LRP6_HUMAN
ID LRP6_HUMAN Reviewed; 1613 AA.
AC O75581; Q17RZ2;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Low-density lipoprotein receptor-related protein 6;
DE Short=LRP-6;
DE Flags: Precursor;
GN Name=LRP6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-1062.
RC TISSUE=Kidney;
RX PubMed=9704021; DOI=10.1006/bbrc.1998.9061;
RA Brown S.D., Twells R.C., Hey P.J., Cox R.D., Levy E.R., Soderman A.R.,
RA Metzker M.L., Caskey C.T., Todd J.A., Hess J.F.;
RT "Isolation and characterization of LRP6, a novel member of the low density
RT lipoprotein receptor gene family.";
RL Biochem. Biophys. Res. Commun. 248:879-888(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH DKK1, AND FUNCTION.
RX PubMed=11448771; DOI=10.1016/s0960-9822(01)00290-1;
RA Semenov M.V., Tamai K., Brott B.K., Kuhl M., Sokol S., He X.;
RT "Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6.";
RL Curr. Biol. 11:951-961(2001).
RN [5]
RP INTERACTION WITH WNT1, AND FUNCTION.
RX PubMed=11357136; DOI=10.1038/35077108;
RA Mao B., Wu W., Li Y., Hoppe D., Stannek P., Glinka A., Niehrs C.;
RT "LDL-receptor-related protein 6 is a receptor for Dickkopf proteins.";
RL Nature 411:321-325(2001).
RN [6]
RP INTERACTION WITH FZD5; DKK1 AND DKK2.
RX PubMed=12857724; DOI=10.1074/jbc.m300191200;
RA Caricasole A., Ferraro T., Iacovelli L., Barletta E., Caruso A.,
RA Melchiorri D., Terstappen G.C., Nicoletti F.;
RT "Functional characterization of WNT7A signaling in PC12 cells: interaction
RT with A FZD5 x LRP6 receptor complex and modulation by Dickkopf proteins.";
RL J. Biol. Chem. 278:37024-37031(2003).
RN [7]
RP INTERACTION WITH SOST, AND FUNCTION.
RX PubMed=15778503; DOI=10.1074/jbc.m413274200;
RA Li X., Zhang Y., Kang H., Liu W., Liu P., Zhang J., Harris S.E., Wu D.;
RT "Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling.";
RL J. Biol. Chem. 280:19883-19887(2005).
RN [8]
RP INTERACTION WITH WNT1 IN THE WNT-FZD-LRP5-LRP6 COMPLEX, AND INTERACTION
RP WITH SOST.
RX PubMed=15908424; DOI=10.1074/jbc.m504308200;
RA Semenov M., Tamai K., He X.;
RT "SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor.";
RL J. Biol. Chem. 280:26770-26775(2005).
RN [9]
RP PHOSPHORYLATION OF PPPSP MOTIFS, PHOSPHORYLATION AT SER-1490 AND THR-1493,
RP AND FUNCTION.
RX PubMed=16341017; DOI=10.1038/nature04185;
RA Zeng X., Tamai K., Doble B., Li S., Huang H., Habas R., Okamura H.,
RA Woodgett J., He X.;
RT "A dual-kinase mechanism for Wnt co-receptor phosphorylation and
RT activation.";
RL Nature 438:873-877(2005).
RN [10]
RP INTERACTION WITH MACF1.
RX PubMed=16815997; DOI=10.1101/gad.1411206;
RA Chen H.J., Lin C.M., Lin C.S., Perez-Olle R., Leung C.L., Liem R.K.;
RT "The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt
RT signaling pathway.";
RL Genes Dev. 20:1933-1945(2006).
RN [11]
RP PHOSPHORYLATION AT SER-1420 AND SER-1430, FUNCTION, INTERACTION WITH CSNKIE
RP AND AXIN1, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF SER-1420
RP AND SER-1430.
RX PubMed=16513652; DOI=10.1074/jbc.m510580200;
RA Swiatek W., Kang H., Garcia B.A., Shabanowitz J., Coombs G.S., Hunt D.F.,
RA Virshup D.M.;
RT "Negative regulation of LRP6 function by casein kinase I epsilon
RT phosphorylation.";
RL J. Biol. Chem. 281:12233-12241(2006).
RN [12]
RP INTERACTION WITH RSPO1, FUNCTION, AND PHOSPHORYLATION.
RX PubMed=17400545; DOI=10.1074/jbc.m701927200;
RA Wei Q., Yokota C., Semenov M.V., Doble B., Woodgett J., He X.;
RT "R-spondin1 is a high affinity ligand for LRP6 and induces LRP6
RT phosphorylation and beta-catenin signaling.";
RL J. Biol. Chem. 282:15903-15911(2007).
RN [13]
RP PROTEOLYTIC PROCESSING, AND FUNCTION.
RX PubMed=17326769; DOI=10.1111/j.1471-4159.2007.04447.x;
RA Mi K., Johnson G.V.;
RT "Regulated proteolytic processing of LRP6 results in release of its
RT intracellular domain.";
RL J. Neurochem. 101:517-529(2007).
RN [14]
RP GLYCOSYLATION, PHOSPHORYLATION AT SER-1490, INTERACTION WITH AXIN1,
RP HOMODIMERIZATION, INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17698587; DOI=10.1128/mcb.00773-07;
RA Khan Z., Vijayakumar S., de la Torre T.V., Rotolo S., Bafico A.;
RT "Analysis of endogenous LRP6 function reveals a novel feedback mechanism by
RT which Wnt negatively regulates its receptor.";
RL Mol. Cell. Biol. 27:7291-7301(2007).
RN [15]
RP INTERACTION WITH KREM1 AND DKK1.
RX PubMed=17804805; DOI=10.1073/pnas.0702305104;
RA Binnerts M.E., Kim K.A., Bright J.M., Patel S.M., Tran K., Zhou M.,
RA Leung J.M., Liu Y., Lomas W.E. III, Dixon M., Hazell S.A., Wagle M.,
RA Nie W.S., Tomasevic N., Williams J., Zhan X., Levy M.D., Funk W.D., Abo A.;
RT "R-Spondin1 regulates Wnt signaling by inhibiting internalization of
RT LRP6.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:14700-14705(2007).
RN [16]
RP PHOSPHORYLATION AT THR-1479, INTERACTION WITH AXIN1, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=17569865; DOI=10.1126/science.1137065;
RA Bilic J., Huang Y.L., Davidson G., Zimmermann T., Cruciat C.M., Bienz M.,
RA Niehrs C.;
RT "Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6
RT phosphorylation.";
RL Science 316:1619-1622(2007).
RN [17]
RP INTERACTION WITH AXIN1, PHOSPHORYLATION, AND MUTAGENESIS OF LEU-1485;
RP ASN-1486; PRO-1487; PRO-1488; PRO-1489; SER-1490; PRO-1491; ALA-1492;
RP THR-1493; GLU-1494; ARG-1495; THR-1529; THR-1530; PRO-1531; THR-1572;
RP SER-1590 AND SER-1607.
