Atlas of Genetics and Cytogenetics in Oncology and Haematology
HYAL1 (hyaluronoglucosaminidase 1)
| Identity |
| Other names | EC 3.2.1.35 |
| HYAL-1 | |
| NT6 | |
| LUCA1 | |
| LUCA-1 | |
| FUS2 | |
| Hyaluronidase-1 precursor | |
| Hyaluronoglucosaminidase-1 | |
| Hs.75619 | |
| MGC45987 | |
| HGNC | HYAL1 |
| Location | 3p21.3 |
| Location_base_pair | Starts at 50312325 and ends at 50316008 bp from pter (hg18-Mar_2006). |
| Local_order | The gene of Hyal1 is tightly clustered with HYAL-2 and HYAL-3. The gene for Hyal-2, HYAL2, the earliest known lysosomal hyaluronidase, resides immediately centromeric to HYAL1. |
 | |
| Note | The HYAL1 gene was identified as identical with LUCA-1, a candidate tumour suppressor gene, especially for tobacco-related cancers. |
| DNA/RNA |
| Description | The HYAL1 gene contains three exons and spans 12,492 bases (start: 50,312,324 bp to end 50,324,816 from 13pter) oriented at the minus strand. |
| Transcription | Eight alternatively spliced transcript variants of this gene encoding six distinct isoforms have been described. The longest transcript has a length of 2,518 bps, however it is not translated to protein, since, by retaining intron 1 (occurring within exon 1), it has a number of stop codons. The longest transcript that produces active HYAL1 has a length of 2075 bps. |
| Pseudogene | PHYAL1 |
| Protein |
 | |
| Description | Size: 435 amino acids; Molecular mass: 48368 Da. The enzyme belongs to the group of carbohydrate-active enzymes (CASy), termed glycosyl hydrolase 56 family. |
| Expression | HYAL1 is highly expressed in liver, kidney and heart and weakly expressed in lung, placenta and skeletal muscle. No expression is detected in adult brain. Isoform 1 is expressed only in bladder and prostate cancer cells, G2/G3 bladder tumor tissues and lymph node specimens showing tumor invasive tumors cells. Isoform 3, isoform 4, isoform 5 and isoform 6 are expressed in normal bladder and bladder tumor tissues. HYAL1 expression has been described in squamous cell carcinoma, in small cell lung cancer and glioma lines. |
| Localisation | It is a secreted enzyme found in plasma and it is also present in lysosomes. |
| Function | It is a hydrolytic enzyme (endo-beta-acetyl-D-hexosaminidase) with optimum pH about 3.7, acting on hyaluronan, chondroitin and chondroitin sulphate. It possesses also transglycosidase activity using hyaluronan and chondroitin sulphate or chondroitin as substrates. This reaction is not well understood, and the precise enzymatic mechanism is not known. |
| Homology | The enzyme possesses 70-80 % homology to orthologue hyaluronidases, 40% homology to paralogue hyaluronidases of the human and high homology with HYAL1 of other species. |
| Mutations |
| Somatic | There are not extended reports regarding mutations of HYAL1 gene. The patient with hyaluronidase deficiency was a compound heterozygote for two mutations in the HYAL1 gene: a 1412G-A mutation that introduced a nonconservative amino acid substitution (glu268 to lys) in a putative active site residue, and a complex intragenic rearrangement, 1361del37ins14, that resulted in a premature termination codon. In addition, the mutated HYAL1 gene has a markedly different expression pattern than the normal one. |
| Implicated in |
| Entity | Mucopolysaccharidosis type IX (MPS9). |
| Note | Defects in HYAL1 are the cause of mucopolysaccharidosis type IX, also called hyaluronidase deficiency. |
| Disease | The clinical features are periarticular soft tissue masses, mild short stature and acetabular erosions, absence of neurological or visceral involvement and high hyaluronan concentration in the serum. |
| Entity | Cancer |
| Note | HYAL1 is inactivated in most lung cancers in a conventional manner, by loss of heterozygosity or by homozygous deletion, at the DNA level. It is also inactivated in many head and neck carcinomas that are tobacco-related by aberrant splicing of the mRNA, so that only the nontranslatable form is transcribed. In addition, the expression of an alternative spliced isoform resulting in active enzyme may negatively regulate bladder tumor growth, infiltration, and angiogenesis. On the other hand, HYAL1 can function as oncogene in many cancers of the prostate and urinary tract and seems to play important role in squamous cell laryngeal carcinoma. |
| External links |
| Bibliography |
| Purification and microsequencing of hyaluronidase isozymes from human urine. |
