LPH_HUMAN
ID LPH_HUMAN Reviewed; 1927 AA.
AC P09848; Q4ZG58;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Lactase/phlorizin hydrolase {ECO:0000305|PubMed:16400612};
DE AltName: Full=Lactase/glycosylceramidase {ECO:0000305|PubMed:9762914};
DE Includes:
DE RecName: Full=Lactase {ECO:0000305|PubMed:9762914};
DE EC=3.2.1.108 {ECO:0000269|PubMed:12594539, ECO:0000269|PubMed:16400612, ECO:0000269|PubMed:3929764, ECO:0000269|PubMed:9762914};
DE Includes:
DE RecName: Full=Glycosylceramidase {ECO:0000250|UniProtKB:Q02401};
DE EC=3.2.1.62 {ECO:0000250|UniProtKB:Q02401};
DE AltName: Full=Phlorizin hydrolase {ECO:0000305|PubMed:9762914};
DE Flags: Precursor;
GN Name=LCT {ECO:0000312|HGNC:HGNC:6530};
GN Synonyms=LPH {ECO:0000303|PubMed:9762914};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-362.
RX PubMed=2460343; DOI=10.1002/j.1460-2075.1988.tb03124.x;
RA Mantei N., Villa M., Enzler T., Wacker H., Boll W., James P., Hunziker W.,
RA Semenza G.;
RT "Complete primary structure of human and rabbit lactase-phlorizin
RT hydrolase: implications for biosynthesis, membrane anchoring and evolution
RT of the enzyme.";
RL EMBO J. 7:2705-2713(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-219; VAL-362 AND
RP SER-1639.
RX PubMed=1902057;
RA Boll W., Wagner P., Mantei N.;
RT "Structure of the chromosomal gene and cDNAs coding for lactase-phlorizin
RT hydrolase in humans with adult-type hypolactasia or persistence of
RT lactase.";
RL Am. J. Hum. Genet. 48:889-902(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=3929764; DOI=10.1007/bf00499084;
RA Potter J., Ho M.W., Bolton H., Furth A.J., Swallow D.M., Griffiths B.;
RT "Human lactase and the molecular basis of lactase persistence.";
RL Biochem. Genet. 23:423-439(1985).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, REGION, ACTIVE SITE, AND MUTAGENESIS
RP OF GLU-1273 AND GLU-1749.
RX PubMed=9762914; DOI=10.1016/s0014-5793(98)01076-x;
RA Zecca L., Mesonero J.E., Stutz A., Poiree J.C., Giudicelli J., Cursio R.,
RA Gloor S.M., Semenza G.;
RT "Intestinal lactase-phlorizin hydrolase (LPH): the two catalytic sites; the
RT role of the pancreas in pro-LPH maturation.";
RL FEBS Lett. 435:225-228(1998).
RN [6]
RP SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, GLYCOSYLATION, AND REGION.
RX PubMed=9593732; DOI=10.1074/jbc.273.22.13861;
RA Panzer P., Preuss U., Joberty G., Naim H.Y.;
RT "Protein domains implicated in intracellular transport and sorting of
RT lactase-phlorizin hydrolase.";
RL J. Biol. Chem. 273:13861-13869(1998).
RN [7]
RP INVOLVEMENT IN ADULT-TYPE HYPOLACTASIA.
RX PubMed=11788828; DOI=10.1038/ng826;
RA Enattah N.S., Sahi T., Savilahti E., Terwilliger J.D., Peltonen L.,
RA Jaervelae I.;
RT "Identification of a variant associated with adult-type hypolactasia.";
RL Nat. Genet. 30:233-237(2002).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12594539; DOI=10.1007/s00394-003-0397-3;
RA Nemeth K., Plumb G.W., Berrin J.-G., Juge N., Jacob R., Naim H.Y.,
RA Williamson G., Swallow D.M., Kroon P.A.;
RT "Deglycosylation by small intestinal epithelial cell beta-glucosidases is a
RT critical step in the absorption and metabolism of dietary flavonoid
RT glycosides in humans.";
RL Eur. J. Nutr. 42:29-42(2003).
