LCT

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000016 lactase activity	IBA GO_REF:0000033	ACCEPT	Summary: Lactase (EC 3.2.1.108) activity, the hydrolysis of lactose to D-glucose and D-galactose at the enterocyte brush border, is the defining molecular function of LCT. The IBA reflects conservation of lactase activity across vertebrate LPH orthologs; human LCT is itself experimentally characterised. Reason: Core catalytic function, consistent with direct human biochemistry and the localisation of lactase activity to the region IV glycosyl hydrolase domain. Supporting Evidence: file:human/LCT/LCT-uniprot.txt membrane that hydrolyzes lactose, the main sugar in mammalian milk, to PMID:9762914 In the human enzyme lactase comprises Glu-1749, phlorizin hydrolase Glu-1273.
GO:0000016 lactase activity	IDA PMID:12594539 Deglycosylation by small intestinal epithelial cell beta-glu...	ACCEPT	Summary: Nemeth et al. isolated LPH from human small intestinal mucosa as one of two beta-glucosidases; LPH is the brush-border lactase. Reason: Purified human enzyme; supports lactase activity (the paper focuses on flavonoid glucosides, but LPH identity and lactase activity are established). Supporting Evidence: PMID:12594539 Two beta-glucosidases with activity towards flavonoid glycosides were isolated from human small intestine mucosa file:human/LCT/LCT-uniprot.txt membrane that hydrolyzes lactose, the main sugar in mammalian milk, to
GO:0000016 lactase activity	IDA PMID:3929764 Human lactase and the molecular basis of lactase persistence...	ACCEPT	Summary: Potter et al. purified human jejunal lactase and characterised its substrate range; lactase activity co-purifies with phlorizin hydrolase in a single dimeric protein. Reason: Direct assay of purified human enzyme. Supporting Evidence: PMID:3929764 Lactase hydrolyzes, besides lactose, cellobiose and the synthetic substrates PMID:3929764 Phlorizin hydrolase is associated with lactase under all conditions investigated
GO:0000016 lactase activity	IDA PMID:9762914 Intestinal lactase-phlorizin hydrolase (LPH): the two cataly...	ACCEPT	Summary: Zecca et al. assigned the lactase catalytic site of human LPH to Glu-1749 within the mature enzyme, separate from the phlorizin hydrolase site. Reason: Direct biochemical support for lactase activity of the human enzyme. Supporting Evidence: PMID:9762914 Brush border lactase-phlorizin hydrolase carries two catalytic sites. PMID:9762914 In the human enzyme lactase comprises Glu-1749, phlorizin hydrolase Glu-1273.
GO:0000016 lactase activity	IEA GO_REF:0000120	ACCEPT	Summary: Lactase (EC 3.2.1.108) activity, the hydrolysis of lactose to D-glucose and D-galactose at the enterocyte brush border, is the defining molecular function of LCT. The combined IEA (ARBA/Rhea/EC 3.2.1.108) mapping is correct. Reason: Electronic mapping agrees with experimental human data. Supporting Evidence: file:human/LCT/LCT-uniprot.txt membrane that hydrolyzes lactose, the main sugar in mammalian milk, to
GO:0000016 lactase activity	IMP PMID:16400612 Mutations in the translated region of the lactase gene (LCT)...	ACCEPT	Summary: Congenital lactase deficiency patients carry nonsense, frameshift and missense LCT coding mutations with near-total loss of jejunal lactase activity, providing human loss-of-function support for lactase activity. Reason: Human genetic loss-of-function evidence for the core lactase activity. Supporting Evidence: PMID:16400612 Here we report the molecular background of CLD via characterization of five distinct mutations in the coding region of the lactase (LCT) gene PMID:16400612 the severe infancy form represents the outcome of mutations affecting the structure of the protein inactivating the enzyme
GO:0004336 galactosylceramidase activity	ISS GO_REF:0000024	UNDECIDED	Summary: Galactosylceramidase activity is transferred by sequence similarity from rabbit LPH (Q02401), where the phlorizin hydrolase site also hydrolyses glycosylceramides. No direct measurement for the human enzyme was found, and purified human lactase was reported not to hydrolyse glucocerebroside. Reason: Ortholog evidence conflicts with the only direct human substrate-range study I could access; full rabbit evidence was not reviewed. The physiological relevance of brush-border glycosylceramide hydrolysis in humans is unresolved. Supporting Evidence: file:human/LCT/LCT-uniprot.txt Broad specificity glycosidase of the intestinal brush border PMID:3929764 but it does not hydrolyze glucocerebroside
GO:0004348 glucosylceramidase activity	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Glucosylceramidase activity is transferred by similarity from rabbit LPH (Q02401). Purified human jejunal lactase was reported not to hydrolyse glucocerebroside. Reason: A direct human assay is negative for glucocerebroside hydrolysis, so the ortholog-based transfer is at best unconfirmed for human LPH. It is not removed because rabbit data and the dual-site architecture make some activity plausible. Supporting Evidence: PMID:3929764 but it does not hydrolyze glucocerebroside
