Summary: Hyaluronidase

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Wikipedia: Glycoside hydrolase family 56
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Glycoside hydrolase family 56 Edit Wikipedia article

Hyaluronidase

crystal structure of bee venom hyaluronidase in complex with hyaluronic acid tetramer

Identifiers

Symbol

Glyco_hydro_56

Pfam clan

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

In molecular biology, glycoside hydrolase family 56 is a family of glycoside hydrolases.

Glycoside hydrolases EC 3.2.1. are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycoside hydrolases, based on sequence similarity, has led to the definition of >100 different families.^[1]^[2]^[3] This classification is available on the CAZy(http://www.cazy.org/GH1.html) web site,^[4] and also discussed at CAZypedia, an online encyclopedia of carbohydrate active enzymes.^[5]

Glycoside hydrolase family 56 CAZY GH_56 includes enzymes with hyaluronidase EC 3.2.1.35 activity. The venom of Apis mellifera (Honeybee) contains several biologically-active peptides and two enzymes, one of which is a hyaluronidase.^[6] The amino acid sequence of bee venom hyaluronidase contains 349 amino acids, and includes four cysteines and a number of potential glycosylation sites.^[6] The sequence shows a high degree of similarity to PH-20, a membrane protein of mammalian sperm involved in sperm-egg adhesion, supporting the view that hyaluronidases play a role in fertilisation.^[6]

PH-20 is required for sperm adhesion to the egg zona pellucida; it is located on both the sperm plasma membrane and acrosomal membrane.^[7] The amino acid sequence of the mature protein contains 468 amino acids, and includes six potential N-linked glycosylation sites and twelve cysteines, eight of which are tightly clustered near the C-terminus.^[7]

References

^ Henrissat B, Callebaut I, Mornon JP, Fabrega S, Lehn P, Davies G (1995). "Conserved catalytic machinery and the prediction of a common fold for several families of glycosyl hydrolases". Proc. Natl. Acad. Sci. U.S.A. 92 (15): 7090–7094. doi:10.1073/pnas.92.15.7090. PMC 41477. PMID 7624375.
^ Henrissat B, Davies G (1995). "Structures and mechanisms of glycosyl hydrolases". Structure. 3 (9): 853–859. doi:10.1016/S0969-2126(01)00220-9. PMID 8535779.
^ Bairoch, A. "Classification of glycosyl hydrolase families and index of glycosyl hydrolase entries in SWISS-PROT". 1999.
^ Henrissat, B. and Coutinho P.M. "Carbohydrate-Active Enzymes server". 1999.
^ CAZypedia, an online encyclopedia of carbohydrate-active enzymes.
^ ^a ^b ^c Gmachl M, Kreil G (1993). "Bee venom hyaluronidase is homologous to a membrane protein of mammalian sperm". Proc. Natl. Acad. Sci. U.S.A. 90 (8): 3569–3573. doi:10.1073/pnas.90.8.3569. PMC 46342. PMID 7682712.
^ ^a ^b Lathrop WF, Carmichael EP, Myles DG, Primakoff P (1990). "cDNA cloning reveals the molecular structure of a sperm surface protein, PH-20, involved in sperm-egg adhesion and the wide distribution of its gene among mammals". J. Cell Biol. 111 (6): 2939–2949. doi:10.1083/jcb.111.6.2939. PMC 2116349. PMID 2269661.

This article incorporates text from the public domain Pfam and InterPro IPR018155

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

v t e Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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

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Hyaluronidase Provide feedback

No Pfam abstract.

Literature references

Gmachl M, Sagan S, Ketter S, Kreil G; , FEBS Lett 1993;336:545-548.: The human sperm protein PH-20 has hyaluronidase activity. PUBMED:8282124 EPMC:8282124

External database links

CAZY:	GH56
SCOP:	1fcv

This tab holds annotation information from the InterPro database.

InterPro entry IPR018155

O-Glycosyl hydrolases (EC) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [PUBMED:7624375, PUBMED:8535779]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site.

Glycoside hydrolase family 56 CAZY comprises enzymes with only one known activity; hyaluronidase EC.