RN [9]
RP VARIANTS COLACD HIS-268 AND SER-1363, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16400612; DOI=10.1086/500053;
RA Kuokkanen M., Kokkonen J., Enattah N.S., Ylisaukko-Oja T., Komu H.,
RA Varilo T., Peltonen L., Savilahti E., Jaervelae I.;
RT "Mutations in the translated region of the lactase gene (LCT) underlie
RT congenital lactase deficiency.";
RL Am. J. Hum. Genet. 78:339-344(2006).
CC -!- FUNCTION: Broad specificity glycosidase of the intestinal brush border
CC membrane that hydrolyzes lactose, the main sugar in mammalian milk, to
CC produce D-glucose and D-galactose (PubMed:3929764, PubMed:9762914,
CC PubMed:12594539, PubMed:16400612). The mature protein is composed of
CC two domains that catalyze the hydrolysis of beta-glucopyranosides and
CC beta-galactopyranosides, with a preference for hydrophilic aglycones
CC (in lactose and cellobiose) for one domain and hydrophobic aglycones
CC (in phlorizin and glycosylceramides) for the other (PubMed:3929764,
CC PubMed:9762914, PubMed:12594539). {ECO:0000269|PubMed:12594539,
CC ECO:0000269|PubMed:16400612, ECO:0000269|PubMed:3929764,
CC ECO:0000269|PubMed:9762914}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + lactose = beta-D-galactose + D-glucose;
CC Xref=Rhea:RHEA:10076, ChEBI:CHEBI:4167, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17716, ChEBI:CHEBI:27667; EC=3.2.1.108;
CC Evidence={ECO:0000269|PubMed:12594539, ECO:0000269|PubMed:16400612,
CC ECO:0000269|PubMed:3929764, ECO:0000269|PubMed:9762914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10077;
CC Evidence={ECO:0000269|PubMed:16400612};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + phlorizin = beta-D-glucose + phloretin;
CC Xref=Rhea:RHEA:69639, ChEBI:CHEBI:8113, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15903, ChEBI:CHEBI:17276;
CC Evidence={ECO:0000269|PubMed:12594539, ECO:0000269|PubMed:3929764,
CC ECO:0000269|PubMed:9762914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69640;
CC Evidence={ECO:0000305|PubMed:3929764};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-cellobiose + H2O = beta-D-glucose + D-glucose;
CC Xref=Rhea:RHEA:30679, ChEBI:CHEBI:4167, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15903, ChEBI:CHEBI:17057;
CC Evidence={ECO:0000269|PubMed:3929764};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30680;
CC Evidence={ECO:0000305|PubMed:3929764};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + quercetin 4'-O-beta-D-glucoside = beta-D-glucose +
CC quercetin; Xref=Rhea:RHEA:69647, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15903, ChEBI:CHEBI:57694, ChEBI:CHEBI:187902;
CC Evidence={ECO:0000269|PubMed:12594539};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69648;
CC Evidence={ECO:0000305|PubMed:12594539};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + quercetin 3-O-beta-D-glucoside = beta-D-glucose +
CC quercetin; Xref=Rhea:RHEA:69655, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15903, ChEBI:CHEBI:57694, ChEBI:CHEBI:144437;
CC Evidence={ECO:0000269|PubMed:12594539};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69656;
CC Evidence={ECO:0000305|PubMed:12594539};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + kaempferol 3-O-beta-D-glucoside = beta-D-glucose +
CC kaempferol; Xref=Rhea:RHEA:69659, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15903, ChEBI:CHEBI:58573, ChEBI:CHEBI:169942;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69660;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + luteolin 7-O-beta-D-glucoside = beta-D-glucose +
CC luteolin; Xref=Rhea:RHEA:69663, ChEBI:CHEBI:15377, ChEBI:CHEBI:15903,
CC ChEBI:CHEBI:57545, ChEBI:CHEBI:77791;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69664;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + luteolin 4'-O-beta-D-glucoside = beta-D-glucose +
CC luteolin; Xref=Rhea:RHEA:69667, ChEBI:CHEBI:15377, ChEBI:CHEBI:15903,
CC ChEBI:CHEBI:57545, ChEBI:CHEBI:187903;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69668;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S)-naringenin 7-O-beta-D-glucoside + H2O = (2S)-naringenin +
CC beta-D-glucose; Xref=Rhea:RHEA:69671, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15903, ChEBI:CHEBI:17846, ChEBI:CHEBI:28327;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69672;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eriodictyol-7-O-beta-D-glucoside + H2O = (S)-eriodictyol +
CC beta-D-glucose; Xref=Rhea:RHEA:69675, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15903, ChEBI:CHEBI:28412, ChEBI:CHEBI:139458;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69676;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=apigenin 7-O-beta-D-glucoside + H2O = apigenin + beta-D-
CC glucose; Xref=Rhea:RHEA:69679, ChEBI:CHEBI:15377, ChEBI:CHEBI:15903,
CC ChEBI:CHEBI:58470, ChEBI:CHEBI:77722;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69680;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=daidzein 7-O-beta-D-glucoside + H2O = beta-D-glucose +
CC daidzein + H(+); Xref=Rhea:RHEA:69683, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15903, ChEBI:CHEBI:42202,
CC ChEBI:CHEBI:77764; Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69684;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=genistein 7-O-beta-D-glucoside + H2O = beta-D-glucose +
CC genistein; Xref=Rhea:RHEA:69687, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15903, ChEBI:CHEBI:74224, ChEBI:CHEBI:140305;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69688;
CC Evidence={ECO:0000250|UniProtKB:W5PLZ6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycosyl-N-acylsphingosine + H2O = N-acylsphingosine + a
CC sugar.; EC=3.2.1.62; Evidence={ECO:0000250|UniProtKB:Q02401};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-(1<->1')-N-hexadecanoylsphing-4-enine + H2O =
CC beta-D-glucose + N-hexadecanoylsphing-4-enine; Xref=Rhea:RHEA:69699,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15903, ChEBI:CHEBI:72959,
CC ChEBI:CHEBI:84716; Evidence={ECO:0000250|UniProtKB:Q02401};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69700;
CC Evidence={ECO:0000250|UniProtKB:Q02401};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-galactosyl-(1<->1')-N-hexadecanoylsphingosine + H2O =
CC beta-D-galactose + N-hexadecanoylsphing-4-enine;
CC Xref=Rhea:RHEA:69703, ChEBI:CHEBI:15377, ChEBI:CHEBI:27667,
CC ChEBI:CHEBI:72959, ChEBI:CHEBI:83259;
CC Evidence={ECO:0000250|UniProtKB:Q02401};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69704;
CC Evidence={ECO:0000250|UniProtKB:Q02401};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-galactosyl-(1<->1')-N-hexadecanoylsphinganine + H2O =
CC beta-D-galactose + N-hexadecanoylsphinganine; Xref=Rhea:RHEA:69707,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:27667, ChEBI:CHEBI:67042,
CC ChEBI:CHEBI:84783; Evidence={ECO:0000250|UniProtKB:Q02401};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69708;
CC Evidence={ECO:0000250|UniProtKB:Q02401};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-(1<->1')-N-hexadecanoylsphinganine + H2O =
CC beta-D-glucose + N-hexadecanoylsphinganine; Xref=Rhea:RHEA:69711,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15903, ChEBI:CHEBI:67042,
CC ChEBI:CHEBI:84782; Evidence={ECO:0000250|UniProtKB:Q02401};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69712;
CC Evidence={ECO:0000250|UniProtKB:Q02401};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:3929764,
CC ECO:0000269|PubMed:9593732}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:9593732}; Single-pass type I membrane protein
CC {ECO:0000305|PubMed:9593732}. Note=Brush border.
CC {ECO:0000250|UniProtKB:P09849}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in small intestine.
CC {ECO:0000269|PubMed:2460343}.
CC -!- DOMAIN: The glycosyl hydrolase-1 3/region III carries the phlorizin
CC hydrolase/glycosylceramidase activities. {ECO:0000269|PubMed:9762914}.
CC -!- DOMAIN: The glycosyl hydrolase-1 4/region IV carries the lactase
CC activity. {ECO:0000269|PubMed:9762914}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9593732}.
CC -!- DISEASE: Congenital lactase deficiency (COLACD) [MIM:223000]: Autosomal
CC recessive, rare and severe gastrointestinal disorder. It is
CC characterized by watery diarrhea in infants fed with breast milk or
CC other lactose-containing formulas. An almost total lack of LCT activity
CC is found in jejunal biopsy material of patients with congenital lactase
CC deficiency. Opposite to congenital lactase deficiency, also known as
CC lactose intolerance, is the most common enzyme deficiency worldwide. It
CC is caused by developmental down-regulation of lactase activity during
CC childhood or early adulthood. The decline of lactase activity is a
CC normal physiological phenomenon; however, the majority of Northern
CC Europeans have the ability to maintain lactase activity and digest
CC lactose throughout life (lactase persistence). The down-regulation of
CC lactase activity operates at the transcriptional level and it is
CC associated with a noncoding variation in the MCM6 gene, located in the
CC upstream vicinity of LCT. {ECO:0000269|PubMed:16400612}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 1 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Lactase entry;
CC URL="https://en.wikipedia.org/wiki/Lactase";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Darwin's dessert - Issue 111
CC of November 2009;
CC URL="https://web.expasy.org/spotlight/back_issues/111";
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DR EMBL; X07994; CAA30801.1; -; mRNA.
DR EMBL; M61850; AAA59504.1; -; Genomic_DNA.
DR EMBL; M61834; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61835; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61836; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61837; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61838; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61839; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61840; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61841; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61842; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61843; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61844; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61845; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61846; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61847; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61848; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; M61849; AAA59504.1; JOINED; Genomic_DNA.
DR EMBL; AC011893; AAX88924.1; -; Genomic_DNA.
DR CCDS; CCDS2178.1; -.
DR PIR; S01168; S01168.
DR RefSeq; NP_002290.2; NM_002299.3.
DR AlphaFoldDB; P09848; -.
DR SMR; P09848; -.
DR BioGRID; 110130; 4.
DR IntAct; P09848; 1.
DR MINT; P09848; -.
DR STRING; 9606.ENSP00000264162; -.
DR BindingDB; P09848; -.
DR ChEMBL; CHEMBL1075131; -.
DR DrugBank; DB04659; (1S,2S,3R,4S,5S)-2,3,4-TRIHYDROXY-5-(HYDROXYMETHYL)CYCLOHEXYL (1E)-2-PHENYL-N-(SULFOOXY)ETHANIMIDOTHIOATE.
DR DrugBank; DB04282; 2-deoxy-2-fluoro-Alpha-D-glucose.
DR DrugBank; DB08558; 2-HYDROXYMETHYL-6-OCTYLSULFANYL-TETRAHYDRO-PYRAN-3,4,5-TRIOL.
DR DrugBank; DB03389; alpha-D-Xylopyranose.
DR DrugBank; DB02376; D-gluconhydroximo-1,5-lactam.
DR DrugBank; DB04779; ETHYL (1E)-2-PHENYL-N-(SULFOOXY)ETHANIMIDOTHIOATE.
DR DrugBank; DB04564; Gluconolactone.
DR DrugBank; DB02471; Nojirimycine Tetrazole.
DR DrugCentral; P09848; -.
DR CAZy; GH1; Glycoside Hydrolase Family 1.
DR iPTMnet; P09848; -.
DR PhosphoSitePlus; P09848; -.
DR BioMuta; LCT; -.
DR DMDM; 311033425; -.
DR jPOST; P09848; -.
DR MassIVE; P09848; -.
DR MaxQB; P09848; -.
DR PaxDb; P09848; -.
DR PeptideAtlas; P09848; -.
DR PRIDE; P09848; -.
DR ProteomicsDB; 52269; -.
DR Antibodypedia; 2365; 393 antibodies from 16 providers.
DR DNASU; 3938; -.
DR Ensembl; ENST00000264162.7; ENSP00000264162.2; ENSG00000115850.10.
DR GeneID; 3938; -.
DR KEGG; hsa:3938; -.
DR MANE-Select; ENST00000264162.7; ENSP00000264162.2; NM_002299.4; NP_002290.2.
DR UCSC; uc002tuu.2; human.
DR CTD; 3938; -.
DR DisGeNET; 3938; -.
DR GeneCards; LCT; -.
DR HGNC; HGNC:6530; LCT.
DR HPA; ENSG00000115850; Tissue enriched (intestine).
DR MalaCards; LCT; -.
DR MIM; 223000; phenotype.
DR MIM; 603202; gene.
DR neXtProt; NX_P09848; -.
DR OpenTargets; ENSG00000115850; -.
DR Orphanet; 53690; Congenital lactase deficiency.
DR Orphanet; 319681; NON RARE IN EUROPE: Lactase non-persistence in adulthood.
DR PharmGKB; PA30315; -.
DR VEuPathDB; HostDB:ENSG00000115850; -.
DR eggNOG; KOG0626; Eukaryota.
DR GeneTree; ENSGT00940000155324; -.
DR HOGENOM; CLU_001859_5_3_1; -.
DR InParanoid; P09848; -.
DR OMA; RIYYLRT; -.
DR OrthoDB; 408001at2759; -.
DR PhylomeDB; P09848; -.
DR TreeFam; TF314803; -.
DR BioCyc; MetaCyc:HS03945-MON; -.
DR BRENDA; 3.2.1.108; 2681.
DR BRENDA; 3.2.1.62; 2681.
DR BRENDA; 3.7.1.4; 2681.
DR PathwayCommons; P09848; -.
DR Reactome; R-HSA-189085; Digestion of dietary carbohydrate.
DR Reactome; R-HSA-5659898; Intestinal saccharidase deficiencies.
DR SignaLink; P09848; -.
DR SIGNOR; P09848; -.
DR BioGRID-ORCS; 3938; 8 hits in 1070 CRISPR screens.
DR ChiTaRS; LCT; human.
DR GenomeRNAi; 3938; -.
DR Pharos; P09848; Tbio.
DR PRO; PR:P09848; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P09848; protein.
DR Bgee; ENSG00000115850; Expressed in jejunal mucosa and 13 other tissues.
DR ExpressionAtlas; P09848; baseline and differential.
DR Genevisible; P09848; HS.
DR GO; GO:0098591; C:external side of apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008422; F:beta-glucosidase activity; IDA:UniProtKB.
DR GO; GO:0080079; F:cellobiose glucosidase activity; IEA:RHEA.
DR GO; GO:0004336; F:galactosylceramidase activity; ISS:UniProtKB.
DR GO; GO:0004348; F:glucosylceramidase activity; ISS:UniProtKB.
DR GO; GO:0017042; F:glycosylceramidase activity; IEA:UniProtKB-EC.
DR GO; GO:0000016; F:lactase activity; IDA:UniProtKB.
DR GO; GO:0140749; F:phlorizin hydrolase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:2000892; P:cellobiose catabolic process; IDA:UniProtKB.
DR GO; GO:0046477; P:glycosylceramide catabolic process; ISS:UniProtKB.
DR GO; GO:0005990; P:lactose catabolic process; IDA:UniProtKB.
DR GO; GO:1901733; P:quercetin catabolic process; IDA:UniProtKB.
DR InterPro; IPR001360; Glyco_hydro_1.
DR InterPro; IPR018120; Glyco_hydro_1_AS.
DR InterPro; IPR033132; Glyco_hydro_1_N_CS.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR PANTHER; PTHR10353; PTHR10353; 4.
DR Pfam; PF00232; Glyco_hydro_1; 4.
DR PRINTS; PR00131; GLHYDRLASE1.
DR SUPFAM; SSF51445; SSF51445; 4.
DR PROSITE; PS00572; GLYCOSYL_HYDROL_F1_1; 2.
DR PROSITE; PS00653; GLYCOSYL_HYDROL_F1_2; 3.
PE 1: Evidence at protein level;
KW Cell membrane; Disease variant; Glycoprotein; Glycosidase; Hydrolase;
KW Membrane; Multifunctional enzyme; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Zymogen.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..868
FT /note="XBetaGly"
FT /evidence="ECO:0000250|UniProtKB:P09849"
FT /id="PRO_0000011767"
FT CHAIN 869..1927
FT /note="Lactase/phlorizin hydrolase"
FT /evidence="ECO:0000250|UniProtKB:P09849"
FT /id="PRO_0000011768"
FT TOPO_DOM 20..1882
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1883..1901
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1902..1927
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 44..286
FT /note="Glycosyl hydrolase-1 1; Region I"
FT /evidence="ECO:0000255"
FT REGION 362..855
FT /note="Glycosyl hydrolase-1 2; Region II"
FT /evidence="ECO:0000255"
FT REGION 902..1366
FT /note="Glycosyl hydrolase-1 3; Region III. Phlorizin
FT hydrolase/glycosylceramidase activity"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:9762914"
FT REGION 1220..1244
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1373..1846
FT /note="Glycosyl hydrolase-1 4; Region IV. Lactase activity"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:9762914"
FT REGION 1647..1927
FT /note="Required for homodimerization and transport to the
FT plasma membrane"
FT /evidence="ECO:0000269|PubMed:9593732"
FT ACT_SITE 1065
FT /note="Proton donor; for phlorizin
FT hydrolase/Glycosylceramidase activity"
FT /evidence="ECO:0000305|PubMed:9762914"
FT ACT_SITE 1273
FT /note="Nucleophile; for phlorizin
FT hydrolase/Glycosylceramidase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10055,
FT ECO:0000305|PubMed:9762914"
FT ACT_SITE 1538
FT /note="Proton donor; for lactase activity"
FT /evidence="ECO:0000305|PubMed:9762914"
FT ACT_SITE 1749
FT /note="Nucleophile; for lactase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10055,
FT ECO:0000305|PubMed:9762914"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 418
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 512
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 821
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 934
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 946
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 989
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1508
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1656
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1672
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1761
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1814
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 190
FT /note="S -> L (in dbSNP:rs35156533)"
FT /id="VAR_055882"
FT VARIANT 219
FT /note="V -> I (in dbSNP:rs3754689)"
FT /evidence="ECO:0000269|PubMed:1902057"
FT /id="VAR_026705"
FT VARIANT 268
FT /note="Q -> H (in COLACD; dbSNP:rs121908937)"
FT /evidence="ECO:0000269|PubMed:16400612"
FT /id="VAR_026706"
FT VARIANT 362
FT /note="I -> V (in dbSNP:rs4954449)"
FT /evidence="ECO:0000269|PubMed:1902057,
FT ECO:0000269|PubMed:2460343"
FT /id="VAR_026707"
FT VARIANT 1363
FT /note="G -> S (in COLACD; dbSNP:rs386833833)"
FT /evidence="ECO:0000269|PubMed:16400612"
FT /id="VAR_026708"
FT VARIANT 1593
FT /note="V -> M (in dbSNP:rs35891837)"
FT /id="VAR_055883"
FT VARIANT 1639
FT /note="N -> S (in dbSNP:rs2322659)"
FT /evidence="ECO:0000269|PubMed:1902057"
FT /id="VAR_026709"
FT MUTAGEN 1273
FT /note="E->G: No effect on lactase activity. Decreased
FT phlorizin hydrolase activity. No effect on localization to
FT the plasma membrane."
FT /evidence="ECO:0000269|PubMed:9762914"
FT MUTAGEN 1749
FT /note="E->G: Loss of lactase activity. No effect on
FT phlorizin hydrolase activity. No effect on localization to
FT the plasma membrane."
FT /evidence="ECO:0000269|PubMed:9762914"
FT CONFLICT 1096
FT /note="A -> T (in Ref. 1; CAA30801)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1927 AA; 218587 MW; 2FCD55CB47BBA35A CRC64;
MELSWHVVFI ALLSFSCWGS DWESDRNFIS TAGPLTNDLL HNLSGLLGDQ SSNFVAGDKD
MYVCHQPLPT FLPEYFSSLH ASQITHYKVF LSWAQLLPAG STQNPDEKTV QCYRRLLKAL
KTARLQPMVI LHHQTLPAST LRRTEAFADL FADYATFAFH SFGDLVGIWF TFSDLEEVIK
ELPHQESRAS QLQTLSDAHR KAYEIYHESY AFQGGKLSVV LRAEDIPELL LEPPISALAQ
DTVDFLSLDL SYECQNEASL RQKLSKLQTI EPKVKVFIFN LKLPDCPSTM KNPASLLFSL
FEAINKDQVL TIGFDINEFL SCSSSSKKSM SCSLTGSLAL QPDQQQDHET TDSSPASAYQ
RIWEAFANQS RAERDAFLQD TFPEGFLWGA STGAFNVEGG WAEGGRGVSI WDPRRPLNTT
EGQATLEVAS DSYHKVASDV ALLCGLRAQV YKFSISWSRI FPMGHGSSPS LPGVAYYNKL
IDRLQDAGIE PMATLFHWDL PQALQDHGGW QNESVVDAFL DYAAFCFSTF GDRVKLWVTF
HEPWVMSYAG YGTGQHPPGI SDPGVASFKV AHLVLKAHAR TWHHYNSHHR PQQQGHVGIV
LNSDWAEPLS PERPEDLRAS ERFLHFMLGW FAHPVFVDGD YPATLRTQIQ QMNRQCSHPV
AQLPEFTEAE KQLLKGSADF LGLSHYTSRL ISNAPQNTCI PSYDTIGGFS QHVNHVWPQT
SSSWIRVVPW GIRRLLQFVS LEYTRGKVPI YLAGNGMPIG ESENLFDDSL RVDYFNQYIN
EVLKAIKEDS VDVRSYIARS LIDGFEGPSG YSQRFGLHHV NFSDSSKSRT PRKSAYFFTS
IIEKNGFLTK GAKRLLPPNT VNLPSKVRAF TFPSEVPSKA KVVWEKFSSQ PKFERDLFYH
GTFRDDFLWG VSSSAYQIEG AWDADGKGPS IWDNFTHTPG SNVKDNATGD IACDSYHQLD
ADLNMLRALK VKAYRFSISW SRIFPTGRNS SINSHGVDYY NRLINGLVAS NIFPMVTLFH
WDLPQALQDI GGWENPALID LFDSYADFCF QTFGDRVKFW MTFNEPMYLA WLGYGSGEFP
PGVKDPGWAP YRIAHAVIKA HARVYHTYDE KYRQEQKGVI SLSLSTHWAE PKSPGVPRDV
EAADRMLQFS LGWFAHPIFR NGDYPDTMKW KVGNRSELQH LATSRLPSFT EEEKRFIRAT
ADVFCLNTYY SRIVQHKTPR LNPPSYEDDQ EMAEEEDPSW PSTAMNRAAP WGTRRLLNWI
KEEYGDIPIY ITENGVGLTN PNTEDTDRIF YHKTYINEAL KAYRLDGIDL RGYVAWSLMD
NFEWLNGYTV KFGLYHVDFN NTNRPRTARA SARYYTEVIT NNGMPLARED EFLYGRFPEG
FIWSAASAAY QIEGAWRADG KGLSIWDTFS HTPLRVENDA IGDVACDSYH KIAEDLVTLQ
NLGVSHYRFS ISWSRILPDG TTRYINEAGL NYYVRLIDTL LAASIQPQVT IYHWDLPQTL
QDVGGWENET IVQRFKEYAD VLFQRLGDKV KFWITLNEPF VIAYQGYGYG TAAPGVSNRP
GTAPYIVGHN LIKAHAEAWH LYNDVYRASQ GGVISITISS DWAEPRDPSN QEDVEAARRY
VQFMGGWFAH PIFKNGDYNE VMKTRIRDRS LAAGLNKSRL PEFTESEKRR INGTYDFFGF
NHYTTVLAYN LNYATAISSF DADRGVASIA DRSWPDSGSF WLKMTPFGFR RILNWLKEEY
NDPPIYVTEN GVSQREETDL NDTARIYYLR TYINEALKAV QDKVDLRGYT VWSAMDNFEW
ATGFSERFGL HFVNYSDPSL PRIPKASAKF YASVVRCNGF PDPATGPHAC LHQPDAGPTI
SPVRQEEVQF LGLMLGTTEA QTALYVLFSL VLLGVCGLAF LSYKYCKRSK QGKTQRSQQE
LSPVSSF
