SUPERFAMILY 1.73 HMM library and genome assignments server


Thymidylate synthase/dCMP hydroxymethylase superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   Alpha and beta proteins (a+b) [ 53931] (334)
  Mainly antiparallel beta sheets (segregated alpha and beta regions)
Fold:   Thymidylate synthase/dCMP hydroxymethylase [ 55830]
  contains large mixed beta-sheet
Superfamily:   Thymidylate synthase/dCMP hydroxymethylase [ 55831]
Families:   Thymidylate synthase/dCMP hydroxymethylase [ 55832] (3)


Superfamily statistics
Genomes (911) UniProt 15.0 PDB chains (SCOP 1.73)
Domains 1,013 1,339 47
Proteins 1,012 1,338 47


Functional annotation
General category Metabolism
Detailed category Nucleotide metabolism and transport

Function annotation of SCOP domain superfamilies
InterPro annotation
Cross references IPR000398 SSF55831 Protein matches
Abstract Thymidylate synthase [PubMed6996564, PubMed2117882] catalyzes the reductive methylation of dUMP to dTMP with concomitant conversion of 5,10-methylenetetrahydrofolate to dihydrofolate: 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP This provides the sole de novo pathway for production of dTMP and is the only enzyme in folate metabolism in which the 5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer [PubMed3099389]. The enzyme is essential for regulating the balanced supply of the 4 DNA precursors in normal DNA replication: defects in the enzyme activity affecting the regulation process cause various biological and genetic abnormalities, such as thymineless death [PubMed2243092]. The enzyme is an important target for certain chemotherapeutic drugs. Thymidylate synthase is an enzyme of about 30 to 35 Kd in most species except in protozoan and plants where it exists as a bifunctional enzyme that includes a dihydrofolate reductase domain [PubMed3099389]. A cysteine residue is involved in the catalytic mechanism (it covalently binds the 5,6-dihydro-dUMP intermediate). The sequence around the active site of this enzyme is conserved from phages to vertebrates.

InterPro database

PDBeMotif information about ligands, sequence and structure motifs
Cross references PDB entries
Ligand binding statistics
Nucleic-acid binding statistics
Occurrence of secondary structure elements
Occurrence of small 3D structural motifs

PDBeMotif resource

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Internal database links

Browse genome assignments for this superfamily. The SUPERFAMILY hidden Markov model library has been used to carry out SCOP domain assignments to all genomes at the superfamily level.


Alignments of sequences to 10 models in this superfamily are available by clicking on the 'Alignments' icon above. PDB sequences less than 40% identical are shown by default, but any other sequence(s) may be aligned. Select PDB sequences, genome sequences, or paste in or upload your own sequences.


Browse and view proteins in genomes which have different domain combinations including a Thymidylate synthase/dCMP hydroxymethylase domain.


Examine the distribution of domain superfamilies, or families, across the major taxonomic kingdoms or genomes within a kingdom. This gives an immediate impression of how superfamilies, or families, are restricted to certain kingdoms of life.


Explore domain occurrence network where nodes represent genomes and edges are domain architectures (shared between genomes) containing the superfamily of interest.

There are 10 hidden Markov models representing the Thymidylate synthase/dCMP hydroxymethylase superfamily. Information on how the models are built, and plots showing hydrophobicity, match emmission probabilities and insertion/deletion probabilities can be inspected.


Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Internal database links ]