Summary: Sel1 repeat
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Cytochrome c oxidase Edit Wikipedia article
|Cytochrome c oxidase|
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
It is the last enzyme in the respiratory electron transport chain of mitochondria (or bacteria) located in the mitochondrial (or bacterial) membrane. It receives an electron from each of four cytochrome c molecules, and transfers them to one oxygen molecule, converting molecular oxygen to two molecules of water. In the process, it binds four protons from the inner aqueous phase to make water, and in addition translocates four protons across the membrane, helping to establish a transmembrane difference of proton electrochemical potential that the ATP synthase then uses to synthesize ATP.
The complex is a large integral membrane protein composed of several metal prosthetic sites and 14  protein subunits in mammals. In mammals, eleven subunits are nuclear in origin, and three are synthesized in the mitochondria. The complex contains two hemes, a cytochrome a and cytochrome a3, and two copper centers, the CuA and CuB centers. In fact, the cytochrome a3 and CuB form a binuclear center that is the site of oxygen reduction. Cytochrome c, which is reduced by the preceding component of the respiratory chain (cytochrome bc1 complex, complex III), docks near the CuA binuclear center and passes an electron to it, being oxidized back to cytochrome c containing Fe3+. The reduced CuA binuclear center now passes an electron on to cytochrome a, which in turn passes an electron on to the cytochrome a3-CuB binuclear center. The two metal ions in this binuclear center are 4.5 Å apart and coordinate a hydroxide ion in the fully oxidized state.
Crystallographic studies of cytochrome c oxidase show an unusual post-translational modification, linking C6 of Tyr(244) and the ε-N of His(240) (bovine enzyme numbering). It plays a vital role in enabling the cytochrome a3- CuB binuclear center to accept four electrons in reducing molecular oxygen to water. The mechanism of reduction was formerly thought to involve a peroxide intermediate, which was believed to lead to superoxide production. However, the currently accepted mechanism involves a rapid four-electron reduction involving immediate oxygen-oxygen bond cleavage, avoiding any intermediate likely to form superoxide.
Site of assembly is believed to occur near TOM/TIM, where complex intermediates are accessible to bind with subunits imported from cytosol. Hemes and cofactors are inserted into subunits I & II. Subunits I and IV initiate assembly. Other subunits may form sub-complex intermediates that later bind to others to form COX complex. In post-assembly modifications, the enzyme is dimerized, which is required for active/efficient enzyme action. Dimers are connected by a cardiolipin molecule.
|No.||Subunit name||Human protein||Protein description from UniProt||Pfam family with Human protein
|1||Cox1||COX1_HUMAN||Cytochrome c oxidase subunit 1||Pfam PF00115|
|2||Cox2||COX2_HUMAN||Cytochrome c oxidase subunit 2||Pfam PF02790, Pfam PF00116|
|3||Cox3||COX3_HUMAN||Cytochrome c oxidase subunit 3||Pfam PF00510|
|4||Cox4i1||COX41_HUMAN||Cytochrome c oxidase subunit 4 isoform 1, mitochondrial||Pfam PF02936|
|5||Cox4a2||COX42_HUMAN||Cytochrome c oxidase subunit 4 isoform 2, mitochondrial||Pfam PF02936|
|6||Cox5a||COX5A_HUMAN||Cytochrome c oxidase subunit 5A, mitochondrial||Pfam PF02284|
|7||Cox5b||COX5B_HUMAN||Cytochrome c oxidase subunit 5B, mitochondrial||Pfam PF01215|
|8||Cox6a1||CX6A1_HUMAN||Cytochrome c oxidase subunit 6A1, mitochondrial||Pfam PF02046|
|9||Cox6a2||CX6A2_HUMAN||Cytochrome c oxidase subunit 6A2, mitochondrial||Pfam PF02046|
