Summary: Hemocyanin, ig-like domain
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Hemocyanin Edit Wikipedia article
|Hemocyanin, copper containing domain|
Single oxygenated functional unit from the hemocyanin of an octopus
|SCOPe||1lla / SUPFAM|
|Hemocyanin, all-alpha domain|
Crystal structure of hexameric haemocyanin from Panulirus interruptus refined at 3.2 angstroms resolution
|SCOPe||1lla / SUPFAM|
|Hemocyanin, ig-like domain|
crystallographic analysis of oxygenated and deoxygenated states of arthropod hemocyanin shows unusual differences
|SCOPe||1lla / SUPFAM|
Hemocyanins (also spelled haemocyanins and abbreviated Hc) are proteins that transport oxygen throughout the bodies of some invertebrate animals. These metalloproteins contain two copper atoms that reversibly bind a single oxygen molecule (O2). They are second only to hemoglobin in frequency of use as an oxygen transport molecule. Unlike the hemoglobin in red blood cells found in vertebrates, hemocyanins are not bound to blood cells but are instead suspended directly in the hemolymph. Oxygenation causes a color change between the colorless Cu(I) deoxygenated form and the blue Cu(II) oxygenated form.
Hemocyanins are found only in the Mollusca and Arthropoda: the earliest discoveries of hemocyanins were in the snail Helix pomatia (a mollusc) and in the horseshoe crab (an arthropod). They were subsequently found to be common among cephalopods and crustaceans and are utilized by some land arthropods such as the tarantula Eurypelma californicum, the emperor scorpion, and the centipede Scutigera coleoptrata. Also, larval storage proteins in many insects appear to be derived from hemocyanins.
The hemocyanin superfamily
Phenoloxidase are copper containing tyrosinases. These proteins are involved in the process of sclerotization of arthropod cuticle, in wound healing, and humoral immune defense. Phenoloxidase is synthesized by zymogens and are activated by cleaving a N-terminal peptide.
Pseudohemocyanin and cryptocyanins genetic sequences are closely related to hemocyanins in crustaceans. These proteins have a similar structure and function, but lack the copper binding sites.
The evolutionary changes within the phylogeny of the hemocyanin superfamily are closely related to the emergence of these different proteins in various species. The understanding of proteins within this superfamily would not be well understood without the extensive studies of hemocyanin in arthropods.
Structure and mechanism
Although the respiratory function of hemocyanin is similar to that of hemoglobin, there are a significant number of differences in its molecular structure and mechanism. Whereas hemoglobin carries its iron atoms in porphyrin rings (heme groups), the copper atoms of hemocyanin are bound as prosthetic groups coordinated by histidine residues. The active site of hemocyanin is composed of a pair of copper(I) cations which are directly coordinated to the protein through the driving force of imidazolic rings of six histidine residues. It has been noted that species using hemocyanin for oxygen transportation include crustaceans living in cold environments with low oxygen pressure. Under these circumstances hemoglobin oxygen transportation is less efficient than hemocyanin oxygen transportation. Nevertheless, there are also terrestrial arthropods using hemocyanin, notably spiders and scorpions, that live in warm climates. The molecule is conformationally stable and fully functioning at temperatures up to 90 degrees C.
Most hemocyanins bind with oxygen non-cooperatively and are roughly one-fourth as efficient as hemoglobin at transporting oxygen per amount of blood. Hemoglobin binds oxygen cooperatively due to steric conformation changes in the protein complex, which increases hemoglobin's affinity for oxygen when partially oxygenated. In some hemocyanins of horseshoe crabs and some other species of arthropods, cooperative binding is observed, with Hill coefficients of 1.6â€“3.0. Hill coefficients vary depending on species and laboratory measurement settings. Hemoglobin, for comparison, has a Hill coefficient of usually 2.8â€“3.0. In these cases of cooperative binding hemocyanin was arranged in protein sub-complexes of 6 subunits (hexamer) each with one oxygen binding site; binding of oxygen on one unit in the complex would increase the affinity of the neighboring units. Each hexamer complex was arranged together to form a larger complex of dozens of hexamers. In one study, cooperative binding was found to be dependent on hexamers being arranged together in the larger complex, suggesting cooperative binding between hexamers. Hemocyanin oxygen-binding profile is also affected by dissolved salt ion levels and pH.
