Summary: Squalene-hopene cyclase C-terminal domain

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Wikipedia: Prenyltransferase
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Prenyltransferase Edit Wikipedia article

Prenyltransferase and squalene oxidase repeat

Structure of a squalene cyclase.^[1]

Identifiers

Symbol

Prenyltrans

Pfam clan

1sqc / SUPFAM

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

Prenyltransferases are a class of enzymes that transfer allylic prenyl groups to acceptor molecules. Prenyl transferases commonly refer to prenyl diphosphate synthases.^[2]

Prenyltransferases are commonly divided into two classes, cis (or Z) and trans (or E), depending upon the stereochemistry 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 a precursor to dolichol).

The beta subunit of the farnesyltransferases is responsible for peptide binding. Squalene-hopene cyclase is a bacterial enzyme that catalyzes the cyclization of squalene into hopene, a key step in hopanoid (triterpenoid) metabolism.^[1] Lanosterol synthase (EC 5.4.99.7) (oxidosqualene-lanosterol cyclase) catalyzes 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.^[3] Cycloartenol synthase (EC 5.4.99.8) (2,3-epoxysqualene-cycloartenol cyclase) is a plant enzyme that catalyzes the cyclization of (S)-2,3-epoxysqualene to cycloartenol.

Human proteins containing this domain

FNTB; LSS; PGGT1B; RABGGTB

References

^ ^a ^b Wendt KU, Poralla K, Schulz GE (1997). "Structure and function of a squalene cyclase". Science. 277 (5333): 1811â€“1815. doi:10.1126/science.277.5333.1811. PMID 9295270.
^ Takahashi S, Koyama T (2006). "Structure and function of cis-prenyl chain elongating enzymes". Chem Rec. 6 (4): 194â€“205. doi:10.1002/tcr.20083. PMID 16900467.
^ Prestwich GD, Poralla K, Hewelt A, Abe I, Reipen I, Sprenger G (1994). "A specific amino acid repeat in squalene and oxidosqualene cyclases". Trends Biochem. Sci. 19 (4): 157â€“158. doi:10.1016/0968-0004(94)90276-3. PMID 8016864.

External links

Prenyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)
Protein prenyltransferases alpha subunit repeat in PROSITE

This article incorporates text from the public domain Pfam and InterPro: IPR001330

v t e Transferases: alkyl and aryl (EC 2.5)
2.5.1	Dimethylallyltranstransferase Thiaminase I Methionine adenosyltransferase Riboflavin synthase Dihydropteroate synthase Spermidine synthase Glutathione S-transferase Farnesyl-diphosphate farnesyltransferase Spermine synthase Alkylglycerone phosphate synthase Farnesyltransferase Geranylgeranyltransferase type 1 Porphobilinogen deaminase

This enzyme-related article is a stub. You can help Wikipedia by expanding it.

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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.

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:	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 ]. 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 29 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 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

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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 (5687)	Representative proteomes				UniProt (16043)
	Seed (14)	Full (5687)	RP15 (638)	RP35 (2573)	RP55 (4831)	RP75 (7398)	UniProt (16043)
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 (5687)	Representative proteomes				UniProt (16043)
	Seed (14)	Full (5687)	RP15 (638)	RP35 (2573)	RP55 (4831)	RP75 (7398)	UniProt (16043)
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 (5687)	Representative proteomes				UniProt (16043)
	Seed (14)	Full (5687)	RP15 (638)	RP35 (2573)	RP55 (4831)	RP75 (7398)	UniProt (16043)
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:

5687

Average length of the domain:

280.90 aa

Average identity of full alignment:

31 %

Average coverage of the sequence by the domain:

44.12 %

HMM information

HMM build commands:

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

search method: hmmsearch -Z 57096847 -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:

8

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.

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".

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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 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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Family: SQHop_cyclase_C (PF13243)

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