Summary: Sulfotransferase family
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Carbohydrate sulfotransferase Edit Wikipedia article
Example carbohydrate sulfotransferase with PAPS cosubstrate and carbohydrate substrate: Crystal Structure of human 3-O-Sulfotransferase-3 with bound PAPS and tetrasaccharide substrate. Enzyme chain A (blue), Enzyme chain B (green), PAPS (red), tetrasaccharide substrate (white), sodium ion (purple sphere).
Carbohydrate sulfotransferases are sulfotransferase enzymes that transfer sulfate to carbohydrate groups in glycoproteins and glycolipids. Carbohydrates are used by cells for a wide range of functions from structural purposes to extracellular communication. Carbohydrates are suitable for such a wide variety of functions due to the diversity in structure generated from monosaccharide composition, glycosidic linkage positions, chain branching, and covalent modification. Possible covalent modifications include acetylation, methylation, phosphorylation, and sulfation. Sulfation, performed by carbohydrate sulfotransferases, generates carbohydrate sulfate esters. These sulfate esters are only located extracellularly, whether through excretion into the extracellular matrix (ECM) or by presentation on the cell surface. As extracellular compounds, sulfated carbohydrates are mediators of intercellular communication, cellular adhesion, and ECM maintenance.
Sulfotransferases catalyze the transfer of a sulfonyl group from an activated sulfate donor onto a hydroxyl group (or an amino group, although this is less common) of an acceptor molecule. In eukaryotic cells the activated sulfate donor is 3'-phosphoadenosine-5'-phosphosulfate (PAPS) (Figure 1).
PAPS is synthesized in the cytosol from ATP and sulfate through the sequential action of ATP sulfurylase and APS kinase. ATP sulfurylase first generates adenosine-5'-phosphosulfate (APS) and then APS kinase transfers a phosphate from ATP to APS to create PAPS. The importance of PAPS and sulfation has been discerned in previous studies by using chlorate, an analogue of sulfate, as a competitive inhibitor of ATP sulfurylase. PAPS is a cosubstrate and source of activated sulfate for both cytosolic sulfotransferases and carbohydrate sulfotransferases, which are located in the Golgi. PAPS moves between the cytosol and the Golgi lumen via PAPS/PAP (3’-phosphoadenosine-5’-phosphate) translocase, a transmembrane antiporter.
The exact mechanism used by sulfotransferases is still being elucidated, but studies have indicated that sulfotransferases use an in-line sulfonyl-transfer mechanism that is analogous to the phosphoryl transfer mechanism used by many kinases, which is logical given the great level of structural and functional similarities between kinases and sulfotransferases (Figure 2). In carbohydrate sulfotransferases a conserved lysine has been identified in the active PAPS binding site, which is analogous to a conserved lysine in the active ATP binding site of kinases. Protein sequence alignment studies indicate that this lysine is conserved in cytosolic sulfotransferases as well.
In addition to the conserved lysine, sulfotransferases have a highly conserved histidine in the active site. Based on the conservation of these residues, theoretical models, and experimental measurements a theoretical transition state for catalyzed sulfation has been proposed (Figure 3).
Carbohydrate sulfotransferases are transmembrane enzymes in the Golgi that modify carbohydrates on glycolipids or glyoproteins as they move along the secretory pathway. They have a short cytoplasmic N-terminal, one transmembrane domain, and a large C-terminal Golgi luminal domain. They are distinct from cytosolic sulfotransferases in both structure and function. While cytosolic sulfotransferases play a metabolic role by modifying small molecule substrates such as steroids, flavonoids, neurotransmitters, and phenols, carbohydrate sulfotransferases have a fundamental role in extracellular signalling and adhesion by generating unique ligands through the modification of carbohydrate scaffolds. Since the substrates of carbohydrate sulfotransferases are larger, they have larger active sites than cytosolic sulfotransferases.
