Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1990-5-4
pubmed:databankReference
pubmed:abstractText
Saposins are small, heat-stable glycoproteins required for the hydrolysis of sphingolipids by specific lysosomal hydrolases. Saposins A, B, C, and D are derived by proteolytic processing from a single precursor protein named prosaposin. Saposin B, previously known as SAP-1 and sulfatide activator, stimulates the hydrolysis of a wide variety of substrates including cerebroside sulfate, GM1 ganglioside, and globotriaosylceramide by arylsulfatase A, acid beta-galactosidase, and alpha-galactosidase, respectively. Human saposin B deficiency, transmitted as an autosomal recessive trait, results in tissue accumulation of cerebroside sulfate and a clinical picture resembling metachromatic leukodystrophy (activator-deficient metachromatic leukodystrophy). We have examined transformed lymphoblasts from the initially reported saposin B-deficient patient and found normal amounts of saposins A, C, and D. After preparing first-strand cDNA from lymphoblast total RNA, we used the polymerase chain reaction to amplify the prosaposin cDNA. The patient's mRNA differed from the normal sequence by only one C----T transition in the 23rd codon of saposin B, resulting in a threonine to isoleucine amino acid substitution. An affected male sibling has the same mutation as the proband and their heterozygous mother carries both the normal and mutant sequences, providing additional evidence that this base change is the disease-causing mutation. This base change results in the replacement of a polar amino acid (threonine) with a nonpolar amino acid (isoleucine) and, more importantly, eliminates the glycosylation signal in this activator protein. One explanation for the deficiency of saposin B in this disease is that the mutation may increase the degradation of saposin B by exposing a potential proteolytic cleavage site (arginine) two amino acids to the amino-terminal side of the glycosylation site when the carbohydrate side chain is absent.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-23173, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-239890, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-2448875, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-2498298, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-2717620, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-2762168, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-2764035, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-2842863, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-2845979, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-2981875, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-3048308, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-3360793, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-3408492, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-3651384, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-4835697, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-5829234, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-6119902, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-6134282, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-6313655, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-7046800, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-7126630, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-814123, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-901460, http://linkedlifedata.com/resource/pubmed/commentcorrection/2320574-999651
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:volume
87
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2541-4
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect.
pubmed:affiliation
Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla 92093.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't