Summary: DNA polymerase type B, organellar and viral
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DNA polymerase Edit Wikipedia article
|DNA-directed DNA polymerase|
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
A DNA polymerase is a cellular or viral polymerase enzyme that synthesizes DNA molecules from their nucleotide building blocks. DNA polymerases are essential for DNA replication, and usually function in pairs while copying one double-strand DNA molecule into two double-strand DNAs in a process termed semiconservative DNA replication. DNA polymerases also play key roles in other processes within cells, including DNA repair, genetic recombination, reverse transcription, and the generation of antibody diversity via the specialized DNA polymerase, terminal deoxynucleotidyl transferase. DNA polymerases are widely used in molecular biology laboratories, notably for the polymerase chain reaction (PCR), DNA sequencing, and molecular cloning.
- 1 History
- 2 Function
- 3 Variation across species
- 3.1 Prokaryotic DNA polymerase
- 3.2 Eukaryotic DNA polymerase
- 3.2.1 Polymerases Î², Î», Ï and Î¼ (Polymerases beta, lambda, sigma, and mu)
- 3.2.2 Polymerases Î±, Î´ and Îµ (Polymerases alpha, delta, and epsilon)
- 3.2.3 Polymerases Î·, Î¹ and Îº (Polymerases eta, iota, and kappa)
- 3.2.4 Polymerases Rev1 and Î¶ (Polymerases Rev1 and zeta)
- 3.2.5 Telomerase
- 3.2.6 Polymerases Î³ and Î¸ (Polymerases gamma and theta)
- 3.2.7 Reverse transcriptase
- 4 See also
- 5 References
- 6 Further reading
- 7 External links
In 1956, Arthur Kornberg and colleagues discovered the enzyme DNA polymerase I, also known as Pol I, in Escherichia coli. They described the DNA replication process by which DNA polymerase copies the base sequence of a template DNA strand. Subsequently in 1959, Kornberg was awarded the Nobel Prize in Physiology or Medicine for this work. DNA polymerase II was also discovered by Kornberg and Malcolm E. Gefter in 1970 while further elucidating the role of Pol I in E. coli DNA replication.
DNA polymerase can add free nucleotides only to the 3' end of the newly forming strand. This results in elongation of the newly forming strand in a 5'-3' direction. No known DNA polymerase is able to begin a new chain (de novo). DNA polymerase can add a nucleotide only onto a pre-existing 3'-OH group, and, therefore, needs a primer at which it can add the first nucleotide. Primers consist of RNA and/or DNA bases. In DNA replication, the first two bases are always RNA, and are synthesized by another enzyme called primase. An enzyme known as a helicase is required to unwind DNA from a double-strand structure to a single-strand structure to facilitate replication of each strand consistent with the semiconservative model of DNA replication.
It is important to note that the directionality of the newly forming strand (the daughter strand) is opposite to the direction in which DNA polymerase moves along the template strand. Since DNA polymerase requires a free 3' OH group for initiation of synthesis, it can synthesize in only one direction by extending the 3' end of the preexisting nucleotide chain. Hence, DNA polymerase moves along the template strand in a 3'-5' direction, and the daughter strand is formed in a 5'-3' direction. This difference enables the resultant double-strand DNA formed to be composed of two DNA strands that are antiparallel to each other.
Error correction is a property of some, but not all, DNA polymerases. This process corrects mistakes in newly synthesized DNA. When an incorrect base pair is recognized, DNA polymerase moves backwards by one base pair of DNA. The 3'-5' exonuclease activity of the enzyme allows the incorrect base pair to be excised (this activity is known as proofreading). Following base excision, the polymerase can re-insert the correct base and replication can continue forwards.
Various DNA polymerases are extensively used in molecular biology experiments.
The known DNA polymerases have highly conserved structure, which means that their overall catalytic subunits vary very little from species to species, independent of their domain structures. The shape can be described as resembling a right hand with thumb, finger, and palm domains. The palm domain appears to function in catalyzing the transfer of phosphoryl groups in the phosphoryl transfer reaction. DNA is palm when the enzyme is active. This reaction is believed to be catalyzed by a two metal ion mechanism. The finger domain functions to bind the nucleotide triphosphate with the template base. The thumb domain plays a potential role in the processivity, translocation, and positioning of the DNA. Conserved structures usually indicate important, irreplaceable functions of the cell, the maintenance of which provides evolutionary advantages.
DNA polymeraseâs rapid catalysis is due to its processive nature. Processivity is a characteristic of enzymes that function on polymeric substrates. In the case of DNA polymerase, the degree of processivity refers to the average number of nucleotides added each time the enzyme binds a template. The average DNA polymerase requires about one second locating and binding a primer/template junction. Once it is bound, a nonprocessive DNA polymerase adds nucleotides at a rate of one nucleotide per second.:207â208 Processive DNA polymerases, however, add multiple nucleotides per second drastically increasing the rate of DNA synthesis. The degree of processivity is directly proportional to the rate of DNA synthesis. The rate of DNA synthesis in a living cell was first determined as the rate of phage T4 DNA elongation in phage infected E. coli. During the period of exponential DNA increase at 37Â°C, the rate was 749 nucleotides per second.
DNA polymeraseâs ability to slide along the DNA template allows increased processivity. There is a dramatic increase in processivity at the replication fork. This increase is facilitated by the DNA polymeraseâs association with proteins known as the sliding DNA clamp. The clamps are multiple protein subunits associated in the shape of a ring. Using the hydrolysis of ATP, a class of proteins known as the sliding clamp loading proteins open up the ring structure of the sliding DNA clamps allowing binding to and/or release from the DNA strand. Protein-protein interaction with the clamp prevents DNA polymerase from diffusing from the DNA template, thereby ensuring that the enzyme binds the same primer/template junction and continues replication.:207â208 DNA polymerase changes conformation, increasing affinity to the clamp when associated with it and decreasing affinity when it completes the replication of a stretch of DNA to allow release from the clamp.
Variation across species
|DNA polymerase family A|
c:o6-methyl-guanine pair in the polymerase-2 basepair position
|DNA polymerase family B|
crystal structure of rb69 gp43 in complex with dna containing thymine glycol
|DNA polymerase type B, organellar and viral|
phi29 dna polymerase, orthorhombic crystal form, ssdna complex
Based on sequence homology, DNA polymerases can be further subdivided into seven different families: A, B, C, D, X, Y, and RT.
Some viruses also encode special DNA polymerases, such as Hepatitis B virus DNA polymerase. These may selectively replicate viral DNA through a variety of mechanisms. Retroviruses encode an unusual DNA polymerase called reverse transcriptase, which is an RNA-dependent DNA polymerase (RdDp). It polymerizes DNA from a template of RNA.
|Family||Types of DNA polymeras||Species||Examples|
|A||Replicative and Repair Polymerases||Eukaryotic and Prokaryotic||T7 DNA polymerase, Pol I, and DNA Polymerase Î³|
|B||Replicative and Repair Polymerases||Eukaryotic and Prokaryotic||Pol II, Pol B, Pol Î¶, Pol Î±, Î´, and Îµ|
|C||Replicative Polymerases||Prokaryotic||Pol III|
|D||Replicative Polymerases||Euryarchaeota||Not well-characterized|
|X||Replicative and Repair Polymerases||Eukaryotic||Pol Î², Pol Ï, Pol Î», Pol Î¼, and Terminal deoxynucleotidyl transferase|
|Y||Replicative and Repair Polymerases||Eukaryotic and Prokaryotic||Pol Î¹ (iota), Pol Îº (kappa), Pol IV, and Pol V|
|RT||Replicative and Repair Polymerases||Viruses, Retroviruses, and Eukaryotic||Telomerase, Hepatitis B virus|
Prokaryotic DNA polymerase
Prokaryotic Family A polymerases include the DNA polymerase I (Pol I) enzyme, which is encoded by the polA gene and ubiquitous among prokaryotes. This repair polymerase is involved in excision repair with 3'-5' and 5'-3' exonuclease activity and processing of Okazaki fragments generated during lagging strand synthesis. Pol I is the most abundant polymerase accounting for >95% of polymerase activity in E. coli, yet cells lacking Pol I have been found suggesting Pol I activity can be replaced by the other four polymerases. Pol I adds ~15-20 nucleotides per second, thus showing poor processivity. Instead, Pol I starts adding nucleotides at the RNA primer:template junction known as the origin of replication (ori). Approximately 400 bp downstream from the origin, the Pol III holoenzyme is assembled and takes over replication at a highly processive speed and nature.
