Summary: RyR domain

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Wikipedia: Ryanodine receptor
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Ryanodine receptor Edit Wikipedia article

RyR domain

Identifiers

Symbol

RyR

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

Ryanodine receptors (RyRs) form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons. It is the major cellular mediator of calcium-induced calcium release (CICR) in animal cells.

[edit] Etymology

The receptors are named after the plant alkaloid ryanodine, to which they show high affinity:

Ryanodine

[edit] Isoforms

There are multiple isoforms of ryanodine receptors:

RyR1 is primarily expressed in skeletal muscle
RyR2 in myocardium (heart muscle)
A third form, RyR3, is expressed more widely, but especially in the brain.^[1]
There is also a fourth form found only in fish.

ryanodine receptor 1 (skeletal)
Identifiers
Symbol	RYR1
Alt. symbols	MHS, MHS1, CCO
Entrez	6261
HUGO	10483
OMIM	180901
RefSeq	NM_000540
UniProt	P21817
Other data
Locus	Chr. 19 q13.1

ryanodine receptor 2 (cardiac)
Identifiers
Symbol	RYR2
Entrez	6262
HUGO	10484
OMIM	180902
RefSeq	NM_001035
UniProt	Q92736
Other data
Locus	Chr. 1 q42.1-q43

ryanodine receptor 3
Identifiers
Symbol	RYR3
Entrez	6263
HUGO	10485
OMIM	180903
RefSeq	NM_001036
UniProt	Q15413
Other data
Locus	Chr. 15 q14-q15

[edit] Physiology

Ryanodine receptors mediate the release of calcium ions from the sarcoplasmic reticulum, an essential step in muscle contraction. In skeletal muscle, it is thought that activation occurs via a physical coupling to the dihydropyridine receptor, whereas, in cardiac muscle, the primary mechanism is calcium-induced calcium release from the sarcoplasmic reticulum.^[2]

It has been shown that calcium release from a number of ryanodine receptors in a ryanodine receptor cluster results in a spatiotemporally restricted rise in cytosolic calcium that can be visualised as a calcium spark.^[3]

Ryanodine receptors are similar to the inositol trisphosphate (IP₃) receptor, and stimulated to transport Ca²⁺ into the cytosol by recognizing Ca²⁺ on its cytosolic side, thus establishing a positive feedback mechanism; a small amount of Ca²⁺ in the cytosol near the receptor will cause it to release even more Ca²⁺ (calcium-induced calcium release/CICR).^[1]

RyRs are especially important in neurons and muscle cells. In heart and pancreas cells, another second messenger (cyclic ADP-ribose) takes part in the receptor activation.

The localized and time-limited activity of Ca²⁺ in the cytosol is also called a Ca²⁺ wave. The building of the wave is done by

the feedback mechanism of the ryanodine receptor
the activation of phospholipase C by GPCR or TRK, which leads to the production of inositol trisphosphate, which in turn activates the InsP₃ receptor.

[edit] Associated proteins

Many other proteins with various functions are associated with RyR^{[citation needed]} . For instance in RyR2 from luminal side it is calsequestrin which forms quaternary structure of RyR along with junctin and triadin. Calsequestrin has multiple Ca2+ binding sites and binds Ca2+ ions with very low affinty so they can be easily released.

Ryanodine receptors are usually found in clusters of 3 or 4 (i.e. they are associated with each other)and it was observed that they are to some extent able to open and close simultaneously. This happens more often in physiological conditions and is less observed in vitro.