The venom of Apis mellifera (Honeybee) contains several biologically-active peptides and two enzymes, one of which is a hyaluronidase [PUBMED:7682712]. The amino acid sequence of bee venom hyaluronidase contains 349 amino acids, and includes four cysteines and a number of potential glycosylation sites [PUBMED:7682712]. The sequence shows a high degree of similarity to PH-20, a membrane protein of mammalian sperm involved in sperm-egg adhesion, supporting the view that hyaluronidases play a role in fertilisation [PUBMED:7682712].

PH-20 is required for sperm adhesion to the egg zona pellucida; it is located on both the sperm plasma membrane and acrosomal membrane [PUBMED:2269661]. The amino acid sequence of the mature protein contains 468 amino acids, and includes six potential N-linked glycosylation sites and twelve cysteines, eight of which are tightly clustered near the C terminus [PUBMED:2269661].

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	carbohydrate metabolic process (GO:0005975)

Domain organisation

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

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Pfam Clan

This family is a member of clan Glyco_hydro_tim (CL0058), which has the following description:

This large superfamily contains a range of glycosyl hydrolase enzymes that possess a TIM barrel fold. This CLAN merges clans GH-A, GH-D, GH-H and GH-K from CAZy.

The clan contains the following 54 members:

Alpha-amylase Alpha_L_fucos Cellulase Cellulase-like DUF4015 DUF4038 DUF4434 DUF4838 DUF4849 GHL10 GHL13 GHL15 GHL5 GHL6 Glyco_hydr_30_2 Glyco_hydro_1 Glyco_hydro_10 Glyco_hydro_101 Glyco_hydro_114 Glyco_hydro_129 Glyco_hydro_14 Glyco_hydro_17 Glyco_hydro_18 Glyco_hydro_20 Glyco_hydro_25 Glyco_hydro_26 Glyco_hydro_2_C Glyco_hydro_3 Glyco_hydro_30 Glyco_hydro_31 Glyco_hydro_35 Glyco_hydro_39 Glyco_hydro_42 Glyco_hydro_44 Glyco_hydro_53 Glyco_hydro_56 Glyco_hydro_59 Glyco_hydro_66 Glyco_hydro_70 Glyco_hydro_71 Glyco_hydro_72 Glyco_hydro_77 Glyco_hydro_79n Glyco_hydro_85 Glyco_hydro_97 Glyco_hydro_99 Glyco_hydro_cc Glyco_tran_WbsX hDGE_amylase Melibiase Melibiase_2 NAGidase NAGLU Raffinose_syn

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM
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

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

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You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

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 (130)	Full (864)	Representative proteomes				UniProt (1410)	NCBI (2670)	Meta (2)
	Seed (130)	Full (864)	RP15 (216)	RP35 (363)	RP55 (593)	RP75 (752)	UniProt (1410)	NCBI (2670)	Meta (2)
Jalview	View	View	View	View	View	View	View	View	View
HTML	View	View
PP/heatmap	₁	View

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

Key: available, not generated, — not available.

Format an alignment

	Seed (130)	Full (864)	Representative proteomes				UniProt (1410)	NCBI (2670)	Meta (2)
	Seed (130)	Full (864)	RP15 (216)	RP35 (363)	RP55 (593)	RP75 (752)	UniProt (1410)	NCBI (2670)	Meta (2)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

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 (130)	Full (864)	Representative proteomes				UniProt (1410)	NCBI (2670)	Meta (2)
	Seed (130)	Full (864)	RP15 (216)	RP35 (363)	RP55 (593)	RP75 (752)	UniProt (1410)	NCBI (2670)	Meta (2)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	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.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

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_1150 (release 4.1)

Previous IDs:

none

Type:

Domain

Author:

Bateman A

Number in seed:

130

Number in full:

864

Average length of the domain:

266.70 aa

Average identity of full alignment:

35 %

Average coverage of the sequence by the domain:

73.79 %

HMM information

HMM build commands:

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

search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	18.7	18.7
Trusted cut-off	18.7	18.8
Noise cut-off	18.4	18.3

Model length:

336

Family (HMM) version:

17

Download:

download the raw HMM for this family

Species distribution

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Archea	Eukaryota
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

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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As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

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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.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

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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Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

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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.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

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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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 Glyco_hydro_56 domain has been found. There are 6 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.

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Family: Glyco_hydro_56 (PF01630)

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