Summary: Caspase domain
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Caspase Edit Wikipedia article
Structure of caspase-1 (CASP1), originally called interleukin-1 beta-converting enzyme (ICE), the first human caspase to be identified.
Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death (including apoptosis, pyroptosis and necroptosis) and inflammation. They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. As of 2009, there are 11 or 12 confirmed caspases in humans[note 1] and 10 in mice, carrying out a variety of cellular functions.
The role of these enzymes in programmed cell death was first identified in 1993, with their functions in apoptosis well characterised. This is a form of programmed cell death, occurring widely during development, and throughout life to maintain cell homeostasis. Activation of Caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues.
Caspases have other identified roles in programmed cell death such as pyroptosis and necroptosis. These forms of cell death are important for protecting an organism from stress signals and pathogenic attack. Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β. These are signalling molecules that allow recruitment of immune cells to an infected cell or tissue. There are other identified roles of caspases such as cell proliferation, tumour suppression, cell differentiation, neural development and axon guidance and ageing.
Caspase deficiency has been identified as a cause of tumour development. Tumour growth can occur by a combination of factors, including a mutation in a cell cycle gene which removes the restraints on cell growth, combined with mutations in apoptopic proteins such as Caspases that would respond by inducing cell death in abnormally growing cells. Conversely, over-activation of some caspases such as caspase-3 can lead to excessive programmed cell death. This is seen in several neurodegenerative diseases where neural cells are lost, such as Alzheimer's disease. Caspases involved with processing inflammatory signals are also implicated in disease. Insufficient activation of these caspases can increase an organism's susceptibility to infection, as an appropriate immune response may not be activated. The integral role caspases play in cell death and disease has led to research on using caspases as a drug target. For example, inflammatory caspase-1 has been implicated in causing autoimmune diseases; drugs blocking the activation of Caspase-1 have been used to improve the health of patients. Additionally, scientists have used caspases as cancer therapy to kill unwanted cells in tumours.
Functional classification of capsizes
Most caspases play a role in programmed cell death. These are summarized in the table below. The enzymes are sub classified into three types: Initiator, Executioner and Inflammatory.
|Programmed Cell Death||Type of Caspase||Enzyme||Organism|
|Apoptosis||Initiator||Caspase 2||human and mouse|
|Caspase 8||human and mouse|
|Caspase 9||human and mouse|
|Caspase 10||human only |
|Executioner||Caspase 3||human and mouse|
|Caspase 6||human and mouse|
|Caspase 7||human and mouse|
|Pyroptosis||Inflammatory||Caspase 1||human and mouse|
|Caspase 4||human [note 2]|
|Caspase 5||human [note 2]|
|Caspase 11||mouse [note 2]|
|Caspase 12||mouse and some humans [note 1]|
|Caspase 13||cattle only |
|Other roles||Other||Caspase 14||human and mouse|
Note that in addition to apoptosis, Caspase-8 is also required for the inhibition of another form of programmed cell death called Necroptosis. Caspase-14 plays a role in epithelial cell keratinocyte differentiation and can form an epidermal barrier that protects against dehydration and UVB radiation.
Activation of caspases
Caspases are synthesised as inactive zymogens (pro-caspases) that are only activated following an appropriate stimulus. This post-translational level of control allows rapid and tight regulation of the enzyme.
Activation involves dimerization and often oligomerisation of pro-caspases, followed by cleavage into a small subunit and large subunit. The large and small subunit associate with each other to form an active heterodimer caspase. The active enzyme often exists as a heterotetramer in the biological environment, where a pro-caspase dimer is cleaved together to form a heterotetramer.
The activation of initiator caspases and inflammatory caspases is initiated by dimerisation, which is facilitated by binding to adaptor proteins via protein–protein interaction motifs that are collectively referred to as death folds. The death folds are located in a structural domain of the caspases known as the pro-domain, which is larger in those caspases that contain death folds than in those that do not. The pro-domain of the intrinsic initiator caspases and the inflammatory caspases contains a single death fold known as caspase recruitment domain (CARD), while the pro-domain of the extrinsic initiator caspases contains two death folds known as death effector domains (DED).
