Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.36 (hyaluronidase)
4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently cloned and expressed the major hyaluronidase activity from human plasma, HYAL1, and found that the protein is 40% identical to the testicular hyaluronidase, PH-20. The HYAL1 mRNA sequence was used in a homology search of the mouse database of expressed sequence tags (dbEST). Two ESTs were obtained and, in combination with 5'RACE-PCR, were used to clone the mouse HYAL1 ortholog (Hyal1). Hyal1 codes for a protein of 462 amino acids that is 73% identical to the human sequence. Hyal1 stably expressed in human embryonic kidney cells resulted in a 20,000-fold increase of hyaluronidase activity. Sequence-tagged sites derived from the HYAL1 gene from both species were used to isolate P1 genomic clones that were used as probes for fluorescence in situ hybridization. The human gene was localized to chromosome 3p21 and the mouse gene to a syntenic region on chromosome 9F1-F2. In mouse, serum hyaluronidase polymorphism has previously been mapped by an interspecific backcross to 60 cM from the centromere of chromosome 9, which corresponds to a cytogenetic location of 9F1-F2. The mouse Hyal1 gene is therefore very likely to be responsible for the hyaluronidase polymorphism linked to this locus. We also present evidence that human HYAL1 is identical to an uncharacterized gene positionally cloned by others from chromosome 3p21.3 that is homozygously deleted in several small-cell lung carcinoma cell lines.
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PMID:The hyaluronidase gene HYAL1 maps to chromosome 3p21.2-p21.3 in human and 9F1-F2 in mouse, a conserved candidate tumor suppressor locus. 950 17

Capacitated cynomolgus macaque sperm have a surface hyaluronidase (PH-20) that is evenly distributed over the entire head and can be visualized at the ultrastructural level using a secondary antibody labeled with colloidal gold . Exposure of sperm to mono-specific, bivalent polyclonal antibodies to PH-20 causes a rapid clustering of PH-20. The predominant morphological consequence of PH-20 redistribution is its aggregation along the lateral edge of the sperm head. Monovalent Fab fragments of the anti-PH-20 antibody bound to the sperm head but did not induce a change in PH-20 distribution. PH-20 aggregation was observed in almost all sperm following treatment with the polyclonal antibody, but only about 20% of the sperm had morphological acrosome reactions, regardless of the time of exposure or the concentration of antibody. There was morphological evidence of swelling of the acrosomal matrix in over 50% of the sperm following exposure to anti-PH-20 antibodies. Anti-PH-20 Fab fragments did not induce the acrosome reaction or acrosomal matrix swelling. Sperm bound to macaque zona pellucida also showed aggregation of the PH-20 protein as soon as 30 sec after sperm-zona interaction. This aggregation was not observed when macaque sperm were bound to hamster zona pellucida. When macaque sperm were surface-labeled with biotin and then incubated with anti-PH-20 antibodies or macaque zona pellucida, there was no evidence of a global surface protein rearrangement, although PH-20 protein was aggregated on the surface of the same sperm cells. An increase in levels of internal sperm Ca++ was measured in association with the antibody-induced PH-20 aggregation. Fab fragments did not increase Ca++ levels, but when they were crosslinked with anti-Fab antibody there was a significant Ca++ increase and induction of acrosome reactions. Anti-PH-20 Fab fragments did not block macaque sperm binding to macaque zona pellucida or the zona-induced acrosome reaction. We conclude that PH-20 on the sperm surface is involved in sperm-zona pellucida interaction and the zona-induced acrosome reaction.
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PMID:Rearrangement of the PH-20 protein on the surface of macaque spermatozoa following exposure to anti-PH-20 antibodies or binding to zona pellucida. 959 May 38

The human HYAL2 gene encodes a lysosomal hyaluronidase that is related to the testicular PH-20 hyaluronidase. Regions conserved in these proteins have been used to design PCR primers suitable for the isolation of a fragment of the murine Hyal2 gene. This fragment was used to isolate the Hyal2 cDNA from a cDNA library. The cloned cDNA has an open reading frame of 473 codons and a 3'-untranslated region of 302 bases plus a poly(A) tail. Using this cDNA, the corresponding genomic DNA was characterized from 129SVJ mice. The murine Hyal2 gene is approximately 3.5 kb, contains the coding sequence for the mRNA on four exons, and is localized on chromosome 9 between the microsatellite markers D9Mit183 and D9Mit17 near the genes for dystroglycan and transferrin. The gene is expressed ubiquitously, the sole exception being adult brain.
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PMID:Structural organization and chromosomal localization of Hyal2, a gene encoding a lysosomal hyaluronidase. 979 Jul 70

