Summary: Squalene-hopene cyclase C-terminal domain

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Wikipedia: Prenyltransferase
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InterPro

This is the Wikipedia entry entitled "Prenyltransferase". More...

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Prenyltransferase Edit Wikipedia article

Prenyltransferases are a class of enzymes that transfer allylic prenyl groups to acceptor molecules. Prenyl transferases commonly refer to prenyl diphosphate synthases ^[1].

There are two classes of prenyltransferases, cis (or Z) and trans (or E), depending upon the stereo chemistry of the resulting products. Examples of trans-prenyltranferases include dimethylallyltranstransferase, and geranylgeranyl pyrophosphate synthase. Cis prenyltransferases include dehydrodolichol diphosphate synthase (involved in the production of dolichol precursors.

^ "Chem Rec. 2006;6(4):194-205."

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Squalene-hopene cyclase C-terminal domain Provide feedback

Squalene-hopene cyclase, EC:5.4.99.17, catalyses the cyclisation of squalene into hopene in bacteria. This reaction is part of a cationic cyclisation cascade, which is homologous to a key step in cholesterol biosynthesis. This family is the C-terminal half of the molecule.

Literature references

Wendt KU, Lenhart A, Schulz GE;, J Mol Biol. 1999;286:175-187.: The structure of the membrane protein squalene-hopene cyclase at 2.0 A resolution. PUBMED:9931258 EPMC:9931258
Lenhart A, Reinert DJ, Aebi JD, Dehmlow H, Morand OH, Schulz GE;, J Med Chem. 2003;46:2083-2092.: Binding structures and potencies of oxidosqualene cyclase inhibitors with the homologous squalene-hopene cyclase. PUBMED:12747780 EPMC:12747780
Milla P, Viola F, Oliaro Bosso S, Rocco F, Cattel L, Joubert BM, LeClair RJ, Matsuda SP, Balliano G;, Lipids. 2002;37:1171-1176.: Subcellular localization of oxidosqualene cyclases from Arabidopsis thaliana, Trypanosoma cruzi, and Pneumocystis carinii expressed in yeast. PUBMED:12617471 EPMC:12617471

Internal database links

SCOOP:	Glyco_hydro_127 Pec_lyase Prenyltrans SQHop_cyclase_N TED_complement
Similarity to PfamA using HHSearch:	Prenyltrans Prenyltrans TED_complement TED_complement Pec_lyase SQHop_cyclase_N SQHop_cyclase_N

This tab holds annotation information from the InterPro database.

InterPro entry IPR032696

Several enzymes catalyse mechanistically related reactions which involve the highly complex cyclic rearrangement of squalene or its 2,3 oxide. Squalene cyclase (SQCY) and 2,3-oxidosqualene cyclase (OSQCY) are integral membrane proteins that catalyse a cationic cyclization cascade converting linear triterpenes to fused ring compounds [ PUBMED:11027983 , PUBMED:9295270 ]. Lanosterol synthase ( EC ) (oxidosqualene--lanosterol cyclase) catalyses the cyclization of (S)-2,3-epoxysqualene to lanosterol, the initial precursor of cholesterol, steroid hormones and vitamin D in vertebrates and of ergosterol in fungi (gene ERG7). Cycloartenol synthase ( EC ) (2,3-epoxysqualene--cycloartenol cyclase), is a plant enzyme that catalyses the cyclization of (S)-2,3-epoxysqualene to cycloartenol [ PUBMED:9519404 ], and hopene synthase ( EC ) (squalene--hopene cyclase), is a bacterial enzyme that catalyses the cyclization of squalene into hopene or diplopterol, a key step in hopanoid (triterpenoid) metabolism [ PUBMED:9931258 , PUBMED:2253626 ] also found in Aspergillus fumigatus as part of the gene cluster that mediates the biosynthesis fumihopaside A [ PUBMED:30977375 ]. These enzymes are evolutionary related [ PUBMED:7505443 ] proteins of about 70 to 85kDa and have an alpha 6 - alpha 6 barrel fold. Deletion of a single glycine residue of Alicyclobacillus acidocaldarius SQCY alters its substrate specificity into that of eukaryotic OSQCY [ PUBMED:15593147 ]. Both enzymes have a second minor domain, which forms an alpha-alpha barrel that is inserted into the major domain.

This entry represents the C-terminal domain of squalene cyclases [ PUBMED:9931258 , PUBMED:12747780 , PUBMED:12617471 ].

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 6_Hairpin (CL0059), which has the following description:

This Clan includes CAZy clans GH-L, GH-M and GH-G. The members of this clan share a common structure composed of 6 helical hairpins. Most members of this superfamily are glycosyl hydrolase enzymes.