Multiprotein complexes often form during caspase activation. Some activating multiprotein complexes includes:
- The death-inducing signaling complex (DISC) during extrinsic apoptosis
- The apoptosome during intrinsic apoptosis
- The inflammasome during pyroptosis
Once appropriately dimerised, the Caspases cleave at inter domain linker regions, forming a large and small subunit. This cleavage allows the active-site loops to take up a conformation favourable for enzymatic activity.
Cleavage of Initiator and Executioner caspases occur by different methods outlined in the table below.
- Initiator caspases auto-proteolytically cleave whereas Executioner caspases are cleaved by initiator caspases. This hierarchy allows an amplifying chain reaction or cascade for degrading cellular components, during controlled cell death.
Some roles of caspases
Apoptosis is a form of programmed cell death where the cell undergoes morphological changes, to minimize its effect on surrounding cells to avoid inducing an immune response. The cell shrinks and condenses - the cytoskeleton will collapse, the nuclear envelope disassembles and the DNA fragments up. This results in the cell forming self-enclosed bodies called 'blebs', to avoid release of cellular components into the extracellular medium. Additionally, the cell membrane phospholipid content is altered, which makes the dying cell more susceptible to phagocytic attack and removal.
Apoptopic caspases are subcategorised as:
- Initiator Caspases (Caspase 2, Caspase 8, Caspase-9, Caspase 10)
- Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7)
Once initiator caspases are activated, they produce a chain reaction, activating several other executioner caspases. Executioner caspases degrade over 600 cellular components in order to induce the morphological changes for apoptosis.
Examples of caspase cascade during apoptosis:
- Intrinsic apoptopic pathway: During times of cellular stress, mitochondrial cytochrome c is released into the cytosol. This molecule binds an adaptor protein (APAF-1), which recruits initiator Caspase-9 (via CARD-CARD interactions). This leads to the formation of a Caspase activating multiprotein complex called the Apoptosome. Once activated, initiator caspases such as Caspase 9 will cleave and activate other executioner caspases. This leads to degradation of cellular components for apoptosis.
- Extrinsic apoptopic pathway: The caspase cascade is also activated by extracellular ligands, via cell surface Death Receptors. This is done by the formation of a multiprotein Death Inducing Signalling Complex (DISC) that recruits and activates a pro-caspase. For example, the Fas Ligand binds the FasR receptor at the receptor's extracellular surface; this activates the death domains at the cytoplasmic tail of the receptor. The adaptor protein FADD will recruit (by a Death domain-Death domain interaction). The other end of the adaptor contains a DED domain for pro-caspase recruitment. This FasR, FADD and pro-Caspase 8 form the Death Inducing Signalling Complex (DISC) where Caspase-8 is activated. This could lead to either downstream activation of the intrinsic pathway by inducing mitochondrial stress, or direct activation of Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) to degrade cellular components as shown in the adjacent diagram.
Pyroptosis is a form of programmed cell death that inherently induces an immune response. It is morphologically distinct from other types of cell death – cells swell up, rupture and release pro-inflammatory cellular contents. This is done in response to a range of stimuli including microbial infections as well as heart attacks (myocardial infarctions). Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death by Pyroptosis. This limits the life and proliferation time of intracellular and extracellular pathogens.
Pyroptosis by caspase-1
Caspase-1 activation is mediated by a repertoire of proteins, allowing detection of a range of pathogenic ligands. Some mediators of Caspase-1activation are: NOD-like Leucine Rich Repeats (NLRs), AIM2-Like Receptors (ALRs), Pyrin and IFI16.
These proteins allow caspase-1 activation by forming a multiprotein activating complex called Inflammasomes. For example, a NOD Like Leucine Rich Repeat NLRP3 will sense an efflux of potassium ions from the cell. This cellular ion imbalance leads to oligomerisation of NLRP3 molecules to form a multiprotein complex called the NLRP3 Inflammasome. The pro-caspase-1 is brought into close proximity with other pro-caspase molecule in order to dimerise and undergo auto-proteolytic cleavage.
Some pathogenic signals that lead to Pyroptosis by Caspase-1 are listed below:
- DNA in the host cytosol binds to AIM2-Like Receptors inducing Pyroptosis
- Type III secretion system apparatus from bacteria bind NOD Like Leucine Rich Repeats receptors called NAIP’s (1 in humans and 4 in mice)
Pyroptosis by Caspase -4 and Caspase-5 in humans and Caspase-11 in mice
These caspases have the ability to induce direct pyroptosis when lipopolysaccharide (LPS) molecules (found in the cell wall of gram negative bacteria) are found in the cytoplasm of the host cell. For example, Caspase 4 acts as a receptor and is proteolytically activated, without the need of an inflammasome complex or Caspase-1 activation.
