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P09848

- LPH_HUMAN

UniProt

P09848 - LPH_HUMAN

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Protein

Lactase-phlorizin hydrolase

Gene

LCT

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

LPH splits lactose in the small intestine.

Catalytic activityi

Lactose + H2O = D-galactose + D-glucose.
Glycosyl-N-acylsphingosine + H2O = N-acylsphingosine + a sugar.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei1065 – 10651Proton donorSequence Analysis
Active sitei1273 – 12731NucleophilePROSITE-ProRule annotation
Active sitei1538 – 15381Proton donorSequence Analysis
Active sitei1749 – 17491NucleophilePROSITE-ProRule annotation

GO - Molecular functioni

  1. glycosylceramidase activity Source: UniProtKB-EC
  2. lactase activity Source: Reactome

GO - Biological processi

  1. carbohydrate metabolic process Source: Reactome
  2. polysaccharide digestion Source: Reactome
  3. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Enzyme and pathway databases

BioCyciMetaCyc:HS03945-MONOMER.
ReactomeiREACT_9472. Digestion of dietary carbohydrate.

Protein family/group databases

CAZyiGH1. Glycoside Hydrolase Family 1.

Names & Taxonomyi

Protein namesi
Recommended name:
Lactase-phlorizin hydrolase
Alternative name(s):
Lactase-glycosylceramidase
Including the following 2 domains:
Phlorizin hydrolase (EC:3.2.1.62)
Gene namesi
Name:LCT
Synonyms:LPH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:6530. LCT.

Subcellular locationi

GO - Cellular componenti

  1. integral component of plasma membrane Source: ProtInc
  2. membrane Source: ProtInc
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti268 – 2681Q → H in COLACD. 1 Publication
VAR_026706
Natural varianti1363 – 13631G → S in COLACD. 1 Publication
VAR_026708

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi223000. phenotype.
Orphaneti53690. Congenital lactase deficiency.
319681. Lactase non-persistence in adulthood.
PharmGKBiPA30315.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Add
BLAST
Propeptidei20 – 866847Beta-glucosidasePRO_0000011767Add
BLAST
Chaini867 – 19271061Lactase-phlorizin hydrolasePRO_0000011768Add
BLAST

Keywords - PTMi

Zymogen

Proteomic databases

MaxQBiP09848.
PaxDbiP09848.
PRIDEiP09848.

PTM databases

PhosphoSiteiP09848.

Expressioni

Tissue specificityi

Intestine.

Gene expression databases

BgeeiP09848.
CleanExiHS_LCT.
ExpressionAtlasiP09848. baseline and differential.
GenevestigatoriP09848.

Organism-specific databases

HPAiHPA007408.

Interactioni

Protein-protein interaction databases

BioGridi110130. 2 interactions.
IntActiP09848. 1 interaction.
MINTiMINT-3380713.
STRINGi9606.ENSP00000264162.

Structurei

3D structure databases

ProteinModelPortaliP09848.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 18821863ExtracellularSequence AnalysisAdd
BLAST
Topological domaini1902 – 192726CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei1883 – 190119HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati87 – 172861Add
BLAST
Repeati363 – 8484862Add
BLAST
Repeati884 – 13654823Add
BLAST
Repeati1370 – 18414724Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni87 – 184117554 X approximate repeatsAdd
BLAST

Domaini

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

Sequence similaritiesi

Belongs to the glycosyl hydrolase 1 family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG2723.
GeneTreeiENSGT00550000074452.
HOGENOMiHOG000024957.
HOVERGENiHBG006290.
InParanoidiP09848.
KOiK01229.
OMAiFADYATF.
PhylomeDBiP09848.
TreeFamiTF314803.

Family and domain databases

Gene3Di3.20.20.80. 4 hits.
InterProiIPR001360. Glyco_hydro_1.
IPR018120. Glyco_hydro_1_AS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PANTHERiPTHR10353. PTHR10353. 1 hit.
PfamiPF00232. Glyco_hydro_1. 4 hits.
[Graphical view]
PRINTSiPR00131. GLHYDRLASE1.
SUPFAMiSSF51445. SSF51445. 4 hits.
PROSITEiPS00572. GLYCOSYL_HYDROL_F1_1. 2 hits.
PS00653. GLYCOSYL_HYDROL_F1_2. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P09848-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MELSWHVVFI ALLSFSCWGS DWESDRNFIS TAGPLTNDLL HNLSGLLGDQ
60 70 80 90 100
SSNFVAGDKD MYVCHQPLPT FLPEYFSSLH ASQITHYKVF LSWAQLLPAG
110 120 130 140 150
STQNPDEKTV QCYRRLLKAL KTARLQPMVI LHHQTLPAST LRRTEAFADL
160 170 180 190 200
FADYATFAFH SFGDLVGIWF TFSDLEEVIK ELPHQESRAS QLQTLSDAHR
210 220 230 240 250
KAYEIYHESY AFQGGKLSVV LRAEDIPELL LEPPISALAQ DTVDFLSLDL
260 270 280 290 300
SYECQNEASL RQKLSKLQTI EPKVKVFIFN LKLPDCPSTM KNPASLLFSL
310 320 330 340 350
FEAINKDQVL TIGFDINEFL SCSSSSKKSM SCSLTGSLAL QPDQQQDHET
360 370 380 390 400
TDSSPASAYQ RIWEAFANQS RAERDAFLQD TFPEGFLWGA STGAFNVEGG
410 420 430 440 450
WAEGGRGVSI WDPRRPLNTT EGQATLEVAS DSYHKVASDV ALLCGLRAQV
460 470 480 490 500
YKFSISWSRI FPMGHGSSPS LPGVAYYNKL IDRLQDAGIE PMATLFHWDL
510 520 530 540 550
PQALQDHGGW QNESVVDAFL DYAAFCFSTF GDRVKLWVTF HEPWVMSYAG
560 570 580 590 600
YGTGQHPPGI SDPGVASFKV AHLVLKAHAR TWHHYNSHHR PQQQGHVGIV
610 620 630 640 650
LNSDWAEPLS PERPEDLRAS ERFLHFMLGW FAHPVFVDGD YPATLRTQIQ
660 670 680 690 700
QMNRQCSHPV AQLPEFTEAE KQLLKGSADF LGLSHYTSRL ISNAPQNTCI
710 720 730 740 750
PSYDTIGGFS QHVNHVWPQT SSSWIRVVPW GIRRLLQFVS LEYTRGKVPI
760 770 780 790 800
YLAGNGMPIG ESENLFDDSL RVDYFNQYIN EVLKAIKEDS VDVRSYIARS
810 820 830 840 850
LIDGFEGPSG YSQRFGLHHV NFSDSSKSRT PRKSAYFFTS IIEKNGFLTK
860 870 880 890 900
GAKRLLPPNT VNLPSKVRAF TFPSEVPSKA KVVWEKFSSQ PKFERDLFYH
910 920 930 940 950
GTFRDDFLWG VSSSAYQIEG AWDADGKGPS IWDNFTHTPG SNVKDNATGD
960 970 980 990 1000
IACDSYHQLD ADLNMLRALK VKAYRFSISW SRIFPTGRNS SINSHGVDYY
1010 1020 1030 1040 1050
NRLINGLVAS NIFPMVTLFH WDLPQALQDI GGWENPALID LFDSYADFCF
1060 1070 1080 1090 1100
QTFGDRVKFW MTFNEPMYLA WLGYGSGEFP PGVKDPGWAP YRIAHAVIKA
1110 1120 1130 1140 1150
HARVYHTYDE KYRQEQKGVI SLSLSTHWAE PKSPGVPRDV EAADRMLQFS
1160 1170 1180 1190 1200
LGWFAHPIFR NGDYPDTMKW KVGNRSELQH LATSRLPSFT EEEKRFIRAT
1210 1220 1230 1240 1250
ADVFCLNTYY SRIVQHKTPR LNPPSYEDDQ EMAEEEDPSW PSTAMNRAAP
1260 1270 1280 1290 1300
WGTRRLLNWI KEEYGDIPIY ITENGVGLTN PNTEDTDRIF YHKTYINEAL
1310 1320 1330 1340 1350
KAYRLDGIDL RGYVAWSLMD NFEWLNGYTV KFGLYHVDFN NTNRPRTARA
1360 1370 1380 1390 1400
SARYYTEVIT NNGMPLARED EFLYGRFPEG FIWSAASAAY QIEGAWRADG
1410 1420 1430 1440 1450
KGLSIWDTFS HTPLRVENDA IGDVACDSYH KIAEDLVTLQ NLGVSHYRFS
1460 1470 1480 1490 1500
ISWSRILPDG TTRYINEAGL NYYVRLIDTL LAASIQPQVT IYHWDLPQTL
1510 1520 1530 1540 1550
QDVGGWENET IVQRFKEYAD VLFQRLGDKV KFWITLNEPF VIAYQGYGYG
1560 1570 1580 1590 1600
TAAPGVSNRP GTAPYIVGHN LIKAHAEAWH LYNDVYRASQ GGVISITISS
1610 1620 1630 1640 1650
DWAEPRDPSN QEDVEAARRY VQFMGGWFAH PIFKNGDYNE VMKTRIRDRS
1660 1670 1680 1690 1700
LAAGLNKSRL PEFTESEKRR INGTYDFFGF NHYTTVLAYN LNYATAISSF
1710 1720 1730 1740 1750
DADRGVASIA DRSWPDSGSF WLKMTPFGFR RILNWLKEEY NDPPIYVTEN
1760 1770 1780 1790 1800
GVSQREETDL NDTARIYYLR TYINEALKAV QDKVDLRGYT VWSAMDNFEW
1810 1820 1830 1840 1850
ATGFSERFGL HFVNYSDPSL PRIPKASAKF YASVVRCNGF PDPATGPHAC
1860 1870 1880 1890 1900
LHQPDAGPTI SPVRQEEVQF LGLMLGTTEA QTALYVLFSL VLLGVCGLAF
1910 1920
LSYKYCKRSK QGKTQRSQQE LSPVSSF
Length:1,927
Mass (Da):218,587
Last modified:November 2, 2010 - v3
Checksum:i2FCD55CB47BBA35A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1096 – 10961A → T in CAA30801. (PubMed:2460343)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti190 – 1901S → L.
Corresponds to variant rs35156533 [ dbSNP | Ensembl ].
VAR_055882
Natural varianti219 – 2191V → I.1 Publication
Corresponds to variant rs3754689 [ dbSNP | Ensembl ].
VAR_026705
Natural varianti268 – 2681Q → H in COLACD. 1 Publication
VAR_026706
Natural varianti362 – 3621I → V.2 Publications
Corresponds to variant rs4954449 [ dbSNP | Ensembl ].
VAR_026707
Natural varianti1363 – 13631G → S in COLACD. 1 Publication
VAR_026708
Natural varianti1593 – 15931V → M.
Corresponds to variant rs35891837 [ dbSNP | Ensembl ].
VAR_055883
Natural varianti1639 – 16391N → S.1 Publication
Corresponds to variant rs2322659 [ dbSNP | Ensembl ].
VAR_026709