The accumulation of hyaluronan (HA) in the renal cortex is a characteristic feature of inflammatory renal diseases. Fragments of HA derived from high molecular weight precursors are known to display inflammatory effects in vitro and could, therefore, participate in immune renal injury. To understand the mechanisms of HA fragmentation in vivo we examined the expression of recently characterized mammalian hyaluronidases in normal and autoimmune kidneys and in cell lines. We found that transcripts for the lysosomal-type hyaluronidases Hyal1 and Hyal2 were constitutively expressed in normal and autoimmune kidneys as well as in tubular epithelial cells and in a macrophage cell line. The expression of hyaluronidase genes in the cell lines did not increase in response to treatment with tumor necrosis factor alpha or gamma interferon. Interestingly, transcripts for the testicular-type hyaluronidase PH-20 (Spam1, Hyal3) were also detected in normal and autoimmune kidneys as well as in tubular cells and macrophages. Transcript levels were higher in kidneys from male mice as compared with age-matched females. Again, transcript levels did not change in vitro in response to cytokines. We conclude that mRNA for three different hyaluronidases is found in murine kidneys. The functional role played by these hyaluronidases in the degradation and metabolism of HA remains to be investigated further.
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PMID:Expression profile of hyaluronidase mRNA transcripts in the kidney and in renal cells. 993 25

Hyaluronic acid (HA) is a component of the extracellular matrix (ECM) that exists as a high molecular weight polymer composed of alternating disaccharides, D-glucuronic acid and N-acetyl D-glucosamine. The interaction of hyaluronidase with HA results in the disruption of basement membrane integrity and produces an angiogenic response that has been implicated in tumor invasiveness and metastasis. Although hyaluronidase is present in several neoplasms, levels of hyaluronidase expression in breast cancer are not known. This investigation defines the correlation of elevated levels of hyaluronidase with breast adenocarcinoma invasiveness. Utilizing RT-PCR, RNA was extracted from paraffin embedded tissues (n=6) of patients diagnosed with fibrocystic breast changes, ductal carcinoma in situ (DCIS), and invasive adenocarcinoma. After constructing cDNA primers for base pairs 504 and 759 of the PH-20 gene (which is homologous to the hyaluronidase gene), PCR was performed and the products were visualized with ethidium bromide using gel electrophoresis. Invasive breast adenocarcinoma had a significantly higher level of hyaluronidase expression compared to other breast tissue samples; (32+/-15 vs. 8+/-3; p<0.03). Elevated levels of hyaluronidase correlated with invasive breast adenocarcinoma. Our data suggests that elevated levels of hyaluronidase are associated with breast adenocarcinoma invasive potential. Hyaluronidase may play an integral role in breast cancer invasion and metastasis.
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PMID:Association of hyaluronidase and breast adenocarcinoma invasiveness. 1020

The sperm plasma membrane protein PH-20 has previously been shown to be an effective immunogen for protection against fertilization in guinea pigs. To identify immunodominant regions on gpPH-20 that may be related to this contraceptive effect, we used several high-titer immune sera obtained from animals rendered infertile by gpPH-20 injections to screen a set of overlapping peptides that cover the entire 494-residue sequence. Multiple clusters of peptide sequences exhibited specific reactivity. Some of these sequences were then constructed as octameric synthetic peptides and tested for immunogenicity in female guinea pigs. Our results indicated two regions (res. 94-119 and res. 424-444) to be highly immunogenic and both are surface accessible when native gpPH-20 is in solution or anchored on sperm surface. Both anti-peptide antibodies are specific for gpPH-20 and one of them inhibited hyaluronidase activity partially. These monospecific antibodies should be useful probes for further molecular definition of gpPH-20 structure-function relationships.
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PMID:Identification of linear surface epitopes on the guinea pig sperm membrane protein PH-20. 1037 24

Two new members of a family of putative hyaluronidase genes involved in glycosaminoglycan catabolism have been identified and mapped by FISH and YAC library screening to chromosome 7q31.3. One of these (HYALP1) is an expressed pseudogene with mutations in the genomic DNA and cDNA. The six members of the hyaluronidase family are grouped into two tightly linked triplets on human chromosomes 3p21.3 (HYAL1, HYAL2, and HYAL3) and 7q31.3 (HYAL4, SPAM1 (PH-20), and HYALP1). This arrangement could arise by an ancient cluster formation, followed by a more recent cluster block-duplication. All of the hyaluronidase genes have unique tissue-specific expression patterns as determined by Northern blot analysis of 23 human tissues. HYAL1, HYAL2, and HYALP1 are widely expressed, but HYAL3 is differentially expressed in bone marrow and testis, while HYAL4 is differentially expressed in placenta and skeletal muscle. SPAM1 (PH-20) was detectable only in testis by Northern blot as previously reported, but was detectable in fetal and placental cDNA libraries by PCR, suggesting a possible role for this gene during embryonic development.
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PMID:Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31. 1049 34