GO:0004553 hydrolase activity, hydrolyzing O-glycosyl compounds	IEA GO_REF:0000002	ACCEPT	Summary: InterPro GH1 mapping to O-glycosyl hydrolase activity; correct but general parent of lactase, phlorizin hydrolase and beta-glucosidase activities. Reason: Correct general term; the specific child activities are separately annotated. Supporting Evidence: file:human/LCT/LCT-uniprot.txt Broad specificity glycosidase of the intestinal brush border
GO:0005886 plasma membrane	TAS PMID:2460343 Complete primary structure of human and rabbit lactase-phlor...	MODIFY	Summary: Mantei et al. described LPH as a brush border membrane beta-glycosidase with a C-terminal membrane anchor and Nout-Cin topology. Plasma membrane is correct but less specific than brush border membrane. Reason: The source supports the more specific brush border membrane (GO:0031526). Proposed replacements: brush border membrane Supporting Evidence: PMID:2460343 brush border membrane beta-glycosidase complexes PMID:2460343 the protein has an Nout-Cin orientation
GO:0005886 plasma membrane	TAS Reactome:R-HSA-189062	MODIFY	Summary: Reactome places LPH at the plasma membrane for lactose hydrolysis; the summary specifies the external face of enterocyte microvilli, i.e. the brush border. Reason: Correct but general; the cited Reactome summary itself supports the more specific brush border membrane (GO:0031526). Proposed replacements: brush border membrane Supporting Evidence: Reactome:R-HSA-189062 lactase-phlorzin hydrolase is found on the external face of enterocytes in microvilli of the small intestine
GO:0005886 plasma membrane	TAS Reactome:R-HSA-5658001	MODIFY	Summary: Reactome places LPH at the plasma membrane for lactose hydrolysis; the summary specifies the external face of enterocyte microvilli, i.e. the brush border. Reason: Correct but general; the cited Reactome summary itself supports the more specific brush border membrane (GO:0031526). Proposed replacements: brush border membrane Supporting Evidence: Reactome:R-HSA-189062 lactase-phlorzin hydrolase is found on the external face of enterocytes in microvilli of the small intestine
GO:0005975 carbohydrate metabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro GH1 mapping to carbohydrate metabolic process; correct but general. Reason: True but uninformative; lactose catabolic process captures the specific role. Supporting Evidence: file:human/LCT/LCT-uniprot.txt membrane that hydrolyzes lactose, the main sugar in mammalian milk, to
GO:0005990 lactose catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: LPH carries out the first and rate-limiting step of dietary lactose utilisation, hydrolysing lactose at the brush border to absorbable glucose and galactose. Reason: Core process; direct consequence of the core lactase activity, and loss causes congenital lactase deficiency. Supporting Evidence: file:human/LCT/LCT-uniprot.txt membrane that hydrolyzes lactose, the main sugar in mammalian milk, to Reactome:R-HSA-189062 Extracellular lactose is hydrolyzed to yield molecules of glucose and galactose
GO:0005990 lactose catabolic process	IDA PMID:12594539 Deglycosylation by small intestinal epithelial cell beta-glu...	ACCEPT	Summary: LPH carries out the first and rate-limiting step of dietary lactose utilisation, hydrolysing lactose at the brush border to absorbable glucose and galactose. Reason: Core process; direct consequence of the core lactase activity, and loss causes congenital lactase deficiency. Supporting Evidence: PMID:12594539 Two beta-glucosidases with activity towards flavonoid glycosides were isolated from human small intestine mucosa file:human/LCT/LCT-uniprot.txt membrane that hydrolyzes lactose, the main sugar in mammalian milk, to
GO:0005990 lactose catabolic process	IDA PMID:3929764 Human lactase and the molecular basis of lactase persistence...	ACCEPT	Summary: LPH carries out the first and rate-limiting step of dietary lactose utilisation, hydrolysing lactose at the brush border to absorbable glucose and galactose. Reason: Core process; direct consequence of the core lactase activity, and loss causes congenital lactase deficiency. Supporting Evidence: PMID:3929764 Lactase hydrolyzes, besides lactose, cellobiose and the synthetic substrates
GO:0005990 lactose catabolic process	IDA PMID:9762914 Intestinal lactase-phlorizin hydrolase (LPH): the two cataly...	ACCEPT	Summary: LPH carries out the first and rate-limiting step of dietary lactose utilisation, hydrolysing lactose at the brush border to absorbable glucose and galactose. Reason: Core process; direct consequence of the core lactase activity, and loss causes congenital lactase deficiency. Supporting Evidence: PMID:9762914 In the human enzyme lactase comprises Glu-1749, phlorizin hydrolase Glu-1273.
