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Thymidylate synthase/dCMP hydroxymethylase superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   Alpha and beta proteins (a+b) [ 53931] (376)
Fold:   Thymidylate synthase/dCMP hydroxymethylase [ 55830]
Superfamily:   Thymidylate synthase/dCMP hydroxymethylase [ 55831]
Families:   Thymidylate synthase/dCMP hydroxymethylase [ 55832] (3)


Superfamily statistics
Genomes (2,355) Uniprot 2017_06 genome PDB chains (SCOP 1.75)
Domains 2,716 17,333 48
Proteins 2,693 17,241 48


Functional annotation
General category Metabolism
Detailed category Nucleotide metabolism and transport

Document:
Function annotation of SCOP domain superfamilies

Gene Ontology (high-quality)

(show details)
GO termFDR (singleton)FDR (all)SDFO levelAnnotation (direct or inherited)
Biological Process (BP)cellular aromatic compound metabolic process0.0000000000094820.00000000000002769Least InformativeDirect
Biological Process (BP)heterocycle metabolic process0.0000000000098870.00000000000002273Least InformativeDirect
Biological Process (BP)organic cyclic compound metabolic process0.000000000039390.000000000000114Least InformativeDirect
Biological Process (BP)cellular nitrogen compound metabolic process0.000000000050570.000000000000215Least InformativeDirect
Biological Process (BP)biosynthetic process0.000000000093760.00000006254Least InformativeDirect
Biological Process (BP)single-organism metabolic process0.0000000068480.0000000003623Least InformativeDirect
Biological Process (BP)single-organism cellular process0.0000010190.0001634Least InformativeDirect
Biological Process (BP)organonitrogen compound metabolic process0.026580.01763Least InformativeInherited
Biological Process (BP)primary metabolic process0.00000023940.2674Least InformativeInherited
Biological Process (BP)carbohydrate derivative metabolic process00.00000000001852Moderately InformativeDirect
Biological Process (BP)aromatic compound biosynthetic process00.00000000001928Moderately InformativeDirect
Biological Process (BP)heterocycle biosynthetic process00.00000000005269Moderately InformativeDirect
Biological Process (BP)organophosphate biosynthetic process00.0000000001313Moderately InformativeDirect
Biological Process (BP)organic cyclic compound biosynthetic process00.0000000002649Moderately InformativeDirect
Biological Process (BP)nucleoside phosphate metabolic process00.00000008437Moderately InformativeDirect
Biological Process (BP)nucleotide biosynthetic process00InformativeDirect
Biological Process (BP)pyrimidine-containing compound biosynthetic process0.0000000000099140InformativeDirect
Biological Process (BP)deoxyribonucleotide metabolic process00Highly InformativeDirect
Biological Process (BP)deoxyribose phosphate metabolic process00Highly InformativeDirect
Biological Process (BP)pyrimidine nucleotide biosynthetic process0.00000026380.000000001722Highly InformativeDirect
Molecular Function (MF)transferase activity0.0000000000000092970.00000002234Least InformativeDirect
Molecular Function (MF)transferase activity, transferring one-carbon groups00InformativeDirect

Document: GO annotation of SCOP domains

Gene Ontology (high-coverage)

(show details)
GO term FDR (all) SDFO level Annotation (direct or inherited)
Biological Process (BP) cellular aromatic compound metabolic process 0.00000000000002769 Least Informative Direct
Biological Process (BP) heterocycle metabolic process 0.00000000000002273 Least Informative Direct
Biological Process (BP) organic cyclic compound metabolic process 0.000000000000114 Least Informative Direct
Biological Process (BP) cellular nitrogen compound metabolic process 0.000000000000215 Least Informative Direct
Biological Process (BP) biosynthetic process 0.00000006254 Least Informative Direct
Biological Process (BP) single-organism metabolic process 0.0000000003623 Least Informative Direct
Biological Process (BP) single-organism cellular process 0.0001634 Least Informative Direct
Biological Process (BP) organonitrogen compound metabolic process 0.01763 Least Informative Inherited
Biological Process (BP) primary metabolic process 0.2674 Least Informative Inherited
Biological Process (BP) carbohydrate derivative metabolic process 0.00000000001852 Moderately Informative Direct
Biological Process (BP) aromatic compound biosynthetic process 0.00000000001928 Moderately Informative Direct
Biological Process (BP) heterocycle biosynthetic process 0.00000000005269 Moderately Informative Direct
Biological Process (BP) organophosphate biosynthetic process 0.0000000001313 Moderately Informative Direct
Biological Process (BP) organic cyclic compound biosynthetic process 0.0000000002649 Moderately Informative Direct
Biological Process (BP) nucleoside phosphate metabolic process 0.00000008437 Moderately Informative Direct
Biological Process (BP) nucleotide biosynthetic process 0 Informative Direct
Biological Process (BP) pyrimidine-containing compound biosynthetic process 0 Informative Direct
Biological Process (BP) deoxyribonucleotide metabolic process 0 Highly Informative Direct
Biological Process (BP) deoxyribose phosphate metabolic process 0 Highly Informative Direct
Biological Process (BP) pyrimidine nucleotide biosynthetic process 0.000000001722 Highly Informative Direct
Molecular Function (MF) transferase activity 0.00000002234 Least Informative Direct
Molecular Function (MF) transferase activity, transferring one-carbon groups 0 Informative Direct

Document: GO annotation of SCOP domains

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEO levelAnnotation (direct or inherited)
Enzyme Commission (EC)Transferring one-carbon groups0Least InformativeDirect
Enzyme Commission (EC)Oxidoreductases1Least InformativeInherited
Enzyme Commission (EC)Methyltransferases0Moderately InformativeDirect
Enzyme Commission (EC)Acting on the CH-NH group of donors0.00000000002717Moderately InformativeDirect
Enzyme Commission (EC)With NAD(+) or NADP(+) as acceptor0.000000000004276InformativeDirect

Document: EC annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processOne-carbon metabolism0.000000545Highly InformativeDirect
Cellular componentCytoplasm0Least InformativeDirect
Post-translational modificationTransferase0Least InformativeDirect
Post-translational modificationMethyltransferase0InformativeDirect

Document: KW annotation of SCOP domains

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

Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Gene Ontology (high-quality) · Gene Ontology (high-coverage) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) ]

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 · Gene Ontology (high-quality) · Gene Ontology (high-coverage) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) · Internal database links ]