Summary: Histone methylation protein DOT1
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Histone methylation protein DOT1 Provide feedback
Sawada K, Yang Z, Horton JR, Collins RE, Zhang X, Cheng X; , J Biol Chem 2004;279:43296-43306.: Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase. PUBMED:15292170 EPMC:15292170
Giannattasio M, Lazzaro F, Plevani P, Muzi-Falconi M; , J Biol Chem 2005; [Epub ahead of print]: The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. PUBMED:15632126 EPMC:15632126
Internal database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR025789
This entry represents the DOT1 domain.
The Dot1 protein (Dot1p) is an histone-lysine N-methyltransferase (EC 220.127.116.11) that methylates lysine 79 (Lys-79) of histone H3. It was first identified as a Disruptor Of Telomeric silencing in yeast where Dot1p is implicated in gene silencing and localization of the Silent Information Regulator (SIR) complex; in higher eukaryotes the methylation carried out by this enzyme may be used for differentiating chromatin domains. Unlike other histone-lysine methyltransferases (HKMTs), Dot1p displays a Rossmann-like (Class I) S-adenosyl-L-methyionine (SAM)-dependent MT fold while other HKMTs contain the SET domain and hence belong to a whole different structural class [ PUBMED:15292170 , PUBMED:12628190 ].
Whereas most HKMTs, such as Suvar3-9 methylate Lys on the N-terminal tails of histones that stick out from the nucleosome, Dot1p substrate (Lys-79 of histone H3) is located in the conserved histone core, in a short turn connecting the first and second helices, exposed on the nucleosome disk surface [ PUBMED:15292170 , PUBMED:12628190 ]. In order for Lys-79 of H3 to be methylated by Dot1p, another lysine, Lys-123 of histone H2B, needs to be ubiquitinated. A possible reason put forward for this requirement is that the ubiquitination may create a space between adjacent nucleosomes, permitting access of Dot1p to its substrate [ PUBMED:15292170 , PUBMED:12628190 ]. In yeast, different states of methylation on Lys-79 of histone H3 (unmodified, mono-, di- and trimethylated) co-exist at the same time, but no clear function is associated with these different methylation states [ PUBMED:15292170 ].
The strucure of the evolutionary conserved core of Dot1p, the DOT1 domain, has first been described for the yeast Dot1p in complex with S-adenosyl-L-homocysteine (AdoHcy) and then for the human Dot1-like protein (Dot1Lp) in complex with SAM. The DOT1 domain is about 300-350 amino acids long and is usually located at either of the extremities of the protein sequence: it stands at the C terminus of the yeast Dot1p and at the N terminus of the human Dot1Lp [ PUBMED:15292170 , PUBMED:12628190 ]. DOT1 displays a rather elongated structure and can be subdivided into two parts: the N- and the C-terminal subdomains [ PUBMED:12628190 ]. The N-terminal part is made up of five alpha helices and two pairs of short beta strand hairpins. The C-terminal part displays a Rossmann-like fold: it consists in a seven-stranded beta sheet tucked by five alpha helices (three helices on one side of the sheet and two on the other), the sheet contains a central topological switchpoint resulting in a deep pocket where SAM is bound. The two subdomains are linked covalently by a loop. Altogether the SAM binding pocket is formed by five segments of the DOT1 domain of which four are located in the C-terminal substructure of the DOT1 domain and one in the loop connecting both parts; two of these segments are conserved across different Class I SAM-dependent MTs [ PUBMED:12628190 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||histone-lysine N-methyltransferase activity (GO:0018024)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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A class of redox enzymes are two domain proteins. One domain, termed the catalytic domain, confers substrate specificity and the precise reaction of the enzyme. The other domain, which is common to this class of redox enzymes, is a Rossmann-fold domain. The Rossmann domain binds nicotinamide adenine dinucleotide (NAD+) and it is this cofactor that reversibly accepts a hydride ion, which is lost or gained by the substrate in the redox reaction. Rossmann domains have an alpha/beta fold, which has a central beta sheet, with approximately five alpha helices found surrounding the beta sheet.The strands forming the beta sheet are found in the following characteristic order 654123. The inter sheet crossover of the stands in the sheet form the NAD+ binding site . In some more distantly relate Rossmann domains the NAD+ cofactor is replaced by the functionally similar cofactor FAD.
