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 ... See more...

Aliases for HYAL2 Gene

Aliases for HYAL2 Gene

  • Hyaluronidase 2 2 3 5
  • Hyaluronoglucosaminidase 2 2 3
  • Lung Carcinoma Protein 2 3 4
  • Lysosomal Hyaluronidase 2 3
  • Hyaluronidase-2 3 4
  • PH-20 Homolog 2 3
  • EC 3.2.1.35 4 52
  • Hyal-2 3 4
  • LUCA2 3 4
  • Hyaluronoglucosaminidase-2 4
  • PH20 Homolog 3
  • LuCa-2 4

External Ids for HYAL2 Gene

Previous GeneCards Identifiers for HYAL2 Gene

  • GC03P049626
  • GC03P049796
  • GC03M050209
  • GC03M050314
  • GC03M050330
  • GC03M050355

Summaries for HYAL2 Gene

Entrez Gene Summary for HYAL2 Gene

  • 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]

GeneCards Summary for HYAL2 Gene

HYAL2 (Hyaluronidase 2) is a Protein Coding gene. Diseases associated with HYAL2 include Cleft Lip And Palate-Craniofacial Dysmorphism-Congenital Heart Defect-Hearing Loss Syndrome and Cor Triatriatum Sinister. Among its related pathways are Microglia Activation During Neuroinflammation: Overview and Metabolism. Gene Ontology (GO) annotations related to this gene include enzyme binding and virus receptor activity. An important paralog of this gene is HYAL1.

UniProtKB/Swiss-Prot Summary for HYAL2 Gene

  • Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product which is further hydrolyzed by sperm hyaluronidase to give small oligosaccharides. Displays very low levels of activity. Associates with and negatively regulates MST1R.

Gene Wiki entry for HYAL2 Gene

Additional gene information for HYAL2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HYAL2 Gene

Genomics for HYAL2 Gene

GeneHancer (GH) Regulatory Elements for HYAL2 Gene

Promoters and enhancers for HYAL2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J050316 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 500.7 +2.2 2240 9.1 FOXK2 ZBTB40 ZNF217 EP300 CTCF NRF1 MYC POLR2G USF1 SP1 HYAL2 RBM6 AMT RBM5 HYAL3 RHOA-IT1 TMEM115 SEMA3F-AS1 HEMK1 GMPPB
GH03J050154 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 4 +159.2 159181 19 EP300 FOXK2 POLR2G NCOR1 FOS ZFX CTCF ZIC2 REST POLR2A SEMA3F RBM6 ENSG00000230454 RBM5 NAA80 MON1A GNAI2 HYAL3 NICN1 CYB561D2
GH03J050327 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 0.4 -5.1 -5065 2.2 ZBTB40 ZNF217 TCF12 POLR2G SP1 PHF8 ZFX ZNF10 REST POLR2A TUSC2 HYAL3 NAA80 HYAL1 MST1 HYAL2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HYAL2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HYAL2

Top Transcription factor binding sites by QIAGEN in the HYAL2 gene promoter:
  • ATF-2

Genomic Locations for HYAL2 Gene

Genomic Locations for HYAL2 Gene
chr3:50,317,790-50,322,850
(GRCh38/hg38)
Size:
5,061 bases
Orientation:
Minus strand
chr3:50,355,221-50,360,337
(GRCh37/hg19)
Size:
5,117 bases
Orientation:
Minus strand

Genomic View for HYAL2 Gene

Genes around HYAL2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HYAL2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HYAL2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HYAL2 Gene

Proteins for HYAL2 Gene

  • Protein details for HYAL2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q12891-HYAL2_HUMAN
    Recommended name:
    Hyaluronidase-2
    Protein Accession:
    Q12891
    Secondary Accessions:
    • B3KRZ2
    • O15177
    • Q9BW29

    Protein attributes for HYAL2 Gene

    Size:
    473 amino acids
    Molecular mass:
    53860 Da
    Quaternary structure:
    • Interacts with MST1R.
    SequenceCaution:
    • Sequence=AAC28656.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

neXtProt entry for HYAL2 Gene

Selected DME Specific Peptides for HYAL2 Gene

Q12891:
  • ELKPTAPPIFTGRPFVVAW
  • NDQLAWLWAE
  • GHGRCVR
  • QNITIFY
  • WRPVWVRNWQ
  • YLFPDCYN
  • GLAVIDWE
  • RNFVSFRV
  • YTGRCPDVEV

Post-translational modifications for HYAL2 Gene

  • Glycosylation at Asn74, Asn103, and Asn357
  • Modification sites at PhosphoSitePlus

Domains & Families for HYAL2 Gene

Gene Families for HYAL2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for HYAL2 Gene

Blocks:
  • Type I EGF
  • Glycosyl hydrolase family 56 signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for HYAL2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ46055 fis, clone SYNOV4009139, highly similar to Hyaluronidase-2 (EC 3.2.1.35) (B3KRZ2_HUMAN)
  • Lung carcinoma protein 2 (HYAL2_HUMAN)
  • Hyaluronoglucosaminidase 2 (Q5ZEZ9_HUMAN)
  • Hyaluronoglucosaminidase 2 (Q5ZF00_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q12891

