P09848 (LPH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1927 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Signal Transmembrane Transmembrane helix
Molecular function	Glycosidase Hydrolase
PTM	Zymogen
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Traceable author statement. Source: Reactome polysaccharide digestion Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	glycosylceramidase activity Inferred from electronic annotation. Source: EC lactase activity Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19
	Propeptide	20 – 866	847	Beta-glucosidase		PRO_0000011767
	Chain	867 – 1927	1061	Lactase-phlorizin hydrolase		PRO_0000011768
Regions
	Topological domain	20 – 1882	1863	Extracellular Potential
	Transmembrane	1883 – 1901	19	Helical; Potential
	Topological domain	1902 – 1927	26	Cytoplasmic Potential
	Repeat	87 – 172	86	1
	Repeat	363 – 848	486	2
	Repeat	884 – 1365	482	3
	Repeat	1370 – 1841	472	4
	Region	87 – 1841	1755	4 X approximate repeats
Sites
	Active site	1065	1	Proton donor Potential
	Active site	1273	1	Nucleophile By similarity
	Active site	1538	1	Proton donor Potential
	Active site	1749	1	Nucleophile By similarity
Natural variations
	Natural variant	190	1	S → L. Corresponds to variant rs35156533 [ dbSNP | Ensembl ].		VAR_055882
	Natural variant	219	1	V → I. Ref.2 Corresponds to variant rs3754689 [ dbSNP | Ensembl ].		VAR_026705
	Natural variant	268	1	Q → H in COLACD. Ref.5		VAR_026706
	Natural variant	362	1	I → V. Ref.1 Ref.2 Corresponds to variant rs4954449 [ dbSNP | Ensembl ].		VAR_026707
	Natural variant	1363	1	G → S in COLACD. Ref.5		VAR_026708
	Natural variant	1593	1	V → M. Corresponds to variant rs35891837 [ dbSNP | Ensembl ].		VAR_055883
	Natural variant	1639	1	N → S. Ref.2 Corresponds to variant rs2322659 [ dbSNP | Ensembl ].		VAR_026709
Experimental info
	Sequence conflict	1096	1	A → T in CAA30801. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P09848 [UniParc]. Last modified November 2, 2010. Version 3. Checksum: 2FCD55CB47BBA35A	FASTA	1,927	218,587
	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

References

	« Hide 'large scale' referencesShow '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. , 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 , 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.
IPI	IPI00017648.
PIR	S01168.
RefSeq	NP_002290.2. NM_002299.2.
UniGene	Hs.551506.
3D structure databases
ProteinModelPortal	P09848.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-3380713.
STRING	9606.ENSP00000264162.
Protein family/group databases
CAZy	GH1. Glycoside Hydrolase Family 1.
PTM databases
PhosphoSite	P09848.
Polymorphism databases
DMDM	311033425.
Proteomic databases
PaxDb	P09848.
PRIDE	P09848.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264162; ENSP00000264162; ENSG00000115850.
GeneID	3938.
KEGG	hsa:3938.
UCSC	uc002tuu.1. human.
Organism-specific databases
CTD	3938.
GeneCards	GC02M136567.
H-InvDB	HIX0030024. HIX0117702.
HGNC	HGNC:6530. LCT.
HPA	HPA007408.
MIM	223000. phenotype. 603202. gene.
neXtProt	NX_P09848.
Orphanet	53690. Congenital lactase deficiency.
PharmGKB	PA30315.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2723.
HOGENOM	HOG000024957.
HOVERGEN	HBG006290.
InParanoid	P09848.
KO	K01229.
OMA	HWAEPKS.
OrthoDB	EOG4548XP.
PhylomeDB	P09848.
Enzyme and pathway databases
BioCyc	MetaCyc:HS03945-MONOMER.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P09848.
Bgee	P09848.
CleanEx	HS_LCT.
Genevestigator	P09848.
GermOnline	ENSG00000115850. Homo sapiens.
Family and domain databases
Gene3D	3.20.20.80. 4 hits.
InterPro	IPR001360. Glyco_hydro_1. IPR018120. Glyco_hydro_1_AS. IPR013781. Glyco_hydro_catalytic_dom. IPR017853. Glycoside_hydrolase_SF. [Graphical view]
PANTHER	PTHR10353. PTHR10353. 1 hit.
Pfam	PF00232. Glyco_hydro_1. 4 hits. [Graphical view]
PRINTS	PR00131. GLHYDRLASE1.
SUPFAM	SSF51445. Glyco_hydro_cat. 4 hits.
PROSITE	PS00572. GLYCOSYL_HYDROL_F1_1. 2 hits. PS00653. GLYCOSYL_HYDROL_F1_2. 3 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1075131.
ChiTaRS	LCT. human.
GenomeRNAi	3938.
NextBio	15465.
SOURCE	Search...

Entry information

Entry name

LPH_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 138 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.