DNA polymerase II, a Family B polymerase, is a polB gene product also known as DinA. Pol II has 3'-5' exonuclease activity and participates in DNA repair, replication restart to bypass lesions, and its cell presence can jump from ~30-50 copies per cell to ~200-300 during SOS induction. Pol II is also thought to be a backup to Pol III as it can interact with holoenzyme proteins and assume a high level of processivity. The main role of Pol II is thought to be the ability to direct polymerase activity at the replication fork and helped stalled Pol III bypass terminal mismatches.
DNA polymerase III holoenzyme is the primary enzyme involved in DNA replication in E. coli and belongs to Family C polymerases. It consists of three assemblies: the pol III core, the beta sliding clamp processivity factor and the clamp-loading complex. The core consists of three subunits - Î±, the polymerase activity hub, É, exonucleolytic proofreader, and Î¸, which may act as a stabilizer for É. The holoenzyme contains two cores, one for each strand, the lagging and leading. The beta sliding clamp processivity factor is also present in duplicate, one for each core, to create a clamp that encloses DNA allowing for high processivity. The third assembly is a seven-subunit (Ï2Î³Î´Î´â²ÏÏ) clamp loader complex. Recent research has classified Family C polymerases as a subcategory of Family X with no eukaryotic equivalents.
In E. coli, DNA polymerase IV (Pol 4) is an error-prone DNA polymerase involved in non-targeted mutagenesis. Pol IV is a Family Y polymerase expressed by the dinB gene that is switched on via SOS induction caused by stalled polymerases at the replication fork. During SOS induction, Pol IV production is increased 10-fold and one of the functions during this time is to interfere with Pol III holoenzyme processivity. This creates a checkpoint, stops replication, and allows time to repair DNA lesions via the appropriate repair pathway. Another function of Pol IV is to perform translesion synthesis at the stalled replication fork like, for example, bypassing N2-deoxyguanine adducts at a faster rate than transversing undamaged DNA. Cells lacking dinB gene have a higher rate of mutagenesis caused by DNA damaging agents.
DNA polymerase V (Pol V) is a Y-family DNA polymerase that is involved in SOS response and translesion synthesis DNA repair mechanisms. Transcription of Pol V via the umuDC genes is highly regulated to produce only Pol V when damaged DNA is present in the cell generating an SOS repsonse. Stalled polymerases causes RecA to bind to the ssDNA, which causes the LexA protein to autodigest. LexA then loses is ability to repress the transcription of the umuDC operon. The same RecA-ssDNA nucleoprotein posttranslationally modifies the UmuD protein into UmuD' protein. UmuD and UmuD' form a heterodimer that interacts with UmuC, which in turn activates umuC's polymerase catalytic activity on damaged DNA.
Eukaryotic DNA polymerase
Polymerases Î², Î», Ï and Î¼ (Polymerases beta, lambda, sigma, and mu)
Family X polymerases contain the well-known eukaryotic polymerase pol Î² (beta), as well as other eukaryotic polymerases such as Pol Ï (sigma), Pol Î» (lambda), Pol Î¼ (mu), and Terminal deoxynucleotidyl transferase (TdT). Family X polymerases are found mainly in vertebrates, and a few are found in plants and fungi. These polymerases have highly conserved regions that include two helix-hairpin-helix motifs that are imperative in the DNA-polymerase interactions. One motif is located in the 8 kDa domain that interacts with downstream DNA and one motif is located in the thumb domain that interacts with the primer strand. Pol Î², encoded by POLB gene, is required for short-patch base excision repair, a DNA repair pathway that is essential for repairing alkylated or oxidized bases as well as abasic sites. Pol Î» and Pol Î¼, encoded by the POLL and POLM genes respectively, are involved in non-homologous end-joining, a mechanism for rejoining DNA double-strand breaks due to hydrogen peroxide and ionizing radition, respectively. TdT is expressed only in lymphoid tissue, and adds "n nucleotides" to double-strand breaks formed during V(D)J recombination to promote immunological diversity.
