The sugar isomerase (SIS) domain is a phosphosugar-binding module that is found in a variety of eubacterial, archaebacterial and eukaryotic proteins that have a role in phosphosugar isomerization or regulation [1]. In enzymes, the SIS domain can have a catalytic function as an isomerase and bind to phosphorylated sugars. In bacterial transcriptional regulators of the rpiR family, the domain seems to bind substrates implicated in the genes for sugar metabolism that are controlled by the regulator. The SIS domain is found in one or two copies and can be linked to additional domains, such as helix-turn-helix (HTH) (see <PDOC51071>), CBS (see <PDOC51371>), glutamine amidotransferases type 2 (see <PDOC00406>), or phosphopantetheine-attachment (see <PDOC00012>) [1,2].

The SIS domain has an α-β structure and is dominated by a five-stranded parallel β sheet flanked on either side by α helices forming a three-layer α-β-α sandwich (see <PDB:1MOQ>) [3]. The fold shows similarities to that of glucose-6-phosphate isomerase (see <PDOC00157>).

Some proteins known to contain a SIS domain are listed below:

• Eukaryotic and prokaryotic glucosamine--fructose-6-phosphate aminotransferase [isomerizing] (EC 2.6.1.16).
• Eukaryotic glucokinase regulator (GCKR) family (see <PDOC00979>).
• Bacterial rpiR family of HTH transcriptional regulators (see <PDOC51071>).
• Escherichia coli arabinose 5-phosphate isomerase (kdsD) (EC 5.3.1.13).
• Escherichia coli fructoselysine 6-phosphate deglycase (frlB) (EC 3.5.-.-).
• Escherichia coli gutQ, which is encoded by the glucitol-synthesis operon and is thought to contain a nucleotide-binding site.
• Escherichia coli polysialic acid capsule expression protein kpsF.
• Bacterial phosphoheptose isomerase (gmhA/lpcA) or sedoheptulose 7-phosphate isomerase (EC 5.3.1.-).
• Prokaryotic 3-hexulose-6-phosphate isomerase (PHI) (EC 5.3.1.27).
• Enterobacterial dnaA initiator-associating protein diaA.
• Proteobacterial N-acetylmuramic acid 6-phosphate etherase (murQ) (EC 4.2.-.-), which catalyzes the cleavage of the D-lactyl ether substituent of MurNAc 6-phosphate, producing GlcNAc 6-phosphate and D-lactate.
• Bacterial putative tagatose-6-phosphate ketose/aldose isomerase (agaS) (EC 5.3.1.-).

The profile we developed covers the entire SIS domain.