Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
28  structures 5471  species 1  interaction 12285  sequences 87  architectures

Family: N6_N4_Mtase (PF01555)

Summary: DNA methylase

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "DNA methyltransferase". More...

DNA methyltransferase Edit Wikipedia article

N-6 DNA Methylase
2ar0 structure.png
crystal structure of type i restriction enzyme ecoki m protein (ec (m.ecoki)
Pfam clanCL0063
HsdM N-terminal domain
C-5 cytosine-specific DNA methylase
1g55 structure.png
structure of human dnmt2, an enigmatic dna methyltransferase homologue
Pfam clanCL0063
DNA methylase
1g60 structure.png
crystal structure of methyltransferase mboiia (moraxella bovis)
Pfam clanCL0063

In biochemistry, the DNA methyltransferase (DNA MTase) family of enzymes catalyze the transfer of a methyl group to DNA. DNA methylation serves a wide variety of biological functions. All the known DNA methyltransferases use S-adenosyl methionine (SAM) as the methyl donor.



MTases can be divided into three different groups on the basis of the chemical reactions they catalyze:

m6A and m4C methyltransferases are found primarily in prokaryotes (although recent evidence has suggested that m6A is abundant in eukaryotes[1]). m5C methyltransfereases are found in some lower eukaryotes, in most higher plants, and in animals beginning with the echinoderms.

The m6A methyltransferases (N-6 adenine-specific DNA methylase) (A-Mtase) are enzymes that specifically methylate the amino group at the C-6 position of adenines in DNA. They are found in the three existing types of bacterial restriction-modification systems (in type I system the A-Mtase is the product of the hsdM gene, and in type III it is the product of the mod gene). These enzymes are responsible for the methylation of specific DNA sequences in order to prevent the host from digesting its own genome via its restriction enzymes. These methylases have the same sequence specificity as their corresponding restriction enzymes. These enzymes contain a conserved motif Asp/Asn-Pro-Pro-Tyr/Phe in their N-terminal section, this conserved region could be involved in substrate binding or in the catalytic activity.[2][3][4][5] The structure of N6-MTase TaqI (M.TaqI) has been resolved to 2.4 A. The molecule folds into 2 domains, an N-terminal catalytic domain, which contains the catalytic and cofactor binding sites, and comprises a central 9-stranded beta-sheet, surrounded by 5 helices; and a C-terminal DNA recognition domain, which is formed by 4 small beta-sheets and 8 alpha-helices. The N- and C-terminal domains form a cleft that accommodates the DNA substrate.[6] A classification of N-MTases has been proposed, based on conserved motif (CM) arrangements.[5] According to this classification, N6-MTases that have a DPPY motif (CM II) occurring after the FxGxG motif (CM I) are designated D12 class N6-adenine MTases. The type I restriction and modification system is composed of three polypeptides R, M and S. The M (hsdM) and S subunits together form a methyltransferase that methylates two adenine residues in complementary strands of a bipartite DNA recognition sequence. In the presence of the R subunit, the complex can also act as an endonuclease, binding to the same target sequence but cutting the DNA some distance from this site. Whether the DNA is cut or modified depends on the methylation state of the target sequence. When the target site is unmodified, the DNA is cut. When the target site is hemimethylated, the complex acts as a maintenance methyltransferase, modifying the DNA so that both strands become methylated. hsdM contains an alpha-helical domain at the N-terminus, the HsdM N-terminal domain.[7]

Among the m6A methyltransferases (N-6 adenine-specific DNA methylase) there is a group of orphan MTases that do not participate in the bacterial restriction/methylation system.[8] These enzymes have a regulatory role in gene expression and cell cycle regulation. EcoDam from E. coli [9] and CcrM from Caulobacter crescentus [10] are well characterized members of these family.

