PMID- 10610716
OWN - NLM
STAT- MEDLINE
DCOM- 20000209
LR  - 20141120
IS  - 0888-7543 (Print)
IS  - 0888-7543 (Linking)
VI  - 62
IP  - 2
DP  - 1999 Dec 1
TI  - The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation 
      analysis, and expression.
PG  - 223-31
AB  - Acid ceramidase (AC) is the lysosomal enzyme that degrades ceramide into
      sphingosine and fatty acid. A deficiency in human AC activity leads to the
      lysosomal storage disorder, Farber disease (FD). The human AC gene (HGMW-approved
      symbol ASAH) was cloned and characterized, revealing an organization similar to
      that of the murine AC gene. The human gene spans about 30 kb in length and
      contains 14 exons ranging in size from 46 to 1201 bp. The exon/intron junctions
      were determined and found to follow the GT-AG rule. The putative promoter region 
      had a GC content over 60%, lacked a TATA box, and contained several sequences
      matching transcription factor binding sites, including nine SP-1 sites, one AP-1 
      site, and three CACC boxes. The promoter activity of a 475-bp fragment from
      within this region was demonstrated by chloramphenicol acyltransferase assays.
      Northern blotting revealed variable expression of the human AC RNA; i.e.,
      expression of the major 2.4-kb transcript was high in heart and kidney, followed 
      by lung and placenta, but low in pancreas, liver, brain, and skeletal muscle. Two
      minor AC transcripts of 1.7 and 1.2 kb also were detected in heart and skeletal
      muscle. The human AC gene was mapped to the chromosomal region 8p21.3-p22 by in
      situ hybridization and FISH analyses, syntenic with the mouse chromosomal
      location. Finally, three new missense mutations, E138V, R254G, and P362R, were
      identified in the human AC gene from FD patients. Mutant AC cDNAs containing
      these point mutations were constructed and examined using the FLAG-tagged
      expression system. Although the levels of protein expression for these mutant ACs
      were about equivalent to that of the controls, their enzymatic activity was
      markedly reduced, confirming their authenticity.
CI  - Copyright 1999 Academic Press.
FAU - Li, C M
AU  - Li CM
AD  - Department of Human Genetics, Mount Sinai School of Medicine, New York 10029,
      USA.
FAU - Park, J H
AU  - Park JH
FAU - He, X
AU  - He X
FAU - Levy, B
AU  - Levy B
FAU - Chen, F
AU  - Chen F
FAU - Arai, K
AU  - Arai K
FAU - Adler, D A
AU  - Adler DA
FAU - Disteche, C M
AU  - Disteche CM
FAU - Koch, J
AU  - Koch J
FAU - Sandhoff, K
AU  - Sandhoff K
FAU - Schuchman, E H
AU  - Schuchman EH
LA  - eng
GR  - DK 54830/DK/NIDDK NIH HHS/United States
GR  - HD 28607/HD/NICHD NIH HHS/United States
GR  - RR 0071/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genomics
JT  - Genomics
JID - 8800135
RN  - 0 (DNA, Complementary)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptides)
RN  - 63231-63-0 (RNA)
RN  - 98849-88-8 (FLAG peptide)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.23 (ASAH1 protein, human)
RN  - EC 3.5.1.23 (Acid Ceramidase)
RN  - EC 3.5.1.23 (Asah1 protein, mouse)
RN  - EC 3.5.1.23 (Ceramidases)
SB  - IM
MH  - 3T3 Cells
MH  - Acid Ceramidase
MH  - Amidohydrolases/biosynthesis/*chemistry/*genetics
MH  - Animals
MH  - Base Sequence
MH  - COS Cells
MH  - Ceramidases
MH  - Chromosomes, Human, Pair 8/*genetics
MH  - DNA Mutational Analysis
MH  - DNA, Complementary/biosynthesis
MH  - Gene Expression Regulation, Enzymologic
MH  - Humans
MH  - Lysosomal Storage Diseases/enzymology/genetics
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation, Missense
MH  - Oligopeptides
MH  - Organ Specificity/genetics
MH  - Peptides/genetics
MH  - RNA/biosynthesis
EDAT- 1999/12/28 00:00
MHDA- 1999/12/28 00:01
CRDT- 1999/12/28 00:00
PHST- 1999/12/28 00:00 [pubmed]
PHST- 1999/12/28 00:01 [medline]
PHST- 1999/12/28 00:00 [entrez]
AID - 10.1006/geno.1999.5940 [doi]
AID - S0888-7543(99)95940-2 [pii]
PST - ppublish
SO  - Genomics. 1999 Dec 1;62(2):223-31. doi: 10.1006/geno.1999.5940.