Summary: Hyaluronidase protein (HylP)

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Wikipedia: Hyaluronidase
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Hyaluronidase Edit Wikipedia article

hyaluronoglucosaminidase

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PDB structures

AmiGO / EGO

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PMC	articles
PubMed	articles
NCBI	proteins

Hyaluronidase protein (HylP)

Identifiers

Symbol

Hyaluronidase_1

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Hyaluronidase

Identifiers

Symbol

Hyaluronidase_2

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

The hyaluronidases (EC 3.2.1.35) are a family of enzymes that degrade hyaluronic acid.

In humans, there are six associated genes, including HYAL1, HYAL2, HYAL3, and PH-20/SPAM1.^[1]

[edit] Use as a drug

Hyaluronidase
Systematic (IUPAC) name
hyaluronidase
Clinical data
AHFS/Drugs.com	Consumer Drug Information
Pregnancy cat.	C
Legal status	?
Routes	subcutaneous
Identifiers
CAS number	488712-31-8^Y
ATC code	B06AA03
DrugBank	DB00070
UNII	8KOG53Z5EM^Y
ChEMBL	CHEMBL1201636^N
Chemical data
Formula	C₂₄₅₅H₃₇₇₅N₆₁₇O₇₀₄S₂₁
Mol. mass	53870.9 g/mol
N (what is this?) (verify)

By catalyzing the hydrolysis of hyaluronan, a constituent of the extracellular matrix (ECM), hyaluronidase lowers the viscosity of hyaluronan, thereby increasing tissue permeability. It is, therefore, used in medicine in conjunction with other drugs to speed their dispersion and delivery. Common applications are ophthalmic surgery, in combination with local anesthetics. It also increases the absorption rate of parenteral fluids given by hypodermoclysis, and is an adjunct in subcutaneous urography for improving resorption of radiopaque agents. Hyaluronidase is also used for extravasation of hyperosmolar solutions.

Brand names of animal-derived hyaluronidase include Hydase^TM (developed and manufactured by PrimaPharm Inc., distributed by Akorn Inc.), which has been FDA-approved as a "thimerosal-free" animal-derived hyaluronidase, Vitrase (ISTA Pharmaceuticals), Amphadase (Amphastar Pharmaceuticals), and Wydase. Wydase, however, is no longer manufactured.

On December 2, 2005, the FDA approved a synthetic (recombinant or rDNA) "human" hyaluronidase, Hylenex (Halozyme Therapeutics).^[2]

[edit] Role in cancer

The role of hyaluronidases in cancer is controversial. Limited data support a role of lysosomal hyaluronidases in metastasis, while other data support a role in tumor suppression. Other studies suggest no contribution or effects independent of enzyme activity. Non-specific inhibitors (apigenin, sulfated glycosaminoglycans) or crude enzyme extracts have been used to test most hypotheses, making data difficult to interpret. It has been hypothesized that, by helping degrade the ECM surrounding the tumor, hyaluronidases help cancer cells escape from primary tumor masses. However, studies show that removal of hyaluronan from tumors prevents tumor invasion. Hyaluronidases are also thought to play a role in the process of angiogenesis, although most hyaluronidase preparations are contaminated with large amounts of angiogeneic growth factors.^[3] As previously mentioned, there are six hyaluronidase genes in the human genome, three of which can express active hyaluronidases (HYAL1, HYAL2 and PH20).

[edit] Role in pathogenesis

Some bacteria, such as Staphylococcus aureus, Streptococcus pyogenes,^[4] and Clostridium perfringens,^[5] produce hyaluronidase as a means of using hyaluronan as a carbon source. It is often speculated that Streptococcus and Staphylococcus pathogens use hyaluronidase as a virulence factor to destroy the polysaccharide that holds animal cells together, making it easier for the pathogen to spread through the tissues of the host organism, but no valid experimental data are available to support this hypothesis.

