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HYAL1 (hyaluronoglucosaminidase 1)

Written2007-10Demitrios H Vynios
Department of Chemistry, University of Patras, 26500 Patras, Greece

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)LUCA1
HYAL-1
FUS2
NAT6
Other aliasEC 3.2.1.35
NT6
LUCA-1
Hyaluronidase-1 precursor
Hyaluronoglucosaminidase-1
Hs.75619
MGC45987
HGNC (Hugo) HYAL1
LocusID (NCBI) 3373
Atlas_Id 40903
Location 3p21.31  [Link to chromosome band 3p21]
Location_base_pair Starts at 50299889 and ends at 50303601 bp from pter ( according to hg19-Feb_2009)  [Mapping HYAL1.png]
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

Note HYAL1 is a secreted somatic tissue hyaluronidase, and the predominant hyaluronidase in human plasma. Although HYAL1 is predominantly secreted, it has an acid pH optimum in vitro. HYAL1 can degrade high molecular weight hyaluronan to small oligomers, primarily to tetrasaccharides, whereas HYAL2 (the other major human hyaluronidase) high molecular mass hyaluronan to an approximately 20 kDa product (approximatively 50 saccharide units).
 
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

Note
  
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.
  

Bibliography

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
 
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
 
Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31.
Csóka AB, Scherer SW, Stern R
Genomics. 1999 ; 60 (3) : 356-361.
PMID 10493834
 
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
 
Purification, cloning, and expression of human plasma hyaluronidase.
Frost GI, Csóka AB, Wong T, Stern R
Biochemical and biophysical research communications. 1997 ; 236 (1) : 10-15.
PMID 9223416
 
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, Csóka AB, Gray JW, Stern R
Oncogene. 2000 ; 19 (7) : 870-877.
PMID 10702795
 
Structures of vertebrate hyaluronidases and their unique enzymatic mechanism of hydrolysis.
Jedrzejas MJ, Stern R
Proteins. 2005 ; 61 (2) : 227-238.
PMID 16104017
 
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
 
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
 
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
 
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
 
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
 
Hyaluronidases: their genomics, structures, and mechanisms of action.
Stern R, Jedrzejas MJ
Chemical reviews. 2006 ; 106 (3) : 818-839.
PMID 16522010
 
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
 

Citation

This paper should be referenced as such :
Vynios, DH
HYAL1 (hyaluronoglucosaminidase 1)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(3):217-219.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/HYAL1ID40903ch3p21.html