Role in inflammation
Inflammation is a protective attempt by an organism to restore a homeostatic state, following disruption from harmful stimulus, such as tissue damage or bacterial infection.
Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'.
- Caspase-1 is key in activating pro-inflammatory cytokines; these act as signals to immune cells and make the environment favourable for immune cell recruitment to the site of damage. Caspase-1 therefore plays a fundamental role in the innate immune system. The enzyme is responsible for processing cytokines such as pro-ILβ and pro-IL18, as well as secreting them.
- Caspase-4 and -5 in humans, and Caspase-11 in mice have a unique role as a receptor, whereby it binds to LPS, a molecule abundant in gram negative bacteria. This can lead to the processing and secretion of IL-1β and IL-18 cytokines by activating Caspase-1; this downstream effect is the same as described above. It also leads to the secretion of another inflammatory cytokine that is not processed. This is called pro-IL1α. There is also evidence of an inflammatory caspase, caspase-11 aiding cytokine secretion; this is done by inactivating a membrane channel that blocks IL-1β secretion
- Caspases can also induce an inflammatory response on a transcriptional level. There is evidence where it promotes transcription of nuclear factor-κB (NF-κB), a transcription factor that assists in transcribing inflammatory cytokines such as IFNs, TNF, IL-6 and IL-8. For example, Caspase-1 activates Caspase-7, which in turn cleaves the poly (ADP) ribose – this activates transcription of NF-κB controlled genes.
Discovery of caspases
H. Robert Horvitz initially established the importance of caspases in apoptosis and found that the ced-3 gene is required for the cell death that took place during the development of the nematode C. elegans. Horvitz and his colleague Junying Yuan found in 1993 that the protein encoded by the ced-3 gene is cysteine protease with similar properties to the mammalian interleukin-1-beta converting enzyme (ICE) (now known as caspase 1). At the time, ICE was the only known caspase. Other mammalian caspases were subsequently identified, in addition to caspases in organisms such as fruit fly Drosophila melanogaster.
Researchers decided upon the nomenclature of the caspase in 1996. In many instances, a particular caspase had been identified simultaneously by more than one laboratory; each would then give the protein a different name. For example, caspase 3 was variously known as CPP32, apopain and Yama. Caspases, therefore, were numbered in the order in which they were identified. ICE was, therefore, renamed as caspase 1. ICE was the first mammalian caspase to be characterised because of its similarity to the nematode death gene ced-3, but it appears that the principal role of this enzyme is to mediate inflammation rather than cell death.
In animals apoptosis is induced by caspases and in fungi and plants, apoptosis is induced by by arginine and lysine-specific caspase like proteases called metacaspases. Homology searches revealed a close homology between caspases and the caspase-like proteins of Reticulomyxa (a unicellular organism). The phylogenetic study indicates that divergence of caspase and metacaspase sequences occurred before the divergence of eukaryotes.
- Wilson KP, Black JA, Thomson JA, et al. (July 1994). "Structure and mechanism of interleukin-1 beta converting enzyme". Nature. 370 (6487): 270–5. doi:10.1038/370270a0. PMID 8035875.
- Saleh, Maya; Vaillancourt, John P; Graham, Rona K; Huyck, Matthew; Srinivasula, Srinivasa M; Alnemri, Emad S; Steinberg, Martin H; Nolan, Vikki; Baldwin, Clinton T; Hotchkiss, Richard S; Buchman, Timothy G; Zehnbauer, Barbara A; Hayden, Michael R; Farrer, Lindsay A; Roy, Sophie; Nicholson, Donald W (2004). "Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms". Nature. 429 (6987): 75. doi:10.1038/nature02451. PMID 15129283.
- Rathore, S.; Datta, G.; Kaur, I.; Malhotra, P.; Mohmmed, A. (2015-07-02). "Disruption of cellular homeostasis induces organelle stress and triggers apoptosis like cell-death pathways in malaria parasite". Cell Death & Disease. 6 (7): e1803. doi:10.1038/cddis.2015.142. PMC . PMID 26136076.