[edit] Role in fertilization

In most mammalian fertilization, hyaluronidase is released by the acrosome of the sperm cell after it has reached the oocyte, by digesting hyaluronan in the corona radiata, thus enabling conception. Gene-targeting studies show that hyaluronidases such as PH20 are not essential for fertilization, although exogenous hyaluronidases can disrupt the cumulus matrix.

The majority of mammalian ova are covered in a layer of granulosa cells intertwined in an ECM that contains a high concentration of hyaluronan. When a capacitated sperm reaches the ovum, it is able to penetrate this layer with the assistance of hyaluronidase enzymes present on the surface of the sperm. Once this occurs, the sperm is capable of binding with the zona pellucida, and the acrosome reaction can occur.^[6]

[edit] References

^ Csoka AB, Frost GI, Stern R (December 2001). "The six hyaluronidase-like genes in the human and mouse genomes". Matrix biology : journal of the International Society for Matrix Biology 20 (8): 499â508. doi:10.1016/S0945-053X(01)00172-X. PMID 11731267.
^ "Halozyme Therapeutics and Baxter Healthcare Corporation Announce FDA Approval of Hylenex". Retrieved 2008-11-07. ^{[dead link]}
^ <Int J Cancer. 2002 Feb 10;97(5):601-7>[1]
^ Starr CR, Engleberg NC (January 2006). "Role of hyaluronidase in subcutaneous spread and growth of group A streptococcus". Infection and immunity 74 (1): 40â8. doi:10.1128/IAI.74.1.40-48.2006. PMC 1346594. PMID 16368955.
^ Zukaite V, Biziulevicius GA (March 2000). "Acceleration of hyaluronidase production in the course of batch cultivation of Clostridium perfringens can be achieved with bacteriolytic enzymes". Letters in applied microbiology 30 (3): 203â6. doi:10.1046/j.1472-765x.2000.00693.x. PMID 10747251.
^ Alberts, Bruce (2008). Molecular biology of the cell. New York: Garland Science. p. 1298. ISBN 0-8153-4105-9.

[edit] External links

Hyaluronidase at the US National Library of Medicine Medical Subject Headings (MeSH)

Hydrolase: sugar hydrolases (EC 3.2)

3.2.1: Glycoside hydrolases

Disaccharidase	Sucrase/Sucrase-isomaltase/Invertase Maltase Trehalase Lactase

Glucosidases	Cellulase Alpha-glucosidase Acid Neutral AB Neutral C Beta-glucosidase cytosolic Debranching enzyme

Other	Amylase Alpha-amylase Chitinase Lysozyme Neuraminidase NEU1 NEU2 NEU3 NEU4 Bacterial neuraminidase Viral neuraminidase Galactosidases Alpha Beta alpha-Mannosidase Glucuronidase Hyaluronidase Pullulanase Glucosylceramidase lysosomal non-lysosomal Galactosylceramidase Alpha-N-acetylgalactosaminidase NAGA Alpha-N-acetylglucosaminidase Fucosidase Hexosaminidase HEXA HEXB Iduronidase Maltase-glucoamylase Heparanase HPSE2

3.2.2: Hydrolysing
N-Glycosyl compounds

DNA glycosylases: Oxoguanine glycosylase

B
enzm
1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
2.7.10
2.7.11-12
3.1
- - 3.1.3.48
- 2
- 3
- 4
  - 3.4.21
- 5
- 6
- 7
- 22
- 23
- 24
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Hyaluronidase protein (HylP) Provide feedback

This family consists of several phage associated hyaluronidase proteins ( EC:3.2.1.35) which seem to be specific to Streptococcus pyogenes and Streptococcus pyogenes bacteriophages. The substrate of hyaluronidase is hyaluronic acid, a sugar polymer composed of alternating N-acetylglucosamine and glucuronic acid residues. Hyaluronic acid is found in the ground substance of human connective tissue and the vitreous of the eye and also is the sole component of the capsule of group A streptococci. The capsule has been shown to be an important virulence factor of this organism by virtue of its ability to resist phagocytosis. Production by S. pyogenes of both a hyaluronic acid capsule and hyaluronidase enzymatic activity capable of destroying the capsule is an interesting, yet-unexplained, phenomenon [1].