m4C methyltransferases (N-4 cytosine-specific DNA methylases) are enzymes that specifically methylate the amino group at the C-4 position of cytosines in DNA.[5] Such enzymes are found as components of type II restriction-modification systems in prokaryotes. Such enzymes recognise a specific sequence in DNA and methylate a cytosine in that sequence. By this action they protect DNA from cleavage by type II restriction enzymes that recognise the same sequence

m5C methyltransferases (C-5 cytosine-specific DNA methylase) (C5 Mtase) are enzymes that specifically methylate the C-5 carbon of cytosines in DNA to produce C5-methylcytosine.[11][12][13] In mammalian cells, cytosine-specific methyltransferases methylate certain CpG sequences, which are believed to modulate gene expression and cell differentiation. In bacteria, these enzymes are a component of restriction-modification systems and serve as valuable tools for the manipulation of DNA.[12][14] The structure of HhaI methyltransferase (M.HhaI) has been resolved to 2.5 A: the molecule folds into 2 domains - a larger catalytic domain containing catalytic and cofactor binding sites, and a smaller DNA recognition domain.[15]

De novo vs. maintenance

De novo methyltransferases recognize something in the DNA that allows them to newly methylate cytosines. These are expressed mainly in early embryo development and they set up the pattern of methylation.

Maintenance methyltransferases add methylation to DNA when one strand is already methylated. These work throughout the life of the organism to maintain the methylation pattern that had been established by the de novo methyltransferases.


Three active DNA methyltransferases have been identified in mammals. They are named DNMT1,[16] DNMT3a,[17] and DNMT3b.[18] A fourth enzyme previously known as DNMT2 is not a DNA methyltransferase (see below).

DNMT3L[19] is a protein closely related to DNMT3a and DNMT3b in structure and critical for DNA methylation, but appears to be inactive on its own.


DNMT1 is the most abundant DNA methyltransferase in mammalian cells, and considered to be the key maintenance methyltransferase in mammals. It predominantly methylates hemimethylated CpG di-nucleotides in the mammalian genome. This enzyme is 7– to 100-fold more active on hemimethylated DNA as compared with unmethylated substrate in vitro, but it is still more active at de novo methylation than other DNMTs. The recognition motif for the human enzyme involves only three of the bases in the CpG dinucleotide pair: a C on one strand and CpG on the other. This relaxed substrate specificity requirement allows it to methylate unusual structures like DNA slippage intermediates at de novo rates that equal its maintenance rate.[20] Like other DNA cytosine-5 methyltransferases the human enzyme recognizes flipped out cytosines in double stranded DNA and operates by the nucleophilic attack mechanism.[21] In human cancer cells DNMT1 is responsible for both de novo and maintenance methylation of tumor suppressor genes.[22][23] The enzyme is about 1,620 amino acids long. The first 1,100 amino acids constitute the regulatory domain of the enzyme, and the remaining residues constitute the catalytic domain. These are joined by Gly-Lys repeats. Both domains are required for the catalytic function of DNMT1.

DNMT1 has several isoforms, the somatic DNMT1, a splice variant (DNMT1b) and an oocyte-specific isoform (DNMT1o). DNMT1o is synthesized and stored in the cytoplasm of the oocyte and translocated to the cell nucleus during early embryonic development, while the somatic DNMT1 is always found in the nucleus of somatic tissue.

DNMT1 null mutant embryonic stem cells were viable and contained a small percentage of methylated DNA and methyltransferase activity. Mouse embryos homozygous for a deletion in Dnmt1 die at 10–11 days gestation.[24]


Although this enzyme has strong sequence similarities with 5-methylcytosine methyltransferases of both prokaryotes and eukaryotes, in 2006, the enzyme was shown to methylate position 38 in aspartic acid transfer RNA and does not methylate DNA.[25] The name for this methyltransferase has been changed from DNMT2 to TRDMT1 (tRNA aspartic acid methyltransferase 1) to better reflect its biological function.[26] TRDMT1 is the first RNA cytosine methyltransferase to be identified in human cells.


DNMT3 is a family of DNA methyltransferases that could methylate hemimethylated and unmethylated CpG at the same rate. The architecture of DNMT3 enzymes is similar to that of DNMT1, with a regulatory region attached to a catalytic domain. There are three known members of the DNMT3 family: DNMT3a, 3b, and 3L.

DNMT3a and DNMT3b can mediate methylation-independent gene repression. DNMT3a can co-localize with heterochromatin protein (HP1) and methyl-CpG-binding protein (MeCBP). They can also interact with DNMT1, which might be a co-operative event during DNA methylation. DNMT3a prefers CpG methylation to CpA, CpT, and CpC methylation, though there appears to be some sequence preference of methylation for DNMT3a and DNMT3b. DNMT3a methylates CpG sites at a rate much slower than DNMT1, but greater than DNMT3b.