RX PubMed=18362152; DOI=10.1074/jbc.m800327200;
RA MacDonald B.T., Yokota C., Tamai K., Zeng X., He X.;
RT "Wnt signal amplification via activity, cooperativity, and regulation of
RT multiple intracellular PPPSP motifs in the Wnt co-receptor LRP6.";
RL J. Biol. Chem. 283:16115-16123(2008).
RN [18]
RP INTERACTION WITH CAPRIN2, AND PHOSPHORYLATION AT SER-1490.
RX PubMed=18762581; DOI=10.1083/jcb.200803147;
RA Ding Y., Xi Y., Chen T., Wang J.Y., Tao D.L., Wu Z.L., Li Y.P., Li C.,
RA Zeng R., Li L.;
RT "Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6
RT phosphorylation.";
RL J. Cell Biol. 182:865-872(2008).
RN [19]
RP PHOSPHORYLATION ON PPPSP MOTIFS, AND FUNCTION.
RX PubMed=19107203; DOI=10.1371/journal.pone.0004046;
RA Piao S., Lee S.H., Kim H., Yum S., Stamos J.L., Xu Y., Lee S.J., Lee J.,
RA Oh S., Han J.K., Park B.J., Weis W.I., Ha N.C.;
RT "Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of
RT LRP6 in Wnt/beta-catenin signaling.";
RL PLoS ONE 3:E4046-E4046(2008).
RN [20]
RP PALMITOYLATION AT CYS-1394 AND CYS-1399, UBIQUITINATION AT LYS-1403,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-1394 AND CYS-1399.
RX PubMed=18378904; DOI=10.1073/pnas.0710389105;
RA Abrami L., Kunz B., Iacovache I., van der Goot F.G.;
RT "Palmitoylation and ubiquitination regulate exit of the Wnt signaling
RT protein LRP6 from the endoplasmic reticulum.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:5384-5389(2008).
RN [21]
RP DOMAIN PPPSP MOTIF, AND PHOSPHORYLATION AT SER-1490.
RX PubMed=20059949; DOI=10.1016/j.devcel.2009.11.006;
RA Davidson G., Shen J., Huang Y.L., Su Y., Karaulanov E., Bartscherer K.,
RA Hassler C., Stannek P., Boutros M., Niehrs C.;
RT "Cell cycle control of wnt receptor activation.";
RL Dev. Cell 17:788-799(2009).
RN [22]
RP PHOSPHORYLATION OF PPPSP MOTIFS, PHOSPHORYLATION AT SER-1490, AND FUNCTION.
RX PubMed=19801552; DOI=10.1074/jbc.m109.047456;
RA Chen M., Philipp M., Wang J., Premont R.T., Garrison T.R., Caron M.G.,
RA Lefkowitz R.J., Chen W.;
RT "G Protein-coupled receptor kinases phosphorylate LRP6 in the Wnt
RT pathway.";
RL J. Biol. Chem. 284:35040-35048(2009).
RN [23]
RP PHOSPHORYLATION OF PPPSP MOTIFS, AND FUNCTION.
RX PubMed=19293931; DOI=10.1371/journal.pone.0004926;
RA Wu G., Huang H., Garcia Abreu J., He X.;
RT "Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated
RT PPPSPXS motifs of Wnt coreceptor LRP6.";
RL PLoS ONE 4:E4926-E4926(2009).
RN [24]
RP INTERACTION WITH WNT3A; WNT9B AND FZD8 IN THE WNT/FZD/LRP6 COMPLEX, AND
RP INTERACTION WITH DKK1.
RX PubMed=20093360; DOI=10.1074/jbc.m109.092130;
RA Bourhis E., Tam C., Franke Y., Bazan J.F., Ernst J., Hwang J., Costa M.,
RA Cochran A.G., Hannoush R.N.;
RT "Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals
RT multiple Wnt and Dkk1 binding sites on LRP6.";
RL J. Biol. Chem. 285:9172-9179(2010).
RN [25]
RP INTERACTION WITH TMEM198.
RX PubMed=21536646; DOI=10.1128/mcb.05103-11;
RA Liang J., Fu Y., Cruciat C.M., Jia S., Wang Y., Tong Z., Tao Q.,
RA Ingelfinger D., Boutros M., Meng A., Niehrs C., Wu W.;
RT "Transmembrane protein 198 promotes LRP6 phosphorylation and Wnt signaling
RT activation.";
RL Mol. Cell. Biol. 31:2577-2590(2011).
RN [26]
RP INTERACTION WITH DAB2.
RX PubMed=22491013; DOI=10.1038/emboj.2012.83;
RA Jiang Y., He X., Howe P.H.;
RT "Disabled-2 (Dab2) inhibits Wnt/beta-catenin signalling by binding LRP6 and
RT promoting its internalization through clathrin.";
RL EMBO J. 31:2336-2349(2012).
RN [27]
RP UBIQUITINATION BY ZNRF3.
RX PubMed=22575959; DOI=10.1038/nature11019;
RA Hao H.X., Xie Y., Zhang Y., Charlat O., Oster E., Avello M., Lei H.,
RA Mickanin C., Liu D., Ruffner H., Mao X., Ma Q., Zamponi R., Bouwmeester T.,
RA Finan P.M., Kirschner M.W., Porter J.A., Serluca F.C., Cong F.;
RT "ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner.";
RL Nature 485:195-200(2012).
RN [28]
RP INTERACTION WITH LYPD6, AND SUBCELLULAR LOCATION.
RX PubMed=23987510; DOI=10.1016/j.devcel.2013.07.020;
RA Oezhan G., Sezgin E., Wehner D., Pfister A.S., Kuehl S.J.,
RA Kagermeier-Schenk B., Kuehl M., Schwille P., Weidinger G.;
RT "Lypd6 enhances Wnt/beta-catenin signaling by promoting Lrp6
RT phosphorylation in raft plasma membrane domains.";
RL Dev. Cell 26:331-345(2013).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1490, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [30]
RP INTERACTION WITH CAPRIN2, AND PHOSPHORYLATION AT SER-1490.
RX PubMed=25331957; DOI=10.1074/jbc.m114.591636;
RA Miao H., Jia Y., Xie S., Wang X., Zhao J., Chu Y., Zhou Z., Shi Z.,
RA Song X., Li L.;
RT "Structural insights into the C1q domain of Caprin-2 in canonical Wnt
RT signaling.";
RL J. Biol. Chem. 289:34104-34113(2014).
RN [31]
RP IDENTIFICATION IN A COMPLEX WITH CAPRIN2; CCNY AND CDK14, AND
RP PHOSPHORYLATION AT SER-1490.
RX PubMed=27821587; DOI=10.1074/jbc.m116.744607;
RA Wang X., Jia Y., Fei C., Song X., Li L.;
RT "Caprin-2 positively regulates CDK14/Cyclin Y-mediated LRP5/6 constitutive
RT phosphorylation.";
RL J. Biol. Chem. 291:26427-26434(2016).
RN [32]
RP IDENTIFICATION IN A TERNARY COMPLEX WITH KREM1 AND LRP6.
RX PubMed=27524201; DOI=10.1016/j.str.2016.06.020;
RA Zebisch M., Jackson V.A., Zhao Y., Jones E.Y.;
RT "Structure of the dual-mode wnt regulator Kremen1 and insight into ternary
RT complex formation with LRP6 and Dickkopf.";
RL Structure 24:1599-1605(2016).
