Summary: Jumonji domain-containing protein 2A Tudor domain
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Tudor domain Edit Wikipedia article
Structure of a TUDOR domain.
In molecular biology a tudor domain is a conserved protein structural domain originally identified as a region of 50 amino acids found in the Tudor protein encoded in Drosophila. The structurally characterized Tudor domain in human SMN (survival of motor neuron) is a strongly bent anti-parallel β-sheet consisting of five β-strands with a barrel-like fold and recognizes symmetrically dimethylated arginine.
The proteins TP53BP1 (Tumor suppressor p53-binding protein 1) and its fission yeast homolog Crb2 and JMJD2A (Jumonji domain containing 2A) contain either tandem or double Tudor domains and recognize methylated histones.
Other tudor domain containing proteins include AKAP1 (A-kinase anchor protein 1) and ARID4A (AT rich interactive domain 4A) among others. A well known Tudor domain containing protein is Staphylococcal Nuclease Domain Containing 1 (SND1)/Tudor-SN/p100 co activator. SND1 is involved in RISC complex and interacts with AEG-1 oncogene. SND1 is also acts as an oncogene and plays a very important role in HCC and colon cancer. The SND1 tudor domain binds to methylated arginine in the PIWIL1 protein. Tudor containing SND1 promotes tumor angiogenesis in human hepatocellular carcinoma through a novel pathway which involves NF-kappaB and miR-221. Tudor SND1 is also present in the Drosophila melanogaster. 
- Sprangers R, Groves MR, Sinning I, Sattler M (March 2003). "High-resolution X-ray and NMR structures of the SMN Tudor domain: conformational variation in the binding site for symmetrically dimethylated arginine residues". J. Mol. Biol. 327 (2): 507–20. PMID 12628254. doi:10.1016/S0022-2836(03)00148-7.
- Botuyan MV, Lee J, Ward IM, et al. (December 2006). "Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair". Cell. 127 (7): 1361–73. PMC . PMID 17190600. doi:10.1016/j.cell.2006.10.043.
- Huang Y, Fang J, Bedford MT, Zhang Y, Xu RM (May 2006). "Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A". Science. 312 (5774): 748–51. PMID 16601153. doi:10.1126/science.1125162.
- Lee J, Thompson JR, Botuyan MV, Mer G (January 2008). "Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor". Nat. Struct. Mol. Biol. 15 (1): 109–11. PMC . PMID 18084306. doi:10.1038/nsmb1326.
- Rogne M, Landsverk HB, Van Eynde A, et al. (December 2006). "The KH-Tudor domain of a-kinase anchoring protein 149 mediates RNA-dependent self-association". Biochemistry. 45 (50): 14980–9. PMID 17154535. doi:10.1021/bi061418y.
- Caudy AA, Ketting RF, Hammond SM, Denli AM, Bathoorn AM, Tops BB, Silva JM, Myers MM, Hannon GJ, Plasterk RH (September 2003). "A micrococcal nuclease homologue in RNAi effector complexes". Nature. 425 (6956): 411–4. PMID 14508492. doi:10.1038/nature01956.
- Yoo BK, Santhekadur PK, Gredler R, Chen D, Emdad L, Bhutia S, Pannell L, Fisher PB, Sarkar D (2011). "Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma". Hepatology. 53 (5): 1538–48. PMC . PMID 21520169. doi:10.1002/hep.24216.
- Yoo BK, Emdad L, Lee SG, Su ZZ, Santhekadur P, Chen D, Gredler R, Fisher PB, Sarkar D (April 2011). "Astrocyte elevated gene-1 (AEG-1): A multifunctional regulator of normal and abnormal physiology". Pharmacol. Ther. 130 (1): 1–8. PMC . PMID 21256156. doi:10.1016/j.pharmthera.2011.01.008.
- Liu K, Chen C, Guo Y, et al. (October 2010). "Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain". Proc. Natl. Acad. Sci. U.S.A. 107 (43): 18398–403. PMC . PMID 20937909. doi:10.1073/pnas.1013106107.
- Santhekadur PK, Das SK, Gredler R, et al. (April 2012). "Multifunction Protein Staphylococcal Nuclease Domain Containing 1 (SND1) Promotes Tumor Angiogenesis in Human Hepatocellular Carcinoma through Novel Pathway That Involves Nuclear Factor κB and miR-221". J. Biol. Chem. 287 (17): 13952–8. PMC . PMID 22396537. doi:10.1074/jbc.M111.321646.
- Muying Ying; Dahua Chen (2012). "Tudor domain-containing proteins of Drosophila melanogaster.". Development, Growth & Differentiation.
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Jumonji domain-containing protein 2A Tudor domain Provide feedback
This is the tudor domain found in histone demethylase Jumonji domain-containing protein 2A (JMJD2A). Structure and function analysis indicate that this domain can recognize equally well two unrelated histone peptides, H3K4me3 and H4K20me3, by means of two very different binding mechanisms . JMJD2 also known as KDM4, is a conserved iron (II)-dependent jumonji-domain demethylase subfamily that is essential during development. Vertebrate KDM4A-C proteins contain a conserved double tudor domain (DTD) .
