GHMP C-terminal domain superfamily

The GHMP kinases are a group of structurally related small kinases which are mostly involved in intermediary metabolism. The group is named after four members - galactokinase, homserine kinase, mevalonate kinase and phosphomevalonate kinase. It also includes 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase, isopentenyl monophosphate kinase, mevalonate diphosphate decarboxylase, archaeal shikimate kinases, N-acetyl galactosamine kinase, L-threonine kinase, glucuronokinase and galacturonic acid kinase. In addition to these enzymes, two proteins without catalytic activity - the Saccharomyces cerevisiae transcriptional regulator, Gal3p and the Caenorhabditis elegans sex fate determining protein XOL-1 have similar folds [1]. Of the seven enzymes, six kinases and one decarboxylase, two have been linked to human disease, two are involved in the biosynthesis of aromatic and nonaromatic amino acids, folates, and ubiquinones, one is needed to deliver galactose to the glycolytic pathway, and four are essential for either the mevalonate- or non-mevalonate-dependent synthesis of isoprenoids. The structural scaffold of the family has been evolutionary maintained, while the residues have been allowed to drift, however there are highly conserved solvent-accessible residues that are characteristic of the GHMP kinase family [2]. This clan represents the structurally conserved C-terminal domain which has a central alpha-beta plait fold and an insertion of four helices. Together with the N-terminal fold it creates a nucleotide binding fold with the active site located at the domain interface [3].

This clan contains 3 families and the total number of domains in the clan is 26579. The clan was built by S El-Gebali.

Literature references

1. Megarity CF, Huang M, Warnock C, Timson DJ;, Bioorg Chem. 2011;39:120-126.: The role of the active site residues in human galactokinase: implications for the mechanisms of GHMP kinases. PUBMED:21474160 EPMC:21474160
2. Andreassi JL 2nd, Leyh TS;, Biochemistry. 2004;43:14594-14601.: Molecular functions of conserved aspects of the GHMP kinase family. PUBMED:15544330 EPMC:15544330
3. Zhou T, Daugherty M, Grishin NV, Osterman AL, Zhang H;, Structure. 2000;8:1247-1257.: Structure and mechanism of homoserine kinase: prototype for the GHMP kinase superfamily. PUBMED:11188689 EPMC:11188689

Members

This clan contains the following 3 member families:

Below is a listing of the unique domain organisations or architectures from this clan. More...

The table below shows the number of occurrences of each domain throughout the sequence database. More...

Please note: Clan alignments can be very large and can cause problems for some browsers. Read the note above before viewing.

This diagram shows the relationships between members of this clan. More...

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the MSD group, to allow us to map Pfam domains onto UniProt three-dimensional structures. The table below shows the mapping between the Pfam families in this clan, the corresponding UniProt entries, and the region of the three-dimensional structures that are available for that sequence.