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Septin Edit Wikipedia article
|Cell division/GTP binding protein|
Septins are a group of GTP-binding proteins found primarily in eukaryotic cells of fungi and animals, but also in some green algae. Different septins form protein complexes with each other. These complexes can further assemble into filaments, rings and gauzes. Assembled as such, septins function in cells by localizing other proteins, either by providing a scaffold to which proteins can attach, or by preventing diffusion of molecules from one compartment of the cell to another.
Septins have been implicated in the localization of cellular processes at the site of cell division, at the plasma membrane, at sites where specialized structures like cilia or flagella are attached to the cell body. In yeast cells, they compartmentalize parts of the cell and build scaffolding to provide structural support during cell division at the septum, from which they derive their name. Recent research in human cells suggests that septins build cages around bacterial pathogens, immobilizing the harmful microbes and preventing them from invading other cells.
As filament forming proteins, septins can be considered part of the cytoskeleton. Apart from forming non-polar filaments, septins associate with cell membranes, actin filaments and microtubules. Although present in most eukaryotes, septins have not been observed in plants.
- 1 Structure
- 2 Occurrence
- 3 In Saccharomyces cerevisiae
- 4 In Filamentous fungi
- 5 In metazoa
- 6 In mitochondria
- 7 History
- 8 References
- 9 Further reading
Septins are P-Loop-NTPase proteins that range in weight from 30-65 kDa. Septins are highly conserved between different eukaryotic species. They are composed of a variable-length proline rich N-terminus with a basic phosphoinositide binding motif important for membrane association, a GTP-binding domain, a highly conserved Septin Unique Element domain, and a C-terminal extension including a coiled coil domain of varying length.
Septins interact either via their respective GTP-binding domains, or via both their N- and C-termini. Different organisms express a different number of septins, and from those symmetric oligomeres are formed. For example, in humans Sept7-Sept6-Sept2-Sept2-Sept6-Sept7 form one complex, and in yeast Cdc11-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11 form another one. These complexes then associate to form non-polar filaments, filament bundles, cages or ring structures in cells.
|Species||Group (phylogenetic)||Septin genes|
|Cdc11||Cdc11, Shs1, Spr28|
|Spn3||Spn3, Spn5, Spn7|
|Cdc11||Cdc11, Sep7, Spr28|
|Animals||Humans||Sept2||Sept1, Spet2, Sept4, Sept5|
|Sept3||Sept3, Sept9, Sept12|
|Sept6||Sept6, Sept8, Sept10, Sept11, Sept14|
|Sept7||Sept7 (Sept13 as a pseudogene)|
In Saccharomyces cerevisiae
There are seven different septins in Saccharomyces cerevisiae. Five of those are involved in mitosis, while two (Spr3 and Spr28) are specific to sporulation. Mitotic septins (Cdc3, Cdc10, Cdc11, Cdc12, Shs1) form a ring structure at the bud neck during cell division. They are involved in the selection of the bud-site, the positioning of the mitotic spindle, polarized growth, and cytokinesis. The sporulating septins (Spr3, Spr28) localize together with Cdc3 and Cdc11 to the edges of prospore membranes.
The septin cortex undergoes several changes throughout the cell cycle: The first visible septin structure is a distinct ring which appears ~15 min before bud emergence. After bud emergence, the ring broadens to assume the shape of an hourglass around the mother-bud neck. During cytokinesis, the septin cortex splits into a double ring which eventually disappears. How can the septin cortex undergo such dramatic changes, although some of its functions may require it to be a stable structure? FRAP analysis has revealed that the turnover of septins at the neck undergoes multiple changes during the cell cycle. The predominant, functional conformation is characterized by a low turnover rate (frozen state), during which the septins are phosphorylated. Structural changes require a destabilization of the septin cortex (fluid state) induced by dephosphorylation prior to bud emergence, ring splitting and cell separation.
The composition of the septin cortex does not only vary throughout the cell cycle but also along the mother-bud axis. This polarity of the septin network allows concentration of some proteins primarily to the mother side of the neck, some to the center and others to the bud site.
The septins act as a scaffold, recruiting many proteins. These protein complexes are involved in cytokinesis, chitin deposition, cell polarity, spore formation, in the morphogenesis checkpoint, spindle alignment checkpoint and bud site selection.