The clan contains the following 209 members:2-Hacid_dh_C 3Beta_HSD 3HCDH_N 3HCDH_RFF adh_short adh_short_C2 ADH_zinc_N ADH_zinc_N_2 AdoHcyase_NAD AdoMet_MTase AlaDh_PNT_C Amino_oxidase ApbA AviRa B12-binding Bac_GDH Bin3 Bmt2 BMT5-like BpsA_C CARME CbiJ CheR CMAS CmcI CoA_binding CoA_binding_2 CoA_binding_3 Cons_hypoth95 CoV_ExoN CoV_Methyltr_2 DAO DapB_N DFP DNA_methylase DOT1 DRE2_N DREV DUF1442 DUF1611_N DUF166 DUF1776 DUF268 DUF2855 DUF3410 DUF364 DUF5129 DUF5130 DUF6094 DUF938 DXP_reductoisom DXPR_C Eco57I ELFV_dehydrog Eno-Rase_FAD_bd Eno-Rase_NADH_b Enoyl_reductase Epimerase F420_oxidored FAD_binding_2 FAD_binding_3 FAD_oxidored Fibrillarin FMO-like FmrO FtsJ fvmX7 G6PD_N GCD14 GDI GDP_Man_Dehyd GFO_IDH_MocA GIDA GidB GLF Glu_dehyd_C Glyco_hydro_4 Glyco_tran_WecG GMC_oxred_N Gp_dh_N GRAS GRDA HcgC HI0933_like HIM1 IlvN ISPD_C KR LCM Ldh_1_N LpxI_N Lycopene_cycl Lys_Orn_oxgnase Malic_M Mannitol_dh MCRA Met_10 Methyltr_RsmB-F Methyltr_RsmF_N Methyltrans_Mon Methyltrans_SAM Methyltransf_10 Methyltransf_11 Methyltransf_12 Methyltransf_14 Methyltransf_15 Methyltransf_16 Methyltransf_17 Methyltransf_18 Methyltransf_19 Methyltransf_2 Methyltransf_20 Methyltransf_21 Methyltransf_22 Methyltransf_23 Methyltransf_24 Methyltransf_25 Methyltransf_28 Methyltransf_29 Methyltransf_3 Methyltransf_30 Methyltransf_31 Methyltransf_32 Methyltransf_33 Methyltransf_34 Methyltransf_4 Methyltransf_5 Methyltransf_7 Methyltransf_8 Methyltransf_9 Methyltransf_PK MethyltransfD12 MetW Mg-por_mtran_C MmeI_Mtase MOLO1 Mqo MT-A70 MTS Mur_ligase N6-adenineMlase N6_Mtase N6_N4_Mtase NAD_binding_10 NAD_binding_2 NAD_binding_3 NAD_binding_4 NAD_binding_5 NAD_binding_7 NAD_binding_8 NAD_binding_9 NAD_Gly3P_dh_N NAS NmrA NNMT_PNMT_TEMT NodS OCD_Mu_crystall OpcA_G6PD_assem Orbi_VP4 PALP PARP_regulatory PCMT PDH_N PglD_N Polysacc_syn_2C Polysacc_synt_2 Pox_MCEL Pox_mRNA-cap Prenylcys_lyase PrmA PRMT5 Pyr_redox Pyr_redox_2 Pyr_redox_3 Reovirus_L2 RmlD_sub_bind Rossmann-like rRNA_methylase RrnaAD Rsm22 RsmJ Sacchrp_dh_NADP SAM_MT SE Semialdhyde_dh Shikimate_DH Spermine_synth SRR1 TehB THF_DHG_CYH_C Thi4 ThiF TPM_phosphatase TPMT TrkA_N TRM TRM13 TrmK tRNA_U5-meth_tr Trp_halogenase TylF Ubie_methyltran UDPG_MGDP_dh_N UPF0020 UPF0146 Urocanase V_cholerae_RfbT XdhC_C YjeF_N
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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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|Seed source:||Pfam-B_12064 (release 16.0)|
|Author:||Mistry J , Wood V|
|Number in seed:||11|
|Number in full:||2571|
|Average length of the domain:||174 aa|
|Average identity of full alignment:||30 %|
|Average coverage of the sequence by the domain:||23.45 %|
|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:||16|
|Download:||download the raw HMM for this family|
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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.
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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.
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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 DOT1 domain has been found. There are 60 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.