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   27-MAR-2024, entry version 210.
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=a beta-D-galactosyl-N-acylsphingosine + H2O = a ceramide +
CC         beta-D-galactose.; EC=3.2.1.62;
CC         Evidence={ECO:0000250|UniProtKB:Q02401};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a flavonoid-O-beta-D-glucoside + H2O = a flavonoid + beta-D-
CC         glucose.; 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   GlyCosmos; P09848; 15 sites, No reported glycans.
DR   GlyGen; P09848; 15 sites.
DR   iPTMnet; P09848; -.
DR   PhosphoSitePlus; P09848; -.
DR   BioMuta; LCT; -.
DR   DMDM; 311033425; -.
DR   jPOST; P09848; -.
DR   MassIVE; P09848; -.
DR   MaxQB; P09848; -.
DR   PaxDb; 9606-ENSP00000264162; -.
DR   PeptideAtlas; P09848; -.
DR   ProteomicsDB; 52269; -.
DR   Antibodypedia; 2365; 405 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   AGR; HGNC:6530; -.
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; QITHYKV; -.
DR   OrthoDB; 3373839at2759; -.
DR   PhylomeDB; P09848; -.
DR   TreeFam; TF314803; -.
DR   BioCyc; MetaCyc:HS03945-MONOMER; -.
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; 11 hits in 1153 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 14 other cell types or tissues.
DR   ExpressionAtlas; P09848; baseline and differential.
DR   GO; GO:0098591; C:external side of apical plasma membrane; IDA:UniProtKB.
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   Gene3D; 3.20.20.80; Glycosidases; 4.
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; GLYCOSYL HYDROLASE; 1.
DR   PANTHER; PTHR10353:SF36; KLOTHO (MAMMALIAN AGING-ASSOCIATED PROTEIN) HOMOLOG; 1.
DR   Pfam; PF00232; Glyco_hydro_1; 4.
DR   PRINTS; PR00131; GLHYDRLASE1.
DR   SUPFAM; SSF51445; (Trans)glycosidases; 4.
DR   PROSITE; PS00572; GLYCOSYL_HYDROL_F1_1; 2.
DR   PROSITE; PS00653; GLYCOSYL_HYDROL_F1_2; 3.
DR   Genevisible; P09848; HS.
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
//