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)

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

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 human genome contains six hyaluronidase-like genes. Three genes (HYAL1, HYAL2 and HYAL3) are clustered on chromosome 3p21.3, and another two genes (HYAL4 and PH-20/SPAM1) and one expressed pseudogene (HYALP1) are similarly clustered on chromosome 7q31.3. The extensive homology between the different hyaluronidase genes suggests ancient gene duplication, followed by en masse block duplication, events that occurred before the emergence of modern mammals. Very recently we have found that the mouse genome also has six hyaluronidase-like genes that are also grouped into two clusters of three, in regions syntenic with the human genome. Surprisingly, the mouse ortholog of HYALP1 does not contain any mutations, and unlike its human counterpart may actually encode an active enzyme. Hyal-1 is the only hyaluronidase in mammalian plasma and urine, and is also found at high levels in major organs such as liver, kidney, spleen, and heart. A model is proposed suggesting that Hyal-2 and Hyal-1 are the major mammalian hyaluronidases in somatic tissues, and that they act in concert to degrade high molecular weight hyaluronan to the tetrasaccharide. Twenty-kDa hyaluronan fragments are generated at the cell surface in unique endocytic vesicles resulting from digestion by the glycosylphosphatidyl-inositol-anchored Hyal-2, transported intracellularly by an unknown process, and then further digested by Hyal-1. The two beta-exoglycosidases, beta-glucuronidase and beta-N-acetyl glucosaminidase, remove sugars from reducing termini of hyaluronan oligomers, and supplement the hyaluronidases in the catabolism of hyaluronan.
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PMID:The six hyaluronidase-like genes in the human and mouse genomes. 1173 Dec 67

Besides SPAM1 (sperm adhesion molecule 1; formerly named PH-20), further hyaluronidase-like proteins, HYAL5 (hyaluronoglucosaminidase 5) and HYALP1 (hyaluronoglucosaminidase pseudogene 1) are also expressed in murine testicular tissue. As they share a high degree of sequence similarity with known hyaluronidases, all three polypeptides could potentially exhibit hyaluronidase activity, a function that is beneficial for spermatozoa in order to penetrate the hyaluronan-rich cumulus, which surrounds the oocyte. Recently, it was reported that SPAM1-deficient mice are fertile and spermatozoa derived from mutant mice still exhibit hyaluronidase activity [Baba, Kashiwabara, Honda, Yamagata, Wu, Ikawa, Okabe and Baba (2002) J. Biol. Chem. 277, 30310-30314]. We have now recombinantly expressed mouse SPAM1, HYAL5 and HYALP1 in Xenopus laevis oocytes and determined their respective expression pattern in testis. Transcripts of all three genes are expressed in seminiferous tubules in regions where maturing spermatogenic cells reside. SPAM1 and HYAL5 but not HYALP1 proteins exhibit hyaluronidase activity at neutral pH. The two active hyaluronidases are both bound to the cell surface via a glycosylphosphatidylinositol anchor. Furthermore, structural characteristics are discussed that are necessary for hyaluronidases in order to exhibit hyaluronan cleavage.
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PMID:Mouse testicular hyaluronidase-like proteins SPAM1 and HYAL5 but not HYALP1 degrade hyaluronan. 1692 24

Hyaluronidases are endoglycosidases that initiate the breakdown of hyaluronan (HA), an abundant component of the vertebrate extracellular matrix. In humans, six paralogous genes encoding hyaluronidase-like sequences have been identified on human chromosomes 3p21.3 (HYAL2-HYAL1-HYAL3) and 7q31.3 (SPAM1-HYAL4-HYALP1). Mutations in one of these genes, HYAL1, were reported in a patient with mucopolysaccharidosis (MPS) IX. Despite the broad distribution of HA, the HYAL1-deficient patient exhibited a mild phenotype, suggesting other hyaluronidase family members contribute to constitutive HA degradation. Hyal3 knockout (Hyal3-/-) mice were generated to determine if HYAL3 had a role in constitutive HA degradation. Hyal3-/- mice were viable, fertile, and exhibited no gross phenotypic changes. X-ray analysis, histological studies of joints, whole-body weights, organ weights and the serum HA levels of Hyal3-/- mice were normal. No evidence of glycosaminoglycan accumulation, including vacuolization, was identified in the Hyal3-/- tissues analyzed. Remarkably, the only difference identified in Hyal3-/- mice was a subtle change in the alveolar structure and extracellular matrix thickness in lung-tissue sections at 12-14 months-of-age. We conclude that HYAL3 does not play a major role in constitutive HA degradation.
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PMID:Hyaluronidase 3 (HYAL3) knockout mice do not display evidence of hyaluronan accumulation. 1876 56

Canine mast cell tumours (CMCT) are one of the most common skin tumours in dogs with a major impact on canine health. Certain breeds have a higher risk of developing mast cell tumours, suggesting that underlying predisposing germ-line genetic factors play a role in the development of this disease. The genetic risk factors are largely unknown, although somatic mutations in the oncogene C-KIT have been detected in a proportion of CMCT, making CMCT a comparative model for mastocytosis in humans where C-KIT mutations are frequent. We have performed a genome wide association study in golden retrievers from two continents and identified separate regions in the genome associated with risk of CMCT in the two populations. Sequence capture of associated regions and subsequent fine mapping in a larger cohort of dogs identified a SNP associated with development of CMCT in the GNAI2 gene (p = 2.2x10-16), introducing an alternative splice form of this gene resulting in a truncated protein. In addition, disease associated haplotypes harbouring the hyaluronidase genes HYAL1, HYAL2 and HYAL3 on cfa20 and HYAL4, SPAM1 and HYALP1 on cfa14 were identified as separate risk factors in European and US golden retrievers, respectively, suggesting that turnover of hyaluronan plays an important role in the development of CMCT.
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PMID:Genome-Wide Association Study of Golden Retrievers Identifies Germ-Line Risk Factors Predisposing to Mast Cell Tumours. 2658 71