DNMT3L contains DNA methyltransferase motifs and is required for establishing maternal genomic imprints, despite being catalytically inactive. DNMT3L is expressed during gametogenesis when genomic imprinting takes place. The loss of DNMT3L leads to bi-allelic expression of genes normally not expressed by the maternal allele. DNMT3L interacts with DNMT3a and DNMT3b and co-localized in the nucleus. Though DNMT3L appears incapable of methylation, it may participate in transcriptional repression.

Clinical significance

DNMT inhibitors

Because of the epigenetic effects of the DNMT family, some DNMT inhibitors are under investigation for treatment of some cancers:[27]

See also


  1. ^ Iyer LM, Zhang D, Aravind L (January 2016). "Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification". BioEssays. 38 (1): 27–40. doi:10.1002/bies.201500104. PMC 4738411. PMID 26660621.
  2. ^ Loenen WA, Daniel AS, Braymer HD, Murray NE (November 1987). "Organization and sequence of the hsd genes of Escherichia coli K-12". Journal of Molecular Biology. 198 (2): 159–70. doi:10.1016/0022-2836(87)90303-2. PMID 3323532.
  3. ^ Narva KE, Van Etten JL, Slatko BE, Benner JS (December 1988). "The amino acid sequence of the eukaryotic DNA [N6-adenine]methyltransferase, M.CviBIII, has regions of similarity with the prokaryotic isoschizomer M.TaqI and other DNA [N6-adenine] methyltransferases". Gene. 74 (1): 253–9. doi:10.1016/0378-1119(88)90298-3. PMID 3248728.
  4. ^ Lauster R (March 1989). "Evolution of type II DNA methyltransferases. A gene duplication model". Journal of Molecular Biology. 206 (2): 313–21. doi:10.1016/0022-2836(89)90481-6. PMID 2541254.
  5. ^ a b c Timinskas A, Butkus V, Janulaitis A (May 1995). "Sequence motifs characteristic for DNA [cytosine-N4] and DNA [adenine-N6] methyltransferases. Classification of all DNA methyltransferases". Gene. 157 (1–2): 3–11. doi:10.1016/0378-1119(94)00783-O. PMID 7607512.
  6. ^ Labahn J, Granzin J, Schluckebier G, Robinson DP, Jack WE, Schildkraut I, Saenger W (November 1994). "Three-dimensional structure of the adenine-specific DNA methyltransferase M.Taq I in complex with the cofactor S-adenosylmethionine". Proceedings of the National Academy of Sciences of the United States of America. 91 (23): 10957–61. doi:10.1073/pnas.91.23.10957. PMC 45145. PMID 7971991.
  7. ^ Kelleher JE, Daniel AS, Murray NE (September 1991). "Mutations that confer de novo activity upon a maintenance methyltransferase". Journal of Molecular Biology. 221 (2): 431–40. doi:10.1016/0022-2836(91)80064-2. PMID 1833555.
  8. ^ Adhikari, Satish; Curtis, Patrick D. (2016-09-01). "DNA methyltransferases and epigenetic regulation in bacteria". FEMS Microbiology Reviews. 40 (5): 575–591. doi:10.1093/femsre/fuw023. ISSN 0168-6445.
  9. ^ Chahar, Sanjay; Elsawy, Hany; Ragozin, Sergey; Jeltsch, Albert (January 2010). "Changing the DNA Recognition Specificity of the EcoDam DNA-(Adenine-N6)-Methyltransferase by Directed Evolution". Journal of Molecular Biology. 395 (1): 79–88. doi:10.1016/j.jmb.2009.09.027.
  10. ^ Maier, Johannes A. H.; Albu, Razvan F.; Jurkowski, Tomasz P.; Jeltsch, Albert (2015-12-01). "Investigation of the C-terminal domain of the bacterial DNA-(adenine N6)-methyltransferase CcrM". Biochimie. 119: 60–67. doi:10.1016/j.biochi.2015.10.011. ISSN 0300-9084.
  11. ^ Pósfai J, Bhagwat AS, Roberts RJ (December 1988). "Sequence motifs specific for cytosine methyltransferases". Gene. 74 (1): 261–5. doi:10.1016/0378-1119(88)90299-5. PMID 3248729.
  12. ^ a b Kumar S, Cheng X, Klimasauskas S, Mi S, Posfai J, Roberts RJ, Wilson GG (January 1994). "The DNA (cytosine-5) methyltransferases". Nucleic Acids Res. 22 (1): 1–10. doi:10.1093/nar/22.1.1. PMC 307737. PMID 8127644.
  13. ^ Lauster R, Trautner TA, Noyer-Weidner M (March 1989). "Cytosine-specific type II DNA methyltransferases. A conserved enzyme core with variable target-recognizing domains". J. Mol. Biol. 206 (2): 305–12. doi:10.1016/0022-2836(89)90480-4. PMID 2716049.
  14. ^ Cheng X (February 1995). "DNA modification by methyltransferases". Curr. Opin. Struct. Biol. 5 (1): 4–10. doi:10.1016/0959-440X(95)80003-J. PMID 7773746.
  15. ^ Cheng X, Kumar S, Posfai J, Pflugrath JW, Roberts RJ (July 1993). "Crystal structure of the HhaI DNA methyltransferase complexed with S-adenosyl-L-methionine". Cell. 74 (2): 299–307. doi:10.1016/0092-8674(93)90421-L. PMID 8343957.
  16. ^ "DNMT1". Gene Symbol Report. HUGO Gene Nomenclature Committee. Retrieved 2012-09-27.
  17. ^ "DNMT3A". Gene Symbol Report. HUGO Gene Nomenclature Committee. Retrieved 2012-09-27.
  18. ^ "DNMT3B". Gene Symbol Report. HUGO Gene Nomenclature Committee. Retrieved 2012-09-27.
  19. ^ "DNMT3L". Gene Symbol Report. HUGO Gene Nomenclature Committee. Retrieved 2012-09-27.
  20. ^ Kho MR, Baker DJ, Laayoun A, Smith SS (1998). "Stalling of Human DNA (Cytosine-5) Methyltransferase at Single Strand Conformers form a Site of Dynamic Mutation". Journal of Molecular Biology. 275 (1): 67–79. doi:10.1006/jmbi.1997.1430. PMID 9451440.
  21. ^ Smith SS, Kaplan BE, Sowers LC, Newman EM (1992). "Mechanism of human methyl-directed DNA methyltransferase and the fidelity of cytosine methylation". Proceedings of the National Academy of Sciences of the United States of America. 89 (10): 4744–4748. doi:10.1073/pnas.89.10.4744. PMC 49160. PMID 1584813.
  22. ^ Jair KW, Bachman KE, Suzuki H, Ting AH, Rhee I, Yen RW, Baylin SB, Schuebel KE (2006). "De novo CpG Island Methylation in Human Cancer Cells". Cancer Research. 66 (2): 682–692. doi:10.1158/0008-5472.CAN-05-1980. PMID 16423997.
  23. ^ Ting AH, Jair KW, Schuebel KE, Baylin SB (2006). "Differential Requirement for DNA Methyltransferse 1 In Maintaining Cancer Cell Gene Promoter Hypermethylation". Cancer Research. 66 (2): 729–735. doi:10.1158/0008-5472.CAN-05-1537. PMID 16424002.
  24. ^ Li E, Bestor TH, Jaenisch R (1992). "Targeted Mutation of the DNA Methyltransferase Gene Results in Embryonic Lethality". Cell. 69 (6): 915–926. doi:10.1016/0092-8674(92)90611-F. PMID 1606615.
  25. ^ Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, Golic KG, Jacobsen SE, Bestor TH (2006). "Methylation of tRNAAsp by the DNA Methyltransferase Homolog Dnmt2". Science. 311 (5759): 395–398. doi:10.1126/science.1120976. PMID 16424344.
  26. ^ "TRDMT1 tRNA aspartic acid methyltransferase 1 (Homo sapiens)". Entrez Gene. NCBI. 2010-11-01. Retrieved 2010-11-07.
  27. ^ Mack GS (2010). "To selectivity and beyond". Nat. Biotechnol. 28 (12): 1259–66. doi:10.1038/nbt.1724. PMID 21139608.
  28. ^ "EC Approves Marketing Authorization Of DACOGEN For Acute Myeloid Leukemia". 2012-09-28. Retrieved 28 September 2012.