Heparan sulfate is a glycosaminoglycan (GAG) that is linked by xylose to serine residues of proteins such as perlecan, syndecan, or glypican. Sulfation of heparan sulfate GAGs helps give diversity to cell surface proteins and provides them with a unique sulfation pattern that allows them to specifically interact with other proteins. For example, in mast cells the AT-III-binding pentasaccharaide is synthesized with essential heparan sulfate sulfation steps. The binding of the heparan sulfate in this pentasaccharide to AT-III inactivates the blood-coagulation factors thrombin and Factor Xa. Heparan sulfates are also known to interact with growth factors, cytokines, chemokines, lipid and membrane binding proteins, and adhesion molecules.
GSTs catalyze sulfation at the 6-hydroxyl group of galactose, N-acetylgalactosamine, or N-acetylglucosamine. Like heparan sulfotransferases, GSTs are responsible for post-translational protein sulfation that assists in cell-signaling. GSTs are also responsible for the sulfation of extracellular matrix (ECM) proteins that assist with maintaining the structure between cells For example, GSTs catalyze the sulfation of glycoproteins displaying the L-selectin binding epitope 6-sulfo sialyl Lewis x, which recruits leukocytes to areas of chronic inflammation. GSTs are also responsible for the proper function of the ECM in the cornea; improper sulfation by GSTs can lead to opaque corneas.
Carbohydrate sulfotransferases are of great interest as drug targets because of their essential roles in cell-cell signalling, adhesion, and ECM maintenance. Their roles in blood coagulation, chronic inflammation, and cornea maintenance mentioned in the Biological Function section above are all of interest for potential therapeutic purposes. In addition to these roles, carbohydrate sulfotransferases are of pharmacological interest because of their roles in viral infection, including herpes simplex virus 1 (HSV-1) and human immunodeficiency virus 1 (HIV-1). Heparan sulfate sites have been shown to be essential for HSV-1 binding that leads to the virus entering the cell. In contrast, heparan sulfate complexes have been shown to bind to HIV-1 and prevent it from entering the cell through its intended target, the CD4 receptor.
Mutation in Carbohydrate sulfotransferases 6 (CHST6) is associated with Macular Corneal Dystrophy (MCD) Inheritance: Autosomal recessive. Genetic Locus: 16q22 Online Mendelian Inheritance in man (OMIM) Entry OMIM #217800
Human proteins from this family
- Carbohydrate sulfotransferases 6 (CHST6) Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues of keratan. Mediates sulfation of keratan in cornea. Keratan sulfate plays a central role in maintaining corneal transparency.
- Carbohydrate sulfotransferases 8 (CHST8) and 9 (CHST9), which transfer sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. They function in the biosynthesis of glycoprotein hormones lutropin and thyrotropin, by mediating sulfation of their carbohydrate structures.
- Carbohydrate sulfotransferase 10 (CHST10), which transfers sulfate to position 3 of the terminal glucuronic acid in both protein- and lipid-linked oligosaccharides. It directs the biosynthesis of the HNK-1 carbohydrate structure, a sulfated glucuronyl-lactosaminyl residue carried by many neural recognition molecules, which is involved in cell interactions during ontogenetic development and in synaptic plasticity in the adult.
- Carbohydrate sulfotransferases 11 - 13 (CHST11, CHST12, CHST13), which catalyze the transfer of sulfate to position 4 of the GalNAc residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Some, thought not all, of these enzymes also transfer sulfate to dermatan.
- Carbohydrate sulfotransferase D4ST1 (D4ST1), which transfers sulfate to position 4 of the GalNAc residue of dermatan sulfate.
- Moon, AF.; Edavettal, SC.; Krahn, JM.; Munoz, EM.; Negishi, M.; Linhardt, RJ.; Liu, J.; Pedersen, LC. (Oct 2004). "Structural analysis of the sulfotransferase (3-o-sulfotransferase isoform 3) involved in the biosynthesis of an entry receptor for herpes simplex virus 1". J Biol Chem. 279 (43): 45185–93. doi:10.1074/jbc.M405013200. PMID 15304505.
