Russell for advice. This work was supported by the National Institutes of Health CA61823 and the Texas Advanced Research Program.
PY - 1996/6/15
Y1 - 1996/6/15
N2 - Palmitoyl-protein thioesterase (PPT) is a small glycoprotein that removes palmitate groups from cysteine residues in lipid-modified proteins. We recently reported mutations in PPT in patients with infantile neuronal ceroid lipofuscinosis (INCL), a severe neurodegenerative disorder (J. Vesa et al., 1995, Nature 376: 584-587). INCL is characterized by the accumulation of proteolipid storage material in brain and other tissues, suggesting that the disease is a consequence of abnormal catabolism of acylated proteins. In the current paper, we report the sequence of the human PeT cDNA and the structure of the human PPT gene. The cDNA predicts a protein of 306 amino acids that contains a 25-amino-acid signal peptide, three N-linked glycosylation sites, and consensus motifs characteristic of thioesterases. Northern analysis of a human tissue blot revealed ubiquitous expression of a single 2.5-kb mRNA, with highest expression in lung, brain, and heart. The human PPT gene spans 25 kb and is composed of seven coding exons and a large eighth exon, containing the entire 3'-untranslated region of 1388 bp. An Alu repeat and promoter elements corresponding to putative binding sites for several general transcription factors were identified in the 1060 nucleotides upstream of the transcription start site. The human PPT cDNA sequence and gene structure will provide the means for the identification of further causative mutations in INCL and facilitate genetic screening in selected high-risk populations.
AB - Palmitoyl-protein thioesterase (PPT) is a small glycoprotein that removes palmitate groups from cysteine residues in lipid-modified proteins. We recently reported mutations in PPT in patients with infantile neuronal ceroid lipofuscinosis (INCL), a severe neurodegenerative disorder (J. Vesa et al., 1995, Nature 376: 584-587). INCL is characterized by the accumulation of proteolipid storage material in brain and other tissues, suggesting that the disease is a consequence of abnormal catabolism of acylated proteins. In the current paper, we report the sequence of the human PeT cDNA and the structure of the human PPT gene. The cDNA predicts a protein of 306 amino acids that contains a 25-amino-acid signal peptide, three N-linked glycosylation sites, and consensus motifs characteristic of thioesterases. Northern analysis of a human tissue blot revealed ubiquitous expression of a single 2.5-kb mRNA, with highest expression in lung, brain, and heart. The human PPT gene spans 25 kb and is composed of seven coding exons and a large eighth exon, containing the entire 3'-untranslated region of 1388 bp. An Alu repeat and promoter elements corresponding to putative binding sites for several general transcription factors were identified in the 1060 nucleotides upstream of the transcription start site. The human PPT cDNA sequence and gene structure will provide the means for the identification of further causative mutations in INCL and facilitate genetic screening in selected high-risk populations.
UR - http://www.scopus.com/inward/record.url?scp=0030585740&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030585740&partnerID=8YFLogxK
U2 - 10.1006/geno.1996.0292
DO - 10.1006/geno.1996.0292
M3 - Article
C2 - 8786130
AN - SCOPUS:0030585740
SN - 0888-7543
VL - 34
SP - 317
EP - 322
JO - Genomics
JF - Genomics
IS - 3
ER -