|10||Cox6b1||CX6B1_HUMAN||Cytochrome c oxidase subunit 6B1||Pfam PF02297|
|11||Cox6b2||CX6B2_HUMAN||Cytochrome c oxidase subunit 6B2||Pfam PF02297|
|12||Cox6c||COX6C_HUMAN||Cytochrome c oxidase subunit 6C||Pfam PF02937|
|13||Cox7a1||CX7A1_HUMAN||Cytochrome c oxidase subunit 7A1, mitochondrial||Pfam PF02238|
|14||Cox7a2||CX7A2_HUMAN||Cytochrome c oxidase subunit 7A2, mitochondrial||Pfam PF02238|
|15||Cox7a3||COX7S_HUMAN||Putative cytochrome c oxidase subunit 7A3, mitochondrial||Pfam PF02238|
|16||Cox7b||COX7B_HUMAN||Cytochrome c oxidase subunit 7B, mitochondrial||Pfam PF05392|
|17||Cox7c||COX7C_HUMAN||Cytochrome c oxidase subunit 7C, mitochondrial||Pfam PF02935|
|18||Cox7r||COX7R_HUMAN||Cytochrome c oxidase subunit 7A-related protein, mitochondrial||Pfam PF02238|
|19||Cox8a||COX8A_HUMAN||Cytochrome c oxidase subunit 8A, mitochondrial P||Pfam PF02285|
|20||Cox8c||COX8C_HUMAN||Cytochrome c oxidase subunit 8C, mitochondrial||Pfam PF02285|
|1||Coa1||COA1_HUMAN||Cytochrome c oxidase assembly factor 1 homolog||Pfam PF08695|
|2||Coa3||COA3_HUMAN||Cytochrome c oxidase assembly factor 3 homolog, mitochondrial||Pfam PF09813|
|3||Coa4||COA4_HUMAN||Cytochrome c oxidase assembly factor 4 homolog, mitochondrial||Pfam PF06747|
|4||Coa5||COA5_HUMAN||Cytochrome c oxidase assembly factor 5||Pfam PF10203|
|5||Coa6||COA6_HUMAN||Cytochrome c oxidase assembly factor 6 homolog||Pfam PF02297|
|6||Coa7||COA7_HUMAN||Cytochrome c oxidase assembly factor 7,||Pfam PF08238|
|7||Cox11||COX11_HUMAN||Cytochrome c oxidase assembly protein COX11 mitochondrial||Pfam PF04442|
|8||Cox14||COX14_HUMAN||Cytochrome c oxidase assembly protein||Pfam PF14880|
|9||Cox15||COX15_HUMAN||Cytochrome c oxidase assembly protein COX15 homolog||Pfam PF02628|
|10||Cox16||COX16_HUMAN||Cytochrome c oxidase assembly protein COX16 homolog mitochondrial||Pfam PF14138|
|11||Cox17||COX17_HUMAN||Cytochrome c oxidase copper chaperone||Pfam PF05051|
|12||Cox18||COX18_HUMAN||Mitochondrial inner membrane protein (Cytochrome c oxidase assembly protein 18)||Pfam PF02096|
|13||Cox19||COX19_HUMAN||Cytochrome c oxidase assembly protein||Pfam PF06747|
|14||Cox20||COX20_HUMAN||Cytochrome c oxidase protein 20 homolog||Pfam PF12597|
- 4 Fe2+-cytochrome c + 8 H+in + O2 → 4 Fe3+-cytochrome c + 2 H2O + 4 H+out
Two electrons are passed from two cytochrome c's, through the CuA and cytochrome a sites to the cytochrome a3- CuB binuclear center, reducing the metals to the Fe2+ form and Cu+. The hydroxide ligand is protonated and lost as water, creating a void between the metals that is filled by O2. The oxygen is rapidly reduced, with two electrons coming from the Fe2+cytochrome a3, which is converted to the ferryl oxo form (Fe4+=O). The oxygen atom close to CuB picks up one electron from Cu+, and a second electron and a proton from the hydroxyl of Tyr(244), which becomes a tyrosyl radical: The second oxygen is converted to a hydroxide ion by picking up two electrons and a proton. A third electron arising from another cytochrome c is passed through the first two electron carriers to the cytochrome a3- CuB binuclear center, and this electron and two protons convert the tyrosyl radical back to Tyr, and the hydroxide bound to CuB2+ to a water molecule. The fourth electron from another cytochrome c flows through CuA and cytochrome a to the cytochrome a3- CuB binuclear center, reducing the Fe4+=O to Fe3+, with the oxygen atom picking up a proton simultaneously, regenerating this oxygen as a hydroxide ion coordinated in the middle of the cytochrome a3- CuB center as it was at the start of this cycle. The net process is that four reduced cytochrome c's are used, along with 4 protons, to reduce O2 to two water molecules.
Cyanide, sulfide, azide, and carbon monoxide all bind to cytochrome c oxidase, thus competitively inhibiting the protein from functioning, which results in chemical asphyxiation of cells. Methanol in methylated spirits is converted into formic acid, which also inhibits the same oxidase system. High levels of ATP can allosterically inhibit cytochrome c oxidase, binding from within the mitochondrial matrix.
Subcellular Localization and Presence at Extramitochondrial Sites
Cytochrome c oxidase has 3 subunits which are encoded by mitochondrial DNA. Of these 3 subunits encoded by mitochondrial DNA, two have been identified in extramitochondrial locations. In pancreatic acinar tissue, these subunits were found in zymogen granules. Additionally, in the anterior pituitary, relatively high amounts of these subunits were found in growth hormone secretory granules. The extramitochondrial function of these cytochrome c oxidase subunits has not yet been characterized. Besides cytochrome c oxidase subunits, extramitochondrial localization has also been observed for large numbers of other mitochondrial proteins., This raises the possibility about existence of yet unidentified specific mechanisms for protein translocation from mitochondria to other cellular destinations.
Genetic defects and disorders
Defects involving genetic mutations altering cytochrome c oxidase (COX) functionality or structure can result in severe, often fatal metabolic disorders. Such disorders usually manifest in early childhood and affect predominantly tissues with high energy demands (brain, heart, muscle). Among the many classified mitochondrial diseases, those involving dysfunctional COX assembly are thought to be the most severe.
The vast majority of COX disorders are linked to mutations in nuclear-encoded proteins referred to as assembly factors, or assembly proteins. These assembly factors contribute to COX structure and functionality, and are involved in several essential processes, including transcription and translation of mitochondrion-encoded subunits, processing of preproteins and membrane insertion, and cofactor biosynthesis and incorporation.
Currently, mutations have been identified in seven COX assembly factors: SURF1, SCO1, SCO2, COX10, COX15, COX20, COA5 and LRPPRC. Mutations in these proteins can result in altered functionality of sub-complex assembly, copper transport, or translational regulation. Each gene mutation is associated with the etiology of a specific disease, with some having implications in multiple disorders. Disorders involving dysfunctional COX assembly via gene mutations include Leigh syndrome, cardiomyopathy, leukodystrophy, anemia, and sensorineural deafness.
COX histochemistry is used for mapping regional brain metabolism in animals, since there is a direct relation between enzyme activity and neuronal activity. Such brain mapping has been accomplished in spontaneous mutant mice with cerebellar disease such as reeler and a transgenic model of Alzheimer's disease. This technique has also been used to map learning activity in animal brain.
- Cytochrome c oxidase subunit I
- Cytochrome c oxidase subunit II
- Cytochrome c oxidase subunit III
- Heme a
- Balsa E, Marco R, Perales-Clemente E, Szklarczyk R, Calvo E, Landázuri MO, Enríquez JA (September 2012). "NDUFA4 is a subunit of complex IV of the mammalian electron transport chain". Cell Metab. 16 (3): 378–86. doi:10.1016/j.cmet.2012.07.015. PMID 22902835.
- Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K, Nakashima R, Yaono R, Yoshikawa S (August 1995). "Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 A". Science 269 (5227): 1069–74. doi:10.1126/science.7652554. PMID 7652554.
- Voet, Donald (2010). Biochemistry. New York: J. Wiley & Sons. pp. 865–866. ISBN 0-470-57095-4.
- Khalimonchuk O, Rödel G (December 2005). "Biogenesis of cytochrome c oxidase". Mitochondrion 5 (6): 363–88. doi:10.1016/j.mito.2005.08.002. PMID 16199211.
- Fontanesi F, Soto IC, Horn D, Barrientos A (December 2006). "Assembly of mitochondrial cytochrome c-oxidase, a complicated and highly regulated cellular process". Am. J. Physiol., Cell Physiol. 291 (6): C1129–47. doi:10.1152/ajpcell.00233.2006. PMID 16760263.
- Zhang Z, Huang L, Shulmeister VM, Chi YI, Kim KK, Hung LW et al. (1998). "Electron transfer by domain movement in cytochrome bc1.". Nature 392 (6677): 677–84. doi:10.1038/33612. PMID 9565029.