- Nelson, R M; Venot, A; Bevilacqua, M P; Linhardt, R J; Stamenkovic, I (1995). "Carbohydrate-Protein Interactions in Vascular Biology". Annual Review of Cell and Developmental Biology. 11 (1): 601–631. doi:10.1146/annurev.cb.11.110195.003125. ISSN 1081-0706.
- Hooper, L.V.; Baenziger, J.U. (1993). "Sulfotransferase and Glycosyltransferase Analyses Using a 96-Well Filtration Plate". Analytical Biochemistry. 212 (1): 128–133. doi:10.1006/abio.1993.1301. ISSN 0003-2697. PMID 8368484.
- Bowman, K; Bertozzi, C (1999). "Carbohydrate sulfotransferases: mediators of extracellular communication". Chemistry & Biology. 6 (1): R9–R22. doi:10.1016/S1074-5521(99)80014-3. ISSN 1074-5521.
- Klaassen, CD.; Boles, JW. (May 1997). "Sulfation and sulfotransferases 5: the importance of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in the regulation of sulfation". FASEB J. 11 (6): 404–18. PMID 9194521.
- Hemmerich, Stefan (2001). "Carbohydrate sulfotransferases: novel therapeutic targets for inflammation, viral infection and cancer". Drug Discovery Today. 6 (1): 27–35. doi:10.1016/S1359-6446(00)01581-6. ISSN 1359-6446. PMID 11165170.
- Baeuerle, PA.; Huttner, WB. (Dec 1986). "Chlorate--a potent inhibitor of protein sulfation in intact cells". Biochem Biophys Res Commun. 141 (2): 870–7. doi:10.1016/s0006-291x(86)80253-4. PMID 3026396.
- Ozeran, JD.; Westley, J.; Schwartz, NB. (Mar 1996). "Identification and partial purification of PAPS translocase". Biochemistry. 35 (12): 3695–703. doi:10.1021/bi951303m. PMID 8619989.
- Kakuta, Y.; Petrotchenko, EV.; Pedersen, LC.; Negishi, M. (Oct 1998). "The sulfuryl transfer mechanism. Crystal structure of a vanadate complex of estrogen sulfotransferase and mutational analysis". J Biol Chem. 273 (42): 27325–30. doi:10.1074/jbc.273.42.27325. PMID 9765259.
- Kamio, K.; Honke, K.; Makita, A. (Dec 1995). "Pyridoxal 5'-phosphate binds to a lysine residue in the adenosine 3'-phosphate 5'-phosphosulfate recognition site of glycolipid sulfotransferase from human renal cancer cells". Glycoconj J. 12 (6): 762–6. doi:10.1007/bf00731236. PMID 8748152.
- Sueyoshi, Tatsuya; Kakuta, Yoshimitsu; Pedersen, Lars C.; Wall, Frances E.; Pedersen, Lee G.; Negishi, Masahiko (1998). "A role of Lys614 in the sulfotransferase activity of human heparan sulfate N-deacetylase/N-sulfotransferase". FEBS Letters. 433 (3): 211–214. doi:10.1016/S0014-5793(98)00913-2. ISSN 0014-5793. PMID 9744796.
- Chapman, Eli; Best, Michael D.; Hanson, Sarah R.; Wong, Chi-Huey (2004). "Sulfotransferases: Structure, Mechanism, Biological Activity, Inhibition, and Synthetic Utility". Angewandte Chemie International Edition. 43 (27): 3526–3548. doi:10.1002/anie.200300631. ISSN 1433-7851.
- Falany, CN. (Mar 1997). "Enzymology of human cytosolic sulfotransferases". FASEB J. 11 (4): 206–16. PMID 9068609.