GO:0008422 beta-glucosidase activity	IBA GO_REF:0000033	ACCEPT	Summary: LPH hydrolyses beta-D-glucosides (phlorizin, cellobiose, flavonoid glucosides) in addition to the beta-galactoside lactose, so beta-glucosidase activity is a genuine, broader description of its specificity. Electronic/phylogenetic/ortholog inference agrees with human data. Reason: Consistent with direct human biochemistry. Supporting Evidence: file:human/LCT/LCT-uniprot.txt Broad specificity glycosidase of the intestinal brush border PMID:3929764 Lactase hydrolyzes, besides lactose, cellobiose and the synthetic substrates
GO:0008422 beta-glucosidase activity	IDA PMID:12594539 Deglycosylation by small intestinal epithelial cell beta-glu...	ACCEPT	Summary: LPH hydrolyses beta-D-glucosides (phlorizin, cellobiose, flavonoid glucosides) in addition to the beta-galactoside lactose, so beta-glucosidase activity is a genuine, broader description of its specificity. Nemeth et al. showed purified human LPH deglycosylates dietary flavonoid glucosides. Reason: Direct human biochemistry; beta-glucosidase activity contributes to deglycosylation of dietary flavonoid glucosides. Supporting Evidence: PMID:12594539 Two beta-glucosidases with activity towards flavonoid glycosides were isolated from human small intestine mucosa PMID:12594539 The absorption of dietary flavonoid glycosides in humans involves a critical deglycosylation step that is mediated by epithelial beta-glucosidases
GO:0008422 beta-glucosidase activity	IDA PMID:3929764 Human lactase and the molecular basis of lactase persistence...	ACCEPT	Summary: LPH hydrolyses beta-D-glucosides (phlorizin, cellobiose, flavonoid glucosides) in addition to the beta-galactoside lactose, so beta-glucosidase activity is a genuine, broader description of its specificity. Reason: Direct assay of purified human enzyme with beta-glucoside substrates. Supporting Evidence: PMID:3929764 Lactase hydrolyzes, besides lactose, cellobiose and the synthetic substrates
GO:0008422 beta-glucosidase activity	IEA GO_REF:0000116	ACCEPT	Summary: LPH hydrolyses beta-D-glucosides (phlorizin, cellobiose, flavonoid glucosides) in addition to the beta-galactoside lactose, so beta-glucosidase activity is a genuine, broader description of its specificity. Electronic/phylogenetic/ortholog inference agrees with human data. Reason: Consistent with direct human biochemistry. Supporting Evidence: file:human/LCT/LCT-uniprot.txt Broad specificity glycosidase of the intestinal brush border PMID:3929764 Lactase hydrolyzes, besides lactose, cellobiose and the synthetic substrates
GO:0008422 beta-glucosidase activity	ISS GO_REF:0000024	ACCEPT	Summary: LPH hydrolyses beta-D-glucosides (phlorizin, cellobiose, flavonoid glucosides) in addition to the beta-galactoside lactose, so beta-glucosidase activity is a genuine, broader description of its specificity. Electronic/phylogenetic/ortholog inference agrees with human data. Reason: Consistent with direct human biochemistry. Supporting Evidence: file:human/LCT/LCT-uniprot.txt Broad specificity glycosidase of the intestinal brush border PMID:3929764 Lactase hydrolyzes, besides lactose, cellobiose and the synthetic substrates
GO:0016324 apical plasma membrane	EXP PMID:9593732 Protein domains implicated in intracellular transport and so...	ACCEPT	Summary: LPH is a single-pass type I protein sorted to the apical (brush border) membrane of enterocytes. Reason: Core location of the enzyme, supported by sorting studies and human tissue localisation. Supporting Evidence: PMID:9593732 The results strongly suggest that dimerization and transport of pro-LPH implicate a stretch of 87 amino acids in the ectodomain PMID:12594539 localised to the apical membrane of small intestinal epithelial cells
GO:0016324 apical plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: LPH is a single-pass type I protein sorted to the apical (brush border) membrane of enterocytes. Reason: Core location of the enzyme, supported by sorting studies and human tissue localisation. Supporting Evidence: file:human/LCT/LCT-uniprot.txt Apical cell membrane PMID:12594539 localised to the apical membrane of small intestinal epithelial cells
GO:0042803 protein homodimerization activity	IDA PMID:9593732 Protein domains implicated in intracellular transport and so...	KEEP AS NON CORE	Summary: Pro-LPH homodimerises in the ER; dimerisation requires a folded ectodomain and the transmembrane region and is needed for transport out of the ER. Mature human lactase is a dimer of identical subunits. Reason: Homodimerisation is real and required for maturation and trafficking, but it is a structural property supporting the catalytic function rather than a core function. Supporting Evidence: PMID:9593732 The results strongly suggest that dimerization and transport of pro-LPH implicate a stretch of 87 amino acids in the ectodomain PMID:9593732 is not transported beyond the ER and persists as a mannose-rich monomer during its entire life cycle PMID:3929764 appears to be a dimer of subunits identical in Mr (160K)
GO:0046477 glycosylceramide catabolic process	ISS GO_REF:0000024	UNDECIDED	Summary: Glycosylceramide catabolism inferred from rabbit LPH glycosylceramidase activity. Reason: Same conflict as the glycosylceramidase MF annotations: no direct human support and a negative report for glucocerebroside. Supporting Evidence: PMID:3929764 but it does not hydrolyze glucocerebroside
GO:0080079 cellobiose glucosidase activity	EXP PMID:3929764 Human lactase and the molecular basis of lactase persistence...	KEEP AS NON CORE	Summary: Cellobiose hydrolysis by human LPH was shown with purified enzyme; cellobiose is a minor dietary disaccharide. Reason: Real activity of the hydrophilic-aglycone (lactase) site, but of minor physiological importance relative to lactose digestion. Supporting Evidence: PMID:3929764 Lactase hydrolyzes, besides lactose, cellobiose and the synthetic substrates
GO:0080079 cellobiose glucosidase activity	IEA GO_REF:0000116	KEEP AS NON CORE	Summary: Cellobiose hydrolysis by human LPH was shown with purified enzyme; cellobiose is a minor dietary disaccharide. Reason: Real activity of the hydrophilic-aglycone (lactase) site, but of minor physiological importance relative to lactose digestion. Supporting Evidence: PMID:3929764 Lactase hydrolyzes, besides lactose, cellobiose and the synthetic substrates
GO:0098591 external side of apical plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: The mature LPH ectodomain, carrying both catalytic sites, faces the intestinal lumen on the external side of the apical membrane (Nout-Cin topology), where it encounters dietary lactose. Reason: Most precise location for the active enzyme. Supporting Evidence: PMID:2460343 the protein has an Nout-Cin orientation Reactome:R-HSA-189062 lactase-phlorzin hydrolase is found on the external face of enterocytes in microvilli of the small intestine
GO:0098591 external side of apical plasma membrane	IDA PMID:9593732 Protein domains implicated in intracellular transport and so...	ACCEPT	Summary: The mature LPH ectodomain, carrying both catalytic sites, faces the intestinal lumen on the external side of the apical membrane (Nout-Cin topology), where it encounters dietary lactose. Reason: Most precise location for the active enzyme. Supporting Evidence: PMID:2460343 the protein has an Nout-Cin orientation Reactome:R-HSA-189062 lactase-phlorzin hydrolase is found on the external face of enterocytes in microvilli of the small intestine
GO:0140749 phlorizin hydrolase activity	IDA PMID:12594539 Deglycosylation by small intestinal epithelial cell beta-glu...	ACCEPT	Summary: Phlorizin hydrolase activity resides in a second catalytic site (Glu-1273, region III) of the same mature LPH polypeptide and co-purifies with lactase in human jejunum. Reason: Second intrinsic catalytic activity of LPH, directly demonstrated for the human enzyme; part of the core enzymatic identity of LPH. Supporting Evidence: PMID:12594539 Two beta-glucosidases with activity towards flavonoid glycosides were isolated from human small intestine mucosa file:human/LCT/LCT-uniprot.txt Broad specificity glycosidase of the intestinal brush border
GO:0140749 phlorizin hydrolase activity	IDA PMID:3929764 Human lactase and the molecular basis of lactase persistence...	ACCEPT	Summary: Phlorizin hydrolase activity resides in a second catalytic site (Glu-1273, region III) of the same mature LPH polypeptide and co-purifies with lactase in human jejunum. Reason: Second intrinsic catalytic activity of LPH, directly demonstrated for the human enzyme; part of the core enzymatic identity of LPH. Supporting Evidence: PMID:9762914 In the human enzyme lactase comprises Glu-1749, phlorizin hydrolase Glu-1273. PMID:3929764 Phlorizin hydrolase is associated with lactase under all conditions investigated
GO:0140749 phlorizin hydrolase activity	IDA PMID:9762914 Intestinal lactase-phlorizin hydrolase (LPH): the two cataly...	ACCEPT	Summary: Phlorizin hydrolase activity resides in a second catalytic site (Glu-1273, region III) of the same mature LPH polypeptide and co-purifies with lactase in human jejunum. Reason: Second intrinsic catalytic activity of LPH, directly demonstrated for the human enzyme; part of the core enzymatic identity of LPH. Supporting Evidence: PMID:9762914 In the human enzyme lactase comprises Glu-1749, phlorizin hydrolase Glu-1273. PMID:3929764 Phlorizin hydrolase is associated with lactase under all conditions investigated
GO:0140749 phlorizin hydrolase activity	IEA GO_REF:0000116	ACCEPT	Summary: Rhea-based mapping of phlorizin hydrolysis (RHEA:69639) to phlorizin hydrolase activity. Reason: Correct; agrees with direct human biochemistry. Supporting Evidence: file:human/LCT/LCT-uniprot.txt Broad specificity glycosidase of the intestinal brush border PMID:9762914 In the human enzyme lactase comprises Glu-1749, phlorizin hydrolase Glu-1273.
GO:1901733 quercetin catabolic process	IDA PMID:12594539 Deglycosylation by small intestinal epithelial cell beta-glu...	MODIFY	Summary: Nemeth et al. showed that human LPH hydrolyses quercetin glucosides, releasing the quercetin aglycone. This is deglycosylation of flavonoid glucosides, not breakdown of quercetin itself. Reason: Quercetin catabolic process asserts degradation of quercetin, whereas LPH generates quercetin from its glucosides. A flavonoid metabolic process term describes the deglycosylation step without that implication. Proposed replacements: flavonoid metabolic process Supporting Evidence: PMID:12594539 The absorption of dietary flavonoid glycosides in humans involves a critical deglycosylation step that is mediated by epithelial beta-glucosidases
GO:2000892 cellobiose catabolic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Process counterpart of cellobiose hydrolysis by LPH. Reason: Supported by the substrate range of purified human lactase, but peripheral to the core role in lactose digestion. Supporting Evidence: PMID:3929764 Lactase hydrolyzes, besides lactose, cellobiose and the synthetic substrates
GO:2000892 cellobiose catabolic process	IDA PMID:3929764 Human lactase and the molecular basis of lactase persistence...	KEEP AS NON CORE	Summary: Process counterpart of cellobiose hydrolysis by LPH. Reason: Supported by the substrate range of purified human lactase, but peripheral to the core role in lactose digestion. Supporting Evidence: PMID:3929764 Lactase hydrolyzes, besides lactose, cellobiose and the synthetic substrates

Gene Description

Existing Annotations Review

Core Functions

Brush-border lactase: hydrolysis of dietary lactose to D-glucose and D-galactose by the region IV catalytic site of mature LPH on the luminal face of the enterocyte apical membrane, the required first step in absorption of milk sugar.

Phlorizin hydrolase / beta-glucosidase: the region III catalytic site of the same polypeptide hydrolyses beta-glucosides with hydrophobic aglycones, including phlorizin and dietary flavonoid glucosides such as quercetin glucosides, a deglycosylation step in flavonoid absorption.

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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