Budding yeast cytokinesis is driven through two septin dependent, redundant processes: recruitment and contraction of the actomyosin ring and formation of the septum by vesicle fusion with the plasma membrane. In contrast to septin mutants, disruption of one single pathway only leads to a delay in cytokinesis, not complete failure of cell division. Hence, the septins are predicted to act at the most upstream level of cytokinesis.
After the isotropic-apical switch in budding yeast, cortical components, supposedly of the exocyst and polarisome, are delocalized from the apical pole to the entire plasma membrane of the bud, but not the mother cell. The septin ring at the neck serves as a cortical barrier that prevents membrane diffusion of these factors between the two compartments. This asymmetric distribution is abolished in septin mutants.
Some conditional septin mutants do not form buds at their normal axial location. Moreover, the typical localization of some bud-site-selection factors in a double ring at the neck is lost or disturbed in these mutants. This indicates that the septins may serve as anchoring site for such factors in axially budding cells.
In Filamentous fungi
Since their discovery in S. cerevisiae, septin homologues have been found in other eukaryotic species, including filamentous fungi. Septins in filamentous fungi display a variety of different shapes within single cells, where they control aspects of filamentous morphology.
The genome of C. albicans encodes homologues to all S. cerevisiae septins. Without Cdc3 and Cdc12 genes Candida albicans cannot proliferate, other septins affect morphology and chitin deposition, but are not essential. Candida albicans can display different morphologies of vegetative growth, which determines the appearance of septin structures. Newly forming hyphae form a septin ring at the base, Double rings form at sites of hyphal septation, and a septin cap forms at hyphal tips. Elongated septin-filaments encircle the spherical chlamydospores. Double rings of septins at the septation site also bear growth polarity, with the growing tip ring disassembling, while the basal ring remaining intact.
Five septins are found in A. nidulans (AnAspAp, AnAspBp, AnAspCp, AnAspDp, AnAspEp). AnAspBp forms single rings at septation sites that eventually split into double rings. Additionally, AnAspBp forms a ring at sites of branch emergence which broadens into a band as the branch grows. Like in C. albicans, double rings reflect polarity of the hypha. In the case of Aspergillus nidulans polarity is conveyed by disassembly of the more basal ring (the ring further away from the hyphal growth tip), leaving the apical ring intact, potentially as a growth guidance cue.
The ascomycete A. gossypii possesses homologues to all S. cerevisiae septins, with one being duplicated (AgCDC3, AgCDC10, AgCDC11A, AgCDC11B, AgCDC12, AgSEP7). In vivo studies of AgSep7p-GFP have revealed that septins assemble into discontinuous hyphal rings close to growing tips and sites of branch formation, and into asymmetric structures at the base of branching points. Rings are made of filaments which are long and diffuse close to growing tips and short and compact further away from the tip. During septum formation, the septin ring splits into two to form a double ring. Agcdc3Δ, Agcdc10Δ and Agcdc12Δ deletion mutants display aberrant morphology and are defective for actin-ring formation, chitin-ring formation, and sporulation. Due to the lack of septa, septin deletion mutants are highly sensitive, and damage of a single hypha can result in complete lysis of a young mycelium.
In contrast to septins in yeast, and in contrast to other cytoskeletal components of metazoa, septins do not form a continuous network in metazoan cells, but several dispersed ones in the cortical cytoplasm. These are integrated with actin bundles and microtubules. For example, the actin bundling protein anillin is required for correct spatial control of septin organization. In the sperm cells of mammals, septins form a stable ring called annulus in the tail. In mice (and potentially in humans, too), defective annulus formation leads to male infertility.
In humans, septins are involved in cytokinesis, cilium formation and neurogenesis through the capability to recruit other proteins or serve as a diffusion barrier. There are 13 different human genes coding for septins. The septin proteins produced by these genes are grouped into four subfamilies each named after its founding member: (i) SEPT2 (SEPT1, SEPT4, SEPT5), (ii) SEPT3 (SEPT9, SEPT12), (iii) SEPT6 (SEPT8, SEPT10, SEPT11, SEPT14), and (iv) SEPT7. Septin protein complexes are assembled to form either hetero-hexamers (incorporating monomers selected from three different groups and the monomer from each group is present in two copies; 3 x 2 = 6) or hetero-octamers (monomers from four different groups, each monomer present in two copies; 4 x 2 = 8). These hetero-oligomers in turn form higher-order structures such as filaments and rings.