RN [33]
RP INTERACTION WITH LMBR1L.
RX PubMed=31073040; DOI=10.1126/science.aau0812;
RA Choi J.H., Zhong X., McAlpine W., Liao T.C., Zhang D., Fang B., Russell J.,
RA Ludwig S., Nair-Gill E., Zhang Z., Wang K.W., Misawa T., Zhan X., Choi M.,
RA Wang T., Li X., Tang M., Sun Q., Yu L., Murray A.R., Moresco E.M.Y.,
RA Beutler B.;
RT "LMBR1L regulates lymphopoiesis through Wnt/beta-catenin signaling.";
RL Science 364:0-0(2019).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 630-1246 IN COMPLEX WITH DKK1,
RP SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-692; ASN-859; ASN-865;
RP ASN-926 AND ASN-1039.
RX PubMed=22000856; DOI=10.1016/j.devcel.2011.09.003;
RA Ahn V.E., Chu M.L., Choi H.J., Tran D., Abo A., Weis W.I.;
RT "Structural basis of Wnt signaling inhibition by Dickkopf binding to
RT LRP5/6.";
RL Dev. Cell 21:862-873(2011).
RN [35]
RP VARIANT ADCAD2 CYS-611, AND CHARACTERIZATION OF VARIANT ADCAD2 CYS-611.
RX PubMed=17332414; DOI=10.1126/science.1136370;
RA Mani A., Radhakrishnan J., Wang H., Mani A., Mani M.-A.,
RA Nelson-Williams C., Carew K.S., Mane S., Najmabadi H., Wu D., Lifton R.P.;
RT "LRP6 mutation in a family with early coronary disease and metabolic risk
RT factors.";
RL Science 315:1278-1282(2007).
RN [36]
RP VARIANTS ADCAD2 HIS-360; SER-433 AND GLN-473, AND CHARACTERIZATION OF
RP VARIANT ADCAD2 GLN-473.
RX PubMed=23703864; DOI=10.1002/humu.22360;
RA Singh R., Smith E., Fathzadeh M., Liu W., Go G.W., Subrahmanyan L.,
RA Faramarzi S., McKenna W., Mani A.;
RT "Rare nonconservative LRP6 mutations are associated with metabolic
RT syndrome.";
RL Hum. Mutat. 34:1221-1225(2013).
RN [37]
RP INVOLVEMENT IN STHAG7, VARIANT STHAG7 VAL-19, CHARACTERIZATION OF VARIANT
RP STHAG7 VAL-19, AND SUBCELLULAR LOCATION.
RX PubMed=26387593; DOI=10.1016/j.ajhg.2015.08.014;
RA Massink M.P., Creton M.A., Spanevello F., Fennis W.M., Cune M.S.,
RA Savelberg S.M., Nijman I.J., Maurice M.M., van den Boogaard M.J.,
RA van Haaften G.;
RT "Loss-of-Function Mutations in the WNT Co-receptor LRP6 Cause Autosomal-
RT Dominant Oligodontia.";
RL Am. J. Hum. Genet. 97:621-626(2015).
RN [38]
RP VARIANT PHE-1415.
RX PubMed=29983323; DOI=10.1016/j.neuron.2018.06.019;
RA Furey C.G., Choi J., Jin S.C., Zeng X., Timberlake A.T.,
RA Nelson-Williams C., Mansuri M.S., Lu Q., Duran D., Panchagnula S.,
RA Allocco A., Karimy J.K., Khanna A., Gaillard J.R., DeSpenza T., Antwi P.,
RA Loring E., Butler W.E., Smith E.R., Warf B.C., Strahle J.M., Limbrick D.D.,
RA Storm P.B., Heuer G., Jackson E.M., Iskandar B.J., Johnston J.M.,
RA Tikhonova I., Castaldi C., Lopez-Giraldez F., Bjornson R.D., Knight J.R.,
RA Bilguvar K., Mane S., Alper S.L., Haider S., Guclu B., Bayri Y., Sahin Y.,
RA Apuzzo M.L.J., Duncan C.C., DiLuna M.L., Guenel M., Lifton R.P.,
RA Kahle K.T.;
RT "De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human
RT Congenital Hydrocephalus.";
RL Neuron 99:302-314.e4(2018).
CC -!- FUNCTION: Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers
CC beta-catenin signaling through inducing aggregation of receptor-ligand
CC complexes into ribosome-sized signalsomes. Cell-surface coreceptor of
CC Wnt/beta-catenin signaling, which plays a pivotal role in bone
CC formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1
CC polymers to the plasma membrane which, in turn, recruits the
CC AXIN1/GSK3B-complex to the cell surface promoting the formation of
CC signalsomes and inhibiting AXIN1/GSK3-mediated phosphorylation and
CC destruction of beta-catenin. Required for posterior patterning of the
CC epiblast during gastrulation (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:11357136, ECO:0000269|PubMed:11448771,
CC ECO:0000269|PubMed:15778503, ECO:0000269|PubMed:16341017,
CC ECO:0000269|PubMed:16513652, ECO:0000269|PubMed:17326769,
CC ECO:0000269|PubMed:17400545, ECO:0000269|PubMed:19107203,
CC ECO:0000269|PubMed:19293931, ECO:0000269|PubMed:19801552}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Forms phosphorylated oligomer
CC aggregates on Wnt-signaling. Forms a WNT-signaling complex formed of a
CC WNT protein, a FZD protein and LRP5 or LRP6. Interacts (via the
CC extracellular domain) with WNT1; the interaction is enhanced by prior
CC formation of the Wnt/Fzd complex. Interacts (via the beta-propeller
CC regions 3 and 4) with WNT3A. Interacts (via the beta-propeller regions
CC 1 and 2) with WNT9B. Interacts with FZD5; the interaction forms a
CC coreceptor complex for Wnt signaling and is inhibited by DKK1 and
CC DRAXIN. Interacts (via beta propeller region) with DKK1; the
CC interaction inhibits FZD5/LRP6 complex formation. Interacts with DKK2.
CC Interacts with C1orf187/DRAXIN; the interaction inhibits Wnt signaling
CC (By similarity). Interacts (via the phosphorylated PPPSP motifs) with
CC AXIN1; the interaction recruits the AXIN1/GSK3B complex to cell surface
CC LRP6 signalsomes. Interacts with GRB10; the interaction prevents AXIN1
CC binding, thus negatively regulating the Wnt signaling pathway (By
CC similarity). Interacts (via the extracellular domain) with RSPO1; the
CC interaction activates Wnt/beta-catenin signaling. Interacts (via the
CC extracellular domain) with RSPO3 (via the cysteine rich domain); the
CC interaction activates Wnt/beta-catenin signaling. Interacts (via the
CC beta-propeller regions 1 and 2) with SOST; the interaction competes
CC with DKK1 for binding for inhibiting beta-catenin signaling. Interacts
CC with MESD; the interaction prevents the formation of LRP6 aggregates
CC and targets LRP6 to the plasma membrane (By similarity). Interacts (via
CC the cytoplasmic domain) with CSNKIE; the interaction phosphorylates
CC LRP6, binds AXIN1 and inhibits AXIN1/GSK3B-mediated phosphorylation of
CC beta-catenin. Interacts with MACF1. Interacts with DAB2; the
CC interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6
CC towards clathrin-mediated endocytosis. Interacts with TMEM198.
