Top Level Name

  ⌊ Superfamily (extended) Radical SAM Phosphomethylpyrimidine Synthase

    ⌊ Subgroup phosphomethylpyrimidine synthase (ThiC)

     ⌊ Family phosphomethylpyrimidine synthase (ThiC)

Total 100% <100%
Functional domains 6742 6740 2
UniProtKB 13135 13135 0
GI 25820 25816 4
Structures 4
Reactions 0
Functional domains of this family were last updated on June 24, 2017
New functional domains were last added to this family on Dec. 31, 2014

ThiC (4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase; EC is a radical S-adenosylmethionine (AdoMet) enzyme that uses a [4Fe-4S](+) cluster to reductively cleave AdoMet to methionine and a 5'-deoxyadenosyl radical that initiates catalysis. In plants and bacteria, ThiC converts the purine intermediate 5-aminoimidazole ribotide to 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate, an intermediate of thiamine pyrophosphate (coenzyme B1) biosynthesis.

Work be Palmer and Downs has shown that ThiC activity is inhibited by AdoMet metabolites S-adenosylhomocysteine, adenosine, 5'-deoxyadenosine, S-methyl-5'-thioadenosine, methionine, and homocysteine. Given that neither adenosine nor S-methyl-5'-thioadenosine have been shown to inhibit most radical AdoMet enzymes, ThiC is distinct from other family members, further borne out by the fact that members of this family don't have the canonical C[X]3C[X]2C motif.

Chatterjee A, Li Y, Zhang Y, Grove TL, Lee M, Krebs C, Booker SJ, Begley TP, Ealick SE

Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily.

▸ Abstract

Nat Chem Biol 2008;4(12):758-765 | PubMed ID: 18953358

Palmer LD, Downs DM

The Thiamine Biosynthetic Enzyme ThiC Catalyzes Multiple Turnovers and Is Inhibited by S-Adenosylmethionine (AdoMet) Metabolites

▸ Abstract

J Biol Chem 2013;288(42):30693-30699 | PubMed ID: 24014032

Coquille S, Roux C, Mehta A, Begley TP, Fitzpatrick TB, Thore S

High-resolution crystal structure of the eukaryotic HMP-P synthase (THIC) from Arabidopsis thaliana

▸ Abstract

J Struct Biol 2013;None(None):None-None | PubMed ID: 24161603

No notes.

Sequence Similarity Networks

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List of files included in the download. A detailed list of included node attributes, their definitions, and their uses [revised: 1/24/2014].

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Multiple Sequence Alignment

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Multiple Sequence Alignment

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Data Type All (#) Known (#)
Full length FASTA (6742) ()
Complete annotation (.tsv) (6742) ()
Annotation suitable for Excel ® (.tsv) (6742) ()
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Cutoff Value
The least significant edge-score at which pairwise similarities are included in the network. A bit score for the full network, or a mean E value for the Repnet.
XGMML format
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Download the annotation of all sequences as shown in the table below as a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application.
Full length FASTA
Full length sequences in FASTA format.
Functional Domain FASTA
Sequences of the Functional Domain in FASTA format.
Complete annotation
Download complete annotation of sequences sets of this superfamily as a ͟Tab ͟Separated ͟Value (TSV) file. This file has all data but cell size can exceed the maximum supported by spreadsheet programs (such as Microsoft Excel ®).
Spreadsheet ready annotation
Annotation of sequences sets of this superfamily in a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application. Cells which exceed the allowed spreadsheet maximum (32.5K) are preceded by the word "Truncated" and clipped short.
Total number of functional domains in this group.
Number of Functional Domains that have been manually or automatically been assigned to a family.
Number of Functional Domains that have not been assigned to a family.
Number of structures available from the PDB for members of this group.
Number of Functional Domains with 100% of Conserved Residues
Number of Functional Domains with less than 100% Conserved Residues

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