UniProtKB/Swiss-Prot:

HYAL2_HUMAN :
  • Belongs to the glycosyl hydrolase 56 family.
Family:
  • Belongs to the glycosyl hydrolase 56 family.
genes like me logo Genes that share domains with HYAL2: view

Function for HYAL2 Gene

Molecular function for HYAL2 Gene

UniProtKB/Swiss-Prot Function:
Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product which is further hydrolyzed by sperm hyaluronidase to give small oligosaccharides. Displays very low levels of activity. Associates with and negatively regulates MST1R.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.; EC=3.2.1.35;.
GENATLAS Biochemistry:
hyaluroglucosaminidase 2,lysosomal,ubiquitously expressed,but not in adult brain,related to testicular SPAM1,involved in glycosaminoglycan catabolism

Enzyme Numbers (IUBMB) for HYAL2 Gene

Phenotypes From GWAS Catalog for HYAL2 Gene

Gene Ontology (GO) - Molecular Function for HYAL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001618 virus receptor activity IDA 11296287
GO:0003713 transcription coactivator activity IEA --
GO:0003824 catalytic activity IEA --
GO:0004415 hyalurononglucosaminidase activity TAS,IEA --
GO:0005515 protein binding IPI 12676986
genes like me logo Genes that share ontologies with HYAL2: view
genes like me logo Genes that share phenotypes with HYAL2: view

Animal Models for HYAL2 Gene

MGI Knock Outs for HYAL2:

Animal Model Products

  • Taconic Biosciences Mouse Models for HYAL2

CRISPR Products

Clone Products

No data available for Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for HYAL2 Gene

Localization for HYAL2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HYAL2 Gene

Cell membrane; Lipid-anchor, GPI-anchor.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HYAL2 gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 5
lysosome 5
nucleus 4
cytosol 4
golgi apparatus 4
extracellular 3
cytoskeleton 1
mitochondrion 1
endosome 1
peroxisome 0

Gene Ontology (GO) - Cellular Components for HYAL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane ISS 21740893
GO:0005737 cytoplasm IDA 17170110
GO:0005764 lysosome IDA 9712871
GO:0005783 endoplasmic reticulum NAS 16191204
GO:0005829 cytosol IDA 19366691
genes like me logo Genes that share ontologies with HYAL2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HYAL2 Gene

Pathways & Interactions for HYAL2 Gene

genes like me logo Genes that share pathways with HYAL2: view

Gene Ontology (GO) - Biological Process for HYAL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000302 response to reactive oxygen species IDA 20554532
GO:0001822 kidney development ISS --
GO:0002244 hematopoietic progenitor cell differentiation IEA --
GO:0005975 carbohydrate metabolic process IEA --
GO:0006027 glycosaminoglycan catabolic process IDA 9712871
genes like me logo Genes that share ontologies with HYAL2: view

No data available for SIGNOR curated interactions for HYAL2 Gene

Drugs & Compounds for HYAL2 Gene

(3) Drugs for HYAL2 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Water Approved Pharma 0

(4) Additional Compounds for HYAL2 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
N-Acetylgalactosamine
  • 2-(acetylamino)-2-Deoxy-alpha-D-galactopyranose
  • alpha-GalNAc
  • alpha-GalpNAc
  • GalNAc-alpha
  • Tn
1811-31-0
N-Acetylgalactosamine 4-sulphate
  • 2-(acetylamino)-2-Deoxy-D-galactose 4-(hydrogen sulfate)
  • 2-(acetylamino)-2-Deoxy-D-galactose 4-(hydrogen sulphate)
  • GalNAc4S
  • N-Acetyl-D-galactosamine 4-sulfate
  • N-Acetyl-D-galactosamine 4-sulphate
45233-43-0
genes like me logo Genes that share compounds with HYAL2: view

Transcripts for HYAL2 Gene

mRNA/cDNA for HYAL2 Gene

2 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for HYAL2 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b · 2c ^ 3a · 3b · 3c ^ 4a · 4b · 4c · 4d ^ 5 ^ 6
SP1: - - - -
SP2: - - - - - -
SP3: - - - - -
SP4:
SP5: -
SP6:

Relevant External Links for HYAL2 Gene

GeneLoc Exon Structure for
HYAL2

Expression for HYAL2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HYAL2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HYAL2 Gene

This gene is overexpressed in Spleen (x7.6).

Protein differential expression in normal tissues from HIPED for HYAL2 Gene

This gene is overexpressed in Heart (46.7), Lung (10.7), and Placenta (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HYAL2 Gene



Protein tissue co-expression partners for HYAL2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HYAL2

SOURCE GeneReport for Unigene cluster for HYAL2 Gene:

Hs.76873

mRNA Expression by UniProt/SwissProt for HYAL2 Gene:

Q12891-HYAL2_HUMAN
Tissue specificity: Widely expressed. No expression detected in adult brain.

Evidence on tissue expression from TISSUES for HYAL2 Gene

  • Nervous system(4.6)
  • Kidney(4.5)
  • Lung(3.4)
  • Spleen(2.3)
  • Skin(2.1)
genes like me logo Genes that share expression patterns with HYAL2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for HYAL2 Gene

Orthologs for HYAL2 Gene

This gene was present in the common ancestor of animals.