CC Interacts with CAPRIN2; the interaction promotes LRP6 phosphorylation
CC at Ser-1490 (PubMed:18762581, PubMed:25331957). Found in a complex with
CC CAPRIN2, CCNY and CDK14 during G2/M stage; CAPRIN2 functions as a
CC scaffold for the complex by binding to CCNY via its N terminus and to
CC CDK14 via its C terminus (PubMed:27821587). Interacts with LYPD6
CC (PubMed:23987510). Forms a ternary complex with DKK1 and KREM1
CC (PubMed:27524201). Interacts with KREM1 in a DKK1-dependent manner
CC (PubMed:17804805). Interacts with MDK: this interaction is calcium
CC dependent (By similarity). Interacts with LMBR1L (PubMed:31073040).
CC {ECO:0000250|UniProtKB:O88572, ECO:0000269|PubMed:11357136,
CC ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:12857724,
CC ECO:0000269|PubMed:15778503, ECO:0000269|PubMed:15908424,
CC ECO:0000269|PubMed:16513652, ECO:0000269|PubMed:16815997,
CC ECO:0000269|PubMed:17400545, ECO:0000269|PubMed:17569865,
CC ECO:0000269|PubMed:17698587, ECO:0000269|PubMed:17804805,
CC ECO:0000269|PubMed:18362152, ECO:0000269|PubMed:18762581,
CC ECO:0000269|PubMed:20093360, ECO:0000269|PubMed:21536646,
CC ECO:0000269|PubMed:22000856, ECO:0000269|PubMed:22491013,
CC ECO:0000269|PubMed:23987510, ECO:0000269|PubMed:25331957,
CC ECO:0000269|PubMed:27524201, ECO:0000269|PubMed:27821587,
CC ECO:0000305|PubMed:31073040}.
CC -!- INTERACTION:
CC O75581; Q9Y4X0: AMMECR1; NbExp=5; IntAct=EBI-910915, EBI-8583355;
CC O75581; Q9H6X2: ANTXR1; NbExp=3; IntAct=EBI-910915, EBI-905643;
CC O75581; O15169-2: AXIN1; NbExp=3; IntAct=EBI-910915, EBI-10987526;
CC O75581; Q03135: CAV1; NbExp=3; IntAct=EBI-910915, EBI-603614;
CC O75581; Q9UBR5: CKLF; NbExp=3; IntAct=EBI-910915, EBI-17572009;
CC O75581; P98082: DAB2; NbExp=20; IntAct=EBI-910915, EBI-1171238;
CC O75581; O94907: DKK1; NbExp=15; IntAct=EBI-910915, EBI-742864;
CC O75581; P49840: GSK3A; NbExp=3; IntAct=EBI-910915, EBI-1044067;
CC O75581; P49841: GSK3B; NbExp=4; IntAct=EBI-910915, EBI-373586;
CC O75581; O75581: LRP6; NbExp=4; IntAct=EBI-910915, EBI-910915;
CC O75581; Q5S007: LRRK2; NbExp=4; IntAct=EBI-910915, EBI-5323863;
CC O75581; P09619: PDGFRB; NbExp=3; IntAct=EBI-910915, EBI-641237;
CC O75581; Q9BQB4: SOST; NbExp=7; IntAct=EBI-910915, EBI-5746563;
CC O75581; P56704: WNT3A; NbExp=2; IntAct=EBI-910915, EBI-6173037;
CC O75581; Q9ULT6: ZNRF3; NbExp=2; IntAct=EBI-910915, EBI-949772;
CC O75581; O35625: Axin1; Xeno; NbExp=2; IntAct=EBI-910915, EBI-2365912;
CC O75581; O70239: Axin1; Xeno; NbExp=12; IntAct=EBI-910915, EBI-6857773;
CC O75581; Q61091: Fzd8; Xeno; NbExp=4; IntAct=EBI-910915, EBI-6171689;
CC O75581; P47879: Igfbp4; Xeno; NbExp=4; IntAct=EBI-910915, EBI-15706768;
CC O75581; Q9ERE7: Mesd; Xeno; NbExp=2; IntAct=EBI-910915, EBI-6662606;
CC O75581; P04426: Wnt1; Xeno; NbExp=2; IntAct=EBI-910915, EBI-1570911;
CC O75581; P27467: Wnt3a; Xeno; NbExp=4; IntAct=EBI-910915, EBI-2899665;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26387593};
CC Single-pass type I membrane protein. Endoplasmic reticulum
CC {ECO:0000269|PubMed:26387593}. Membrane raft
CC {ECO:0000269|PubMed:23987510}. Note=On Wnt signaling, undergoes a cycle
CC of caveolin- or clathrin-mediated endocytosis and plasma membrane
CC location. Released from the endoplasmic reticulum on palmitoylation.
CC Mono-ubiquitination retains it in the endoplasmic reticulum in the
CC absence of palmitoylation. On Wnt signaling, phosphorylated, aggregates
CC and colocalizes with AXIN1 and GSK3B at the plasma membrane in LRP6-
CC signalsomes. Chaperoned to the plasma membrane by MESD (By similarity).
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely coexpressed with LRP5 during embryogenesis
CC and in adult tissues.
CC -!- INDUCTION: Decreased levels on WNT3A stimulation.
CC {ECO:0000269|PubMed:17698587}.
CC -!- DOMAIN: The YWTD-EGF-like domains 1 and 2 are required for the
CC interaction with Wnt-frizzled complex. The YWTD-EGF-like domains 3 and
CC 4 are required for the interaction with DKK1.
CC {ECO:0000269|PubMed:20059949}.
CC -!- DOMAIN: The PPPSP motifs play a central role in signal transduction by
CC being phosphorylated, leading to activate the Wnt signaling pathway.
CC {ECO:0000269|PubMed:20059949}.
CC -!- PTM: Dual phosphorylation of cytoplasmic PPPSP motifs sequentially by
CC GSK3 and CK1 is required for AXIN1-binding, and subsequent
CC stabilization and activation of beta-catenin via preventing GSK3-
CC mediated phosphorylation of beta-catenin. Phosphorylated, in vitro, by
CC GRK5/6 within and outside the PPPSP motifs. Phosphorylation at Ser-1490
CC by CDK14 during G2/M phase leads to regulation of the Wnt signaling
CC pathway during the cell cycle. Phosphorylation by GSK3B is induced by
CC RPSO1 binding and inhibited by DKK1. Phosphorylated, in vitro, by
CC casein kinase I on Thr-1479. {ECO:0000269|PubMed:16341017,
CC ECO:0000269|PubMed:16513652, ECO:0000269|PubMed:17400545,
CC ECO:0000269|PubMed:17569865, ECO:0000269|PubMed:17698587,
CC ECO:0000269|PubMed:18362152, ECO:0000269|PubMed:19107203,
CC ECO:0000269|PubMed:19293931, ECO:0000269|PubMed:19801552,
CC ECO:0000269|PubMed:20059949}.