Hemocyanin is made of many individual subunit proteins, each of which contains two copper atoms and can bind one oxygen molecule (O2). Each subunit weighs about 75 kilodaltons (kDa). Subunits may be arranged in dimers or hexamers depending on species; the dimer or hexamer complex is likewise arranged in chains or clusters with weights exceeding 1500 kDa. The subunits are usually homogeneous, or heterogeneous with two variant subunit types. Because of the large size of hemocyanin, it is usually found free-floating in the blood, unlike hemoglobin.
Hexamers are characteristic of arthropod hemocyanins. A hemocyanin of the tarantula Eurypelma californicum is made up of 4 hexamers or 24 peptide chains. A hemocyanin from the house centipede Scutigera coleoptrata is made up of 6 hexamers or 36 chains. Horseshoe crabs have an 8-hexamer (i. e. 48-chain) hemocyanin. Simple hexamers are found in the spiny lobster Panulirus interruptus and the isopod Bathynomus giganteus. Peptide chains in crustaceans are about 660 amino acid residues long, and in chelicerates they are about 625. In the large complexes there is a variety of variant chains, all about the same length; pure components do not usually self-assemble.
Hemocyanin is homologous to the phenol oxidases (e.g. tyrosinase) since both proteins share type 3 Cu active site coordination. In both cases inactive proenzymes such as hemocyanin, tyrosinase, and catcholoxidase must be activated first. This is done by removing the amino acid that blocks the entrance channel to the active site when the proenzyme is not active. There is currently no other known modifications necessary to activate the proenzyme and enable catalytic activity. Conformational differences determine the type of catalytic activity that the hemocyanin is able to perform. Hemocyanin also exhibits phenol oxidase activity, but with slowed kinetics from greater steric bulk at the active site. Partial denaturation actually improves hemocyaninâ€™s phenol oxidase activity by providing greater access to the active site.
Spectroscopy of oxyhemocyanin shows several salient features:
- Resonance Raman spectroscopy shows that O2 is bound in a symmetric environment (Î½(O-O) is not IR-allowed).
- OxyHc is EPR-silent indicating the absence of unpaired electrons
- Infrared spectroscopy shows Î½(O-O) of 755 cmâˆ’1
Much work has been devoted to preparing synthetic analogues of the active site of hemocyanin. One such model, which features a pair of copper centers bridged side-on by peroxo ligand, shows Î½(O-O) at 741 cmâˆ’1 and a UV-Vis spectrum with absorbances at 349 and 551 nm. Both of these measurements agree with the experimental observations for oxyHc. The Cu-Cu separation in the model complex is 3.56 Ã…, that of oxyhemocyanin is ca. 3.6 Ã… (deoxyHc: ca. 4.6 Ã…).
The hemocyanin found in the blood of the Chilean abalone, Concholepas concholepas, has immunotherapeutic effects against bladder cancer in murine models. Mice primed with C. concholepas before implantation of bladder tumor (MBT-2) cells. Mice treated with C. concholepas hemocyanin showed antitumor effects: prolonged survival, decreased tumor growth and incidence, and lack of toxic effects and may have a potential use in future immunotherapy for superficial bladder cancer.
Keyhole limpet hemocyanin (KLH) is an immune stimulant derived from circulating glycoproteins of the marine mollusk Megathura crenulata. KLH has been shown to be a significant treatment against the proliferations of breast cancer, pancreas cancer, and prostate cancer cells when delivered in vitro. Keyhole limpet hemocyanin inhibits growth of human Barrett's esophageal cancer through both apoptic and nonapoptic mechanisms of cell death.