Orthologs for HYAL2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia HYAL2 31 30
  • 99.3 (n)
OneToOne
dog
(Canis familiaris)
Mammalia HYAL2 31 30
  • 86.62 (n)
OneToOne
cow
(Bos Taurus)
Mammalia HYAL2 31 30
  • 85.74 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Hyal2 17 31 30
  • 83.37 (n)
rat
(Rattus norvegicus)
Mammalia Hyal2 30
  • 82.59 (n)
oppossum
(Monodelphis domestica)
Mammalia HYAL2 31
  • 63 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia HYAL2 31
  • 63 (a)
OneToOne
chicken
(Gallus gallus)
Aves HYAL2 31 30
  • 65.37 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HYAL2 31
  • 56 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia hyal2 30
  • 63.04 (n)
Str.14988 30
African clawed frog
(Xenopus laevis)
Amphibia hyal2-prov 30
zebrafish
(Danio rerio)
Actinopterygii hyal2 31 30
  • 57.27 (n)
OneToMany
HYAL2 (3 of 3) 31
  • 46 (a)
OneToMany
HYAL2 (1 of 3) 31
  • 46 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea T22C8.2 32
  • 31 (a)
chhy-1 31
  • 26 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 39 (a)
OneToMany
Species where no ortholog for HYAL2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for HYAL2 Gene

ENSEMBL:
Gene Tree for HYAL2 (if available)
TreeFam:
Gene Tree for HYAL2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HYAL2: view image

Paralogs for HYAL2 Gene

Paralogs for HYAL2 Gene

(4) SIMAP similar genes for HYAL2 Gene using alignment to 8 proteins:

  • HYAL2_HUMAN
  • C9J700_HUMAN
  • C9JBF5_HUMAN
  • C9JSD1_HUMAN
  • C9JSI7_HUMAN
  • C9K016_HUMAN
  • Q5ZEZ9_HUMAN
  • Q5ZF00_HUMAN
genes like me logo Genes that share paralogs with HYAL2: view

Variants for HYAL2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HYAL2 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
746855 Benign: not provided 50,319,737(-) A/G SYNONYMOUS_VARIANT
rs35455589 - p.Ile418Leu
rs709210 - p.Ser18Ala

Additional dbSNP identifiers (rs#s) for HYAL2 Gene

Structural Variations from Database of Genomic Variants (DGV) for HYAL2 Gene

Variant ID Type Subtype PubMed ID
dgv8317n54 CNV loss 21841781
esv2759148 CNV loss 17122850
nsv3813 CNV deletion 18451855
nsv460531 CNV loss 19166990
nsv470561 CNV loss 18288195
nsv523662 CNV loss 19592680
nsv590255 CNV loss 21841781
nsv834692 CNV loss 17160897
nsv834693 CNV loss 17160897
nsv954855 CNV deletion 24416366

Variation tolerance for HYAL2 Gene

Residual Variation Intolerance Score: 11.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.65; 82.81% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HYAL2 Gene

Human Gene Mutation Database (HGMD)
HYAL2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HYAL2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HYAL2 Gene

Disorders for HYAL2 Gene

MalaCards: The human disease database

(8) MalaCards diseases for HYAL2 Gene - From: Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
cleft lip and palate-craniofacial dysmorphism-congenital heart defect-hearing loss syndrome
  • hyaluronidase 2 deficiency
cor triatriatum sinister
  • cor triatriatum sinistrum
cor triatriatum
  • triatrial heart
mucopolysaccharidosis, type ix
  • mps9
bronchiolo-alveolar adenocarcinoma
  • bronchioalveolar lung carcinoma
- elite association - COSMIC cancer census association via MalaCards
Search HYAL2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HYAL2

genes like me logo Genes that share disorders with HYAL2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HYAL2 Gene

Publications for HYAL2 Gene

  1. HYAL2, a human gene expressed in many cells, encodes a lysosomal hyaluronidase with a novel type of specificity. (PMID: 9712871) Lepperdinger G … Kreil G (The Journal of biological chemistry 1998) 2 3 4 23 54
  2. Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus. (PMID: 12676986) Danilkovitch-Miagkova A … Lerman MI (Proceedings of the National Academy of Sciences of the United States of America 2003) 3 4 23 54
  3. Candidate tumor suppressor HYAL2 is a glycosylphosphatidylinositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation. (PMID: 11296287) Rai SK … Miller AD (Proceedings of the National Academy of Sciences of the United States of America 2001) 3 4 23 54
  4. Hyal2--less active, but more versatile? (PMID: 11731268) Lepperdinger G … Kreil G (Matrix biology : journal of the International Society for Matrix Biology 2001) 3 4 23 54
  5. Structural organization and chromosomal localization of Hyal2, a gene encoding a lysosomal hyaluronidase. (PMID: 9790770) Strobl B … Lepperdinger G (Genomics 1998) 2 3 23 54

Products for HYAL2 Gene

Sources for HYAL2 Gene