Septins form cage-like structures around bacterial pathogens, immobilizing harmful microbes and preventing them from invading healthy cells. This cellular defence system could potentially be exploited to create therapies for dysentery and other illnesses. For example, Shigella is a bacterium that causes lethal diarrhoea in humans. To propagate from cell to cell, Shigella bacteria develop actin-polymer 'tails', which propel the microbes and allow them to gain entry into neighbouring host cells. As part of the immune response, human cells produce a cell-signalling protein called TNF-α which trigger thick bundles of septin filaments to encircle the microbes within the infected host cell. Microbes that become trapped in these septin cages are broken down by autophagy. Disruptions in septins and mutations in the genes that code for them could be involved in causing leukaemia, colon cancer and neurodegenerative conditions such as Parkinson's disease and Alzheimer's disease. Potential therapies for these, as well as for bacterial conditions such as dysentery caused by Shigella, might bolster the body’s immune system with drugs that mimic the behaviour of TNF-α and allow the septin cages to proliferate.
In the nematode worm Caenorhabditis elegans there are two genes coding for septins, and septin complexes contain the two different septins in a tetrameric UNC59-UNC61-UNC61-UNC59 complex. Septins in C.elegans concentrate at the cleavage furrow and the spindle midbody during cell division. Septins are also involved in cell migration and axon guidance in C.elegans.
The septins were discovered in 1970 by Leland H. Hartwell and colleagues in a screen for temperature-sensitive mutants affecting cell division (cdc mutants) in yeast (Saccharomyces cerevisiae). The screen revealed four mutants which prevented cytokinesis at restrictive temperature. The corresponding genes represent the four original septins, ScCDC3, ScCDC10, ScCDC11, and ScCDC12. Despite disrupted cytokinesis, the cells continued budding, DNA synthesis, and nuclear division, which resulted in large multinucleate cells with multiple, elongated buds. In 1976, analysis of electron micrographs revealed ~20 evenly spaced striations of 10-nm filaments around the mother-bud neck in wild-type but not in septin-mutant cells. Immunofluorescence studies revealed that the septin proteins colocalize into a septin ring at the neck. The localization of all four septins is disrupted in conditional Sccdc3 and Sccdc12 mutants, indicating interdependence of the septin proteins. Strong support for this finding was provided by biochemical studies: The four original septins co-purified on affinity columns, together with a fifth septin protein, encoded by ScSEP7 or ScSHS1. Purified septins from budding yeast, Drosophila, Xenopus, and mammalian cells are able to self associate in vitro to form filaments. How the septins interact in vitro to form heteropentamers that assemble into filaments was studied in detail in S. cerevisiae.
Micrographs of purified filaments raised the possibility that the septins are organized in parallel to the mother-bud axis. The 10-nm striations seen on electron micrographs may be the result of lateral interaction between the filaments. Mutant strains lacking factors important for septin organization support this view. Instead of continuous rings, the septins form bars oriented along the mother-bud axis in deletion mutants of ScGIN4, ScNAP1 and ScCLA4.
- Weirich CS, Erzberger JP, Barral Y (2008). "The septin family of GTPases: architecture and dynamics". Nat. Rev. Mol. Cell Biol. 9 (6): 478–89. doi:10.1038/nrm2407. PMID 18478031.
- Douglas LM, Alvarez FJ, McCreary C, Konopka JB (2005). "Septin function in yeast model systems and pathogenic fungi". Eukaryotic Cell 4 (9): 1503–12. doi:10.1128/EC.4.9.1503-1512.2005. PMC 1214204. PMID 16151244.
- Mostowy S, Cossart P (2012). "Septins: the fourth component of the cytoskeleton". Nat. Rev. Mol. Cell Biol. 13 (3): 183–94. doi:10.1038/nrm3284. PMID 22314400.
- Kinoshita M (2006). "Diversity of septin scaffolds". Curr. Opin. Cell Biol. 18 (1): 54–60. doi:10.1016/j.ceb.2005.12.005. PMID 16356703.
- Mascarelli A (December 2011). "Septin proteins take bacterial prisoners: A cellular defence against microbial pathogens holds therapeutic potential". Nature. doi:10.1038/nature.2011.9540.
- Gladfelter AS (2006). "Control of filamentous fungal cell shape by septins and formins". Nat. Rev. Microbiol. 4 (3): 223–9. doi:10.1038/nrmicro1345. PMID 16429163.