External links

Nomenclature
HGNC (Hugo)HYAL1   5320
Cards
AtlasHYAL1ID40903ch3p21
Entrez_Gene (NCBI)HYAL1  3373  hyaluronoglucosaminidase 1
AliasesHYAL-1; LUCA1; MPS9; NAT6
GeneCards (Weizmann)HYAL1
Ensembl hg19 (Hinxton)ENSG00000114378 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000114378 [Gene_View]  chr3:50299889-50303601 [Contig_View]  HYAL1 [Vega]
ICGC DataPortalENSG00000114378
TCGA cBioPortalHYAL1
AceView (NCBI)HYAL1
Genatlas (Paris)HYAL1
WikiGenes3373
SOURCE (Princeton)HYAL1
Genetics Home Reference (NIH)HYAL1
Genomic and cartography
GoldenPath hg38 (UCSC)HYAL1  -     chr3:50299889-50303601 -  3p21.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)HYAL1  -     3p21.31   [Description]    (hg19-Feb_2009)
EnsemblHYAL1 - 3p21.31 [CytoView hg19]  HYAL1 - 3p21.31 [CytoView hg38]
Mapping of homologs : NCBIHYAL1 [Mapview hg19]  HYAL1 [Mapview hg38]
OMIM601492   607071   
Gene and transcription
Genbank (Entrez)AF118821 AF173154 AF502904 AF502905 AF502906
RefSeq transcript (Entrez)NM_033159 NM_153281 NM_153282 NM_153283 NM_153284 NM_153285 NM_153286
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)HYAL1
Cluster EST : UnigeneHs.75619 [ NCBI ]
CGAP (NCI)Hs.75619
Alternative Splicing GalleryENSG00000114378
Gene ExpressionHYAL1 [ NCBI-GEO ]   HYAL1 [ EBI - ARRAY_EXPRESS ]   HYAL1 [ SEEK ]   HYAL1 [ MEM ]
Gene Expression Viewer (FireBrowse)HYAL1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3373
GTEX Portal (Tissue expression)HYAL1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ12794   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ12794  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ12794
Splice isoforms : SwissVarQ12794
Catalytic activity : Enzyme3.2.1.35 [ Enzyme-Expasy ]   3.2.1.353.2.1.35 [ IntEnz-EBI ]   3.2.1.35 [ BRENDA ]   3.2.1.35 [ KEGG ]   
PhosPhoSitePlusQ12794
Domaine pattern : Prosite (Expaxy)EGF_2 (PS01186)   
Domains : Interpro (EBI)Aldolase_TIM    Glycoside_hydrolase_SF    Hyaluronidase   
Domain families : Pfam (Sanger)Glyco_hydro_56 (PF01630)   
Domain families : Pfam (NCBI)pfam01630   
Conserved Domain (NCBI)HYAL1
DMDM Disease mutations3373
Blocks (Seattle)HYAL1
PDB (SRS)2PE4   
PDB (PDBSum)2PE4   
PDB (IMB)2PE4   
PDB (RSDB)2PE4   
Structural Biology KnowledgeBase2PE4   
SCOP (Structural Classification of Proteins)2PE4   
CATH (Classification of proteins structures)2PE4   
SuperfamilyQ12794
Human Protein AtlasENSG00000114378
Peptide AtlasQ12794
HPRD06146
IPIIPI00178140   IPI00168847   IPI00170520   IPI00170521   IPI00170522   IPI00170523   IPI00654773   IPI00926970   IPI00926767   
Protein Interaction databases
DIP (DOE-UCLA)Q12794
IntAct (EBI)Q12794
FunCoupENSG00000114378
BioGRIDHYAL1
STRING (EMBL)HYAL1
ZODIACHYAL1
Ontologies - Pathways
QuickGOQ12794
Ontology : AmiGOresponse to reactive oxygen species  virus receptor activity  hyalurononglucosaminidase activity  hyalurononglucosaminidase activity  extracellular space  cytoplasm  lysosome  carbohydrate metabolic process  inflammatory response  transcription factor binding  response to virus  positive regulation of epithelial cell migration  chondroitin sulfate catabolic process  hyaluronan metabolic process  hyaluronan biosynthetic process  hyaluronan catabolic process  hyaluronan catabolic process  positive regulation of cell growth  negative regulation of cell growth  cytoplasmic vesicle  hyaluranon cable  cellular response to platelet-derived growth factor stimulus  lysosomal lumen  cellular response to fibroblast growth factor stimulus  positive regulation of angiogenesis  positive regulation of angiogenesis  positive regulation of cell adhesion  positive regulation of growth  response to antibiotic  hyaluronan synthase activity  positive regulation of epithelial cell proliferation  cartilage development  embryonic skeletal joint morphogenesis  extracellular exosome  cellular response to interleukin-1  cellular response to tumor necrosis factor  cellular response to pH  cellular response to UV-B  positive regulation of G1/S transition of mitotic cell cycle  positive regulation of hyaluranon cable assembly  
Ontology : EGO-EBIresponse to reactive oxygen species  virus receptor activity  hyalurononglucosaminidase activity  hyalurononglucosaminidase activity  extracellular space  cytoplasm  lysosome  carbohydrate metabolic process  inflammatory response  transcription factor binding  response to virus  positive regulation of epithelial cell migration  chondroitin sulfate catabolic process  hyaluronan metabolic process  hyaluronan biosynthetic process  hyaluronan catabolic process  hyaluronan catabolic process  positive regulation of cell growth  negative regulation of cell growth  cytoplasmic vesicle  hyaluranon cable  cellular response to platelet-derived growth factor stimulus  lysosomal lumen  cellular response to fibroblast growth factor stimulus  positive regulation of angiogenesis  positive regulation of angiogenesis  positive regulation of cell adhesion  positive regulation of growth  response to antibiotic  hyaluronan synthase activity  positive regulation of epithelial cell proliferation  cartilage development  embryonic skeletal joint morphogenesis  extracellular exosome  cellular response to interleukin-1  cellular response to tumor necrosis factor  cellular response to pH  cellular response to UV-B  positive regulation of G1/S transition of mitotic cell cycle  positive regulation of hyaluranon cable assembly  
Pathways : KEGGGlycosaminoglycan degradation    Lysosome   
REACTOMEQ12794 [protein]
REACTOME PathwaysR-HSA-2160916 [pathway]   
NDEx NetworkHYAL1
Atlas of Cancer Signalling NetworkHYAL1
Wikipedia pathwaysHYAL1
Orthology - Evolution
OrthoDB3373
GeneTree (enSembl)ENSG00000114378
Phylogenetic Trees/Animal Genes : TreeFamHYAL1
HOVERGENQ12794
HOGENOMQ12794
Homologs : HomoloGeneHYAL1
Homology/Alignments : Family Browser (UCSC)HYAL1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerHYAL1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HYAL1
dbVarHYAL1
ClinVarHYAL1
1000_GenomesHYAL1 
Exome Variant ServerHYAL1
ExAC (Exome Aggregation Consortium)HYAL1 (select the gene name)
Genetic variants : HAPMAP3373
Genomic Variants (DGV)HYAL1 [DGVbeta]
DECIPHERHYAL1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisHYAL1 
Mutations
ICGC Data PortalHYAL1 
TCGA Data PortalHYAL1 
Broad Tumor PortalHYAL1
OASIS PortalHYAL1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICHYAL1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDHYAL1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch HYAL1
DgiDB (Drug Gene Interaction Database)HYAL1
DoCM (Curated mutations)HYAL1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)HYAL1 (select a term)
intoGenHYAL1
NCG5 (London)HYAL1
Cancer3DHYAL1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM601492    607071   
Orphanet10901   
MedgenHYAL1
Genetic Testing Registry HYAL1
NextProtQ12794 [Medical]
TSGene3373
GENETestsHYAL1
Target ValidationHYAL1
Huge Navigator HYAL1 [HugePedia]
snp3D : Map Gene to Disease3373
BioCentury BCIQHYAL1
ClinGenHYAL1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3373
Chemical/Pharm GKB GenePA29571
Clinical trialHYAL1
Miscellaneous
canSAR (ICR)HYAL1 (select the gene name)
Probes
Litterature
PubMed67 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineHYAL1
EVEXHYAL1
GoPubMedHYAL1
iHOPHYAL1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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