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X07994 mRNA. Translation: CAA30801.1.
M61850
, 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.
CCDSiCCDS2178.1.
PIRiS01168.
RefSeqiNP_002290.2. NM_002299.2.
UniGeneiHs.551506.

Genome annotation databases

EnsembliENST00000264162; ENSP00000264162; ENSG00000115850.
GeneIDi3938.
KEGGihsa:3938.
UCSCiuc002tuu.1. human.

Polymorphism databases

DMDMi311033425.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Lactase entry

Protein Spotlight

Darwin's dessert - Issue 111 of November 2009

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X07994 mRNA. Translation: CAA30801.1 .
M61850
, 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 .
CCDSi CCDS2178.1.
PIRi S01168.
RefSeqi NP_002290.2. NM_002299.2.
UniGenei Hs.551506.

3D structure databases

ProteinModelPortali P09848.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110130. 2 interactions.
IntActi P09848. 1 interaction.
MINTi MINT-3380713.
STRINGi 9606.ENSP00000264162.

Chemistry

ChEMBLi CHEMBL1075131.
DrugBanki DB00126. Vitamin C.

Protein family/group databases

CAZyi GH1. Glycoside Hydrolase Family 1.

PTM databases

PhosphoSitei P09848.

Polymorphism databases

DMDMi 311033425.

Proteomic databases

MaxQBi P09848.
PaxDbi P09848.
PRIDEi P09848.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000264162 ; ENSP00000264162 ; ENSG00000115850 .
GeneIDi 3938.
KEGGi hsa:3938.
UCSCi uc002tuu.1. human.

Organism-specific databases

CTDi 3938.
GeneCardsi GC02M136567.
H-InvDB HIX0030024.
HIX0117702.
HGNCi HGNC:6530. LCT.
HPAi HPA007408.
MIMi 223000. phenotype.
603202. gene.
neXtProti NX_P09848.
Orphaneti 53690. Congenital lactase deficiency.
319681. Lactase non-persistence in adulthood.
PharmGKBi PA30315.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2723.
GeneTreei ENSGT00550000074452.
HOGENOMi HOG000024957.
HOVERGENi HBG006290.
InParanoidi P09848.
KOi K01229.
OMAi FADYATF.
PhylomeDBi P09848.
TreeFami TF314803.

Enzyme and pathway databases

BioCyci MetaCyc:HS03945-MONOMER.
Reactomei REACT_9472. Digestion of dietary carbohydrate.

Miscellaneous databases

ChiTaRSi LCT. human.
GenomeRNAii 3938.
NextBioi 15465.
PROi P09848.
SOURCEi Search...

Gene expression databases

Bgeei P09848.
CleanExi HS_LCT.
ExpressionAtlasi P09848. baseline and differential.
Genevestigatori P09848.

Family and domain databases

Gene3Di 3.20.20.80. 4 hits.
InterProi IPR001360. Glyco_hydro_1.
IPR018120. Glyco_hydro_1_AS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view ]
PANTHERi PTHR10353. PTHR10353. 1 hit.
Pfami PF00232. Glyco_hydro_1. 4 hits.
[Graphical view ]
PRINTSi PR00131. GLHYDRLASE1.
SUPFAMi SSF51445. SSF51445. 4 hits.
PROSITEi PS00572. GLYCOSYL_HYDROL_F1_1. 2 hits.
PS00653. GLYCOSYL_HYDROL_F1_2. 3 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiLPH_HUMAN
AccessioniPrimary (citable) accession number: P09848
Secondary accession number(s): Q4ZG58
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: November 2, 2010
Last modified: October 29, 2014
This is version 152 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3