HYAL2

Official Full Name

hyaluronidase 2

Organism

Homo sapiens

Gene ID

8692

Background

This gene encodes a weak acid-active hyaluronidase. The encoded protein is similar in structure to other more active hyaluronidases. Hyaluronidases degrade hyaluronan, one of the major glycosaminoglycans of the extracellular matrix. Hyaluronan and fragments of hyaluronan are thought to be involved in cell proliferation, migration and differentiation. Although it was previously thought to be a lysosomal hyaluronidase that is active at a pH below 4, the encoded protein is likely a GPI-anchored cell surface protein. This hyaluronidase serves as a receptor for the oncogenic virus Jaagsiekte sheep retrovirus. The gene is one of several related genes in a region of chromosome 3p21.3 associated with tumor suppression. This gene encodes two alternatively spliced transcript variants which differ only in the 5' UTR.[provided by RefSeq, Mar 2010]

Synonyms

MCCS; LUCA2

Cat.No.	Product Name	Price
CSC-DC007365	Panoply™ Human HYAL2 Knockdown Stable Cell Line	Inquiry
CSC-SC007365	Panoply™ Human HYAL2 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD07841Z	Human HYAL2 adenoviral particles	Inquiry
LV15105L	human HYAL2 (NM_033158) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH136919	shRNA set against Mouse Hyal2(NM_010489.2)	Inquiry
SHH136937	shRNA set against Rat Hyal2(NM_172040.2)	Inquiry
SHH136955	shRNA set against Human HYAL2(NM_033158.4)	Inquiry
SHH316161	shRNA set against Human HYAL2 (NM_003773.4)	Inquiry
SHH316165	shRNA set against Mouse HYAL2 (NM_010489.2)	Inquiry
SHH316169	shRNA set against Rat HYAL2 (NM_172040.2)	Inquiry

Cat.No.	Product Name	Price
CDFL005970	Mouse Hyal2 cDNA Clone(NM_010489.2)	Inquiry
CDFR014712	Rat Hyal2 cDNA Clone(NM_172040.2)	Inquiry
MiUTR1H-04765	HYAL2 miRNA 3'UTR clone	Inquiry
MiUTR1M-05863	HYAL2 miRNA 3'UTR clone	Inquiry
MiUTR1R-02557	HYAL2 miRNA 3'UTR clone	Inquiry
MiUTR3H-06068	HYAL2 miRNA 3'UTR clone	Inquiry
CDCB159228	Human HYAL2 ORF clone (BC000692)	Inquiry
CDCB180414	Rabbit HYAL2 ORF clone (XM_008260692.1)	Inquiry
CDCL119033	Mouse Hyal2 ORF clone (NM_010489.2)	Inquiry
CDCR381593	Rat Hyal2 ORF Clone(NM_172040.2)	Inquiry
CDCS411452	Human HYAL2 ORF Clone (BC000692)	Inquiry

Cat.No.	Product Name	Price
CC-664	Hyal2 Easy KO Kit (Mouse)	Inquiry
CC-665	Hyal2 Easy KO Kit (Human)	Inquiry

Detailed Information

Recent Research Progress

Hyaluronidase 2 (HYAL2) is a membrane-anchored protein that is proposed to initiate the degradation of hyaluronan (HA) in the extracellular matrix. Increasing researches has identified the importance of HA metabolism in several disease processes. As some studies showed, HYAL2 can be detected in many tissues, including the brain. It localize to the surface and cytoplasm of endothelial cells, as well as specialized epithelial cells in several tissues. Accumulated HA detected in tissues from Hyal2-/-mice typically had a higher molecular mass than the control tissue. The accumulated HA is located near areas where HYAL2 is normally found, although it is distant from the site of HYAL2 localization in some tissues. Overall, the content HYAL2 is the highest in tissues from which HA is removed from the circulation (liver, lymph nodes, and spleen), and the levels of HA accumulation in Hyal2-/-mice was highest in tissues of catabolically synthesized HA. The finding of Biswajit Chowdhury et al. supported HYAL2’s role as an extracellular enzyme that initiates HA breakdown in somatic tissues. Meanwhile, HYAL2 contributes to HA degradation through other routes, perhaps as a soluble or secreted form. According to Daisuke Hida et al., CD44 and HYAL2 are bound at the surface of chondrocytes. Enhancement of CD44 shedding by IL-1β resulted in a proportional increase in HYAL2. CD44 knockdown by siRNA also resulted in increased accumulation of HYAL2 in the media of chondrocytes. CD44 and HYAL2 were found to be co-immunoprecipitated and co-localized within the intracellular vesicles and plasma membrane. All these draw a conclusion that the release of HYAL2 could provide a mechanism for weak hyaluronidase activity to occur within cartilage when CD44 is shed.

A recent study revealed a strong association between decreased HYAL2 methylation in peripheral blood and breast cancer (BC), and provided a promising blood-based marker for the detection of early BC. As the study showed, the decreased methylation of HYAL2 was also associated with increased risk of BC. Moreover, the expression and methylation of HYAL2 were inversely correlated with a p-value. To note, the BC-associated decreased HYAL2 methylation was replicated in the T-cell fraction. The methylation level of HYAL2 enabled a powerful discrimination of early stage BC cases (stages 0 and I) from healthy controls, and was robust for the detection of BC in younger women as well. In addition, Rongxi Yang et al. showed the expression of HYAL2 indicated prognostic effect to the overall survival (OS) of triple-negative breast cancer (TNBC) patients. And high expression levels of HYAL2 showed significant association with different clinicopathological characteristics such as more recurrence events and higher occurrence of metastasis.

In addition to breast cancer, HYAL2 is also inextricably linked to colon cancer. Methylation status at HYAL2 can predict overall and progression-free survival of colon cancer patients under 5-FU chemotherapy. DNA methylation variations in gene promoter regions are well documented tumor-specific alterations in human malignancies including colon cancer, which may influence tumor behavior and clinical outcome. As a subset of colon cancer patients does not benefit from adjuvant chemotherapy, predictive biomarkers are desirable. A recent research described that DNA methylation levels at CpG loci of HYLA2 could be used to identify stage II and III colon cancer patients who are most likely to benefit from 5-flourouracil (5-FU) chemotherapy with respect to overall survival and progression-free survival. Patients with methylation levels lower than 10% seem to benefit more from adjuvant 5-FU chemotherapy than those with higher methylation levels and could therefore be suggested for therapy.

References:

Maierthaler M, et al. S100P and HYAL2 as prognostic markers for patients with triple-negative breast cancer. Experimental & Molecular Pathology, 2015, 99(1):180-187.
Yang R, et al. DNA methylation array analyses identified breast cancer‐associated HYAL2 methylation in peripheral blood. International Journal of Cancer, 2015, 136(8):1845-1855.
Chowdhury B, et al. Hyaluronidase 2 (HYAL2) is expressed in endothelial cells, as well as some specialized epithelial cells, and is required for normal hyaluronan catabolism. Histochemistry & Cell Biology, 2016, 145(1):53-66.
Hida D, et al. CD44 knock-down in bovine and human chondrocytes results in release of bound HYAL2. Matrix Biology, 2015, 48:42-54.
Pfütze K, et al. Methylation status at HYAL2 predicts overall and progression-free survival of colon cancer patients under 5-FU chemotherapy. Genomics, 2015, 106(6):348-354.

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