- Kaila VR, Oksanen E, Goldman A, Bloch DA, Verkhovsky MI, Sundholm D et al. (2011). "A combined quantum chemical and crystallographic study on the oxidized binuclear center of cytochrome c oxidase.". Biochim Biophys Acta 1807 (7): 769–78. doi:10.1016/j.bbabio.2010.12.016. PMID 21211513.
- Szklarczyk R, Wanschers BF, Cuypers TD, Esseling JJ, Riemersma M, van den Brand MA et al. (2012). "Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome c oxidase.". Genome Biol 13 (2): R12. doi:10.1186/gb-2012-13-2-r12. PMC 3334569. PMID 22356826.
- Mick DU, Dennerlein S, Wiese H, Reinhold R, Pacheu-Grau D, Lorenzi I et al. (2012). "MITRAC links mitochondrial protein translocation to respiratory-chain assembly and translational regulation.". Cell 151 (7): 1528–41. doi:10.1016/j.cell.2012.11.053. PMID 23260140.
- Kozjak-Pavlovic V, Prell F, Thiede B, Götz M, Wosiek D, Ott C et al. (2014). "C1orf163/RESA1 is a novel mitochondrial intermembrane space protein connected to respiratory chain assembly.". J Mol Biol 426 (4): 908–20. doi:10.1016/j.jmb.2013.12.001. PMID 24333015.
- Gaisne M, Bonnefoy N (2006). "The COX18 gene, involved in mitochondrial biogenesis, is functionally conserved and tightly regulated in humans and fission yeast.". FEMS Yeast Res 6 (6): 869–82. doi:10.1111/j.1567-1364.2006.00083.x. PMID 16911509.
- Alonso JR, Cardellach F, López S, Casademont J, Miró O (September 2003). "Carbon monoxide specifically inhibits cytochrome c oxidase of human mitochondrial respiratory chain". Pharmacol. Toxicol. 93 (3): 142–6. doi:10.1034/j.1600-0773.2003.930306.x. PMID 12969439.
- Arnold S, Kadenbach B. (October 1997). "Cell respiration s controlled by ATP, an allosteric inhibitor of cytochrome-c oxidase.". Eur J Biochem: 350–254.
- Sadacharan, S. K., Singh, B., Bowes, T. and Gupta, R. S. (2005). Localization of mitochondrial DNA encoded cytochrome c oxidase subunits I and II in rat pancreatic zymogen granules and pituitary growth hormone granules. Histochem Cell Biol. 124:409-421.
- Gupta, R. S., Ramachandra, N. B., Bowes, T. and Singh, B. (2008) Unusual cellular disposition of the mitochondrial molecular chaperones Hsp60, Hsp70 and Hsp10. Novartis Found Symp. 291: 59-68.
- Soltys, B. J. and Gupta, R. S. (1999). Mitochondrial proteins at unexpected cellular locations: export of proteins from mitochondria from an evolutionary perspective. International Review of Cytology. 94:133-196.
- Soltys , B. J. and Gupta, R.S. (1999) Mitochondrial proteins at unexpected locations: Are they exported?" Trends Biochem. Sci 24: 174-177.
- Pecina P, Houstková H, Hansíková H, Zeman J, Houstek J (2004). "Genetic defects of cytochrome c oxidase assembly". Physiol Res. 53 Suppl 1: S213–23. PMID 15119951.
- Zee JM, Glerum DM (December 2006). "Defects in cytochrome oxidase assembly in humans: lessons from yeast". Biochem. Cell Biol. 84 (6): 859–69. doi:10.1139/o06-201. PMID 17215873.
- Wong-Riley MT. (1989). "Cytochrome oxidase: an endogenous metabolic marker for neuronal activity.". Trends Neurosci. 12 (3): 94–111. doi:10.1016/0166-2236(89)90165-3. PMID 2469224.
- Strazielle C, Hayzoun K, Derer M, Mariani J, Lalonde R. (April 2006). "Regional brain variations of cytochrome oxidase activity in Relnrl-orl mutant mice.". J. Neurosci. Res. 83 (5): 821–31. doi:10.1002/jnr.20772. PMID 16511878.