Polymerases Î±, Î´ and Îµ (Polymerases alpha, delta, and epsilon)
Pol Î± (alpha), Pol Î´ (delta), and Pol Îµ (epsilon) are members of Family B Polymerases and are the main polymerases involved with nuclear DNA replication. Pol Î± complex (pol Î±-DNA primase complex) consists of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the small and the large primase subunits PRIM1 and PRIM2 respectively. Once primase has created the RNA primer, Pol Î± starts replication elongating the primer with ~20 nucleotides. > Due to their high processivity, Pol Îµ and Pol Î´ take over the leading and lagging strand synthesis from Pol Î± respectively.:218â219 Pol Î´ is expressed by genes POLD1, creating the catalytic subunit, POLD2, POLD3, and POLD4 creating the other subunits that interact with Proliferating Cell Nuclear Antigen (PCNA), which is a DNA clamp that allows Pol Î´ to possess processivity. Pol Îµ is encoded by the POLE, the catalytic subunit, POLE2, and POLE3 genes. While Pol Îµ's main function is to extend the leading strand during replication, Pol Îµ's C-terminus region is thought to be essential to cell vitality as well. The C-terminus region is thought to provide a checkpoint before entering anaphase, provide stability to the holoenzyme, and add proteins to the holoenzyme necessary for initiation of replication.
Polymerases Î·, Î¹ and Îº (Polymerases eta, iota, and kappa)
Pol Î· (eta), Pol Î¹ (iota), and Pol Îº (kappa), are Family Y DNA polymerases involved in the DNA repair by translesion synthesis and encoded by genes POLH, POLI, and POLK respectively. Members of Family Y have 5 common motifs to aid in binding the substrate and primer terminus and they all include the typical right hand thumb, palm and finger domains with added domains like little finger (LF), polymerase-associated domain (PAD), or wrist. The active site, however, differs between family members due to the different lesions being repaired. Polymerases in Family Y are low fidelity polymerases, but have been proven to do more good than harm as mutations can cause various diseases, such as skin cancer and Xeroderma Pigmentosum Variant (XPS). The importance of these polymerases is evidenced by the fact that gene encoding DNA polymerase Î· is referred as XPV, because loss of this gene results in the disease Xeroderma Pigmentosum Variant. Pol Î· is particularly important for allowing accurate translesion synthesis of DNA damage resulting from ultraviolet radiation or UV. The functionality of Pol Îº is not completely understood, but researchers have found two probable functions. Pol Îº is thought to act as an extender or an insterter of a specific base at certain DNA lesions. All three translesion synthesis polymerases, along with Rev1, are recruited to damaged lesions via stalled replicative DNA polymerases. There are two pathways of damage repair leading researchers to conclude that the chosen pathway depends on which strand contains the damage, the leading or lagging strand.
Polymerases Rev1 and Î¶ (Polymerases Rev1 and zeta)
Pol Î¶ another B family polymerase, is made of two subunits Rev3, the catalytic subunit, and Rev7, which increases the catalytic function of the polymerase, and is involved in translesion synthesis. Pol Î¶ lacks 3' to 5' exonuclease activity, is unique in that it can extend primers with terminal mismatches. Rev1 has three regions of interest in the BRCT domain, ubiquitin-binding domain, and C-terminal domain and has dCMP transferase ability, which adds deoxycytidine opposite lesions that would stall replicative polymerases Pol Î´ and Pol Îµ. These stalled polymerases activate ubiquitin complexes that in turn disassociate replication polymerases and recruit Pol Î¶ and Rev1. Together Pol Î¶ and Rev1 add deoxycytidine and Pol Î¶ extends past the lesion. Through a yet undetermined process, Pol Î¶ disassociates and replication polymerases reassociate and continue replication. Pol Î¶ and Rev1 are not required for replication, but loss of REV3 gene in budding yeast can cause increased sensitivity to DNA-damaging agents due to collapse of replication forks where replication polymerases have stalled.