CC -!- PTM: Undergoes gamma-secretase-dependent regulated intramembrane
CC proteolysis (RIP). The extracellular domain is first released by
CC shedding, and then, through the action of gamma-secretase, the
CC intracellular domain (ICD) is released into the cytoplasm where it is
CC free to bind to GSK3B and to activate canonical Wnt signaling.
CC -!- PTM: Palmitoylation on the two sites near the transmembrane domain
CC leads to release of LRP6 from the endoplasmic reticulum.
CC {ECO:0000269|PubMed:18378904}.
CC -!- PTM: Mono-ubiquitinated which retains LRP6 in the endoplasmic
CC reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the
CC proteasome. {ECO:0000269|PubMed:18378904, ECO:0000269|PubMed:22575959}.
CC -!- PTM: N-glycosylation is required for cell surface location.
CC {ECO:0000269|PubMed:17698587, ECO:0000269|PubMed:22000856}.
CC -!- DISEASE: Coronary artery disease, autosomal dominant, 2 (ADCAD2)
CC [MIM:610947]: A common heart disease characterized by reduced or absent
CC blood flow in one or more of the arteries that encircle and supply the
CC heart. Its most important complication is acute myocardial infarction.
CC {ECO:0000269|PubMed:17332414, ECO:0000269|PubMed:23703864}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Tooth agenesis, selective, 7 (STHAG7) [MIM:616724]: An
CC autosomal dominant form of selective tooth agenesis, a common anomaly
CC characterized by the congenital absence of one or more teeth. Selective
CC tooth agenesis without associated systemic disorders has sometimes been
CC divided into 2 types: oligodontia, defined as agenesis of 6 or more
CC permanent teeth, and hypodontia, defined as agenesis of less than 6
CC teeth. The number in both cases does not include absence of third
CC molars (wisdom teeth). {ECO:0000269|PubMed:26387593}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
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DR EMBL; AF074264; AAC33006.1; -; mRNA.
DR EMBL; AC007537; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC007621; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC117136; AAI17137.1; -; mRNA.
DR EMBL; BC126405; AAI26406.1; -; mRNA.
DR CCDS; CCDS8647.1; -.
DR PIR; JE0272; JE0272.
DR RefSeq; NP_002327.2; NM_002336.2.
DR RefSeq; XP_006719141.1; XM_006719078.3.
DR PDB; 3S2K; X-ray; 2.80 A; A/B=630-1246.
DR PDB; 3S8V; X-ray; 3.10 A; A/B=629-1243.
DR PDB; 3S8Z; X-ray; 2.80 A; A=629-1243.
DR PDB; 3S94; X-ray; 2.80 A; A/B=20-630.
DR PDB; 3SOB; X-ray; 1.90 A; B=20-335.
DR PDB; 3SOQ; X-ray; 1.90 A; A=20-326.
DR PDB; 3SOV; X-ray; 1.27 A; A=20-326.
DR PDB; 4A0P; X-ray; 1.90 A; A=629-1244.
DR PDB; 4DG6; X-ray; 2.90 A; A=20-635.
DR PDB; 4NM5; X-ray; 2.30 A; C=1568-1575.
DR PDB; 4NM7; X-ray; 2.30 A; C=1603-1610.
DR PDB; 5AIR; X-ray; 2.53 A; A/B=1565-1575.
DR PDB; 5FWW; X-ray; 3.50 A; A=630-1246.
DR PDB; 5GJE; EM; 21.00 A; A=20-630, B=631-1246.
DR PDB; 6H15; X-ray; 2.60 A; A/B=630-1244.
DR PDB; 6H16; X-ray; 2.90 A; A=630-1244.
DR PDB; 6L6R; X-ray; 3.80 A; A/B=21-630.
DR PDBsum; 3S2K; -.
DR PDBsum; 3S8V; -.
DR PDBsum; 3S8Z; -.
DR PDBsum; 3S94; -.
DR PDBsum; 3SOB; -.
DR PDBsum; 3SOQ; -.
DR PDBsum; 3SOV; -.
DR PDBsum; 4A0P; -.
DR PDBsum; 4DG6; -.
DR PDBsum; 4NM5; -.
DR PDBsum; 4NM7; -.
DR PDBsum; 5AIR; -.
DR PDBsum; 5FWW; -.
DR PDBsum; 5GJE; -.
DR PDBsum; 6H15; -.
DR PDBsum; 6H16; -.
DR PDBsum; 6L6R; -.
DR AlphaFoldDB; O75581; -.
DR SMR; O75581; -.
DR BioGRID; 110219; 164.
DR CORUM; O75581; -.
DR DIP; DIP-29884N; -.
DR IntAct; O75581; 61.
DR MINT; O75581; -.
DR STRING; 9606.ENSP00000261349; -.
DR BindingDB; O75581; -.
DR ChEMBL; CHEMBL3745588; -.
DR GlyGen; O75581; 12 sites.
DR iPTMnet; O75581; -.
DR PhosphoSitePlus; O75581; -.
DR SwissPalm; O75581; -.
DR BioMuta; LRP6; -.
DR EPD; O75581; -.
DR jPOST; O75581; -.
DR MassIVE; O75581; -.
DR MaxQB; O75581; -.
DR PaxDb; O75581; -.
DR PeptideAtlas; O75581; -.
DR PRIDE; O75581; -.
DR ProteomicsDB; 50097; -.
DR ABCD; O75581; 6 sequenced antibodies.
DR Antibodypedia; 3851; 478 antibodies from 38 providers.
DR DNASU; 4040; -.
DR Ensembl; ENST00000261349.9; ENSP00000261349.4; ENSG00000070018.9.
DR Ensembl; ENST00000628182.3; ENSP00000486315.1; ENSG00000281324.3.
DR GeneID; 4040; -.
DR KEGG; hsa:4040; -.
DR MANE-Select; ENST00000261349.9; ENSP00000261349.4; NM_002336.3; NP_002327.2.
DR UCSC; uc001rah.6; human.
DR CTD; 4040; -.
DR DisGeNET; 4040; -.
DR GeneCards; LRP6; -.
DR HGNC; HGNC:6698; LRP6.
DR HPA; ENSG00000070018; Low tissue specificity.
DR MalaCards; LRP6; -.
DR MIM; 603507; gene.
DR MIM; 610947; phenotype.
DR MIM; 616724; phenotype.
DR neXtProt; NX_O75581; -.
DR OpenTargets; ENSG00000070018; -.
DR Orphanet; 411969; NON RARE IN EUROPE: Metabolic syndrome.
DR Orphanet; 99798; Oligodontia.
DR PharmGKB; PA30456; -.
DR VEuPathDB; HostDB:ENSG00000070018; -.
DR eggNOG; KOG1215; Eukaryota.
DR GeneTree; ENSGT00940000158990; -.
DR InParanoid; O75581; -.
DR OMA; TGVNPCK; -.
DR OrthoDB; 121310at2759; -.
DR PhylomeDB; O75581; -.
DR TreeFam; TF315253; -.
DR PathwayCommons; O75581; -.
DR Reactome; R-HSA-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-HSA-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR Reactome; R-HSA-4641263; Regulation of FZD by ubiquitination.
DR Reactome; R-HSA-5340588; Signaling by RNF43 mutants.
DR SignaLink; O75581; -.
DR SIGNOR; O75581; -.
DR BioGRID-ORCS; 4040; 12 hits in 1083 CRISPR screens.
DR ChiTaRS; LRP6; human.
DR EvolutionaryTrace; O75581; -.
DR GeneWiki; LRP6; -.
DR GenomeRNAi; 4040; -.
DR Pharos; O75581; Tbio.
DR PRO; PR:O75581; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O75581; protein.
DR Bgee; ENSG00000070018; Expressed in calcaneal tendon and 105 other tissues.
DR ExpressionAtlas; O75581; baseline and differential.
DR Genevisible; O75581; HS.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:1990909; C:Wnt signalosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:1990851; C:Wnt-Frizzled-LRP5/6 complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:1904928; F:coreceptor activity involved in canonical Wnt signaling pathway; NAS:ParkinsonsUK-UCL.
DR GO; GO:0071936; F:coreceptor activity involved in Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0005109; F:frizzled binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019210; F:kinase inhibitor activity; IMP:BHF-UCL.
DR GO; GO:0005041; F:low-density lipoprotein particle receptor activity; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL.
DR GO; GO:0019534; F:toxin transmembrane transporter activity; IMP:BHF-UCL.
DR GO; GO:0042813; F:Wnt receptor activity; IEA:InterPro.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:BHF-UCL.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0044335; P:canonical Wnt signaling pathway involved in neural crest cell differentiation; IC:BHF-UCL.
DR GO; GO:0044340; P:canonical Wnt signaling pathway involved in regulation of cell proliferation; IC:BHF-UCL.
DR GO; GO:0098609; P:cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0071397; P:cellular response to cholesterol; IMP:BHF-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; ISS:ParkinsonsUK-UCL.
DR GO; GO:1904948; P:midbrain dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:BHF-UCL.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; IMP:BHF-UCL.
DR GO; GO:0014033; P:neural crest cell differentiation; IDA:BHF-UCL.
DR GO; GO:0014029; P:neural crest formation; IDA:BHF-UCL.
DR GO; GO:0045787; P:positive regulation of cell cycle; IMP:BHF-UCL.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; IPI:ParkinsonsUK-UCL.
DR GO; GO:0090118; P:receptor-mediated endocytosis involved in cholesterol transport; IBA:GO_Central.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:1904953; P:Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL.
DR GO; GO:0090244; P:Wnt signaling pathway involved in somitogenesis; IBA:GO_Central.
DR CDD; cd00112; LDLa; 3.
DR Gene3D; 2.120.10.30; -; 4.
DR Gene3D; 4.10.400.10; -; 3.
DR IDEAL; IID00531; -.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR000033; LDLR_classB_rpt.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR017049; LRP5/6.
DR Pfam; PF00057; Ldl_recept_a; 3.
DR Pfam; PF00058; Ldl_recept_b; 11.
DR PIRSF; PIRSF036314; LDL_recpt-rel_p5/6; 1.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 4.
DR SMART; SM00192; LDLa; 3.
DR SMART; SM00135; LY; 20.
DR SUPFAM; SSF57424; SSF57424; 3.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS01209; LDLRA_1; 3.
DR PROSITE; PS50068; LDLRA_2; 3.
DR PROSITE; PS51120; LDLRB; 19.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Developmental protein; Disease variant;
KW Disulfide bond; EGF-like domain; Endocytosis; Endoplasmic reticulum;
KW Glycoprotein; Isopeptide bond; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix; Ubl conjugation; Wnt signaling pathway.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1613
FT /note="Low-density lipoprotein receptor-related protein 6"
FT /id="PRO_0000017330"
FT TOPO_DOM 20..1370
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1371..1393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1394..1613
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 63..106
FT /note="LDL-receptor class B 1"
FT REPEAT 107..149
FT /note="LDL-receptor class B 2"
FT REPEAT 150..193
FT /note="LDL-receptor class B 3"
FT REPEAT 194..236
FT /note="LDL-receptor class B 4"
FT REPEAT 237..276
FT /note="LDL-receptor class B 5"
FT DOMAIN 282..324
FT /note="EGF-like 1"
FT REPEAT 372..414
FT /note="LDL-receptor class B 6"
FT REPEAT 415..457
FT /note="LDL-receptor class B 7"
FT REPEAT 458..501
FT /note="LDL-receptor class B 8"
FT REPEAT 502..542
FT /note="LDL-receptor class B 9"
FT REPEAT 543..584
FT /note="LDL-receptor class B 10"
FT DOMAIN 588..628
FT /note="EGF-like 2"
FT REPEAT 674..716
FT /note="LDL-receptor class B 11"
FT REPEAT 717..759
FT /note="LDL-receptor class B 12"
FT REPEAT 760..802
FT /note="LDL-receptor class B 13"
FT REPEAT 803..842
FT /note="LDL-receptor class B 14"
FT REPEAT 843..885
FT /note="LDL-receptor class B 15"
FT DOMAIN 889..930
FT /note="EGF-like 3"
FT REPEAT 977..1025
FT /note="LDL-receptor class B 16"
FT REPEAT 1026..1068
FT /note="LDL-receptor class B 17"
FT REPEAT 1069..1113
FT /note="LDL-receptor class B 18"
FT REPEAT 1114..1156
FT /note="LDL-receptor class B 19"
FT REPEAT 1157..1198
FT /note="LDL-receptor class B 20"
FT DOMAIN 1203..1244
FT /note="EGF-like 4"
FT DOMAIN 1248..1286
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1287..1323
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1325..1361
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT REGION 20..275
FT /note="Beta-propeller 1"
FT REGION 328..589
FT /note="Beta-propeller 2"
FT REGION 631..890
FT /note="Beta-propeller 3"
FT REGION 933..1202
FT /note="Beta-propeller 4"
FT REGION 1556..1613
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1487..1493
FT /note="PPPSP motif A"
FT MOTIF 1527..1534
FT /note="PPPSP motif B"
FT MOTIF 1568..1575
FT /note="PPPSP motif C"
FT MOTIF 1588..1593
FT /note="PPPSP motif D"
FT MOTIF 1603..1610
FT /note="PPPSP motif E"
FT MOD_RES 1420
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000269|PubMed:16513652"
FT MOD_RES 1430
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000269|PubMed:16513652"
FT MOD_RES 1479
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17569865"
FT MOD_RES 1490
FT /note="Phosphoserine; by CDK14, GRK5 and GRK6"
FT /evidence="ECO:0000269|PubMed:16341017,
FT ECO:0000269|PubMed:17698587, ECO:0000269|PubMed:18762581,
FT ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20059949,
FT ECO:0000269|PubMed:25331957, ECO:0000269|PubMed:27821587,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1493
FT /note="Phosphothreonine; by CK1"
FT /evidence="ECO:0000269|PubMed:16341017"
FT LIPID 1394
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:18378904"
FT LIPID 1399
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:18378904"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 486
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 692
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22000856"
FT CARBOHYD 859
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22000856"
FT CARBOHYD 865
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22000856"
FT CARBOHYD 926
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22000856"
FT CARBOHYD 1039
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22000856"
FT DISULFID 286..297
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 293..308
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 310..323
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 592..603
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 599..612
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 614..627
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 893..904
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000269|PubMed:22000856"
FT DISULFID 900..914
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000269|PubMed:22000856"
FT DISULFID 916..929
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000269|PubMed:22000856"
FT DISULFID 1207..1218
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000269|PubMed:22000856"
FT DISULFID 1214..1228
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000269|PubMed:22000856"
FT DISULFID 1230..1243
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000269|PubMed:22000856"
FT DISULFID 1249..1263
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1256..1276
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1270..1285
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1288..1300
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1295..1313
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1307..1322
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1326..1338
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1333..1351
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1345..1360
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT CROSSLNK 1403
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:18378904"
FT VARIANT 19
FT /note="A -> V (in STHAG7; impairs Wnt signaling; prevents
FT transport to plasma membrane location; dbSNP:rs864309648)"
FT /evidence="ECO:0000269|PubMed:26387593"
FT /id="VAR_076207"
FT VARIANT 360
FT /note="R -> H (in ADCAD2; dbSNP:rs141212743)"
FT /evidence="ECO:0000269|PubMed:23703864"
FT /id="VAR_076208"
FT VARIANT 433
FT /note="N -> S (in ADCAD2; dbSNP:rs397515473)"
FT /evidence="ECO:0000269|PubMed:23703864"
FT /id="VAR_076209"
FT VARIANT 473
FT /note="R -> Q (in ADCAD2; impairs Wnt signaling;
FT dbSNP:rs397515474)"
FT /evidence="ECO:0000269|PubMed:23703864"
FT /id="VAR_076210"
FT VARIANT 483
FT /note="V -> I (in dbSNP:rs7975614)"
FT /id="VAR_030349"
FT VARIANT 611
FT /note="R -> C (in ADCAD2; impairs Wnt signaling in vitro;
FT dbSNP:rs121918313)"
FT /evidence="ECO:0000269|PubMed:17332414"
FT /id="VAR_034701"
FT VARIANT 817
FT /note="S -> C (in dbSNP:rs2302686)"
FT /id="VAR_030350"
FT VARIANT 1062
FT /note="V -> I (in dbSNP:rs2302685)"
FT /evidence="ECO:0000269|PubMed:9704021"
FT /id="VAR_024520"
FT VARIANT 1401
FT /note="R -> H (in dbSNP:rs34815107)"
FT /id="VAR_034702"
FT VARIANT 1415
FT /note="V -> F (found in a patient with congenital
FT hydrocephalus; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:29983323"
FT /id="VAR_083431"
FT MUTAGEN 1394
FT /note="C->A: Some reduction of palmitoylation, little
FT change in plasma membrane location in the presence of MESD
FT nor in Wnt-signaling activity. Completely abolishes
FT palmitoylation, no plasma membrane location, greatly
FT reduced Wnt-signaling activity but no effect on
FT ubiquitination; when associated with A-1399. Exhibits full
FT Wnt-signaling activity and no change in plasma membrane
FT location; when associated with A-1399 and R-1403."
FT /evidence="ECO:0000269|PubMed:18378904"
FT MUTAGEN 1399
FT /note="C->A: Some reduction of palmitoylation, and little
FT change in plasma membrane location in the presence of MESD
FT nor in Wnt-signaling activity. Completely abolishes
FT palmitoylation, no plasma membrane location, greatly
FT reduced Wnt-signaling activity but no effect on
FT ubiquitination; when associated with A-1394. Exhibits full
FT Wnt-signaling activity and no change in plasma membrane
FT location in the in presence of MESD; when associated with
FT A-1394 and R-1403."
FT /evidence="ECO:0000269|PubMed:18378904"
FT MUTAGEN 1403
FT /note="K->R: Abolishes ubiquitination, no change in plasma
FT membrane location in the presence of MESD but greatly
FT reduced Wnt-signaling activity. Exhibits full Wnt-signaling
FT activity and no change in plasma membrane location; when
FT associated with A-1394 and A-1399."
FT MUTAGEN 1420
FT /note="S->A: Enhanced AXIN1 binding and increased beta-
FT catenin activity by 2.2-fold. Further enhanced AXIN1
FT binding and increases beta-catenin activity by 3.3-fold;
FT when associated with A-1430."
FT /evidence="ECO:0000269|PubMed:16513652"
FT MUTAGEN 1430
FT /note="S->A: Enhanced AXIN1 binding. Further enhanced AXIN1
FT binding and increases beta-catenin activity by 3.3-fold;
FT when associated with A-1420."
FT /evidence="ECO:0000269|PubMed:16513652"
FT MUTAGEN 1485
FT /note="L->A: No change in the phosphorylation state of
FT PPPSP motif. Some reduction in Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1486
FT /note="N->A: No change in the phosphorylation state of
FT PPPSP motif. Increased Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1487
FT /note="P->A: No change in the phosphorylation state of
FT PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1487
FT /note="P->C: No change in the phosphorylation state of
FT PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1488
FT /note="P->A: No change in the phosphorylation state of
FT PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1489
FT /note="P->A: No change in the phosphorylation state of
FT PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1490
FT /note="S->A: Greatly reduced phosphorylation of PPPSP motif
FT A. Greatly reduced Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1490
FT /note="S->T: Some loss of phosphorylation of PPPSP motif A.
FT Little reduction in Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1491
FT /note="P->A: Greatly reduced phosphorylation of PPPSP motif
FT A. Greatly reduced Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1492
FT /note="A->G: No change in the phosphorylation state of
FT PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1493
FT /note="T->A: No change in the phosphorylation state of
FT PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1494
FT /note="E->A: No change in the phosphorylation state of
FT PPPSP motif A. Little reduction of Wnt/beta-catenin
FT signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1495
FT /note="R->A: No change in the phosphorylation state of
FT PPPSP motif. No reduction of Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1529
FT /note="T->A: No effect on the phosphorylation state of
FT PPPSP motif B."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1530
FT /note="T->A: Abolishes phosphorylation of PPPSP motif B.
FT Reduced Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1531
FT /note="P->A: Abolishes phosphorylation of PPPSP motif B.
FT Reduced Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1572
FT /note="T->A: Abolishes Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1590
FT /note="S->A: Abolishes Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT MUTAGEN 1607
FT /note="S->A: Abolishes Wnt/beta-catenin signaling."
FT /evidence="ECO:0000269|PubMed:18362152"
FT STRAND 22..26
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 28..35
FT /evidence="ECO:0007829|PDB:3SOV"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:3SOB"
FT STRAND 44..59
FT /evidence="ECO:0007829|PDB:3SOV"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 64..69
FT /evidence="ECO:0007829|PDB:3SOV"
FT TURN 70..73
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 74..79
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 99..103
FT /evidence="ECO:0007829|PDB:3SOV"
FT TURN 104..107
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 108..113
FT /evidence="ECO:0007829|PDB:3SOV"
FT TURN 114..117
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 138..146
FT /evidence="ECO:0007829|PDB:3SOV"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 151..156
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 162..167
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 184..190
FT /evidence="ECO:0007829|PDB:3SOV"
FT TURN 191..194
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:3SOV"
FT TURN 201..204
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 227..233
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 236..241
FT /evidence="ECO:0007829|PDB:3SOV"
FT TURN 242..245
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 246..251
FT /evidence="ECO:0007829|PDB:3SOV"
FT TURN 252..254
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:3SOV"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:3SOV"
FT TURN 285..289
FT /evidence="ECO:0007829|PDB:3SOV"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 294..299
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 305..309
FT /evidence="ECO:0007829|PDB:3SOV"
FT STRAND 328..337
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 339..346
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 360..368
FT /evidence="ECO:0007829|PDB:3S94"
FT TURN 369..372
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 373..378
FT /evidence="ECO:0007829|PDB:3S94"
FT TURN 379..382
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 383..388
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 389..391
FT /evidence="ECO:0007829|PDB:4DG6"
FT STRAND 395..398
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 407..411
FT /evidence="ECO:0007829|PDB:3S94"
FT TURN 412..415
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 416..421
FT /evidence="ECO:0007829|PDB:3S94"
FT TURN 422..425
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 426..431
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 438..441
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 447..454
FT /evidence="ECO:0007829|PDB:3S94"
FT TURN 455..458
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 459..464
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 466..468
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 470..475
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 482..485
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 492..498
FT /evidence="ECO:0007829|PDB:3S94"
FT TURN 499..502
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 503..508
FT /evidence="ECO:0007829|PDB:3S94"
FT TURN 509..512
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 513..521
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 525..529
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 538..541
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 544..548
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 555..562
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 565..569
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 575..584
FT /evidence="ECO:0007829|PDB:3S94"
FT HELIX 591..593
FT /evidence="ECO:0007829|PDB:3S94"
FT HELIX 595..598
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 600..606
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 609..613
FT /evidence="ECO:0007829|PDB:3S94"
FT STRAND 633..638
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 641..648
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 653..655
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 664..670
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 671..674
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 675..680
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 681..684
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 685..690
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 697..700
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 709..713
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 714..717
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 718..723
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 724..727
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 728..733
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 740..743
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 750..756
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 757..760
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 761..766
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 768..770
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 772..777
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 784..787
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 791..799
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 800..803
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 804..809
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 810..813
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 814..819
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 826..830
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 835..841
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 844..849
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 850..853
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 854..859
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 860..862
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 867..870
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 878..882
FT /evidence="ECO:0007829|PDB:4A0P"
FT HELIX 884..886
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 892..896
FT /evidence="ECO:0007829|PDB:4A0P"
FT HELIX 897..899
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 901..907
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 908..910
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 911..915
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 933..940
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 943..947
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 967..973
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 974..977
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 978..983
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 984..987
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 988..993
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1000..1003
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1016..1022
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 1023..1026
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1027..1032
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 1033..1036
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1037..1042
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1047..1052
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1059..1065
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 1066..1069
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1070..1077
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1080..1087
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1094..1097
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1104..1110
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 1111..1114
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1115..1120
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 1121..1124
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1125..1130
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1137..1140
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1147..1153
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1156..1161
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 1162..1165
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1166..1171
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1174..1176
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1179..1182
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1188..1194
FT /evidence="ECO:0007829|PDB:4A0P"
FT HELIX 1199..1204
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 1206..1209
FT /evidence="ECO:0007829|PDB:4A0P"
FT HELIX 1210..1213
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1215..1220
FT /evidence="ECO:0007829|PDB:4A0P"
FT TURN 1222..1224
FT /evidence="ECO:0007829|PDB:3S8Z"
FT STRAND 1226..1229
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1234..1236
FT /evidence="ECO:0007829|PDB:4A0P"
FT STRAND 1238..1241
FT /evidence="ECO:0007829|PDB:3S8Z"
SQ SEQUENCE 1613 AA; 180429 MW; 413D2CF70A5D8B5C CRC64;
MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL EDAAAVDFVF
SHGLIYWSDV SEEAIKRTEF NKTESVQNVV VSGLLSPDGL ACDWLGEKLY WTDSETNRIE
VSNLDGSLRK VLFWQELDQP RAIALDPSSG FMYWTDWGEV PKIERAGMDG SSRFIIINSE
IYWPNGLTLD YEEQKLYWAD AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDILYWT
DWSTHSILAC NKYTGEGLRE IHSDIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS
PVKPFYQCAC PTGVKLLENG KTCKDGATEL LLLARRTDLR RISLDTPDFT DIVLQLEDIR
HAIAIDYDPV EGYIYWTDDE VRAIRRSFID GSGSQFVVTA QIAHPDGIAV DWVARNLYWT
DTGTDRIEVT RLNGTMRKIL ISEDLEEPRA IVLDPMVGYM YWTDWGEIPK IERAALDGSD
RVVLVNTSLG WPNGLALDYD EGKIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL
LGDYVYWTDW QRRSIERVHK RSAEREVIID QLPDLMGLKA TNVHRVIGSN PCAEENGGCS
HLCLYRPQGL RCACPIGFEL ISDMKTCIVP EAFLLFSRRA DIRRISLETN NNNVAIPLTG
VKEASALDFD VTDNRIYWTD ISLKTISRAF MNGSALEHVV EFGLDYPEGM AVDWLGKNLY
WADTGTNRIE VSKLDGQHRQ VLVWKDLDSP RALALDPAEG FMYWTEWGGK PKIDRAAMDG
SERTTLVPNV GRANGLTIDY AKRRLYWTDL DTNLIESSNM LGLNREVIAD DLPHPFGLTQ
YQDYIYWTDW SRRSIERANK TSGQNRTIIQ GHLDYVMDIL VFHSSRQSGW NECASSNGHC
SHLCLAVPVG GFVCGCPAHY SLNADNRTCS APTTFLLFSQ KSAINRMVID EQQSPDIILP
IHSLRNVRAI DYDPLDKQLY WIDSRQNMIR KAQEDGSQGF TVVVSSVPSQ NLEIQPYDLS
IDIYSRYIYW TCEATNVINV TRLDGRSVGV VLKGEQDRPR AVVVNPEKGY MYFTNLQERS
PKIERAALDG TEREVLFFSG LSKPIALALD SRLGKLFWAD SDLRRIESSD LSGANRIVLE
DSNILQPVGL TVFENWLYWI DKQQQMIEKI DMTGREGRTK VQARIAQLSD IHAVKELNLQ
EYRQHPCAQD NGGCSHICLV KGDGTTRCSC PMHLVLLQDE LSCGEPPTCS PQQFTCFTGE
IDCIPVAWRC DGFTECEDHS DELNCPVCSE SQFQCASGQC IDGALRCNGD ANCQDKSDEK
NCEVLCLIDQ FRCANGQCIG KHKKCDHNVD CSDKSDELDC YPTEEPAPQA TNTVGSVIGV
IVTIFVSGTV YFICQRMLCP RMKGDGETMT NDYVVHGPAS VPLGYVPHPS SLSGSLPGMS
RGKSMISSLS IMGGSSGPPY DRAHVTGASS SSSSSTKGTY FPAILNPPPS PATERSHYTM
EFGYSSNSPS THRSYSYRPY SYRHFAPPTT PCSTDVCDSD YAPSRRMTSV ATAKGYTSDL
NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH LYPPPPSPCT DSS
