HYAL2 hyaluronidase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HYAL2provided by HGNC
Official Full Name: hyaluronidase 2provided by HGNC
Primary source: HGNC:HGNC:5321
See related: Ensembl:ENSG00000068001 MIM:603551; AllianceGenome:HGNC:5321
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LUCA2
Summary: 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]
Expression: Broad expression in spleen (RPKM 78.9), lung (RPKM 35.1) and 20 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.31

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (50317808..50322745, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (50347534..50352469, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (50355239..50360176, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Elucidating the clinical spectrum and molecular basis of HYAL2 deficiency.
Title: Elucidating the clinical spectrum and molecular basis of HYAL2 deficiency.
[Detection of DNA methylation of HYAL2 gene for differentiating malignant from benign thyroid tumors].
Title: [Detection of DNA methylation of HYAL2 gene for differentiating malignant from benign thyroid tumors].
Hyal2 Expression in Tumor-Associated Myeloid Cells Mediates Cancer-Related Inflammation in Bladder Cancer.
Title: Hyal2 Expression in Tumor-Associated Myeloid Cells Mediates Cancer-Related Inflammation in Bladder Cancer.
Expression and activity of hyaluronidases HYAL-1, HYAL-2 and HYAL-3 in the human intervertebral disc.
Title: Expression and activity of hyaluronidases HYAL-1, HYAL-2 and HYAL-3 in the human intervertebral disc.
HYAL1/2 suppress colorectal cancer cell metastasis by regulating MMPs/TIMPs balance and rearranging F-actin distribution, inhibiting invasion and migration of cancer cells.
Title: The suppressive role of HYAL1 and HYAL2 in the metastasis of colorectal cancer.
we discovered the existence of p47(phox) /Hyal2 complex. LSS induced the dissociation of p47(phox) /Hyal2 complex, which was inhibited by LKB1 overexpression and AICAR. Furthermore, knockdown of Hyal2 performed a positive feedback on LKB1 activity
Title: Hyaluronidase2 (Hyal2) modulates low shear stress-induced glycocalyx impairment via the LKB1/AMPK/NADPH oxidase-dependent pathway.
an important role for HYAL2 in CD44 alternative splicing.
Title: Nuclear hyaluronidase 2 drives alternative splicing of CD44 pre-mRNA to determine profibrotic or antifibrotic cell phenotype.
genetic variation in HYAL2 influences platelet aggregation
Title: Whole exome sequencing in the Framingham Heart Study identifies rare variation in HYAL2 that influences platelet aggregation.
Knocking down HYAL2 in HUVECs protected against HA degradation in the glycocalyx by inhibiting the expression and activity of HYAL2 and further blocked the dephosphorylation of eNOS-Ser-633 and the decrease in NO production in response to LSS.
Title: The role of HYAL2 in LSS-induced glycocalyx impairment and the PKA-mediated decrease in eNOS-Ser-633 phosphorylation and nitric oxide production.
HYAL2 mutations identified as a cause of syndromic orofacial clefting and cor triatriatum sinister in amish families.
Title: Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice.

Submit: New GeneRIF Correction See all GeneRIFs (37)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-U09577 (e-PCR)
- UniSTS:4387

STS-W79515 (e-PCR)
- UniSTS:67707

STS-U09577 (e-PCR)
- UniSTS:56477

RH91527 (e-PCR)
- UniSTS:85214

PMC26875P5 (e-PCR)
- UniSTS:272362

PMC26875P6 (e-PCR)
- UniSTS:272363

PMC26875P7 (e-PCR)
- UniSTS:272364

PMC26875P8 (e-PCR)
- UniSTS:272365

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables hyaluronic acid binding	IDA Inferred from Direct Assay more info	PubMed
enables hyaluronoglucuronidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables hyaluronoglucuronidase activity	IDA Inferred from Direct Assay more info	PubMed
NOT enables hyalurononglucosaminidase activity	IDA Inferred from Direct Assay more info	PubMed
enables hyalurononglucosaminidase activity	IDA Inferred from Direct Assay more info	PubMed
enables hyalurononglucosaminidase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor signaling protein tyrosine kinase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables receptor tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription coactivator activity	IEA Inferred from Electronic Annotation more info
enables transforming growth factor beta binding	ISS Inferred from Sequence or Structural Similarity more info
enables virus receptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in carbohydrate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in cartilage development	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to UV-B	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to fibroblast growth factor stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to interleukin-1	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to transforming growth factor beta stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to tumor necrosis factor	IEP Inferred from Expression Pattern more info	PubMed
involved_in defense response to virus	IEA Inferred from Electronic Annotation more info
involved_in fusion of virus membrane with host plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in glycosaminoglycan catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in hematopoietic progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in hyaluronan catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in hyaluronan catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in hyaluronan catabolic process	TAS Traceable Author Statement more info
involved_in kidney development	ISS Inferred from Sequence or Structural Similarity more info
involved_in monocyte activation	IDA Inferred from Direct Assay more info	PubMed
involved_in multicellular organismal-level iron ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of MAP kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of fibroblast migration	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of extrinsic apoptotic signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-6 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein import into nucleus	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of urine volume	ISS Inferred from Sequence or Structural Similarity more info
involved_in renal water absorption	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to antibiotic	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to reactive oxygen species	IDA Inferred from Direct Assay more info	PubMed
involved_in response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in skeletal system morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in symbiont entry into host cell	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in Golgi membrane	ISS Inferred from Sequence or Structural Similarity more info	PubMed
part_of RNA polymerase II transcription regulator complex	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasmic vesicle	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in endocytic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	NAS Non-traceable Author Statement more info	PubMed
colocalizes_with external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
located_in microvillus	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: hyaluronidase-2

Names: PH-20 homolog; PH20 homolog; hyal-2; hyaluronoglucosaminidase 2; lung carcinoma protein 2; lysosomal hyaluronidase

NP_003764.3

EC 3.2.1.35

NP_149348.2

EC 3.2.1.35

XP_005265581.1

EC 3.2.1.35

XP_005265582.1

EC 3.2.1.35

XP_054204214.1

EC 3.2.1.35

XP_054204215.1

EC 3.2.1.35

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_003773.5 → NP_003764.3 hyaluronidase-2 precursor

See identical proteins and their annotated locations for NP_003764.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AK127945, DC358776, U09577

Consensus CDS

CCDS2818.1

UniProtKB/Swiss-Prot

B3KRZ2, O15177, Q12891, Q9BW29

Related

ENSP00000350387.4, ENST00000357750.9

Conserved Domains (1) summary

pfam01630
Location:29 → 358

Glyco_hydro_56; Hyaluronidase
NM_033158.5 → NP_149348.2 hyaluronidase-2 precursor

See identical proteins and their annotated locations for NP_149348.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AK092449, AK127945, DC358776, U09577

Consensus CDS

CCDS2818.1

UniProtKB/Swiss-Prot

B3KRZ2, O15177, Q12891, Q9BW29

Related

ENSP00000406657.1, ENST00000442581.1

Conserved Domains (1) summary

pfam01630
Location:29 → 358

Glyco_hydro_56; Hyaluronidase