- Strazielle C, Sturchler-Pierrat C, Staufenbiel M, Lalonde R. (2003). "Regional brain cytochrome oxidase activity in beta-amyloid precursor protein transgenic mice with the Swedish mutation.". Neuroscience 118 (4): 1151–63. doi:10.1016/S0306-4522(03)00037-X. PMID 12732258.
- Conejo NM, González-Pardo H, Gonzalez-Lima F, Arias JL. (2010). "Spatial learning of the water maze: progression of brain circuits mapped with cytochrome oxidase histochemistry.". Neurobiol. Learn. Mem. 93 (3): 362–71. doi:10.1016/j.nlm.2009.12.002. PMID 19969098.
- The Cytochrome Oxidase home page at Rice University
- Interactive Molecular model of cytochrome c oxidase (Requires MDL Chime)
- UMich Orientation of Proteins in Membranes families/superfamily-4
- Cytochrome-c Oxidase at the US National Library of Medicine Medical Subject Headings (MeSH)
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.
Sel1 repeat Provide feedback
This short repeat is found in the Sel1 protein . It is related to TPR repeats.
Grant B, Greenwald I; , Genetics 1996;143:237-247.: The Caenorhabditis elegans sel-1 gene, a negative regulator of lin-12 and glp-1, encodes a predicted extracellular protein. PUBMED:8722778 EPMC:8722778
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR006597
Sel1-like repeats are tetratricopeptide repeat sequences originally identified in a Caenorhabditis elegans receptor molecule which is a key negative regulator of the Notch pathway [PUBMED:8722778]. Mammalian homologues have since been identified although these mainly pancreatic proteins have yet to have a function assigned.
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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This example describes an architecture with one
Gladomain, followed by two consecutive
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- a link to the page in the Pfam site showing information about the sequence that the graphic describes
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Tetratricopeptide-like repeats are found in a numerous and diverse proteins involved in such functions as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.
The clan contains the following 127 members:Adaptin_N Alkyl_sulf_dimr ANAPC3 ANAPC5 API5 Arm Arm_2 Arm_3 Avirulence BTAD CAS_CSE1 ChAPs CLASP_N Clathrin Clathrin-link Clathrin_propel Cnd1 Cnd3 Coatomer_E Cohesin_HEAT Cohesin_load COPI_C CRM1_C Cse1 DNA_alkylation Drf_FH3 Drf_GBD DUF1822 DUF2225 DUF3385 DUF3458 DUF3808 DUF3856 DUF4042 DUF924 EST1 EST1_DNA_bind FAT Fis1_TPR_C Fis1_TPR_N Foie-gras_1 GUN4_N HAT HEAT HEAT_2 HEAT_EZ HEAT_PBS HemY_N IBB IBN_N IFRD KAP Leuk-A4-hydro_C LRV LRV_FeS MA3 MIF4G MIF4G_like MIF4G_like_2 Mo25 MRP-S27 NARP1 Neurochondrin Nipped-B_C Nro1 NSF Paf67 ParcG PC_rep PHAT PI3Ka PknG_TPR PPP5 PPR PPR_1 PPR_2 PPR_3 PPTA Proteasom_PSMB PUF Rab5-bind Rapsyn_N RPN7 Sel1 SHNi-TPR SNAP SPO22 SRP_TPR_like ST7 Suf SusD SusD-like SusD-like_2 SusD-like_3 TAF6_C TAtT Tcf25 TOM20_plant TPR_1 TPR_10 TPR_11 TPR_12 TPR_14 TPR_15 TPR_16 TPR_17 TPR_18 TPR_19 TPR_2 TPR_20 TPR_21 TPR_3 TPR_4 TPR_5 TPR_6 TPR_7 TPR_8 TPR_9 Upf2 V-ATPase_H_C V-ATPase_H_N Vac14_Fab1_bd Vitellogenin_N Vps39_1 W2 Xpo1 YfiO
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.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
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- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- 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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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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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.
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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.
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.
|Seed source:||Pfam-B_49 (Release 17.0)|
|Number in seed:||170|
|Number in full:||155578|
|Average length of the domain:||35.00 aa|
|Average identity of full alignment:||27 %|
|Average coverage of the sequence by the domain:||40.26 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||8|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
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 are 2 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 Sel1 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.
Loading structure mapping...