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.
37  structures 5049  species 0  interactions 9999  sequences 50  architectures

Family: Meth_synt_2 (PF01717)

Summary: Cobalamin-independent synthase, Catalytic domain

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

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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.

Cobalamin-independent synthase, Catalytic domain Provide feedback

This is a family of vitamin-B12 independent methionine synthases or 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferases, EC: from bacteria and plants. Plants are the only higher eukaryotes that have the required enzymes for methionine synthesis [1]. This enzyme catalyses the last step in the production of methionine by transferring a methyl group from 5-methyltetrahydrofolate to homocysteine [1]. The aligned region makes up the carboxy region of the approximately 750 amino acid protein except in some hypothetical archaeal proteins present in the family, where this region corresponds to the entire length. This domain contains the catalytic residues of the enzyme [2].

Literature references

  1. Ravanel S, Gakiere B, Job D, Douce R; , Proc Natl Acad Sci U S A 1998;95:7805-7812.: The specific features of methionine biosynthesis and metabolism in plants. PUBMED:9636232 EPMC:9636232

  2. Ferrer JL, Ravanel S, Robert M, Dumas R; , J Biol Chem 2004;279:44235-44238.: Crystal structures of cobalamin-independent methionine synthase complexed with zinc, homocysteine, and methyltetrahydrofolate. PUBMED:15326182 EPMC:15326182

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002629

The N-terminal half and C-terminal half of MetE in E. coli show some sequence similarity, indicating that the metE gene has evolved from an ancestral metE gene by duplication [ PUBMED:1339288 ]. This entry represents a the C-terminal domain of cobalamin-independent methionine synthase (MetE) from bacteria and plants, which contains the zinc ion responsible for binding and activating homocysteine [ PUBMED:15630480 ]. It also includes archaeal proteins where this domain corresponds to the entire length of the protein [ PUBMED:10469143 ].

Methionine synthases catalyse the the final step of methionine biosynthesis. Two apparently unrelated families of proteins catalyse this step: cobalamin-dependent methionine synthase, which catalyses the transfer of a methyl group from N5-methyltetrahydrofolate to L-homocysteine and requires cobalamin as a cofactor (MetH; 5-methyltetrahydrofolate:L-homocysteine S-methyltransferase; EC ) and cobalamin-independent methionine synthase, which catalyses the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine without using an intermediate methyl carrier (MetE; 5-methyltetrahydropteroyltri-L-glutamate:L-homocysteine S-methyltransferase; EC ). These enzymes display no detectable sequence homology between them, but both require zinc for activation and binding to L-homocysteine. Organisms that cannot obtain cobalamin (vitamin B12) encode only the cobalamin-independent enzyme. Escherichia coli and many other bacteria express both enzymes [ PUBMED:1339288 ]. Mammals utilise only cobalamin-dependent methionine synthase, while plants and yeasts utilise only the cobalamin-independent enzyme.

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 Methionine_synt (CL0160), which has the following description:

The N-terminal and C-terminal cobalamin-independent synthase domains are structurally similar, adopting a TIM beta/alpha barrel. However, the two domain perform functionally different roles. The N-terminal domain and C-terminal domains both define a catalytic cleft in the enzyme. The N-terminal domain is thought to bind the substrate, in particular, the negatively charged polyglutamate chain. The N-terminal domain is also thought to stabilise a loop from the C-terminal domain. The C-terminal domain contains the active site residues[1].

The clan contains the following 3 members:

Meth_synt_1 Meth_synt_2 URO-D


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 and the UniProtKB 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 
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  
Gzipped 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_1909 (release 4.1)
Previous IDs: Methionine_synt;
Type: Domain
Sequence Ontology: SO:0000417
Author: Bashton M , Bateman A
Number in seed: 10
Number in full: 9999
Average length of the domain: 292.60 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 56.96 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 324
Family (HMM) version: 21
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.


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 Meth_synt_2 domain has been found. There are 37 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...

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.

Protein Predicted structure External Information
A0A0R0FQE0 View 3D Structure Click here
A0A0R4J5Z8 View 3D Structure Click here
A0A1D6GL75 View 3D Structure Click here
A1A1F4 View 3D Structure Click here
A1AXN4 View 3D Structure Click here
A1T007 View 3D Structure Click here
A3CL11 View 3D Structure Click here
A3N1F9 View 3D Structure Click here
A4I695 View 3D Structure Click here
A4J5C3 View 3D Structure Click here
A4VNE5 View 3D Structure Click here
A4VXA1 View 3D Structure Click here
A4XSY1 View 3D Structure Click here
A5G0M4 View 3D Structure Click here
A6TGK9 View 3D Structure Click here
A7HQP6 View 3D Structure Click here
A8ACX7 View 3D Structure Click here
A8AV19 View 3D Structure Click here
A8FCD2 View 3D Structure Click here
A9B0A2 View 3D Structure Click here
A9IKD8 View 3D Structure Click here
A9MIY8 View 3D Structure Click here
B0UU16 View 3D Structure Click here
B2JNZ4 View 3D Structure Click here
B2UJ81 View 3D Structure Click here
B2VI65 View 3D Structure Click here
B4EWC2 View 3D Structure Click here
B5YJD3 View 3D Structure Click here
B6UF55 View 3D Structure Click here
B7J432 View 3D Structure Click here
B8DMM2 View 3D Structure Click here
B8DUK6 View 3D Structure Click here
C0P5Y3 View 3D Structure Click here
I1JWK3 View 3D Structure Click here
I1LXY1 View 3D Structure Click here
I1MW49 View 3D Structure Click here
I6YAW3 View 3D Structure Click here
K7KK03 View 3D Structure Click here
K7KNT9 View 3D Structure Click here
K7MME4 View 3D Structure Click here