Summary: LicD family

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Wikipedia: Fukutin
Pfam
InterPro

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

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Fukutin Edit Wikipedia article

Fukutin

Identifiers

Symbols

FKTN; CMD1X; FCMD; LGMD2M; MDDGA4; MDDGB4; MDDGC4

External IDs

OMIM: 607440 MGI: 2179507 HomoloGene: 31402 GeneCards: FKTN Gene

Gene Ontology
Molecular function	• transferase activity
Cellular component	• Golgi membrane • extracellular space • nucleus • endoplasmic reticulum • Golgi apparatus • cis-Golgi network • integral to membrane
Biological process	• nervous system development • muscle organ development • negative regulation of cell proliferation • negative regulation of JNK cascade • regulation of protein glycosylation
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 9:
108.32 – 108.4 Mb

Chr 4:
53.71 – 53.77 Mb

PubMed search

[1]

[2]

Fukutin-related

Identifiers

Symbol

Fukutin-related

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

Fukutin is a eukaryotic protein necessary for the maintenance of muscle integrity, cortical histogenesis, and normal ocular development. Mutations in the fukutin gene have been shown to result in Fukuyama congenital muscular dystrophy characterised by brain malformation - one of the most common autosomal-recessive disorders in Japan.^[1] In humans this protein is encoded by the FCMD gene (also named FKTN), located on chromosome 9q31.^[2]^[3]^[4] Human fukutin exhibits a length of 461 amino acids and a predicted molecular mass of 53.7 kDa.

[edit] Function

Although its function is mostly unknown, fukutin is a putative transmembrane protein that is ubiquitously expressed, although at higher levels in skeletal muscle, heart and brain.^[5] It is localized to the cis-Golgi compartment, where it may be involved in the glycosylation of α-dystroglycan in skeletal muscle. The encoded protein is thought to be a glycosyltransferase and could play a role in brain development.^[3]

[edit] Clinical significance

Defects in this gene are a cause of Fukuyama congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), limb-girdle muscular dystrophy type 2M (LGMD2M), and dilated cardiomyopathy type 1X (CMD1X).^[3]^[6]

[edit] See also

Fukutin-related protein

[edit] References

^ Kobayashi K, Shimizu T, Arai K, Nakamura Y, Fukui T, Toda T, Matsumura K, Imamura M, Takeda S, Kondo M, Sasaki J, Kurahashi H, Kano H, Misaki K, Tachikawa M, Murakami T, Sunada Y, Fujikado T, Terashima T (2003). "Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development". Hum. Mol. Genet. 12 (12): 1449–1459. doi:10.1093/hmg/ddg153. PMID 12783852.
^ Toda T, Segawa M, Nomura Y, Nonaka I, Masuda K, Ishihara T, Sakai M, Tomita I, Origuchi Y, Suzuki M [corrected to Sakai M (November 1993). "Localization of a gene for Fukuyama type congenital muscular dystrophy to chromosome 9q31-33". Nat. Genet. 5 (3): 283–6. doi:10.1038/ng1193-283. PMID 8275093.
^ ^a ^b ^c "Entrez Gene: fukutin". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2218.
^ Online 'Mendelian Inheritance in Man' (OMIM) 607440
^ Hayashi YK, Ogawa M, Tagawa K, Noguchi S, Ishihara T, Nonaka I, Arahata K (July 2001). "Selective deficiency of alpha-dystroglycan in Fukuyama-type congenital muscular dystrophy". Neurology 57 (1): 115–21. PMID 11445638.
^ Murakami T, Hayashi YK, Noguchi S, et al. (November 2006). "Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness". Ann. Neurol. 60 (5): 597–602. doi:10.1002/ana.20973. PMID 17036286.

