2.1.1.296: methyltransferase cap2
This is an abbreviated version!
For detailed information about methyltransferase cap2, go to the full flat file.
Word Map on EC 2.1.1.296
Reaction
Synonyms
AFT, cap2, cap2-MTase, CMTr2, FLJ11171, FTSJD1, hMTr2, mRNA (nucleoside-2'-O)-methyltransferase, MT48, MT57, MTR2, TbMT48, TbMT57
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General Information on EC 2.1.1.296 - methyltransferase cap2
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GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
evolution
malfunction
metabolism
the 5' cap of human messenger RNA contains 2'-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Enzyme responsible for the methylations are CMTr1 and CMTr2, respectively
physiological function
additional information
evolution
MT57 homologs are only found in trypanosomatid protozoa that have a cap 4 structure and in poxviruses, of which vaccinia virus is a prototype, TbMT48 or TbMT57 are two protein components of the cap 4 biosynthetic machinery
evolution
the enzyme belongs to the Rossmann-fold MTase (RFM) family, hMTr1 and hMTr2 are paralogues forming a subfamily with higher eukaryotic and viral members, minimum evolution tree of homologues of known 2'-O-ribose mRNA cap MTases, overview
evolution
the enzyme shows significant sequence and structural similarities to vaccinia virus VP39, another cap-specific RNA 2'-O-methyltransferase. TbMT48 or TbMT57 are two protein components of the cap 4 biosynthetic machinery
malfunction
an observed defect in cap 4 modification is a specific effect of MT48 ablation
malfunction
downregulation by RNAi or genetic ablation of TbMT57 result in the accumulation of SL RNA missing 2'-O-methyl groups at positions +3 and +4 and thus bearing a cap 2 rather than a cap 4. Genetic ablation of MT57 results in viable cells with no apparent defect in SL RNA transsplicing, suggesting that MT57 is not essential or that trypanosomes have developed alternate mechanisms to counteract the absence of this protein
malfunction
the substitutions of residues S78, H86 and Q113 only mildly affect RNA binding and catalysis, so they are not essential for CMTr2 MTase activity
physiological function
TbMT48 or TbMT57 are two protein components of the cap 4 biosynthetic machinery. The enzymes involved in cap 4 biogenesis, TbMT48 and TbMT57, are encoded by non-essential genes, considering that the SL cap 4 structure is a crucial determinant for trans-splicing competence of the SL RNA
physiological function
the 5' cap of human messenger RNA consists of an inverted 7-methylguanosine linked to the first transcribed nucleotide by a unique 5'-5' triphosphate bond followed by 2'-O-ribose methylation of the first and often the second transcribed nucleotides, likely serving to modify efficiency of transcript processing, translation and stability. Cap2 methylates the ribose of the second transcribed nucleotide. Relationship to other cap-modifying enzymes, overview
physiological function
the enzyme is involved in formation of the cap 4 structure, a cap structure of the SL RNA unique in eukaryotes with 4 nucleotides after the cap carrying a total of seven methyl groups. Modifications at the +3 and +4 positions are important for binding to the nuclear cap-binding complex, but MT57 is not essential. The Trypanosoma brucei cap binding complex can distinguish between a cap 4 and an m7G structure and it has a much higher affinity for the cap 4 substrate
physiological function
enzyme Cap2 expression is regulated by Pax6, a key regulator of the entire cascade of ocular lens formation through specific binding to promoters and enhancers of batteries of target genes
additional information
enzyme MT48 structural modeling using the VP39 crystal structure as a template, TbMT48 domains involved in S-adenosyl-methionine and cap binding, overview
additional information
FTSJD1, the candidate hMTr2, is composed of two RFM domains, sequence comparisons, and has a K-D-K active site. Each residue of the K-D-K triad is essential for the activity of the enzyme
additional information
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FTSJD1, the candidate hMTr2, is composed of two RFM domains, sequence comparisons, and has a K-D-K active site. Each residue of the K-D-K triad is essential for the activity of the enzyme
additional information
structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation, homology modeling of the CMTr2 catalytic domain bound to its target using the crystal structure of CMTr1 catalytic domain, overview. CMTr2 is divided into two parts: the amino-terminal part with the catalytic RFM domain (CMTr21-430) and the C-terminal part with the non-catalytic RFM domain (CMTr2430-770). The single domains of CMTr2 do not bind the substrate and do not exhibit any cap MTase activity alone or when mixed together as separately purified chains. Thus, CMTr2 requires both RFM domains in a single polypeptide chain for substrate binding and methylation. Residues K74, L77, W85, T89, K307, H142, and E145 are involved in RNA binding and catalysis, while residues residues S78, H86 and Q113 are not important
additional information
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structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation, homology modeling of the CMTr2 catalytic domain bound to its target using the crystal structure of CMTr1 catalytic domain, overview. CMTr2 is divided into two parts: the amino-terminal part with the catalytic RFM domain (CMTr21-430) and the C-terminal part with the non-catalytic RFM domain (CMTr2430-770). The single domains of CMTr2 do not bind the substrate and do not exhibit any cap MTase activity alone or when mixed together as separately purified chains. Thus, CMTr2 requires both RFM domains in a single polypeptide chain for substrate binding and methylation. Residues K74, L77, W85, T89, K307, H142, and E145 are involved in RNA binding and catalysis, while residues residues S78, H86 and Q113 are not important