- Shalini, S.; Dorstyn, L.; Dawar, S.; Kumar, S. (2015-04-01). "Old, new and emerging functions of caspases". Cell Death & Differentiation. 22 (4): 526–539. doi:10.1038/cdd.2014.216. ISSN 1350-9047. PMC . PMID 25526085.
- Goodsell, David S. (2000-10-01). "The Molecular Perspective: Caspases". The Oncologist. 5 (5): 435–436. doi:10.1634/theoncologist.5-5-435. ISSN 1083-7159. PMID 11040280.
- McIlwain, David R.; Berger, Thorsten; Mak, Tak W. (2013-04-01). "Caspase Functions in Cell Death and Disease". Cold Spring Harbor Perspectives in Biology. 5 (4): a008656. doi:10.1101/cshperspect.a008656. ISSN 1943-0264. PMC . PMID 23545416.
- Galluzzi, Lorenzo; López-Soto, Alejandro; Kumar, Sharad; Kroemer, Guido (2016-02-16). "Caspases Connect Cell-Death Signaling to Organismal Homeostasis". Immunity. 44 (2): 221–231. doi:10.1016/j.immuni.2016.01.020. ISSN 1074-7613. PMID 26885855.
- Jänicke, Reiner U.; Sohn, Dennis; Totzke, Gudrun; Schulze-Osthoff, Klaus (June 2006). "Caspase-10 in Mouse or Not?". Science. 312 (5782): 1874. doi:10.1126/science.312.5782.1874a. PMID 16809511.
- Stowe, Irma; Lee, Bettina; Kayagaki, Nobuhiko (2015). "Caspase-11: arming the guards against bacterial infection". Immunological Reviews. 265 (1): 75–84. doi:10.1111/imr.12292. PMID 25879285.
- Koenig, Ulrich; Eckhart, Leopold; Tschachler, Erwin (2001). "Evidence That Caspase-13 Is Not a Human but a Bovine Gene". Biochemical and Biophysical Research Communications. 285 (5): 1150. doi:10.1006/bbrc.2001.5315. PMID 11478774.
- Denecker, Geertrui; Ovaere, Petra; Vandenabeele, Peter; Declercq, Wim (2008-02-11). "Caspase-14 reveals its secrets". The Journal of Cell Biology. 180 (3): 451–458. doi:10.1083/jcb.200709098. ISSN 0021-9525. PMC . PMID 18250198.
- Shi, Yigong (2004-06-25). "Caspase Activation". Cell. 117 (7): 855–858. doi:10.1016/j.cell.2004.06.007. ISSN 0092-8674. PMID 15210107.
- Lahm, Armin; Paradisi, Andrea; Green, Douglas R; Melino, Gerry (2003). "Death fold domain interaction in apoptosis". Cell Death and Differentiation. 10 (1): 10–2. doi:10.1038/sj.cdd.4401203. PMID 12655289.
- Kumar, S (2006). "Caspase function in programmed cell death". Cell Death and Differentiation. 14 (1): 32–43. doi:10.1038/sj.cdd.4402060. PMID 17082813.
- Riedl, Stefan J.; Shi, Yigong (Nov 2004). "Molecular mechanisms of caspase regulation during apoptosis". Nature Reviews Molecular Cell Biology. 5 (11): 897–907. doi:10.1038/nrm1496. PMID 15520809.
- Lavrik, I.; Krueger, A.; Schmitz, I.; Baumann, S.; Weyd, H.; Krammer, P. H.; Kirchhoff, S. (2003-01-01). "The active caspase-8 heterotetramer is formed at the CD95 DISC". Cell Death & Differentiation. 10 (1): 144–145. doi:10.1038/sj.cdd.4401156. ISSN 1350-9047.
- Elmore, Susan (2007-06-01). "Apoptosis: A Review of Programmed Cell Death". Toxicologic Pathology. 35 (4): 495–516. doi:10.1080/01926230701320337. ISSN 0192-6233. PMC . PMID 17562483.
- Sollberger, Gabriel; Strittmatter, Gerhard E.; Garstkiewicz, Martha; Sand, Jennifer; Beer, Hans-Dietmar (2014-02-01). "Caspase-1: The inflammasome and beyond". Innate Immunity. 20 (2): 115–125. doi:10.1177/1753425913484374. ISSN 1753-4259. PMID 23676582.