Case studies: environmental impact on hemocyanin levels
A 2003 study of the effect of culture conditions of blood metabolites and hemocyanin of the white shrimp Litopenaeus vannamei found that the levels of hemocyanin, oxyhemocyanin in particular, are affected by the diet. The study compared oxyhemocyanin levels in the blood of white shrimp housed in an indoor pond with a commercial diet with that of white shrimp housed in an outdoor pond with a more readily available protein source (natural live food) as well. Oxyhemocyanin and blood glucose levels were higher in shrimp housed in outdoor ponds. It was also found that blood metabolite levels tended to be lower in low activity level species, such as crabs, lobsters, and the indoor shrimp when compared to the outdoor shrimp. This correlation is possibly indicative of the morphological and physiological evolution of crustaceans. The levels of these blood proteins and metabolites appear to be dependent on energetic demands and availability of those energy sources.
- Coates CJ, Nairn J (July 2014). "Diverse immune functions of hemocyanins". Developmental and Comparative Immunology. 45 (1): 43â€“55. doi:10.1016/j.dci.2014.01.021. PMID 24486681.
- Voit R, Feldmaier-Fuchs G, Schweikardt T, Decker H, Burmester T (December 2000). "Complete sequence of the 24-mer hemocyanin of the tarantula Eurypelma californicum. Structure and intramolecular evolution of the subunits". The Journal of Biological Chemistry. 275 (50): 39339â€“44. doi:10.1074/jbc.M005442200. PMID 10961996.
- Jaenicke E, Pairet B, Hartmann H, Decker H (2012). "Crystallization and preliminary analysis of crystals of the 24-meric hemocyanin of the emperor scorpion (Pandinus imperator)". PLOS ONE. 7 (3): e32548. Bibcode:2012PLoSO...732548J. doi:10.1371/journal.pone.0032548. PMC 3293826. PMID 22403673. Lay summary – Johannes Gutenberg-UniversitÃ¤t Mainz (June 22, 2012).
- Beintema JJ, Stam WT, Hazes B, Smidt MP (1994). "Evolution of arthropod hemocyanins and insect storage proteins (hexamerins)". Mol Biol Evol. 11 (3): 493â€“503. doi:10.1093/oxfordjournals.molbev.a040129. PMID 8015442.
- Burmester, T (Feb 2002). "Origin and evolution of arthropod hemocyanins and related proteins". Journal of Comparative Physiology B. 172 (2): 95â€“107. doi:10.1007/s00360-001-0247-7. PMID 11916114.
- Burmester T (February 2001). "Molecular evolution of the arthropod hemocyanin superfamily". Molecular Biology and Evolution. 18 (2): 184â€“95. doi:10.1093/oxfordjournals.molbev.a003792. PMID 11158377.
- Rannulu NS, Rodgers MT (March 2005). "Solvation of copper ions by imidazole: structures and sequential binding energies of Cu+(imidazole)x, x = 1-4. Competition between ion solvation and hydrogen bonding". Physical Chemistry Chemical Physics. 7 (5): 1014â€“25. Bibcode:2005PCCP....7.1014R. doi:10.1039/b418141g. PMID 19791394.
- Strobel A, Hu MY, Gutowska MA, Lieb B, Lucassen M, Melzner F, PÃ¶rtner HO, Mark FC (December 2012). "Influence of temperature, hypercapnia, and development on the relative expression of different hemocyanin isoforms in the common cuttlefish Sepia officinalis" (PDF). Journal of Experimental Zoology Part A. 317 (8): 511â€“23. doi:10.1002/jez.1743. PMID 22791630.
- Extreme thermostability of tarantula hemocyanin - NCBI
- Perton FG, Beintema JJ, Decker H (May 1997). "Influence of antibody binding on oxygen binding behavior of Panulirus interruptus hemocyanin". FEBS Letters. 408 (2): 124â€“6. doi:10.1016/S0014-5793(97)00269-X. PMID 9187351.
- Waxman L (May 1975). "The structure of arthropod and mollusc hemocyanins". The Journal of Biological Chemistry. 250 (10): 3796â€“806. PMID 1126935.
