Reviewed, UniProtKB/Swiss-Prot P09848 (LPH_HUMAN)

Names and origin

Protein names

Recommended name:
    Lactase-phlorizin hydrolase
Alternative name(s):
    Lactase-glycosylceramidase
Including the following 2 domains:
    1- Recommended name:
            Lactase
              EC=3.2.1.108
    2- Recommended name:
            Phlorizin hydrolase
              EC=3.2.1.62

Gene names

Name:	LCT
Synonyms:	LPH

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Defects in LCT are the cause of congenital lactase deficiency [MIM:223000]; also known as hereditary alactasia or disaccharide intolerance II. Congenital lactase deficiency is a an 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, adult-type hypolactasia [MIM:223100], 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.
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
Molecular function	Glycosidase Hydrolase
PTM	Phosphoprotein Zymogen
Technical term	Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc membrane fraction Ref.1 Traceable author statement. Source: ProtInc
Molecular function	cation binding Inferred from electronic annotation. Source: InterPro glycosylceramidase activity Inferred from electronic annotation. Source: EC lactase activity Ref.1 Inferred from Experiment. 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	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
Amino acid modifications
	Modified residue	1303	1	Phosphotyrosine Ref.5
	Modified residue	1313	1	Phosphotyrosine Ref.5
Natural variations
	Natural variant	190	1	S → L: dbSNP rs35156533.		VAR_055882
	Natural variant	219	1	V → I: dbSNP rs3754689. Ref.2		VAR_026705
	Natural variant	268	1	Q → H in congenital lactase deficiency. Ref.6		VAR_026706
	Natural variant	362	1	V → I: dbSNP rs4954449.		VAR_026707
	Natural variant	1363	1	G → S in congenital lactase deficiency. Ref.6		VAR_026708
	Natural variant	1593	1	V → M: dbSNP rs35891837.		VAR_055883
	Natural variant	1639	1	N → S: dbSNP rs2322659. Ref.2		VAR_026709
Experimental info
	Sequence conflict	1096	1	A → T in CAA30801. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P09848-1 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: 959D4D4E366677ED	FASTA	1,927	218,573
	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 RVWEAFANQS 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: 2460343] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 1902057] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-219 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: 15815621] [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: 11788828] [Abstract] Cited for: INVOLVEMENT IN ADULT-TYPE HYPOLACTASIA.
[5]	"Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling." Wang Y., Du D., Fang L., Yang G., Zhang C., Zeng R., Ullrich A., Lottspeich F., Chen Z. EMBO J. 25:5058-5070(2006) [PubMed: 17053785] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1303 AND TYR-1313, MASS SPECTROMETRY.
[6]	"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: 16400612] [Abstract] Cited for: VARIANTS CONGENITAL LACTASE DEFICIENCY HIS-268 AND SER-1363.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Lactase entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	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. No translation available.
IPI	IPI00017648.
PIR	S01168.
RefSeq	NP_002290.2.
UniGene	Hs.551506
3D structure databases
HSSP	HSSP built from PDB template 1OD0 based on UniProtKB Q08638.
ModBase	Search...
Protein-protein interaction databases
STRING	P09848.
Protein family/group databases
CAZy	GH1. Glycoside Hydrolase Family 1.
PTM databases
PhosphoSite	P09848.
Proteomic databases
PRIDE	P09848.
Genome annotation databases
Ensembl	ENST00000264162; ENSP00000264162; ENSG00000115850; Homo sapiens. [Genome view] ENST00000452974; ENSP00000391231; ENSG00000115850; Homo sapiens. [Genome view] ENST00000455227; ENSP00000388225; ENSG00000115850; Homo sapiens. [Genome view]
GeneID	3938.
KEGG	hsa:3938.
Organism-specific databases
CTD	3938.
GeneCards	GC02M136261.
H-InvDB	HIX0021578. HIX0030024.
HGNC	HGNC:6530. LCT.
HPA	HPA007408.
MIM	223000. phenotype. 603202. gene.
Orphanet	53690. Lactase deficiency, congenital.
PharmGKB	PA30315.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P09848.
HOVERGEN	P09848.
Enzyme and pathway databases
BioCyc	MetaCyc:MON-13295.
BRENDA	3.2.1.108. 247. 3.2.1.62. 247.
Reactome	REACT_474. Metabolism of carbohydrates.
Gene expression databases
ArrayExpress	P09848.
Bgee	P09848.
CleanEx	HS_LCT.
Genevestigator	P09848.
GermOnline	ENSG00000115850. Homo sapiens.
Family and domain databases
InterPro	IPR001360. Glyco_hydro_1. IPR018120. Glyco_hydro_1_AS. IPR013781. Glyco_hydro_sg_catalytic. [Graphical view]
Gene3D	G3DSA:3.20.20.80. Glyco_hydro_cat. 4 hits.
PANTHER	PTHR10353. Glyco_hydro_1. 1 hit.
Pfam	PF00232. Glyco_hydro_1. 3 hits. [Graphical view]
PRINTS	PR00131. GLHYDRLASE1.
ProDom	PD000650. Glyco_hydro_euk. 2 hits. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00572. GLYCOSYL_HYDROL_F1_1. 2 hits. PS00653. GLYCOSYL_HYDROL_F1_2. 3 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	15465.
SOURCE	Search...

Entry information

Entry name

LPH_HUMAN

Accession

Primary (citable) accession number: P09848

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	May 5, 2009
Last modified:	October 13, 2009
This is version 105 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.