- Shworak, NW.; Liu, J.; Petros, LM.; Zhang, L.; Kobayashi, M.; Copeland, NG.; Jenkins, NA.; Rosenberg, RD. (Feb 1999). "Multiple isoforms of heparan sulfate D-glucosaminyl 3-O-sulfotransferase. Isolation, characterization, and expression of human cdnas and identification of distinct genomic loci". J Biol Chem. 274 (8): 5170–84. doi:10.1074/jbc.274.8.5170. PMID 9988767.
- Hemmerich, S.; Rosen, SD. (Sep 2000). "Carbohydrate sulfotransferases in lymphocyte homing". Glycobiology. 10 (9): 849–56. doi:10.1093/glycob/10.9.849. PMID 10988246.
- Rosenberg, RD.; Shworak, NW.; Liu, J.; Schwartz, JJ.; Zhang, L. (May 1997). "Heparan sulfate proteoglycans of the cardiovascular system. Specific structures emerge but how is synthesis regulated?". J Clin Invest. 99 (9): 2062–70. doi:10.1172/JCI119377. PMC . PMID 9151776.
- Liu, J.; Shworak, NW.; Fritze, LM.; Edelberg, JM.; Rosenberg, RD. (Oct 1996). "Purification of heparan sulfate D-glucosaminyl 3-O-sulfotransferase". J Biol Chem. 271 (43): 27072–82. doi:10.1074/jbc.271.43.27072. PMID 8900198.
- Grunwell, Jocelyn R.; Rath, Virginia L.; Rasmussen, Jytte; Cabrilo, Zeljka; Bertozzi, Carolyn R. (2002). "Characterization and Mutagenesis of Gal/GlcNAc-6-O-sulfotransferases†". Biochemistry. 41 (52): 15590–15600. doi:10.1021/bi0269557. ISSN 0006-2960. PMID 12501187.
- Shukla, D.; Liu, J.; Blaiklock, P.; Shworak, NW.; Bai, X.; Esko, JD.; Cohen, GH.; Eisenberg, RJ.; et al. (Oct 1999). "A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry". Cell. 99 (1): 13–22. doi:10.1016/S0092-8674(00)80058-6. PMID 10520990.
- Fukuda M, Hiraoka N, Hindsgaul O, Misra A, Belot F (2001). "R in both N- and O-glycans". Glycobiology. 11 (6): –. doi:10.1093/glycob/11.6.495. PMID 11445554.
- Ong E, Fukuda M, Yeh JC, Ding Y, Hindsgaul O (1998). "Expression cloning of a human sulfotransferase that directs the synthesis of the HNK-1 glycan on the neural cell adhesion molecule and glycolipids". J. Biol. Chem. 273 (9): –. doi:10.1074/jbc.273.9.5190. PMID 9478973.
- Ong E, Fukuda M, Fukuda MN, Nakagawa H, Hiraoka N, Akama TO (2000). "Molecular cloning and expression of two distinct human chondroitin 4-O-sulfotransferases that belong to the HNK-1 sulfotransferase gene family". J. Biol. Chem. 275 (26): –. doi:10.1074/jbc.M002443200. PMID 10781601.
- Baenziger JU, Xia G, Evers MR, Kang HG, Schachner M (2001). "Molecular cloning and characterization of a dermatan-specific N-acetylgalactosamine 4-O-sulfotransferase". J. Biol. Chem. 276 (39): –. doi:10.1074/jbc.M105848200. PMID 11470797.
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This family includes a variety of sulfotransferase enzymes. Chondroitin 6-sulfotransferase catalyses the transfer of sulfate to position 6 of the N-acetylgalactosamine residue of chondroitin. This family also includes Heparan sulfate 2-O-sulfotransferase (HS2ST) and Heparan sulfate 6-sulfotransferase (HS6ST). Heparan sulfate (HS) is a co-receptor for a number of growth factors, morphogens, and adhesion proteins. HS biosynthetic modifications may determine the strength and outcome of HS-ligand interactions. Mice that lack HS2ST undergo developmental failure only after midgestation,the most dramatic effect being the complete failure of kidney development . Heparan sulphate 6- O -sulfotransferase (HS6ST) catalyses the transfer of sulphate from adenosine 3'-phosphate, 5'-phosphosulphate to the 6th position of the N -sulphoglucosamine residue in heparan sulphate .