- van Holde KE, Miller KI (1995). Anfinsen CB, Richards FM, Edsall JT, Eisenberg DS (eds.). Hemocyanins. Advances in Protein Chemistry. 47. pp. 1â€“81. doi:10.1016/S0065-3233(08)60545-8. ISBN 978-0-12-034247-1. PMID 8561049.
- Kusche K, Hembach A, Hagner-Holler S, Gebauer W, Burmester T (July 2003). "Complete subunit sequences, structure and evolution of the 6 x 6-mer hemocyanin from the common house centipede, Scutigera coleoptrata". European Journal of Biochemistry. 270 (13): 2860â€“8. doi:10.1046/j.1432-1033.2003.03664.x. PMID 12823556.
- Decker H, Tuczek F (August 2000). "Tyrosinase/catecholoxidase activity of hemocyanins: structural basis and molecular mechanism" (PDF). Trends in Biochemical Sciences. 25 (8): 392â€“7. doi:10.1016/S0968-0004(00)01602-9. PMID 10916160.
- Decker H, Schweikardt T, Nillius D, Salzbrunn U, Jaenicke E, Tuczek F (August 2007). "Similar enzyme activation and catalysis in hemocyanins and tyrosinases". Gene. 398 (1â€“2): 183â€“91. doi:10.1016/j.gene.2007.02.051. PMID 17566671.
- Elwell, Courtney E.; Gagnon, Nicole L.; Neisen, Benjamin D.; Dhar, Debanjan; Spaeth, Andrew D.; Yee, Gereon M.; Tolman, William B. (2017). "Copperâ€“Oxygen Complexes Revisited: Structures, Spectroscopy, and Reactivity". Chemical Reviews. 117 (3): 2059â€“2107. doi:10.1021/acs.chemrev.6b00636. PMC 5963733. PMID 28103018.
- Kitajima N, Fujisawa K, Fujimoto C, Morooka Y, Hashimoto S, Kitagawa T, Toriumi K, Tatsumi K, Nakamura A (1992). "A new model for dioxygen binding in hemocyanin. Synthesis, characterization, and molecular structure of the Î¼-Î·2:Î·2 peroxo dinuclear copper(II) complexes, [Cu(BH(3,5-R2pz)3)]2(O2) (R = i-Pr and Ph)". Journal of the American Chemical Society. 114 (4): 1277â€“91. doi:10.1021/ja00030a025.
- Gaykema WP, Hol WG, Vereijken JM, Soeter NM, Bak HJ, Beintema JJ (1984). "3.2 Ã… structure of the copper-containing, oxygen-carrying protein Panulirus interruptus haemocyanin". Nature. 309 (5963): 23â€“9. Bibcode:1984Natur.309...23G. doi:10.1038/309023a0.
- Kodera M, Katayama K, Tachi Y, Kano K, Hirota S, Fujinami S, Suzuki M (1999). "Crystal Structure and Reversible O2-Binding of a Room Temperature Stable Î¼-Î·2:Î·2-Peroxodicopper(II) Complex of a Sterically Hindered Hexapyridine Dinucleating Ligand". Journal of the American Chemical Society. 121 (47): 11006â€“7. doi:10.1021/ja992295q.
- Atala A (2006). "This Month in Investigative Urology". The Journal of Urology. 176 (6): 2335â€“6. doi:10.1016/j.juro.2006.09.002.
- McFadden DW, Riggs DR, Jackson BJ, Vona-Davis L (November 2003). "Keyhole limpet hemocyanin, a novel immune stimulant with promising anticancer activity in Barrett's esophageal adenocarcinoma". American Journal of Surgery. 186 (5): 552â€“5. doi:10.1016/j.amjsurg.2003.08.002. PMID 14599624.
- Pascual C, Gaxiola G, Rosas C (2003). "Blood metabolites and hemocyanin of the white shrimp, Litopenaeus vannamei: The effect of culture conditions and a comparison with other crustacean species". Marine Biology. 142 (4): 735. doi:10.1007/s00227-002-0995-2.