[edit] Further reading

Matsumoto H, Noguchi S, Sugie K, et al. (2004). "Subcellular localization of fukutin and fukutin-related protein in muscle cells.". J. Biochem. 135 (6): 709–12. doi:10.1093/jb/mvh086. PMID 15213246.
Puckett RL, Moore SA, Winder TL, et al. (2009). "Further evidence of Fukutin mutations as a cause of childhood onset limb-girdle muscular dystrophy without mental retardation.". Neuromuscul. Disord. 19 (5): 352–6. doi:10.1016/j.nmd.2009.03.001. PMC 2698593. PMID 19342235. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2698593/.
Chung W, Winder TL, LeDuc CA, et al. (2009). "Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families.". Prenat. Diagn. 29 (6): 560–9. doi:10.1002/pd.2238. PMC 2735827. PMID 19266496. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2735827/.
Percival JM, Froehner SC (2007). "Golgi complex organization in skeletal muscle: a role for Golgi-mediated glycosylation in muscular dystrophies?". Traffic 8 (3): 184–94. doi:10.1111/j.1600-0854.2006.00523.x. PMID 17319799.
Toda T (1999). "[Fukutin, a novel protein product responsible for Fukuyama-type congenital muscular dystrophy]". Seikagaku 71 (1): 55–61. PMID 10067123.
Toda T, Kobayashi K, Kondo-Iida E, et al. (2000). "The Fukuyama congenital muscular dystrophy story.". Neuromuscul. Disord. 10 (3): 153–9. doi:10.1016/S0960-8966(99)00109-1. PMID 10734260.
Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1356129/.
Cotarelo RP, Valero MC, Prados B, et al. (2008). "Two new patients bearing mutations in the fukutin gene confirm the relevance of this gene in Walker-Warburg syndrome.". Clin. Genet. 73 (2): 139–45. doi:10.1111/j.1399-0004.2007.00936.x. PMID 18177472.
Vuillaumier-Barrot S, Quijano-Roy S, Bouchet-Seraphin C, et al. (2009). "Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype.". Neuromuscul. Disord. 19 (3): 182–8. doi:10.1016/j.nmd.2008.12.005. PMID 19179078.
Yamamoto T, Kawaguchi M, Sakayori N, et al. (2006). "Intracellular binding of fukutin and alpha-dystroglycan: relation to glycosylation of alpha-dystroglycan.". Neurosci. Res. 56 (4): 391–9. doi:10.1016/j.neures.2006.08.009. PMID 17005282.
Yoshioka M (2009). "Phenotypic spectrum of Fukutinopathy: most severe phenotype of Fukutinopathy.". Brain Dev. 31 (6): 419–22. doi:10.1016/j.braindev.2008.07.012. PMID 18834683.
Manzini MC, Gleason D, Chang BS, et al. (2008). "Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East.". Hum. Mutat. 29 (11): E231–41. doi:10.1002/humu.20844. PMC 2577713. PMID 18752264. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2577713/.
Perry JR, Stolk L, Franceschini N, et al. (2009). "Meta-analysis of genome-wide association data identifies two loci influencing age at menarche.". Nat. Genet. 41 (6): HASH(0x118f3f0). doi:10.1038/ng.386. PMC 2942986. PMID 19448620. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2942986/.
Godfrey C, Escolar D, Brockington M, et al. (2006). "Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy.". Ann. Neurol. 60 (5): 603–10. doi:10.1002/ana.21006. PMID 17044012.
Godfrey C, Clement E, Mein R, et al. (2007). "Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan.". Brain 130 (Pt 10): 2725–35. doi:10.1093/brain/awm212. PMID 17878207.
Saredi S, Ruggieri A, Mottarelli E, et al. (2009). "Fukutin gene mutations in an Italian patient with early onset muscular dystrophy but no central nervous system involvement.". Muscle Nerve 39 (6): 845–8. doi:10.1002/mus.21271. PMID 19396839.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. //www.ncbi.nlm.nih.gov/pmc/articles/PMC528928/.
Mercuri E, Messina S, Bruno C, et al. (2009). "Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study.". Neurology 72 (21): 1802–9. doi:10.1212/01.wnl.0000346518.68110.60. PMID 19299310.
Arimura T, Hayashi YK, Murakami T, et al. (2009). "Mutational analysis of fukutin gene in dilated cardiomyopathy and hypertrophic cardiomyopathy.". Circ. J. 73 (1): 158–61. doi:10.1253/circj.CJ-08-0722. PMID 19015585.

[edit] External links

GeneReviews/NCBI/NIH/UW entry on Congenital Muscular Dystrophy Overview
LOVD mutation database: FKTN

Histology: Muscle tissue (TH H2.00.05, H3.3)

Smooth
muscle

Calmodulin · Vascular smooth muscle

Striated
muscle

Skeletal
muscle

Costamere/
DAPC

Membrane/ extracellular	DAP: Sarcoglycan (SGCA, SGCB, SGCD, SGCE, SGCG, SGCZ) · Dystroglycan Sarcospan · Laminin, alpha 2

Intracellular	Dystrophin · Dystrobrevin (A, B) · Syntrophin (A, B1, B2, G1, G2) · Syncoilin · Dysbindin · Synemin/desmuslin related: NOS1 · Caveolin 3

Sarcomere/
(a, i, and h bands;
z and m lines)

Myofilament (thin filament/actin, thick filament/myosin, elastic filament/titin, nebulin)

Tropomyosin

Troponin (T, C, I)