Ballare C, Lange M, Lapinaite A, Martin GM, Morey L, Pascual G, Liefke R, Simon B, Shi Y, Gozani O, Carlomagno T, Benitah SA, Di Croce L;, Nat Struct Mol Biol. 2012;19:1257-1265.: Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity. PUBMED:23104054 EPMC:23104054
Lee J, Thompson JR, Botuyan MV, Mer G;, Nat Struct Mol Biol. 2008;15:109-111.: Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor. PUBMED:18084306 EPMC:18084306
Cai L, Rothbart SB, Lu R, Xu B, Chen WY, Tripathy A, Rockowitz S, Zheng D, Patel DJ, Allis CD, Strahl BD, Song J, Wang GG;, Mol Cell. 2013;49:571-582.: An H3K36 methylation-engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting. PUBMED:23273982 EPMC:23273982
Musselman CA, Avvakumov N, Watanabe R, Abraham CG, Lalonde ME, Hong Z, Allen C, Roy S, Nunez JK, Nickoloff J, Kulesza CA, Yasui A, Cote J, Kutateladze TG;, Nat Struct Mol Biol. 2012;19:1266-1272.: Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1. PUBMED:23142980 EPMC:23142980
Su Z, Wang F, Lee JH, Stephens KE, Papazyan R, Voronina E, Krautkramer KA, Raman A, Thorpe JJ, Boersma MD, Kuznetsov VI, Miller MD, Taverna SD, Phillips GN Jr, Denu JM;, Nat Commun. 2016;7:13387.: Reader domain specificity and lysine demethylase-4 family function. PUBMED:27841353 EPMC:27841353
Internal database links
|SCOOP:||53-BP1_Tudor DUF1325 DUF4537 Tudor_3 Tudor_5 zf-HC5HC2H_2|
|Similarity to PfamA using HHSearch:||DUF1325 Rad9_Rad53_bind 53-BP1_Tudor DUF4537 Tudor_3 Tudor_5|
This tab holds annotation information from the InterPro database.
InterPro entry IPR040477
This is the tudor domain found in lysine-specific demethylase 4A (KDM4A, also known as JMJD2A). Structure and function analysis indicate that this domain can recognize equally well two unrelated histone peptides, H3K4me3 and H4K20me3, by means of two very different binding mechanisms [ PUBMED:18084306 ]. KDM4 belongs to the conserved iron (II)-dependent jumonji-domain demethylase subfamily that is essential during development. Vertebrate KDM4A-C proteins contain a conserved double tudor domain (DTD) [ PUBMED:27841353 ].
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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This clan covers the Tudor domain 'royal family' . This includes chromo, MBT, PWWP and tudor domains. The chromo domain is a comprised of approximately 50 amino acid residues. There are usually one to three Chromo domains found in a single protein. In some chromo domain containing proteins, a second related chromo domain has been found and is referred to as the Chromo-shadow domain. The structure of the Chromo and Chromo-shadow domains reveal an OB-fold, a fold found in a variety of prokaryotic and eukaryotic nucleic acid binding proteins. More specifically,the chromo-domain structure reveals a three beta strands that are packed against an alpha helix. Interestingly, a similar structure is found in the archaeal chromatin proteins (7kDa DNA-binding domain). These are sequence neutral DNA binding proteins. The DNA binding in these archaeal proteins is mediated through the triple stranded beta sheet. These archaeal domains are though to represent an ancestral chromo domain. Homologs of the chromo domain have been found in fission yeast, ciliated protozoa and all animal species, but appear to be absent in eubacteria, budding yeast and plants . The precise function of the chromo domain is unclear, but the chromo domain is thought to act as a targeting module for chromosomal proteins, although the chromosomal contexts and functional contexts being targeted vary. In all cases studies, the chromo domains are found in proteins that are involved in transcription regulation, positive and negative .
The clan contains the following 33 members:53-BP1_Tudor 7kD_DNA_binding Agenet Chromo Chromo_2 Chromo_shadow Cul7 DUF1325 DUF4537 DUF4819 GEN1_C Hva1_TUDOR LBR_tudor LytTR MBT Mtf2_C ProQ_C PWWP Rad9_Rad53_bind RBB1NT SAWADEE SMN SNase TTD TUDOR Tudor-knot Tudor_1_RapA Tudor_2 Tudor_3 Tudor_4 Tudor_5 Tudor_FRX1 Tudor_RapA
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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|Number in seed:||51|
|Number in full:||4702|
|Average length of the domain:||35.10 aa|
|Average identity of full alignment:||42 %|
|Average coverage of the sequence by the domain:||5.91 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||4|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
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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.
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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.
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The tree shows the occurrence of this domain across different species. More...
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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.
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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 Tudor_2 domain has been found. There are 111 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.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.