Literature references

Hynes WL, Hancock L, Ferretti JJ; , Infect Immun 1995;63:3015-3020.: Analysis of a second bacteriophage hyaluronidase gene from Streptococcus pyogenes: evidence for a third hyaluronidase involved in extracellular enzymatic activity. PUBMED:7622224 EPMC:7622224

External database links

PANDIT:	PF07212
Pseudofam:	PF07212
SYSTERS:	Hyaluronidase_1

This tab holds annotation information from the InterPro database.

InterPro entry IPR009860

This family consists of several phage associated hyaluronidase proteins (EC) which seem to be specific to Streptococcus pyogenes and its bacteriophages. The substrate of hyaluronidase is hyaluronic acid, a sugar polymer composed of alternating N-acetylglucosamine and glucuronic acid residues. Hyaluronic acid is found in the ground substance of human connective tissue and the vitreous of the eye and also is the sole component of the capsule of group A streptococci. The capsule has been shown to be an important virulence factor of this organism by virtue of its ability to resist phagocytosis. Production by S. pyogenes of both a hyaluronic acid capsule and hyaluronidase enzymatic activity capable of destroying the capsule is an interesting, yet-unexplained, phenomenon [PUBMED:7622224].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Molecular function	hyalurononglucosaminidase activity (GO:0004415)
Biological process	capsule polysaccharide biosynthetic process (GO:0045227)

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (2)	Full (54)	Representative proteomes				NCBI (52)	Meta (2)
	Seed (2)	Full (54)	RP15 (1)	RP35 (5)	RP55 (6)	RP75 (6)	NCBI (52)	Meta (2)
Jalview	View	View	View	View	View	View	View	View
HTML	View	View	View	View	View	View
PP/heatmap	₁	View	View	View	View	View
Pfam viewer	View	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (2)	Full (54)	Representative proteomes				NCBI (52)	Meta (2)
	Seed (2)	Full (54)	RP15 (1)	RP35 (5)	RP55 (6)	RP75 (6)	NCBI (52)	Meta (2)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (2)	Full (54)	Representative proteomes				NCBI (52)	Meta (2)
	Seed (2)	Full (54)	RP15 (1)	RP35 (5)	RP55 (6)	RP75 (6)	NCBI (52)	Meta (2)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Pfam-B_16578 (release 10.0)

Previous IDs:

Hyaluronidase;

Type:

Family

Author:

Moxon SJ

Number in seed:

2

Number in full:

54

Average length of the domain:

239.80 aa

Average identity of full alignment:

70 %

Average coverage of the sequence by the domain:

77.07 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	25.0	25.0
Trusted cut-off	37.3	56.6
Noise cut-off	19.6	19.6

Model length:

277

Family (HMM) version:

6

Download:

download the raw HMM for this family

Species distribution

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How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

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Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

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Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

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Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

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Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

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Interactions

There is 1 interaction for this family. More...

Hyaluronidase_1

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Hyaluronidase_1 domain has been found. There are 8 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

Loading structure mapping...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: Hyaluronidase_1 (PF07212)

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Summary: Hyaluronidase protein (HylP)

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Hyaluronidase Edit Wikipedia article

Contents

[edit] Use as a drug

[edit] Role in cancer

[edit] Role in pathogenesis

[edit] Role in fertilization

[edit] References

[edit] External links

Hyaluronidase protein (HylP) Provide feedback

Literature references

External database links

InterPro entry IPR009860

Gene Ontology

Domain organisation

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

Selections

Currently selected:

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Interactions

Structures