- Mostowy S, Bonazzi M, Hamon MA, Tham TN, Mallet A, Lelek M, Gouin E, Demangel C, Brosch R, Zimmer C, Sartori A, Kinoshita M, Lecuit M, Cossart P (2010). "Entrapment of intracytosolic bacteria by septin cage-like structures". Cell Host Microbe 8 (5): 433–44. doi:10.1016/j.chom.2010.10.009. PMID 21075354.
- Mostowy S, Sancho-Shimizu V, Hamon MA, Simeone R, Brosch R, Johansen T, Cossart P (2011). "p62 and NDP52 proteins target intracytosolic Shigella and Listeria to different autophagy pathways". J. Biol. Chem. 286 (30): 26987–95. doi:10.1074/jbc.M111.223610. PMC 3143657. PMID 21646350.
- Takahashi S, Inatome R, Yamamura H, Yanagi S (February 2003). "Isolation and expression of a novel mitochondrial septin that interacts with CRMP/CRAM in the developing neurones". Genes Cells 8 (2): 81–93. doi:10.1046/j.1365-2443.2003.00617.x. PMID 12581152.
- Longtine MS, DeMarini DJ, Valencik ML, Al-Awar OS, Fares H, De Virgilio C, Pringle JR (February 1996). "The septins: roles in cytokinesis and other processes". Curr. Opin. Cell Biol. 8 (1): 106–19. doi:10.1016/S0955-0674(96)80054-8. PMID 8791410.
- Gladfelter AS, Pringle JR, Lew DJ (December 2001). "The septin cortex at the yeast mother-bud neck". Curr. Opin. Microbiol. 4 (6): 681–9. doi:10.1016/S1369-5274(01)00269-7. PMID 11731320.
- Faty M, Fink M, Barral Y (June 2002). "Septins: a ring to part mother and daughter". Curr. Genet. 41 (3): 123–31. doi:10.1007/s00294-002-0304-0. PMID 12111093.
- Versele M, Gullbrand B, Shulewitz MJ, Cid VJ, Bahmanyar S, Chen RE, Barth P, Alber T, Thorner J (October 2004). "Protein-protein interactions governing septin heteropentamer assembly and septin filament organization in Saccharomyces cerevisiae". Mol. Biol. Cell 15 (10): 4568–83. doi:10.1091/mbc.E04-04-0330. PMC 519150. PMID 15282341.
- Douglas LM, Alvarez FJ, McCreary C, Konopka JB (September 2005). "Septin function in yeast model systems and pathogenic fungi". Eukaryotic Cell 4 (9): 1503–12. doi:10.1128/EC.4.9.1503-1512.2005. PMC 1214204. PMID 16151244.
- Gladfelter AS (March 2006). "Control of filamentous fungal cell shape by septins and formins". Nat. Rev. Microbiol. 4 (3): 223–9. doi:10.1038/nrmicro1345. PMID 16429163.
- Hall PA, Russell SEH, Pringle JR, (2008). The septins. Oxford: John Wiley-Blackwell. p. 370. ISBN 0-470-51969-X.
- Gonzalez-Novo A, Vázquez de Aldana CR, Jimenez J (2009). "Fungal septins: one ring to rule it all?". Cent. Eur. J. Biol. 4 (3): 274–289. doi:10.2478/s11535-009-0032-2.
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.
Septin Provide feedback
Members of this family include CDC3, CDC10, CDC11 and CDC12/Septin. Members of this family bind GTP. As regards the septins, these are polypeptides of 30-65kDa with three characteristic GTPase motifs (G-1, G-3 and G-4) that are similar to those of the Ras family. The G-4 motif is strictly conserved with a unique septin consensus of AKAD. Most septins are thought to have at least one coiled-coil region, which in some cases is necessary for intermolecular interactions that allow septins to polymerise to form rod-shaped complexes. In turn, these are arranged into tandem arrays to form filaments. They are multifunctional proteins, with roles in cytokinesis, sporulation, germ cell development, exocytosis and apoptosis .
Casamayor A, Snyder M; , Mol Cell Biol 2003;23:2762-2777.: Molecular dissection of a yeast septin: distinct domains are required for septin interaction, localization, and function. PUBMED:12665577 EPMC:12665577
This tab holds annotation information from the InterPro database.