Further reading

  • Smith SS (1994). "Biological implications of the mechanism of action of human DNA (cytosine-5)methyltransferase". Prog. Nucleic Acid Res. Mol. Biol. 49: 65–111. PMID 7863011.
  • Pradhan S, Esteve PO (2003). "Mammalian DNA (cytosine-5) methyltransferases and their expression". Clin. Immunol. 109 (1): 6–16. doi:10.1016/S1521-6616(03)00204-3. PMID 14585271.
  • Goll MG, Bestor TH (2005). "Eukaryotic cytosine methyltransferases". Annu. Rev. Biochem. 74: 481–514. doi:10.1146/annurev.biochem.74.010904.153721. PMID 15952895.
  • Svedruzić ZM (2008). "Mammalian cytosine DNA methyltransferase Dnmt1: enzymatic mechanism, novel mechanism-based inhibitors, and RNA-directed DNA methylation". Curr. Med. Chem. 15 (1): 92–106. doi:10.2174/092986708783330700. PMID 18220765.

External links

This article incorporates text from the public domain Pfam and InterPro: IPR001525
This article incorporates text from the public domain Pfam and InterPro: IPR003356
This article incorporates text from the public domain Pfam and InterPro: IPR012327
This article incorporates text from the public domain Pfam and InterPro: IPR002941

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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 methylase Provide feedback

Members of this family are DNA methylases. The family contains both N-4 cytosine-specific DNA methylases and N-6 Adenine-specific DNA methylases.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002941

This domain is found in DNA methylases. In prokaryotes, the major role of DNA methylation is to protect host DNA against degradation by restriction enzymes. This family contains both N-4 cytosine-specific DNA methylases and N-6 Adenine-specific DNA methylases. N-4 cytosine-specific DNA methylases (EC) [PUBMED:7607512] are enzymes that specifically methylate the amino group at the C-4 position of cytosines in DNA. Such enzymes are found as components of type II restriction-modification systems in prokaryotes. Such enzymes recognise a specific sequence in DNA and methylate a cytosine in that sequence. By this action they protect DNA from cleavage by type II restriction enzymes that recognise the same sequence. N-6 adenine-specific DNA methylases (EC) (A-Mtase) are enzymes that specifically methylate the amino group at the C-6 position of adenines in DNA. Such enzymes are found in the three existing types of bacterial restriction-modification systems (in type I system the A-Mtase is the product of the hsdM gene, and in type III it is the product of the mod gene). All of these enzymes recognise a specific sequence in DNA and methylate an adenine in that sequence.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan NADP_Rossmann (CL0063), which has the following description:

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 [1]. In some more distantly relate Rossmann domains the NAD+ cofactor is replaced by the functionally similar cofactor FAD.

The clan contains the following 204 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 CbiJ CheR CMAS CmcI CoA_binding CoA_binding_2 CoA_binding_3 Cons_hypoth95 DAO DapB_N DFP DNA_methylase DOT1 DRE2_N DREV DUF1188 DUF1442 DUF1611_N DUF166 DUF1776 DUF2431 DUF268 DUF2855 DUF3410 DUF364 DUF43 DUF5129 DUF5130 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 G6PD_N GCD14 GDI GDP_Man_Dehyd GFO_IDH_MocA GIDA GidB GLF Glu_dehyd_C Glyco_hydro_4 Glyco_tran_WecB GMC_oxred_N Gp_dh_N GRAS GRDA HI0933_like HIM1 IlvN ISPD_C K_oxygenase KR LCM Ldh_1_N LpxI_N Lycopene_cycl 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 MOLO1 Mqo MT-A70 MTS Mur_ligase N2227 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 NSP11 NSP16 OCD_Mu_crystall Orbi_VP4 PALP PARP_regulatory PCMT PDH 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 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


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

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.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View  View  View 
HTML View                 
PP/heatmap 1                

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

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.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

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...


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.

Curation View help on the curation process

Seed source: Pfam-B_164 (release 4.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 49
Number in full: 12285
Average length of the domain: 217.80 aa
Average identity of full alignment: 19 %
Average coverage of the sequence by the domain: 55.89 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.7 26.7
Trusted cut-off 26.7 26.7
Noise cut-off 26.6 26.6
Model length: 231
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


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...



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 N6_N4_Mtase domain has been found. There are 28 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...