Telomerase is a ribonucleoprotein recruited to replicate ends of linear chromosomes because normal DNA polymerase cannot replicate the ends, or telomere. The single-strand 3â overhang of the double-strand chromosome with the sequence 5â-TTAGGG-3â recruits telomerase. Telomerase acts like other DNA polymerases by extending the 3â end, but, unlike other DNA polymerases, telomerase does not require a template. The TERT subunit, an example of a reverse transcriptase, uses the RNA subunit to form the primer:template junction that allows telomerase to extend the 3â end of chromosome ends.:248â249
Polymerases Î³ and Î¸ (Polymerases gamma and theta)
Pol Î³ (gamma) and Pol Î¸ (theta) are Family A polymerases. Pol Î³, encoded by the POLG gene, is the only mtDNA polymerase and therefore replicates, repairs, and has proofreading 3'-5' exonuclease and 5' dRP lyase activities. Any mutation that leads to limited or non-functioning Pol Î³ has a significant effect on mtDNA and is the most common cause of autosomal inherited mitochondrial disorders. Pol Î³ contains a C-terminus polymerase domain and an N-terminus 3'-5' exonuclease domain that are connected via the linker region, which binds the accessory subunit. The accessory subunit binds DNA and is required for processivity of Pol Î³. Point mutation A467T in the linker region is responsible for more than one-third of all Pol Î³-associated mitochondrial disorders. While many homologs of Pol Î¸, encoded by the POLQ gene, are found in eukaryotes, its function is not clearly understood. The sequence of amino acids in the C-terminus is what classifies Pol Î¸ as Family A polymerase, although the error rate for Pol Î¸ is more closely related to Family Y polymerases. Pol Î¸ extends mismatched primer termini and can bypass abasic sites by adding a nucleotide opposite the lesion. Pol Î¸ also has Deoxyribophosphodiesterase (dRPase)actitivy in the polymerase domain and can show ATPase activity in close proximity to ssDNA.
Retroviruses encode an unusual DNA polymerase called reverse transcriptase, which is an RNA-dependent DNA polymerase (RdDp) that synthesizes DNA from a template of RNA. The reverse transcriptase family contain both DNA polymerase functionality and RNase H functionality, which degrades RNA base-paired to DNA. Some retrovirus examples include Hepatitis B virus and HIV.:
- DNA repair
- DNA replication
- DNA sequencing
- Genetic recombination
- Molecular cloning
- Polymerase chain reaction
- RNA polymerase
- Reverse transcription
- "The Nobel Prize in Physiology or Medicine 1959". Nobel Foundation. Retrieved December 1, 2012.
- Tessman I, Kennedy MA (February 1994). "DNA polymerase II of Escherichia coli in the bypass of abasic sites in vivo". Genetics 136 (2): 439â48. PMC 1205799. PMID 7908652.
- Steitz TA (June 1999). "DNA polymerases: structural diversity and common mechanisms". J. Biol. Chem. 274 (25): 17395â8. PMID 10364165.
- Losick R, Watson JD, Baker TA, Bell S, Gann A, Levine MW (2008). Molecular biology of the gene (6th ed.). San Francisco: Pearson/Benjamin Cummings. ISBN 0-8053-9592-X.
- McCarthy D, Minner C, Bernstein H, Bernstein C (October 1976). "DNA elongation rates and growing point distributions of wild-type phage T4 and a DNA-delay amber mutant". J. Mol. Biol. 106 (4): 963â81. PMID 789903.
- Maga G, Hubscher U, Spadari S, Villani G (2010). DNA Polymerases: Discovery, Characterization and Functions in Cellular DNA Transactions. World Scientific Publishing Company. ISBN 981-4299-16-2.
- Camps M, Loeb LA (February 2004). "When pol I goes into high gear: processive DNA synthesis by pol I in the cell". Cell Cycle 3 (2): 116â8. PMID 14712068.
- Banach-Orlowska M, Fijalkowska IJ, Schaaper RM, Jonczyk P (October 2005). "DNA polymerase II as a fidelity factor in chromosomal DNA synthesis in Escherichia coli". Mol. Microbiol. 58 (1): 61â70. doi:10.1111/j.1365-2958.2005.04805.x. PMID 16164549.
- Banach-Orlowska M, Fijalkowska IJ, Schaaper RM, Jonczyk P (October 2005). "DNA polymerase II as a fidelity factor in chromosomal DNA synthesis in Escherichia coli". Mol. Microbiol. 58 (1): 61â70. doi:10.1111/j.1365-2958.2005.04805.x. PMID 16164549.