- Rehm P, Pick C, Borner J, Markl J, Burmester T (February 2012). "The diversity and evolution of chelicerate hemocyanins". BMC Evolutionary Biology. 12: 19. doi:10.1186/1471-2148-12-19. PMC 3306762. PMID 22333134.
- Ali SA, Abbasi A (2011). Scorpion Hemocyanin: The blue blood. SaarbrÃ¼cken: VDM Verlag Dr. MÃ¼ller. p. 160. ISBN 978-3-639-33725-9.
|Wikimedia Commons has media related to Hemocyanin.|
- 3D hemocyanin structures in the EM Data Bank (EMDB)
- Overview of all the structural information available in the PDB for UniProt: P04253 (Hemocyanin II) at the PDBe-KB.
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.
Hemocyanin, ig-like domain Provide feedback
This family includes arthropod hemocyanins and insect larval storage proteins.
Jones G, Brown N, Manczak M, Hiremath S, Kafatos FC; , J Biol Chem 1990;265:8596-8602.: Molecular cloning, regulation, and complete sequence of a hemocyanin-related, juvenile hormone-suppressible protein from insect hemolymph. PUBMED:2341396 EPMC:2341396
Willott E, Wang XY, Wells MA; , J Biol Chem 1989;264:19052-19059.: cDNA and gene sequence of Manduca sexta arylphorin, an aromatic amino acid-rich larval serum protein. Homology to arthropod hemocyanins. PUBMED:2808410 EPMC:2808410
Hazes B, Magnus KA, Bonaventura C, Bonaventura J, Dauter Z, Kalk KH, Hol WG; , Protein Sci 1993;2:597-619.: Crystal structure of deoxygenated Limulus polyphemus subunit II hemocyanin at 2.18 A resolution: clues for a mechanism for allosteric regulation. PUBMED:8518732 EPMC:8518732
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR005203
Crustacean and cheliceratan hemocyanins (oxygen-transport proteins) and insect hexamerins (storage proteins) are homologous gene products, although the latter do not bind oxygen [PUBMED:8015442].
Haemocyanins are found in the haemolymph of many invertebrates. They are divided into 2 main groups, arthropodan and molluscan. These have structurally similar oxygen-binding centres, which are similar to the oxygen-binding centre of tyrosinases, but their quaternary structures are arranged differently. The arthropodan proteins exist as hexamers comprising 3 heterogeneous subunits (a, b and c) and possess 1 oxygen-binding centre per subunit; and the molluscan proteins exist as cylindrical oligomers of 10 to 20 subunits and possess 7 or 8 oxygen-binding centres per subunit [PUBMED:3207675]. Although the proteins have similar amino acid compositions, the only real similarity in their primary sequences is in the region corresponding to the second copper-binding domain, which also shows similarity to the copper-binding domain of tyrosinases.
Hexamerins are proteins from the hemolymph of insects, which may serve as a store of amino acids for synthesis of adult proteins. They do not possess the copper-binding histidines present in hemocyanins [PUBMED:8015442].
Homologues are also present in other kinds of organism, for example, AsqI from the yeast Emericella nidulans. This is a tyrosinase involved in biosynthesis of the aspoquinolone mycotoxins, though its exact function is unknown [PUBMED:25251934].
This entry represents the C-terminal domain of hemocyanin and hexamerin proteins.
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This clan includes a diverse range of domains that have an Ig-like fold and appear to be distantly related to each other. The clan includes: PKD domains, cadherins and several families of bacterial Ig-like domains as well as viral tail fibre proteins. it also includes several Fibronectin type III domain-containing families.