- Creagh, Emma M. (December 2014). "Caspase crosstalk: integration of apoptotic and innate immune signalling pathways". Trends in Immunology. 35 (12): 631–640. doi:10.1016/j.it.2014.10.004. PMID 25457353.
- Bergsbaken, Tessa; Fink, Susan L.; Cookson, Brad T. (2009). "Pyroptosis: host cell death and inflammation". Nature Reviews Microbiology. 7 (2): 99–109. doi:10.1038/nrmicro2070. PMC . PMID 19148178.
- Eldridge, Matthew JG; Shenoy, Avinash R (2015). "Antimicrobial inflammasomes: unified signalling against diverse bacterial pathogens". Current Opinion in Microbiology. 23: 32–41. doi:10.1016/j.mib.2014.10.008. PMID 25461570.
- He, Wan-ting; Wan, Haoqiang; Hu, Lichen; Chen, Pengda; Wang, Xin; Huang, Zhe; Yang, Zhang-Hua; Zhong, Chuan-Qi; Han, Jiahuai (2015-12-01). "Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion". Cell Research. 25 (12): 1285–1298. doi:10.1038/cr.2015.139. ISSN 1001-0602. PMC . PMID 26611636.
- Yuan, J; et al. (1993). "The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme". Cell. 75 (4): 641–652. doi:10.1016/0092-8674(93)90485-9. PMID 8242740.
- Alnemri ES, Emad S; et al. (1996). "Human ICE/CED-3 Protease Nomenclature". Cell. 87 (2): 171. doi:10.1016/S0092-8674(00)81334-3. PMID 8861900. Retrieved 6 March 2011.
- Klim, Joanna; Gładki, Arkadiusz; Kucharczyk, Roza; Zielenkiewicz, Urszula; Kaczanowski, Szymon (2018-04-27). "Ancestral State Reconstruction of the Apoptosis Machinery in the Common Ancestor of Eukaryotes". G3: Genes|Genomes|Genetics. 8 (6): 2121–2134. doi:10.1534/g3.118.200295. ISSN 2160-1836. PMC . PMID 29703784.
- Eukaryotic Linear Motif resource motif class CLV_C14_Caspase3-7
- Apoptosis Video Demonstrates a model of a caspase cascade as it occurs in vivo.
- The Mechanisms of Apoptosis Kimball's Biology Pages. Simple explanation of the mechanisms of apoptosis triggered by internal signals (bcl-2), along the caspase-9, caspase-3 and caspase-7 pathway; and by external signals (FAS and TNF), along the caspase 8 pathway. Accessed 25 March 2007.
- Apoptosis & Caspase 7, PMAP-animation
- Caspases at the US National Library of Medicine Medical Subject Headings (MeSH)
- Tumors Beware (from Beaker Blog)
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Wilson KP, Black JA, Thomson JA, Kim EE, Griffith JP, Navia MA, Murcko MA, Chambers SP, Aldape RA, Raybuck SA, et al , Nature 1994;370:270-275.: Structure and mechanism of interleukin-1 beta converting enzyme. PUBMED:8035875 EPMC:8035875
Internal database links
|SCOOP:||CHAT MALT1_Ig Peptidase_C13 Raptor_N|
|Similarity to PfamA using HHSearch:||Peptidase_C13|
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The members of this clan are all endopeptidase that have the catalytic dyad histidine followed by cysteine. The catalytic histidine is preceded by a block of hydrophobic residues and a glycine, where as the cysteine is preceded by a block of hydrophobic residues and a glutamine and an alanine. The members with a know structure adopt an alpha/beta fold .
The clan contains the following 8 members:CHAT Peptidase_C11 Peptidase_C13 Peptidase_C14 Peptidase_C25 Peptidase_C50 Peptidase_C80 Raptor_N
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|Seed source:||Bateman A & Pfam-B_2524 (Release 8.0)|
|Number in seed:||115|
|Number in full:||13065|
|Average length of the domain:||239.50 aa|
|Average identity of full alignment:||16 %|
|Average coverage of the sequence by the domain:||45.47 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||22|
|Download:||download the raw HMM for this family|
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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.
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".
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.
The tree shows the occurrence of this domain across different species. More...
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.
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
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.
There are 4 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 Peptidase_C14 domain has been found. There are 678 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.
Loading structure mapping...