Rat sperm 2B1 antigen (the orthologue of guinea pig sperm PH20) is a plasma membrane-bound glycoprotein that is endoproteolytically cleaved during passage through the epididymis and subsequently migrates from the tail to the acrosomal domain during capacitation. Unlike guinea pig PH20, however, sperm surface 2B1 is insensitive to phosphatidylinositol phospholipase C, nor is it known how endoproteolytic cleavage affects its hyaluronidase activity. In this investigation we have expressed 2B1 cDNA in Chinese hamster ovary cells; we have shown that it contains an internal sequence motif for attachment of a glycosyl phosphatidylinositol (GPI) anchor and that cleavage from a single- into a two-chain molecule causes a significant shift in the optimum pH for hyaluronidase activity. Functionally, these results suggest that 1) 2B1 glycoprotein on rat spermatozoa is attached to the plasma membrane via a GPI anchor and that this is an important factor in its ability to migrate from the tail to the acrosomal domain during capacitation; and 2) endoproteolytic cleavage of 2B1 serves to optimize its hyaluronidase activity immediately before fertilization, thereby facilitating penetration of spermatozoa through the cumulus oophorus.
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PMID:Rat sperm 2B1 glycoprotein (PH20) contains a C-terminal sequence motif for attachment of a glycosyl phosphatidylinositol anchor. Effects of endoproteolytic cleavage on hyaluronidase activity. 1081 70

Some properties of the multiple forms of human hyaluronidases in somatic tissues and in body fluids were investigated. Liver and placenta exhibited seven hyaluronidase forms when analyzed electrophoretically on a polyacrylamide-hyaluronan gel. Ovary, breast, myometrium, endometrium, skin, leukocytes and platelets displayed distinct patterns of enzymatic micropolydispersity. The most acidic forms of hyaluronidase were in synovial fluid and serum, some serum exhibited an additional basic form. Following sialidase treatment, the number of forms decreased to two in placenta, three in liver and to a broad basic form in serum. The native serum and placental hyaluronidases remained fully active after thermal inactivation but desialylated hyaluronidase was inactivated slowly in serum, and quickly in placenta suggesting a higher overall glycosylation of the plasma enzyme. Potential N-glycosylation sites were searched in the amino acid sequences of six human hyaluronidases and several hyaluronidases from different mammalian species using the PROSITE motif database. A potential N-glycosylation site (site 1) with similar tripeptide patterns was observed at the same position in human plasma (HYAL1), human lysosomes (HYAL2) and in two newly reported hyaluronidases (HYAL4 and HYALP1). The same site was also present in mouse plasma (HYAL1) and mouse lysosomes (HYAL2), and in rat lysosomes (HYAL2). This site was absent in human HYAL3 and in all sperm hyaluronidases (PH-20) studied (human, macaque, mouse, guinea pig, rabbit and fox). A second potential N-glycosylation site was observed at a location further in the polypeptide chain. This site is present in all mammalian hyaluronidase isoenzymes reported in the present study whatever the species and organ localization. The pattern at site 2 is NVT for all hyaluronidases except for hyaluronidases of lysosomal origin where it is NVS. Such conserved sites strongly suggest that they may represent actual N-glycosylation sites.
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PMID:Human hyaluronidases: electrophoretic multiple forms in somatic tissues and body fluids. Evidence for conserved hyaluronidase potential N-glycosylation sites in different mammalian species. 1098 27

The gene for the sperm adhesion molecule 1 (PH-20), SPAM1, has been known to be testis-specific and exclusively haploid expressed. We show that in mice, the 2 common isoforms of the protein (Spam1) observed in sperm are also present in the caput, corpus, and cauda epididymides. Both qualitative and quantitative variation of expression of the protein were observed in epididymis with the highest expression detected in the corpus. The endogenous production of enzymatically active (via hyaluronidase) Spam1 by epididymal cells is supported by the detection of steady-state Spam1 epididymal messenger RNA in both wild type and germ cell-deficient mice. In situ transcript hybridization shows the transcript to be localized to the principal cells of the epithelium. The protein was similarly immunolocalized to these cells, predominantly in vesicles near the apical region. The results suggest a mechanism for transportation of Spam1 from the epididymal epithelium to sperm during their transit and storage in the cauda. None of the current categories of spermatogenic-expressed genes shows the dual transcription pattern (haploid testicular/diploid epididymal) observed for Spam1. The work also confirms and extends the finding that Spam1 is expressed in the kidney.
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PMID:Mouse Spam1 (PH-20): evidence for its expression in the epididymis and for a new category of spermatogenic-expressed genes. 1110 8


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