Connective tissue

Epimysium · Fascicle · Perimysium · Endomysium · Connective tissue in skeletal muscle

General

Neuromuscular junction · Motor unit · Muscle spindle · Excitation-contraction coupling · Sliding filament mechanism

Cardiac
muscle

Myocardium · Intercalated disc · Nebulette

Both

Fiber	Muscle fiber (intrafusal, extrafusal) · Myofibril · Microfilament/Myofilament · Sarcomere

Cells	Myoblast/Myocyte · Myosatellite cell

Other	Desmin · Sarcoplasm · Sarcolemma (T-tubule) · Sarcoplasmic reticulum

Other/
ungrouped

Myotilin · Telethonin · Dysferlin · Fukutin · Fukutin-related protein

M: MUS, DF+DRCT

anat (h/n, u, t/d, a/p, l)/phys/devp/hist

noco (m, s, c)/cong (d)/tumr, sysi/epon, injr

proc, drug (M1A/3)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article on a gene on chromosome 9 is a stub. You can help Wikipedia by expanding it.

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.

LicD family Provide feedback

The LICD family of proteins show high sequence similarity and are involved in phosphorylcholine metabolism. There is evidence to show that LicD2 mutants have a reduced ability to take up choline, have decreased ability to adhere to host cells and are less virulent [1]. These proteins are part of the nucleotidyltransferase superfamily [2].

Literature references

Zhang JR, Idanpaan-Heikkila I, Fischer W, Tuomanen EI; , Mol Microbiol 1999;31:1477-1488.: Pneumococcal licD2 gene is involved in phosphorylcholine metabolism. PUBMED:10200966 EPMC:10200966
Kuchta K, Knizewski L, Wyrwicz LS, Rychlewski L, Ginalski K;, Nucleic Acids Res. 2009; [Epub ahead of print]: Comprehensive classification of nucleotidyltransferase fold proteins: identification of novel families and their representatives in human. PUBMED:19833706 EPMC:19833706

External database links

PANDIT:	PF04991
Pseudofam:	PF04991
SYSTERS:	LicD

This tab holds annotation information from the InterPro database.

InterPro entry IPR007074

The LicD family of proteins show high sequence similarity and are involved in phosphorylcholine metabolism. There is evidence to show that LicD2 mutants have a reduced ability to take up choline, have decreased ability to adhere to host cells and are less virulent [PUBMED:10200966].

Fukutin, which is a member of the LicD family, is a human protein which may be involved in the modification of glycan moieties of alpha-dystroglycan; defects in Fukutin are associated with congential muscular dystrophy [PUBMED:11445638].

Domain organisation

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

Loading domain graphics...

Pfam Clan

This family is a member of clan NTP_transf (CL0260), which contains the following 22 members:

Adenyl_cycl_N Adenyl_transf Aminoglyc_resit DNA_pol_B_palm DUF1693 DUF1814 DUF2204 DUF294 DUF925 DZF GlnE GrpB LicD Mab-21 MdcG Mmp37 NTP_transf_2 NTP_transf_5 Nuc-transf PolyA_pol Pox_polyA_pol RelA_SpoT

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, 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
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.
Pfam viewer: an HTML-based viewer that uses DAS to retrieve alignment fragments on request

Reformatting

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

Selex
Stockholm
FASTA
MSF

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 (142)	Full (2479)	Representative proteomes				NCBI (1816)	Meta (209)
	Seed (142)	Full (2479)	RP15 (221)	RP35 (392)	RP55 (560)	RP75 (634)	NCBI (1816)	Meta (209)
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 (142)	Full (2479)	Representative proteomes				NCBI (1816)	Meta (209)
	Seed (142)	Full (2479)	RP15 (221)	RP35 (392)	RP55 (560)	RP75 (634)	NCBI (1816)	Meta (209)
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 (142)	Full (2479)	Representative proteomes				NCBI (1816)	Meta (209)
	Seed (142)	Full (2479)	RP15 (221)	RP35 (392)	RP55 (560)	RP75 (634)	NCBI (1816)	Meta (209)
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.

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_5278 (release 7.6)

Previous IDs:

none

Type:

Domain

Author:

Moxon SJ, Bateman A

Number in seed:

142

Number in full:

2479

Average length of the domain:

187.40 aa

Average identity of full alignment:

23 %

Average coverage of the sequence by the domain:

55.89 %

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	22.6	22.6
Trusted cut-off	22.9	22.6
Noise cut-off	22.4	22.5

Model length:

205

Family (HMM) version:

8

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

Show

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.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

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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Tree controls

Hide

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:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: LicD (PF04991)

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