The clan contains the following 233 members:A2M A2M_BRD A2M_recep Adeno_GP19K AlcCBM31 Alpha-amylase_N Alpha_adaptinC2 Alpha_E2_glycop Arch_flagellin aRib Arylsulfotran_N ASF1_hist_chap ATG19_autophagy BACON BACON_2 BatD BIg21 Big_1 Big_10 Big_11 Big_12 Big_13 Big_2 Big_3 Big_3_2 Big_3_3 Big_3_4 Big_3_5 Big_4 Big_5 Big_6 Big_7 Big_8 Big_9 Bile_Hydr_Trans BiPBP_C bMG1 bMG10 bMG3 bMG5 bMG6 BslA BsuPI Cadherin Cadherin-like Cadherin_2 Cadherin_3 Cadherin_4 Cadherin_5 Cadherin_pro CagX Calx-beta Candida_ALS_N CARDB CBM39 CBM_X2 CD45 CelD_N Ceramidse_alk_C CHB_HEX_C CHB_HEX_C_1 ChitinaseA_N ChiW_Ig_like Chlam_OMP6 CHU_C Coatamer_beta_C COP-gamma_platf CopC CshA_repeat Cyc-maltodext_N Cytomega_US3 DsbC DUF11 DUF1410 DUF1425 DUF1929 DUF2271 DUF3244 DUF3327 DUF3416 DUF3458 DUF3501 DUF3823_C DUF3859 DUF4165 DUF4179 DUF4426 DUF4469 DUF4625 DUF4879 DUF4959 DUF4981 DUF4982 DUF4998 DUF5001 DUF5008 DUF5011 DUF5065 DUF5115 DUF525 DUF5643 DUF916 EB_dh ECD EpoR_lig-bind ERAP1_C EstA_Ig_like Expansin_C Filamin FixG_C Flavi_glycop_C FlgD_ig fn3 Fn3-like fn3_2 fn3_4 fn3_5 fn3_6 FN3_7 Fn3_assoc fn3_PAP GBS_Bsp-like Glucodextran_B Glyco_hydro2_C5 Glyco_hydro_2 Glyco_hydro_61 Gmad2 GMP_PDE_delta GPI-anchored Hanta_G1 He_PIG HECW_N HemeBinding_Shp Hemocyanin_C Herpes_BLLF1 HYR IFNGR1 Ig_GlcNase Ig_mannosidase IL12p40_C Il13Ra_Ig IL17R_fnIII_D1 IL17R_fnIII_D2 IL2RB_N1 IL3Ra_N IL4Ra_N IL6Ra-bind Inhibitor_I42 Inhibitor_I71 InlK_D3 Integrin_alpha2 Interfer-bind Invasin_D3 IRK_C IrmA Iron_transport LEA_2 Lep_receptor_Ig LIFR_N Lipase_bact_N LPMO_10 LRR_adjacent LTD Mannosidase_ig MetallophosC MG1 MG2 MG3 MG4 Mo-co_dimer N_BRCA1_IG Na_K-ATPase NEAT Neocarzinostat Neurexophilin NPCBM_assoc PapD_C PBP-Tp47_c Peptidase_C25_C Phlebo_G2_C PhoD_N PKD PKD_2 PKD_3 PKD_4 Por_Secre_tail Pox_vIL-18BP Psg1 Pur_ac_phosph_N Qn_am_d_aII Qn_am_d_aIII RabGGT_insert Reeler REJ RET_CLD1 RET_CLD3 RET_CLD4 RGI_lyase RHD_dimer Rho_GDI Rib RibLong SCAB-Ig SKICH SLAM SoxZ SprB SusE SVA SWM_repeat T2SS-T3SS_pil_N Tafi-CsgC TarS_C1 TcA_RBD TcfC TIG TIG_2 TIG_plexin Tissue_fac Top6b_C Transglut_C Transglut_N TRAP_beta TraQ_transposon Tuberculin UL16 Velvet WIF Wzt_C Y_Y_Y YBD ZirS_C Zona_pellucida
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|Author:||Finn RD , Sonnhammer ELL , Griffiths-Jones SR|
|Number in seed:||102|
|Number in full:||1014|
|Average length of the domain:||231.80 aa|
|Average identity of full alignment:||30 %|
|Average coverage of the sequence by the domain:||34.92 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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- 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 5 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 Hemocyanin_C domain has been found. There are 64 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...