[edit] Pharmacology

Antagonists:^[4]
- Ryanodine locks the RyRs at half-open state at nanomolar concentrations, yet fully closes them at micromolar concentration.
- Dantrolene the clinically used antagonist
- Ruthenium red
- procaine, tetracaine, etc. (local anesthetics)

Activators:^[5]
- Agonist: 4-chloro-m-cresol and suramin are direct agonists, i.e., direct activators.
- Xanthines like caffeine and pentifylline activate it by potentiating sensitivity to native ligand Ca.
  - Physiological agonist: Cyclic ADP-ribose can act as a physiological gating agent. It has been suggested that it may act by making FKBP12.6 (12.6 kilodalton FK506 binding protein, as opposed to 12 kDa FKBP12 which binds to RyR1) which normally bind (and blocks) RyR2 channel tetramer in an average stoichiometry of 3.6, to fall off RyR2 (which is the predominant RyR in pancreatic beta cells, cardiomyocytes and smooth muscles).^[6]

A variety of other molecules may interact with and regulate Ryanodine receptor. For example: Dimerized Homer physical tether linking inositol trisphosphate receptors (IP3R) and ryanodine receptors on the intracellular calcium stores with cell surface group 1 metabotropic Glutamate Receptors and the alpha 1D adrenergic receptor^[7]

[edit] Ryanodine

The plant alkaloid ryanodine, for which this receptor was named, has become an invaluable investigative tool. It can block the phasic release of calcium, but at low doses may not block the tonic cumulative calcium release. The binding of ryanodine to RyRs is use-dependent, that is the channels have to be in the activated state. At low (<10 MicroMolar, works even at nanomolar) concentrations, ryanodine binding locks the RyRs into a long-lived subconductance (half-open) state and eventually depletes the store, while higher (~100 MicroMolar) concentrations irreversibly inhibit channel-opening.

[edit] Caffeine

RyRs are activated by millimolar caffeine concentrations. High (greater than 5 mmol/L) caffeine concentrations cause a pronounced increase (from micromolar to picomolar) in the sensitivity of RyRs to Ca²⁺ in the presence of caffeine, such that basal Ca²⁺ concentrations become activatory. At low millimolar caffeine concentrations, the receptor opens in a quantal way, but has complicated behavior in terms of repeated use of caffeine or dependence on cytosolic or luminal calcium concentrations.

[edit] Role in disease

RyR1 mutations are associated with malignant hyperthermia and central core disease. RyR2 mutations play a role in stress-induced polymorphic ventricular tachycardia (a form of cardiac arrhythmia) and ARVD.^[1] It has also been shown that levels of type RyR3 are greatly increased in PC12 cells overexpressing mutant human Presenilin 1, and in brain tissue in knockin mice that express mutant Presenilin 1 at normal levels^{[citation needed]}, and thus may play a role in the pathogenesis of neurodegenerative diseases, like Alzheimer's disease.^{[citation needed]}

The presence of antibodies against ryanodine receptors in blood serum has also been associated with myasthenia gravis.^{[citation needed]}

[edit] Human proteins containing this domain

RYR1; RYR2; RYR3;

[edit] See also

Ryanoid, a class of insecticide that act through ryanodine receptors

[edit] References

^ ^a ^b ^c Zucchi R, Ronca-Testoni S (March 1997). "The sarcoplasmic reticulum Ca2+ channel/ryanodine receptor: modulation by endogenous effectors, drugs and disease states". Pharmacol. Rev. 49 (1): 1â51. PMID 9085308.
^ Fabiato A (1983). "Calcium-induced calcium release of calcium from the cardiac sarcoplasmic reticulum". Am J Physiol 245 (1): C1âC14. PMID 6346892.
^ Cheng H, Lederer WJ, Cannell MB (1993). "Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle". Science 262 (5134): 740â744. doi:10.1126/science.8235594. PMID 8235594.
^ Vites A, Pappano A (1994). "Distinct modes of inhibition by ruthenium red and ryanodine of calcium-induced calcium release in avian atrium". J Pharmacol Exp Ther 268 (3): 1476â84. PMID 7511166.
^ Xu L, Tripathy A, Pasek D, Meissner G (1998). "Potential for pharmacology of ryanodine receptor/calcium release channels". Ann N Y Acad Sci 853: 130â48. doi:10.1111/j.1749-6632.1998.tb08262.x. PMID 10603942.
^ Wang Y, Zheng Y, Mei Q, Wang Q, Collier M, Fleischer S, Xin H, Kotlikoff M (2004). "FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells". Am J Physiol Cell Physiol 286 (3): C538â46. doi:10.1152/ajpcell.00106.2003. PMID 14592808.
^ Tu J, Xiao B, Yuan J, Lanahan A, Leoffert K, Li M, Linden D, Worley P (1998). "Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors". Neuron 21 (4): 717â26. doi:10.1016/S0896-6273(00)80589-9. PMID 9808459.

