Molecular characterization of human TRPM-2/clusterin, a gene associated with sperm maturation, apoptosis and neurodegeneration.
The TRPM-2/clusterin gene and its cognate protein has been characterized in a number of species. Although the functional role, or roles, of the TRPM-2/clusterin protein remains to be firmly established, the gene has been implicated in a variety of physiological processes, including sperm maturation, lipid transport, membrane remodelling and inhibition of the complement cascade. TRPM-2/clusterin is induced de novo during the regression of the prostate and other hormone-dependent tissues after hormone ablation, and is over-expressed in several human neurodegenerative diseases including Alzheimer's disease, epilepsy and retinitis pigmentosa. We describe the genomic structure of the human TRPM-2/clusterin gene which is organized into nine exons, ranging in size from 47 bp (exon I) to 412 bp (exon V), spanning a region of 16,580 bp. Comparison with sequences registered in the databases shows that it has extensive similarity to the human protein designated as SP-40,40 or complement-lysis inhibitor (CLI), a protein that appears to block the membrane-attack complex of complement. However, the cDNA sequences reported for SP-40,40 and CLI diverge significantly in the 5' untranslated region of the mRNA (coded for by exon I), raising the possibility that the TRPM-2/clusterin gene is present in the human genome as a small multi-gene family or that there are several alternate exon I sequences in the TRPM-2 gene. Southern analysis and fluorescent in situ hybridization suggest that the clusterin gene is a single-copy gene, and that, if alternative exon I sequences are present in the genome, they lie outside of the lambda clones that have been characterized. Analysis of the promoter region of the human TRPM-2/clusterin gene shows many similarities to the rat TRPM-2/clusterin promoter including a putative control region containing several potential regulatory elements that may regulate the complex tissue-specific control of the gene which must be constitutively expressed in some tissues but is inducible in others.
Wong
P
P
Department of Biochemistry, University of Ottawa, Canada.
Taillefer
D
D
Lakins
J
J
Pineault
J
J
Chader
G
G
Tenniswood
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D051152:Clusterin; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009410:Nerve Degeneration / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013079:Sperm Maturation / Q000235:genetics
C495242:CLU protein, human; D051152:Clusterin; D018076:DNA, Complementary; D006023:Glycoproteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger