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P09848

- LPH_HUMAN

UniProt

P09848 - LPH_HUMAN

Protein

Lactase-phlorizin hydrolase

Gene

LCT

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 151 (01 Oct 2014)
      Sequence version 3 (02 Nov 2010)
      Previous versions | rss
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    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

    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. apical plasma membrane Source: UniProtKB-SubCell
    2. integral component of plasma membrane Source: ProtInc
    3. membrane Source: ProtInc
    4. plasma membrane Source: Reactome

    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

    ArrayExpressiP09848.
    BgeeiP09848.
    CleanExiHS_LCT.
    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.
    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

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    MELSWHVVFI ALLSFSCWGS DWESDRNFIS TAGPLTNDLL HNLSGLLGDQ     50
    SSNFVAGDKD MYVCHQPLPT FLPEYFSSLH ASQITHYKVF LSWAQLLPAG 100
    STQNPDEKTV QCYRRLLKAL KTARLQPMVI LHHQTLPAST LRRTEAFADL 150
    FADYATFAFH SFGDLVGIWF TFSDLEEVIK ELPHQESRAS QLQTLSDAHR 200
    KAYEIYHESY AFQGGKLSVV LRAEDIPELL LEPPISALAQ DTVDFLSLDL 250
    SYECQNEASL RQKLSKLQTI EPKVKVFIFN LKLPDCPSTM KNPASLLFSL 300
    FEAINKDQVL TIGFDINEFL SCSSSSKKSM SCSLTGSLAL QPDQQQDHET 350
    TDSSPASAYQ RIWEAFANQS RAERDAFLQD TFPEGFLWGA STGAFNVEGG 400
    WAEGGRGVSI WDPRRPLNTT EGQATLEVAS DSYHKVASDV ALLCGLRAQV 450
    YKFSISWSRI FPMGHGSSPS LPGVAYYNKL IDRLQDAGIE PMATLFHWDL 500
    PQALQDHGGW QNESVVDAFL DYAAFCFSTF GDRVKLWVTF HEPWVMSYAG 550
    YGTGQHPPGI SDPGVASFKV AHLVLKAHAR TWHHYNSHHR PQQQGHVGIV 600
    LNSDWAEPLS PERPEDLRAS ERFLHFMLGW FAHPVFVDGD YPATLRTQIQ 650
    QMNRQCSHPV AQLPEFTEAE KQLLKGSADF LGLSHYTSRL ISNAPQNTCI 700
    PSYDTIGGFS QHVNHVWPQT SSSWIRVVPW GIRRLLQFVS LEYTRGKVPI 750
    YLAGNGMPIG ESENLFDDSL RVDYFNQYIN EVLKAIKEDS VDVRSYIARS 800
    LIDGFEGPSG YSQRFGLHHV NFSDSSKSRT PRKSAYFFTS IIEKNGFLTK 850
    GAKRLLPPNT VNLPSKVRAF TFPSEVPSKA KVVWEKFSSQ PKFERDLFYH 900
    GTFRDDFLWG VSSSAYQIEG AWDADGKGPS IWDNFTHTPG SNVKDNATGD 950
    IACDSYHQLD ADLNMLRALK VKAYRFSISW SRIFPTGRNS SINSHGVDYY 1000
    NRLINGLVAS NIFPMVTLFH WDLPQALQDI GGWENPALID LFDSYADFCF 1050
    QTFGDRVKFW MTFNEPMYLA WLGYGSGEFP PGVKDPGWAP YRIAHAVIKA 1100
    HARVYHTYDE KYRQEQKGVI SLSLSTHWAE PKSPGVPRDV EAADRMLQFS 1150
    LGWFAHPIFR NGDYPDTMKW KVGNRSELQH LATSRLPSFT EEEKRFIRAT 1200
    ADVFCLNTYY SRIVQHKTPR LNPPSYEDDQ EMAEEEDPSW PSTAMNRAAP 1250
    WGTRRLLNWI KEEYGDIPIY ITENGVGLTN PNTEDTDRIF YHKTYINEAL 1300
    KAYRLDGIDL RGYVAWSLMD NFEWLNGYTV KFGLYHVDFN NTNRPRTARA 1350
    SARYYTEVIT NNGMPLARED EFLYGRFPEG FIWSAASAAY QIEGAWRADG 1400
    KGLSIWDTFS HTPLRVENDA IGDVACDSYH KIAEDLVTLQ NLGVSHYRFS 1450
    ISWSRILPDG TTRYINEAGL NYYVRLIDTL LAASIQPQVT IYHWDLPQTL 1500
    QDVGGWENET IVQRFKEYAD VLFQRLGDKV KFWITLNEPF VIAYQGYGYG 1550
    TAAPGVSNRP GTAPYIVGHN LIKAHAEAWH LYNDVYRASQ GGVISITISS 1600
    DWAEPRDPSN QEDVEAARRY VQFMGGWFAH PIFKNGDYNE VMKTRIRDRS 1650
    LAAGLNKSRL PEFTESEKRR INGTYDFFGF NHYTTVLAYN LNYATAISSF 1700
    DADRGVASIA DRSWPDSGSF WLKMTPFGFR RILNWLKEEY NDPPIYVTEN 1750
    GVSQREETDL NDTARIYYLR TYINEALKAV QDKVDLRGYT VWSAMDNFEW 1800
    ATGFSERFGL HFVNYSDPSL PRIPKASAKF YASVVRCNGF PDPATGPHAC 1850
    LHQPDAGPTI SPVRQEEVQF LGLMLGTTEA QTALYVLFSL VLLGVCGLAF 1900
    LSYKYCKRSK QGKTQRSQQE LSPVSSF 1927
    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.

    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.
    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

    ArrayExpressi P09848.
    Bgeei P09848.
    CleanExi HS_LCT.
    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

    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 1, 2014
    This is version 151 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