[edit] External links

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

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor (1, 2, 3) Â· Ryanodine receptor (1, 2, 3)

Voltage-gated	L-type/Ca_vÎ± (1.1, 1.2, 1.3, 1.4) Â· N-type/Ca_vÎ±2.2 Â· P-type/Ca_vÎ±(2.1) Â· Q-type/Ca_vÎ±2.1 Â· R-type/Ca_vÎ±2.3 Â· T-type/Ca_vÎ±(3.1, 3.2, 3.3) Î±₂Î´-subunits (1, 2) Â· Î²-subunits (Î²1, Î²2, Î²3, Î²4) Â· Î³-subunits (Î³1, Î³2, Î³3, Î³4) Cation channels of sperm (1, 2, 3, 4) Â· Two-pore channel (1, 2)

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel (Î±, Î², Î³, Î´)

Proton-gated	Amiloride-sensitive cation channel (1, 2, 3, 4)

Voltage-gated	Na_vÎ± (1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 7A) Â· Na_vÎ² (1, 2, 3, 4)

K⁺: Potassium channel

Calcium-activated	BK channel (Î±1, Î²1, Î²2, Î²3, Î²4) Â· SK channel (SK1, SK2, SK3) Â· IK channel (IK1) Â· K_Ca (1.1, 2.1, 2.2, 2.3, 3.1, 4.1, 4.2, 5.1)

Inward-rectifier	K_ATP Â· K_ir (1.1, 2.1, 2.2, 2.3, 2.4, 2.6) Â· GIRK/K_ir (3.1, 3.2, 3.3, 3.4) Â· K_ir (4.1, 4.2, 5.1, 6.1, 6.2, 7.1)

Tandem pore domain	K2P (1, 2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 15, 16, 17, 18)

Voltage-gated	K_vÎ±1-6 (1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8) Â· (2.1, 2.2) Â· (3.1, 3.2, 3.3, 3.4) Â· (4.1, 4.2, 4.3) Â· (5.1) Â· (6.1, 6.2, 6.3, 6.4) K_vÎ±7-12 (7.1, 7.2, 7.3, 7.4, 7.5) Â· (8.1, 8.2) Â· (9.1, 9.2, 9.3) Â· (10.1, 10.2) Â· (11.1/hERG, 11.2, 11.3) Â· (12.1, 12.2, 12.3) K_vÎ² (1, 2, 3) Â· KCNIP (1, 2, 3, 4) Â· minK/ISK Â· minK/ISK-like Â· MiRP (1, 2, 3) Â· Shaker gene

Miscellaneous

Cl^-: Chloride channel	ANO1 Â· Bestrophin (1, 2) Â· CFTR Â· CLCA (1, 2, 3, 4) Â· CLCN (1, 2, 3, 4, 5, 6, 7, KA, KB) Â· CLIC (1, 2, 3, 4, 5, 6, L1) Â· CLNS (1A, 1B)

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	Î± (1, 2, 3, 4) Â· Î² (1, 2, 3) Â· HCN (FC, 1, 2, 3, 4)

M⁺: TRP cation channel	TRPA (1) Â· TRPC (1, 2, 3, 4, 4AP, 5, 6, 7) Â· TRPM (1, 2, 3, 4, 5, 6, 7, 8) Â· TRPML (1, 2, 3) Â· TRPN Â· TRPP (1, 2) Â· TRPV (1, 2, 3, 4, 5, 6)

H₂O (+ solutes): Porin	Aquaporin (0, 1, 2, 3, 4, 5, 6, 7, 8, 9) Â· Voltage-dependent anion channel (1, 2, 3) Â· General bacterial porin family