The clan contains the following 30 members:

Bac_rhamnosid6H C5-epim_C Cobalamin_bind DUF608 GDE_C GlcNAc_2-epim Glyco_hydro81C Glyco_hydro_100 Glyco_hydro_125 Glyco_hydro_127 Glyco_hydro_15 Glyco_hydro_36 Glyco_hydro_47 Glyco_hydro_48 Glyco_hydro_63 Glyco_hydro_65m Glyco_hydro_76 Glyco_hydro_8 Glyco_hydro_88 Glyco_hydro_9 Glycoamylase LANC_like Ldi Pec_lyase Prenyltrans SQHop_cyclase_C SQHop_cyclase_N TED_complement Terpene_synth Trehalase

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 and the UniProtKB 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

Viewing

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

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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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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 (14)	Full (6041)	Representative proteomes				UniProt (17111)
	Seed (14)	Full (6041)	RP15 (754)	RP35 (2736)	RP55 (5242)	RP75 (7966)	UniProt (17111)
Jalview	View	View	View	View	View	View	View
HTML	View
PP/heatmap	₁

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

Key: available, not generated, — not available.

Format an alignment

	Seed (14)	Full (6041)	Representative proteomes				UniProt (17111)
	Seed (14)	Full (6041)	RP15 (754)	RP35 (2736)	RP55 (5242)	RP75 (7966)	UniProt (17111)
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 (14)	Full (6041)	Representative proteomes				UniProt (17111)
	Seed (14)	Full (6041)	RP15 (754)	RP35 (2736)	RP55 (5242)	RP75 (7966)	UniProt (17111)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download
Gzipped	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:

Jackhammer:O27751; manual

Previous IDs:

Prenyltrans_1;

Type:

Repeat

Sequence Ontology:

SO:0001068

Author:

Coggill P

Number in seed:

14

Number in full:

6041

Average length of the domain:

282.4 aa

Average identity of full alignment:

31 %

Average coverage of the sequence by the domain:

44.23 %

HMM information

HMM build commands:

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

search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	26.1	26.1
Trusted cut-off	26.1	26.1
Noise cut-off	26.0	26.0

Model length:

319

Family (HMM) version:

9

Download:

download the raw HMM for this family

Species distribution

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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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order
family
genus
species

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Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

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.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

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.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

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The tree shows the occurrence of this domain across different species. More...

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.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

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.

You can use the tree controls to manipulate how the interactive tree is displayed:

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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 SQHop_cyclase_C domain has been found. There are 54 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein	Predicted structure	External Information
A0A0D2EZI9	View 3D Structure	Click here
A0A0R0EDA7	View 3D Structure	Click here
A0A0R0G4T9	View 3D Structure	Click here
A0A0R0G851	View 3D Structure	Click here
A0A0R0IG75	View 3D Structure	Click here
A0A0R0IYV7	View 3D Structure	Click here
A0A0R0J895	View 3D Structure	Click here
A0A0R4J2H1	View 3D Structure	Click here
A0A175W263	View 3D Structure	Click here
A0A1C1CVG5	View 3D Structure	Click here
A0A1D6FEN9	View 3D Structure	Click here
A0A1D6FEP1	View 3D Structure	Click here
A0A1D6GMB7	View 3D Structure	Click here
A0A1D6GVH8	View 3D Structure	Click here
A0A1D6H0A5	View 3D Structure	Click here
A0A1D6IYU4	View 3D Structure	Click here
A0A1D6KEJ9	View 3D Structure	Click here
A0A1D6KEK8	View 3D Structure	Click here
A0A1D6KEK9	View 3D Structure	Click here
A0A1D6LG90	View 3D Structure	Click here
A0A1D6Q2R1	View 3D Structure	Click here
A0A1D6QL70	View 3D Structure	Click here
A0A1D6QT72	View 3D Structure	Click here
A1CVK0	View 3D Structure	Click here
A4HSV6	View 3D Structure	Click here
A9AWD5	View 3D Structure	Click here
B0S5M5	View 3D Structure	Click here
B6EXY6	View 3D Structure	Click here
C0NTW1	View 3D Structure	Click here
C0P0D4	View 3D Structure	Click here
C0PGA6	View 3D Structure	Click here
C1H0A2	View 3D Structure	Click here
D5SJ87	View 3D Structure	Click here
E4V6I8	View 3D Structure	Click here
E7DN63	View 3D Structure	Click here
E7DN64	View 3D Structure	Click here
H2KWF1	View 3D Structure	Click here
I1J4A4	View 3D Structure	Click here
I1MFB9	View 3D Structure	Click here
K7KEK6	View 3D Structure	Click here

Showing 40 matches

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Family: SQHop_cyclase_C (PF13243)

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