| Csˆ„ka AB, Frost GI, Wong T, Stern R |
| FEBS letters. 1997 ; 417 (3) : 307-310. |
| PMID 9409739 |
| Purification, cloning, and expression of human plasma hyaluronidase. |
| Frost GI, Csˆ„ka AB, Wong T, Stern R |
| Biochemical and biophysical research communications. 1997 ; 236 (1) : 10-15. |
| PMID 9223416 |
| The hyaluronidase gene HYAL1 maps to chromosome 3p21.2-p21.3 in human and 9F1-F2 in mouse, a conserved candidate tumor suppressor locus. |
| Csˆ„ka AB, Frost GI, Heng HH, Scherer SW, Mohapatra G, Stern R |
| Genomics. 1998 ; 48 (1) : 63-70. |
| PMID 9503017 |
| HYAL2, a human gene expressed in many cells, encodes a lysosomal hyaluronidase with a novel type of specificity. |
| Lepperdinger G, Strobl B, Kreil G |
| The Journal of biological chemistry. 1998 ; 273 (35) : 22466-22470. |
| PMID 9712871 |
| Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31. |
| Csˆ„ka AB, Scherer SW, Stern R |
| Genomics. 1999 ; 60 (3) : 356-361. |
| PMID 10493834 |
| Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX. |
| Triggs-Raine B, Salo TJ, Zhang H, Wicklow BA, Natowicz MR |
| Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (11) : 6296-6300. |
| PMID 10339581 |
| HYAL1LUCA-1, a candidate tumor suppressor gene on chromosome 3p21.3, is inactivated in head and neck squamous cell carcinomas by aberrant splicing of pre-mRNA. |
| Frost GI, Mohapatra G, Wong TM, Csˆ„ka AB, Gray JW, Stern R |
| Oncogene. 2000 ; 19 (7) : 870-877. |
| PMID 10702795 |
| The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. |
| Lerman MI, Minna JD |
| Cancer research. 2000 ; 60 (21) : 6116-6133. |
| PMID 11085536 |
| The six hyaluronidase-like genes in the human and mouse genomes. |
| Csoka AB, Frost GI, Stern R |
| Matrix biology : journal of the International Society for Matrix Biology. 2001 ; 20 (8) : 499-508. |
| PMID 11731267 |
| Regulation of hyaluronidase activity by alternative mRNA splicing. |
| Lokeshwar VB, Schroeder GL, Carey RI, Soloway MS, Iida N |
| The Journal of biological chemistry. 2002 ; 277 (37) : 33654-33663. |
| PMID 12084718 |
| Characterization of the murine hyaluronidase gene region reveals complex organization and cotranscription of Hyal1 with downstream genes, Fus2 and Hyal3. |
| Shuttleworth TL, Wilson MD, Wicklow BA, Wilkins JA, Triggs-Raine BL |
| The Journal of biological chemistry. 2002 ; 277 (25) : 23008-23018. |
| PMID 11929860 |
| Expression and regulation patterns of hyaluronidases in small cell lung cancer and glioma lines. |
| Junker N, Latini S, Petersen LN, Kristjansen PE |
| Oncology reports. 2003 ; 10 (3) : 609-616. |
| PMID 12684632 |
| Structures of vertebrate hyaluronidases and their unique enzymatic mechanism of hydrolysis. |
| Jedrzejas MJ, Stern R |
| Proteins. 2005 ; 61 (2) : 227-238. |
| PMID 16104017 |
| HYAL1 hyaluronidase in prostate cancer: a tumor promoter and suppressor. |
| Lokeshwar VB, Cerwinka WH, Isoyama T, Lokeshwar BL |
| Cancer research. 2005 ; 65 (17) : 7782-7789. |
| PMID 16140946 |
| Hyaluronidase and CD44 hyaluronan receptor expression in squamous cell laryngeal carcinoma. |
| Christopoulos TA, Papageorgakopoulou N, Theocharis DA, Mastronikolis NS, Papadas TA, Vynios DH |
| Biochimica et biophysica acta. 2006 ; 1760 (7) : 1039-1045. |
| PMID 16713680 |
| HYAL1-v1, an alternatively spliced variant of HYAL1 hyaluronidase: a negative regulator of bladder cancer. |
| Lokeshwar VB, Estrella V, Lopez L, Kramer M, Gomez P, Soloway MS, Lokeshwar BL |
| Cancer research. 2006 ; 66 (23) : 11219-11227. |
| PMID 17145867 |
| Hyaluronidases: their genomics, structures, and mechanisms of action. |
| Stern R, Jedrzejas MJ |
| Chemical reviews. 2006 ; 106 (3) : 818-839. |
| PMID 16522010 |
| Structure of human hyaluronidase-1, a hyaluronan hydrolyzing enzyme involved in tumor growth and angiogenesis. |
| Chao KL, Muthukumar L, Herzberg O |
| Biochemistry. 2007 ; 46 (23) : 6911-6920. |
| PMID 17503783 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 10-2007 | Demitrios H Vynios |
| Department of Chemistry, University of Patras, 26500 Patras, Greece |
| Citation |
| This paper should be referenced as such : |
| Vynios DH . HYAL1 (hyaluronoglucosaminidase 1). Atlas Genet Cytogenet Oncol Haematol. October 2007 . URL : http://AtlasGeneticsOncology.org/Genes/HYAL1ID40903ch3p21.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Oct 11 12:52:16 2008 |
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