Cytoplasm: Gap junction	Connexin: A (GJA1, GJA3, GJA4, GJA5, GJA8, GJA9, GJA10) Â· B (GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GJB7) Â· C (GJC1, GJC2, GJC3) Â· D (GJD2, GJD3, GJD4)) Innexin

By gating mechanism

Ion channel class	Ligand-gated Â· Light-gated Â· Voltage-gated Â· Stretch-activated

see also disorders
B memb: cead, trns (1A, 1C, 1F, 2A, 3A1, 3A2-3, 3D), othr

Cell signaling: calcium signaling / calcium metabolism

Cell membrane

Ion pumps	SERCA Sodium-calcium exchanger

Cell membrane calcium channels	VDCC TRP NMDA receptor AMPA receptor 5-HT3 receptor P2X purinoreceptor

Adhesion molecules	Cadherin

Other	Calcium-sensing receptor

Intracellular signaling
& calc. regulation

Second messengers	IP3 NAADP cADPR

Store gates (ligand gated calcium channel)	IP3 receptor CICR Ryanodine receptor

Molecular switches, and kinases	Troponin C Calmodulin CaM kinases PKC NCS

Chelators and calcium sensors	Calbindin S100 pervalbumin Calretinin Calsequestrin Sarcalumenin Phospholamban Synaptotagmins

Proteases	Calpain

Cytoskeleton remodeling proteins	Gelsolin

Chaperones	Calreticulin Calnexin

Other	Vitamin D

Calcium-binding
protein domains

Extracellular ligands

Calcium-binding proteins

Intracellular calcium-sensing proteins	Calmodulin Calnexin Calreticulin Gelsolin neuronal Hippocalcin Neurocalcin Recoverin

Membrane protein	Annexin A1 A2 A5 Fibulin FBLN1 FBLN2 FBLN5 Vitamin D-dependent calcium-binding protein/Calbindin Calexcitin Calsequestrin Osteocalcin Osteonectin S-100 Synaptotagmin

Cytoskeleton	Troponin C

Extracellular matrix	Matrix gla protein

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

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.

RyR domain Provide feedback

This domain is called RyR for Ryanodine receptor [1]. The domain is found in four copies in the ryanodine receptor. The function of this domain is unknown.

Literature references

Ponting CP; , Trends Biochem Sci 2000;25:48-50.: Novel repeats in ryanodine and IP3 receptors and protein O-mannosyltransferases. PUBMED:10664581 EPMC:10664581

External database links

PANDIT:	PF02026
Pseudofam:	PF02026
SYSTERS:	RyR
Transporter classification:	1.A.3

This tab holds annotation information from the InterPro database.

InterPro entry IPR003032

This domain is called RyR for Ryanodine receptor [PUBMED:10664581]. The domain is found in four copies in the ryanodine receptor. The function of this domain is unknown.

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

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:

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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:

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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 (38)	Full (1192)	Representative proteomes				NCBI (969)	Meta (18)
	Seed (38)	Full (1192)	RP15 (108)	RP35 (161)	RP55 (353)	RP75 (593)	NCBI (969)	Meta (18)
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 (38)	Full (1192)	Representative proteomes				NCBI (969)	Meta (18)
	Seed (38)	Full (1192)	RP15 (108)	RP35 (161)	RP55 (353)	RP75 (593)	NCBI (969)	Meta (18)
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 (38)	Full (1192)	Representative proteomes				NCBI (969)	Meta (18)
	Seed (38)	Full (1192)	RP15 (108)	RP35 (161)	RP55 (353)	RP75 (593)	NCBI (969)	Meta (18)
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:

[1]

Previous IDs:

none

Type:

Family

Author:

Bateman A

Number in seed:

38

Number in full:

1192

Average length of the domain:

92.00 aa

Average identity of full alignment:

37 %

Average coverage of the sequence by the domain:

8.15 %

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	27.4	27.4
Trusted cut-off	28.1	27.7
Noise cut-off	27.1	27.3

Model length:

95

Family (HMM) version:

11

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

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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.

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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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.

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 RyR domain has been found. There are 22 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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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: RyR (PF02026)

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