InterPro entry IPR030379
The P-loop guanosine triphosphatases (GTPases) control a multitude of biological processes, ranging from cell division, cell cycling, and signal transduction, to ribosome assembly and protein synthesis. GTPases exert their control by interchanging between an inactive GDP-bound state and an active GTP-bound state, thereby acting as molecular switches. The common denominator of GTPases is the highly conserved guanine nucleotide-binding (G) domain that is responsible for binding and hydrolysis of guanine nucleotides.
Septins are a family of eukaryotic cytoskeletal proteins conserved from yeasts to humans. The septin family belongs to the guanosine-triphosphate (GTP)ase superclass of P-loop nucleoside triphosphate (NTP)ases. Septins participate in diverse cellular functions including cytokinesis, vesicle trafficking, vesicle fusion, axonal guidance and migration, diffusion barrier, scaffolds, pathogenesis and others. Septin monomers form homo- and hetero-oligomeric complexes that assemble into filaments. Structurally all septins have a GTP- binding domain flanked by N- and C-terminal regions of variable length. The GTP-binding domain is the most highly conserved and is characterised by the presence of three of the five classical GTP-binding motifs. The G1 motif (or Walker A box, GxxxxGKS/T) forms the P-loop, which interacts directly with the nucleotide, whereas the G3 (DxxG) and G4 (xKxD) motifs are respectively essential for Mg(2+) binding and for conferring GTP binding specificity over other nucleotides. The basic structure of the septin-type G domain closely resembles the canonical G domain exemplified by Ras, with six beta-strands and five alpha-helices. A unique feature of the septin-type G domain is the presence of four additional elements compared to Ras. These are the helix alpha5' between alpha4 and beta6, the two antiparallel strands beta7 and beta8, and the alpha6 C-terminal helix that points away from the G domain at a 90deg angle relative to the axis of interaction between subunits [PUBMED:11916378, PUBMED:16009555, PUBMED:17637674, PUBMED:23163726, PUBMED:24367716].
This entry represents the septin-type G domain.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||GTP binding (GO:0005525)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes .
The clan contains the following 200 members:6PF2K AAA AAA-ATPase_like AAA_10 AAA_11 AAA_12 AAA_13 AAA_14 AAA_15 AAA_16 AAA_17 AAA_18 AAA_19 AAA_2 AAA_21 AAA_22 AAA_23 AAA_24 AAA_25 AAA_26 AAA_27 AAA_28 AAA_29 AAA_3 AAA_30 AAA_31 AAA_32 AAA_33 AAA_34 AAA_35 AAA_5 AAA_6 AAA_7 AAA_8 AAA_PrkA ABC_ATPase ABC_tran Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arf ArgK ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 ATPase ATPase_2 Bac_DnaA CbiA CBP_BcsQ CDC73_C CLP1_P CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DUF1611 DUF2075 DUF2326 DUF2478 DUF258 DUF2791 DUF2813 DUF3584 DUF463 DUF815 DUF853 DUF87 DUF927 Dynamin_N ERCC3_RAD25_C Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GTP_EFTU Gtr1_RagA Guanylate_kin GvpD HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD Herpes_Helicase Herpes_ori_bp Herpes_TK IIGP IPPT IPT IstB_IS21 KAP_NTPase KdpD Kinesin Kinesin-relat_1 Kinesin-related KTI12 Lon_2 LpxK MCM MEDS Mg_chelatase Microtub_bd MipZ MMR_HSR1 MobB MukB MutS_V Myosin_head NACHT NB-ARC NOG1 NTPase_1 NTPase_P4 ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK Rad17 Rad51 Ras RecA ResIII RHD3 RHSP RNA12 RNA_helicase Roc RuvB_N SbcCD_C SecA_DEAD Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2_N Spore_IV_A SRP54 SRPRB SulA Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulphotransf T2SSE T4SS-DNA_transf Terminase_1 Terminase_3 Terminase_6 Terminase_GpA Thymidylate_kin TIP49 TK TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind TsaE UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE Zeta_toxin Zot
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, the UniProtKB sequence database, 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.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
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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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
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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.
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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.
|Seed source:||Pfam-B_440 (release 2.1)|
|Number in seed:||14|
|Number in full:||3030|
|Average length of the domain:||235.20 aa|
|Average identity of full alignment:||36 %|
|Average coverage of the sequence by the domain:||61.78 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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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 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:
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".
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 is 1 interaction 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 Septin domain has been found. There are 21 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.
Loading structure mapping...