Heparan sulfate proteoglycan of human colon: partial molecular cloning, cellular expression, and mapping of the gene (HSPG2) to the short arm of human chromosome 1.
We have determined the sequence of two overlapping cDNA clones encoding a portion of the human heparan sulfate proteoglycan core protein (HSPG2) from a human colon library. The cDNA clones encompassed 1.34 kb of nucleotide sequence and showed approximately 85% homology to the murine heparan sulfate proteoglycan of the EHS tumor, BPG-5. The deduced amino acid sequence revealed an identity of 87% between the human and the murine species. Of the 57 different amino acids encoded in the human clones, 20 were substituted with a similar amino acid. Among the specific features that were highly conserved was the 32 cysteine residues with a distinctive repeat pattern characteristic of epidermal growth factor. Northern blotting revealed a single, approximately 12 kb transcript in a variety of cells including human colon carcinoma, endothelial, and fibroblastic cells. The size of this transcript correlated with the estimated molecular weight (approximately 400 kDa) of the protein core precursor. Southern blot analyses of DNA from 120 human/rodent somatic cell hybrids, including subclones with specific translocations or spontaneous breaks of human chromosome 1, demonstrated the presence of HSPG2 gene on the telomeric region of the short arm of chromosome 1 (1p34-pter). Two polymorphisms with TaqI and EcoRI restriction endonucleases, respectively, were also detected. The localization of this proteoglycan locus in the human genome and the availability of new RFLPs provide the tools for future studies of human diseases where the HSPG2 proteoglycan gene is suspected to be involved.
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
G R
GR
Dodge
I
I
Kovalszky
M L
ML
Chu
J R
JR
Hassell
O W
OW
McBride
H F
HF
Yi
R V
RV
Iozzo
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D003106:Colon / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000235:genetics; D005796:Genes; D005819:Genetic Markers; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D051379:Mice / Q000235:genetics; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
D011508:Chondroitin Sulfate Proteoglycans; D004247:DNA; D005819:Genetic Markers; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate