Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P09848 (LPH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lactase-phlorizin hydrolase
Alternative name(s):
Lactase-glycosylceramidase

Including the following 2 domains:

  1. Lactase
    EC=3.2.1.108
  2. Phlorizin hydrolase
    EC=3.2.1.62
Gene names
Name:LCT
Synonyms:LPH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1927 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

LPH splits lactose in the small intestine.

Catalytic activity

Lactose + H2O = D-galactose + D-glucose.

Glycosyl-N-acylsphingosine + H2O = N-acylsphingosine + a sugar.

Subcellular location

Apical cell membrane; Single-pass type I membrane protein. Note: Brush border.

Tissue specificity

Intestine.

Domain

The sequence exhibits 4 regions (I-IV) of internal homology; therefore LPH might have evolved by two cycles of partial gene duplication.

Involvement in disease

Congenital lactase deficiency (COLACD) [MIM:223000]: Autosomal recessive, rare and severe gastrointestinal disorder. It is characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. An almost total lack of LCT activity is found in jejunal biopsy material of patients with congenital lactase deficiency. Opposite to congenital lactase deficiency, also known as lactose intolerance, is the most common enzyme deficiency worldwide. It is caused by developmental down-regulation of lactase activity during childhood or early adulthood. The decline of lactase activity is a normal physiological phenomenon; however, the majority of Northern Europeans have the ability to maintain lactase activity and digest lactose throughout life (lactase persistence). The down-regulation of lactase activity operates at the transcriptional level and it is associated with a noncoding variation in the MCM6 gene, located in the upstream vicinity of LCT.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Sequence similarities

Belongs to the glycosyl hydrolase 1 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919
Propeptide20 – 866847Beta-glucosidase
PRO_0000011767
Chain867 – 19271061Lactase-phlorizin hydrolase
PRO_0000011768

Regions

Topological domain20 – 18821863Extracellular Potential
Transmembrane1883 – 190119Helical; Potential
Topological domain1902 – 192726Cytoplasmic Potential
Repeat87 – 172861
Repeat363 – 8484862
Repeat884 – 13654823
Repeat1370 – 18414724
Region87 – 184117554 X approximate repeats

Sites

Active site10651Proton donor Potential
Active site12731Nucleophile By similarity
Active site15381Proton donor Potential
Active site17491Nucleophile By similarity

Natural variations

Natural variant1901S → L.
Corresponds to variant rs35156533 [ dbSNP | Ensembl ].
VAR_055882
Natural variant2191V → I. Ref.2
Corresponds to variant rs3754689 [ dbSNP | Ensembl ].
VAR_026705
Natural variant2681Q → H in COLACD. Ref.5
VAR_026706
Natural variant3621I → V. Ref.1 Ref.2
Corresponds to variant rs4954449 [ dbSNP | Ensembl ].
VAR_026707
Natural variant13631G → S in COLACD. Ref.5
VAR_026708
Natural variant15931V → M.
Corresponds to variant rs35891837 [ dbSNP | Ensembl ].
VAR_055883
Natural variant16391N → S. Ref.2
Corresponds to variant rs2322659 [ dbSNP | Ensembl ].
VAR_026709

Experimental info

Sequence conflict10961A → T in CAA30801. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P09848 [UniParc].

Last modified November 2, 2010. Version 3.
Checksum: 2FCD55CB47BBA35A

FASTA1,927218,587
        10         20         30         40         50         60 
MELSWHVVFI ALLSFSCWGS DWESDRNFIS TAGPLTNDLL HNLSGLLGDQ SSNFVAGDKD 

        70         80         90        100        110        120 
MYVCHQPLPT FLPEYFSSLH ASQITHYKVF LSWAQLLPAG STQNPDEKTV QCYRRLLKAL 

       130        140        150        160        170        180 
KTARLQPMVI LHHQTLPAST LRRTEAFADL FADYATFAFH SFGDLVGIWF TFSDLEEVIK 

       190        200        210        220        230        240 
ELPHQESRAS QLQTLSDAHR KAYEIYHESY AFQGGKLSVV LRAEDIPELL LEPPISALAQ 

       250        260        270        280        290        300 
DTVDFLSLDL SYECQNEASL RQKLSKLQTI EPKVKVFIFN LKLPDCPSTM KNPASLLFSL 

       310        320        330        340        350        360 
FEAINKDQVL TIGFDINEFL SCSSSSKKSM SCSLTGSLAL QPDQQQDHET TDSSPASAYQ 

       370        380        390        400        410        420 
RIWEAFANQS RAERDAFLQD TFPEGFLWGA STGAFNVEGG WAEGGRGVSI WDPRRPLNTT 

       430        440        450        460        470        480 
EGQATLEVAS DSYHKVASDV ALLCGLRAQV YKFSISWSRI FPMGHGSSPS LPGVAYYNKL 

       490        500        510        520        530        540 
IDRLQDAGIE PMATLFHWDL PQALQDHGGW QNESVVDAFL DYAAFCFSTF GDRVKLWVTF 

       550        560        570        580        590        600 
HEPWVMSYAG YGTGQHPPGI SDPGVASFKV AHLVLKAHAR TWHHYNSHHR PQQQGHVGIV 

       610        620        630        640        650        660 
LNSDWAEPLS PERPEDLRAS ERFLHFMLGW FAHPVFVDGD YPATLRTQIQ QMNRQCSHPV 

       670        680        690        700        710        720 
AQLPEFTEAE KQLLKGSADF LGLSHYTSRL ISNAPQNTCI PSYDTIGGFS QHVNHVWPQT 

       730        740        750        760        770        780 
SSSWIRVVPW GIRRLLQFVS LEYTRGKVPI YLAGNGMPIG ESENLFDDSL RVDYFNQYIN 

       790        800        810        820        830        840 
EVLKAIKEDS VDVRSYIARS LIDGFEGPSG YSQRFGLHHV NFSDSSKSRT PRKSAYFFTS 

       850        860        870        880        890        900 
IIEKNGFLTK GAKRLLPPNT VNLPSKVRAF TFPSEVPSKA KVVWEKFSSQ PKFERDLFYH 

       910        920        930        940        950        960 
GTFRDDFLWG VSSSAYQIEG AWDADGKGPS IWDNFTHTPG SNVKDNATGD IACDSYHQLD 

       970        980        990       1000       1010       1020 
ADLNMLRALK VKAYRFSISW SRIFPTGRNS SINSHGVDYY NRLINGLVAS NIFPMVTLFH 

      1030       1040       1050       1060       1070       1080 
WDLPQALQDI GGWENPALID LFDSYADFCF QTFGDRVKFW MTFNEPMYLA WLGYGSGEFP 

      1090       1100       1110       1120       1130       1140 
PGVKDPGWAP YRIAHAVIKA HARVYHTYDE KYRQEQKGVI SLSLSTHWAE PKSPGVPRDV 

      1150       1160       1170       1180       1190       1200 
EAADRMLQFS LGWFAHPIFR NGDYPDTMKW KVGNRSELQH LATSRLPSFT EEEKRFIRAT 

      1210       1220       1230       1240       1250       1260 
ADVFCLNTYY SRIVQHKTPR LNPPSYEDDQ EMAEEEDPSW PSTAMNRAAP WGTRRLLNWI 

      1270       1280       1290       1300       1310       1320 
KEEYGDIPIY ITENGVGLTN PNTEDTDRIF YHKTYINEAL KAYRLDGIDL RGYVAWSLMD 

      1330       1340       1350       1360       1370       1380 
NFEWLNGYTV KFGLYHVDFN NTNRPRTARA SARYYTEVIT NNGMPLARED EFLYGRFPEG 

      1390       1400       1410       1420       1430       1440 
FIWSAASAAY QIEGAWRADG KGLSIWDTFS HTPLRVENDA IGDVACDSYH KIAEDLVTLQ 

      1450       1460       1470       1480       1490       1500 
NLGVSHYRFS ISWSRILPDG TTRYINEAGL NYYVRLIDTL LAASIQPQVT IYHWDLPQTL 

      1510       1520       1530       1540       1550       1560 
QDVGGWENET IVQRFKEYAD VLFQRLGDKV KFWITLNEPF VIAYQGYGYG TAAPGVSNRP 

      1570       1580       1590       1600       1610       1620 
GTAPYIVGHN LIKAHAEAWH LYNDVYRASQ GGVISITISS DWAEPRDPSN QEDVEAARRY 

      1630       1640       1650       1660       1670       1680 
VQFMGGWFAH PIFKNGDYNE VMKTRIRDRS LAAGLNKSRL PEFTESEKRR INGTYDFFGF 

      1690       1700       1710       1720       1730       1740 
NHYTTVLAYN LNYATAISSF DADRGVASIA DRSWPDSGSF WLKMTPFGFR RILNWLKEEY 

      1750       1760       1770       1780       1790       1800 
NDPPIYVTEN GVSQREETDL NDTARIYYLR TYINEALKAV QDKVDLRGYT VWSAMDNFEW 

      1810       1820       1830       1840       1850       1860 
ATGFSERFGL HFVNYSDPSL PRIPKASAKF YASVVRCNGF PDPATGPHAC LHQPDAGPTI 

      1870       1880       1890       1900       1910       1920 
SPVRQEEVQF LGLMLGTTEA QTALYVLFSL VLLGVCGLAF LSYKYCKRSK QGKTQRSQQE 


LSPVSSF 

« Hide

References

« Hide 'large scale' references
[1]"Complete primary structure of human and rabbit lactase-phlorizin hydrolase: implications for biosynthesis, membrane anchoring and evolution of the enzyme."
Mantei N., Villa M., Enzler T., Wacker H., Boll W., James P., Hunziker W., Semenza G.
EMBO J. 7:2705-2713(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-362.
[2]"Structure of the chromosomal gene and cDNAs coding for lactase-phlorizin hydrolase in humans with adult-type hypolactasia or persistence of lactase."
Boll W., Wagner P., Mantei N.
Am. J. Hum. Genet. 48:889-902(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-219; VAL-362 AND SER-1639.
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Identification of a variant associated with adult-type hypolactasia."
Enattah N.S., Sahi T., Savilahti E., Terwilliger J.D., Peltonen L., Jaervelae I.
Nat. Genet. 30:233-237(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN ADULT-TYPE HYPOLACTASIA.
[5]"Mutations in the translated region of the lactase gene (LCT) underlie congenital lactase deficiency."
Kuokkanen M., Kokkonen J., Enattah N.S., Ylisaukko-Oja T., Komu H., Varilo T., Peltonen L., Savilahti E., Jaervelae I.
Am. J. Hum. Genet. 78:339-344(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS COLACD HIS-268 AND SER-1363.
+Additional computationally mapped references.

Web resources

GeneReviews
Wikipedia

Lactase entry

Protein Spotlight

Darwin's dessert - Issue 111 of November 2009

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X07994 mRNA. Translation: CAA30801.1.
M61850 expand/collapse EMBL AC list , M61834, M61835, M61836, M61837, M61838, M61839, M61840, M61841, M61842, M61843, M61844, M61845, M61846, M61847, M61848, M61849 Genomic DNA. Translation: AAA59504.1.
AC011893 Genomic DNA. Translation: AAX88924.1.
PIRS01168.
RefSeqNP_002290.2. NM_002299.2.
UniGeneHs.551506.

3D structure databases

ProteinModelPortalP09848.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110130. 2 interactions.
IntActP09848. 1 interaction.
MINTMINT-3380713.
STRING9606.ENSP00000264162.

Chemistry

ChEMBLCHEMBL1075131.

Protein family/group databases

CAZyGH1. Glycoside Hydrolase Family 1.

PTM databases

PhosphoSiteP09848.

Polymorphism databases

DMDM311033425.

Proteomic databases

PaxDbP09848.
PRIDEP09848.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264162; ENSP00000264162; ENSG00000115850.
GeneID3938.
KEGGhsa:3938.
UCSCuc002tuu.1. human.

Organism-specific databases

CTD3938.
GeneCardsGC02M136567.
H-InvDBHIX0030024.
HIX0117702.
HGNCHGNC:6530. LCT.
HPAHPA007408.
MIM223000. phenotype.
603202. gene.
neXtProtNX_P09848.
Orphanet53690. Congenital lactase deficiency.
319681. Lactase non-persistence in adulthood.
PharmGKBPA30315.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2723.
HOGENOMHOG000024957.
HOVERGENHBG006290.
InParanoidP09848.
KOK01229.
OMAFADYATF.
PhylomeDBP09848.
TreeFamTF314803.

Enzyme and pathway databases

BioCycMetaCyc:HS03945-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP09848.
BgeeP09848.
CleanExHS_LCT.
GenevestigatorP09848.

Family and domain databases

Gene3D3.20.20.80. 4 hits.
InterProIPR001360. Glyco_hydro_1.
IPR018120. Glyco_hydro_1_AS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PANTHERPTHR10353. PTHR10353. 1 hit.
PfamPF00232. Glyco_hydro_1. 4 hits.
[Graphical view]
PRINTSPR00131. GLHYDRLASE1.
SUPFAMSSF51445. SSF51445. 4 hits.
PROSITEPS00572. GLYCOSYL_HYDROL_F1_1. 2 hits.
PS00653. GLYCOSYL_HYDROL_F1_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLCT. human.
GenomeRNAi3938.
NextBio15465.
PROP09848.
SOURCESearch...

Entry information

Entry nameLPH_HUMAN
AccessionPrimary (citable) accession number: P09848
Secondary accession number(s): Q4ZG58
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: November 2, 2010
Last modified: April 16, 2014
This is version 147 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries