Sucrase-isomaltase, intestinal

Function

Bifunctional enzyme with both sucrase and isomaltase activities involved in breakdown of dietary starch oligosaccharides in small intestine. The isomaltase domain hydrolazes alpha-1,6-glycosidic linkages in isomaltose. The sucrase domain cleaves the alpha-1,2-glycosidic linkages in sucrose to form glucose and fructose, and contributes to the cleavage of the alpha-1,4-glycosidic linkage in maltose to form two glucose monosaccharides.

Classification

Family (Pfam)

PF13802 Gal_mutarotas_2, PF01055 Glyco_hydro_31_2nd, PF21365 Glyco_hydro_31_3rd, PF00088 Trefoil

InterPro

Gal_mutarotase_sf_dom, GH, Glyco_hydro_31_AS, Glyco_hydro_31_C, Glyco_hydro_31_CS, Glyco_hydro_31_N_dom, Glyco_hydro_31_TIM, Glyco_hydro_b, P_trefoil_CS, P_trefoil_dom, P_trefoil_dom_sf

Functional cluster

Secreted Hydrolases & Toxins

Experimental structures · PDB · 2

• 3LPO X-ray 3.20A
• 3LPP X-ray 2.15A

A predicted model is available from AlphaFold.

Gene Ontology · 11

• GO:0016324 apical plasma membrane
• GO:0005903 brush border
• GO:0070062 extracellular exosome
• GO:0005794 Golgi apparatus
• GO:0005886 plasma membrane
• GO:0004558 alpha-1,4-glucosidase activity
• GO:0030246 carbohydrate binding
• GO:0004574 oligo-1,6-glucosidase activity
• GO:0004575 sucrose alpha-glucosidase activity
• GO:0044245 polysaccharide digestion
• GO:0005987 sucrose catabolic process

Disease associations

• congenital sucrase-isomaltase deficiency MONDO:0009114

Drugs targeting this protein · 2

• CELGOSIVIR inhibitor
• VOGLIBOSE inhibitor

Related proteins · sequence + function similarity

• Sucrase-isomaltase, intestinal 0.97
• Sucrase-isomaltase, intestinal 0.96
• Sucrase-isomaltase, intestinal 0.96
• Sucrase-isomaltase, intestinal 0.95
• Sucrase-isomaltase, intestinal 0.95
• Maltase-glucoamylase 0.95
• Probable maltase-glucoamylase 2 0.92
• Alpha-glucosidase 0.79
• Alpha-glucosidase 0.76
• Putative alpha-xylosidase 2 0.76
• Glucosidase 2 subunit alpha 0.75
• Alpha-xylosidase 1 0.75

Co-cited proteins · studied together in the literature

• Dipeptidyl peptidase 4 1 shared papers

Literature · 15 cited papers

• Phylogenetic analysis reveals key residues in substrate hydrolysis in the isomaltase domain of sucrase-isomaltase and its role in starch digestion. Biochim. Biophys. Acta · 2019
• Structure-function analysis of human sucrase-isomaltase identifies key residues required for catalytic activity. J. Biol. Chem. · 2017
• Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains. J. Biol. Chem. · 2010
• The DNA sequence, annotation and analysis of human chromosome 3. Nature · 2006
• Novel mutations in the human sucrase-isomaltase gene (SI) that cause congenital carbohydrate malabsorption. Hum. Mutat. · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Congenital sucrase-isomaltase deficiency because of an accumulation of the mutant enzyme in the endoplasmic reticulum. Gastroenterology · 2003
• Molecular basis of aberrant apical protein transport in an intestinal enzyme disorder. J. Biol. Chem. · 2001
• Congenital sucrase-isomaltase deficiency arising from cleavage and secretion of a mutant form of the enzyme. J. Clin. Invest. · 2000
• Congenital sucrase-isomaltase deficiency: identification of a glutamine to proline substitution that leads to a transport block of sucrase-isomaltase in a pre-Golgi compartment. J. Clin. Invest. · 1996
• Phosphorylation of the N-terminal intracellular tail of sucrase-isomaltase by cAMP-dependent protein kinase. Eur. J. Biochem. · 1995
• Biosynthesis of the human sucrase-isomaltase complex. Differential O-glycosylation of the sucrase subunit correlates with its position within the enzyme complex. J. Biol. Chem. · 1988
• … and 3 more in the literature graph