- Olson MW, Dallmann HG, McHenry CS (December 1995). "DnaX complex of Escherichia coli DNA polymerase III holoenzyme. The chi psi complex functions by increasing the affinity of tau and gamma for delta.delta' to a physiologically relevant range". J. Biol. Chem. 270 (49): 29570â7. PMID 7494000.
- DNA Polymerase Families
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- Mori T (2012). "Escherichia coli DinB inhibits replication fork progression without significantly inducing the SOS response". Genes Genet Syst. 87 (2): 75â87. PMID 22820381.
- Jarosz DF (2007). "Proficient and accurate bypass of persistent DNA lesions by DinB DNA polymerases.". Cell Cycle 6 (7): 817â22. PMID 17377496.
- Patel M, Jiang Q, Woodgate R, Cox MM, Goodman MF (June 2010). "A new model for SOS-induced mutagenesis: how RecA protein activates DNA polymerase V". Crit. Rev. Biochem. Mol. Biol. 45 (3): 171â84. doi:10.3109/10409238.2010.480968. PMC 2874081. PMID 20441441.
- Sutton MD, Walker GC (July 2001). "Managing DNA polymerases: coordinating DNA replication, DNA repair, and DNA recombination". Proc. Natl. Acad. Sci. U.S.A. 98 (15): 8342â9. doi:10.1073/pnas.111036998. PMC 37441. PMID 11459973.
- Yamtich J, Sweasy JB (May 2010). "DNA polymerase family X: function, structure, and cellular roles". Biochim. Biophys. Acta 1804 (5): 1136â50. doi:10.1016/j.bbapap.2009.07.008. PMC 2846199. PMID 19631767.
- Chansky, Michael Lieberman, Allan Marks, Alisa Peet ; illustrations by Matthew (2012). Marks' basic medical biochemistry : a clinical approach (4th ed. ed.). Philadelphia: Wolter Kluwer Health/Lippincott Williams & Wilkins. p. chapter13. ISBN 160831572X.
- Chung DW, Zhang JA, Tan CK, Davie EW, So AG, Downey KM (December 1991). "Primary structure of the catalytic subunit of human DNA polymerase delta and chromosomal location of the gene". Proc. Natl. Acad. Sci. U.S.A. 88 (24): 11197â201. doi:10.1073/pnas.88.24.11197. PMC 53101. PMID 1722322.
- Edwards S, Li CM, Levy DL, Brown J, Snow PM, Campbell JL (April 2003). "Saccharomyces cerevisiae DNA polymerase epsilon and polymerase sigma interact physically and functionally, suggesting a role for polymerase epsilon in sister chromatid cohesion". Mol. Cell. Biol. 23 (8): 2733â48. PMC 152548. PMID 12665575.
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- DNA polymerases at the US National Library of Medicine Medical Subject Headings (MeSH)
- PDB Molecule of the Month pdb3_1
- Unusual repair mechanism in DNA polymerase lambda, Ohio State University, July 25, 2006.
- A great animation of DNA Polymerase from WEHI at 1:45 minutes in
- 3D macromolecular structures of DNA polymerase from the EM Data Bank(EMDB)
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.
DNA polymerase type B, organellar and viral Provide feedback
Like PF00136 members of this family are also DNA polymerase type B proteins. Those included here are found in plant and fungal mitochondria, and in viruses.
Internal database links
|Similarity to PfamA using HHSearch:||Pox_F12L|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR004868This entry is found in DNA polymerase type B proteins. Proteins in this entry are found in plant and fungal mitochondria, and in viruses.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||3'-5' exonuclease activity (GO:0008408)|
|DNA-directed DNA polymerase activity (GO:0003887)|
|DNA binding (GO:0003677)|
|nucleotide binding (GO:0000166)|
|Biological process||DNA replication (GO:0006260)|
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You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
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_236 (release 6.5)|
|Number in seed:||35|
|Number in full:||975|
|Average length of the domain:||307.10 aa|
|Average identity of full alignment:||22 %|
|Average coverage of the sequence by the domain:||53.07 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -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 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 DNA_pol_B_2 domain has been found. There are 25 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...