Li J, Shworak NW, Simons M; , J Cell Sci 2002;115:1951-1959.: Increased responsiveness of hypoxic endothelial cells to FGF2 is mediated by HIF-1alpha-dependent regulation of enzymes involved in synthesis of heparan sulfate FGF2-binding sites. PUBMED:11956326 EPMC:11956326
Habuchi H, Miyake G, Nogami K, Kuroiwa A, Matsuda Y, Kusche-Gullberg M, Habuchi O, Tanaka M, Kimata K; , Biochem J 2003;371:131-142.: Biosynthesis of heparan sulphate with diverse structures and functions: two alternatively spliced forms of human heparan sulphate 6-O-sulphotransferase-2 having different expression patterns and properties. PUBMED:12492399 EPMC:12492399
This tab holds annotation information from the InterPro database.
InterPro entry IPR005331
This entry consists of a number of carbohydrate sulphotransferases that transfer sulphate to carbohydrate groups in glycoproteins and glycolipids. These include:
- Carbohydrate sulphotransferases 8 and 9, which transfer sulphate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans [PUBMED:11445554]. They function in the biosynthesis of glycoprotein hormones lutropin and thyrotropin, by mediating sulphation of their carbohydrate structures.
- Carbohydrate sulphotransferase 10, which transfers sulphate to position 3 of the terminal glucuronic acid in both protein- and lipid-linked oligosaccharides [PUBMED:9478973]. It directs the biosynthesis of the HNK-1 carbohydrate structure, a sulphated glucuronyl-lactosaminyl residue carried by many neural recognition molecules, which is involved in cell interactions during ontogenetic development and in synaptic plasticity in the adult.
- Carbohydrate sulphotransferases 11 - 13, which catalyze the transfer of sulphate to position 4 of the GalNAc residue of chondroitin [PUBMED:10781601]. Chondroitin sulphate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Some, thought not all, of these enzymes also transfer sulphate to dermatan.
- Carbohydrate sulphotransferase D4ST1, which transfers sulphate to position 4 of the GalNAc residue of dermatan sulphate [PUBMED:11470797].
- Heparan sulphate 2-O-sulphotransferase (HS2ST). Heparan sulphate (HS) is a co-receptor for a number of growth factors, morphogens, and adhesion proteins. HS biosynthetic modifications may determine the strength and outcome of HS-ligand interactions. Mice that lack HS2ST undergo developmental failure only after midgestation,the most dramatic effect being the complete failure of kidney development [PUBMED:11956326].
- Heparan-sulphate 6-O-sulphotransferase (HS6ST), which catalyses the transfer of sulphate from adenosine 3'-phosphate, 5'-phosphosulphate to the 6th position of the N -sulphoglucosamine residue in heparan sulphate [PUBMED:12492399].
- Chondroitin 6-sulphotransferase catalyses the transfer of sulphate to position 6 of the N-acetylgalactosamine residue of chondroitin [PUBMED:18697746].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||integral component of membrane (GO:0016021)|
|Molecular function||sulfotransferase activity (GO:0008146)|
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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 199 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 Hydin_ADK IIGP IPPT IPT IstB_IS21 KAP_NTPase KdpD Kinesin 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
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|Author:||Finn RD, Bateman A|
|Number in seed:||66|
|Number in full:||2466|
|Average length of the domain:||219.10 aa|
|Average identity of full alignment:||15 %|
|Average coverage of the sequence by the domain:||65.15 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||12|
|Download:||download the raw HMM for this family|
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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.
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 Sulfotransfer_2 domain has been found. There are 7 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...