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 27-MAR-2024, entry version 202. 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 FUNCTION, AND INTERACTION WITH GPR37. RX PubMed=28341812; DOI=10.15252/embr.201643585; RA Berger B.S., Acebron S.P., Herbst J., Koch S., Niehrs C.; RT "Parkinson's disease-associated receptor GPR37 is an ER chaperone for RT LRP6."; RL EMBO Rep. 18:712-725(2017). RN [34] RP INTERACTION WITH LYPD6. RX PubMed=30069874; DOI=10.1002/1873-3468.13212; RA Zhao Y., Ren J., Lu W., Harlos K., Jones E.Y.; RT "Structure of the Wnt signaling enhancer LYPD6 and its interactions with RT the Wnt coreceptor LRP6."; RL FEBS Lett. 592:3152-3162(2018). RN [35] 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 [36] 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 [37] 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 [38] 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 [39] 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 [40] 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 signalosomes. 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 signalosomes 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 ECO:0000269|PubMed:28341812}. 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 signalosomes. 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 (via CC NxI motif) (PubMed:23987510, PubMed:30069874). Forms a ternary complex CC with DKK1 and KREM1 (PubMed:27524201). Interacts with KREM1 in a DKK1- CC dependent manner (PubMed:17804805). Interacts with MDK: this CC interaction is calcium dependent (By similarity). Interacts with LMBR1L CC (PubMed:31073040). Interacts with GPR37; this interaction promotes LRP6 CC maturation (PubMed:28341812). {ECO:0000250|UniProtKB:O88572, CC ECO:0000269|PubMed:11357136, ECO:0000269|PubMed:11448771, CC ECO:0000269|PubMed:12857724, ECO:0000269|PubMed:15778503, CC ECO:0000269|PubMed:15908424, ECO:0000269|PubMed:16513652, CC ECO:0000269|PubMed:16815997, ECO:0000269|PubMed:17400545, CC ECO:0000269|PubMed:17569865, ECO:0000269|PubMed:17698587, CC ECO:0000269|PubMed:17804805, ECO:0000269|PubMed:18362152, CC ECO:0000269|PubMed:18762581, ECO:0000269|PubMed:20093360, CC ECO:0000269|PubMed:21536646, ECO:0000269|PubMed:22000856, CC ECO:0000269|PubMed:22491013, ECO:0000269|PubMed:23987510, CC ECO:0000269|PubMed:25331957, ECO:0000269|PubMed:27524201, CC ECO:0000269|PubMed:27821587, ECO:0000269|PubMed:28341812, CC ECO:0000269|PubMed:30069874, 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=16; 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 signalosomes. Chaperoned to the plasma membrane by MESD (By CC similarity). {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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7NAM; X-ray; 1.60 A; A=20-326. DR PDB; 8CTG; EM; 3.80 A; C=20-629. DR PDB; 8DVL; X-ray; 2.50 A; A=631-1253. DR PDB; 8DVM; X-ray; 2.00 A; A=631-1253. DR PDB; 8DVN; X-ray; 2.53 A; A=631-1253. DR PDB; 8FFE; X-ray; 1.72 A; A=20-631. 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 PDBsum; 7NAM; -. DR PDBsum; 8CTG; -. DR PDBsum; 8DVL; -. DR PDBsum; 8DVM; -. DR PDBsum; 8DVN; -. DR PDBsum; 8FFE; -. DR AlphaFoldDB; O75581; -. DR EMDB; EMD-26989; -. DR EMDB; EMD-9501; -. DR SMR; O75581; -. DR BioGRID; 110219; 168. DR CORUM; O75581; -. DR DIP; DIP-29884N; -. DR IntAct; O75581; 63. DR MINT; O75581; -. DR STRING; 9606.ENSP00000261349; -. DR BindingDB; O75581; -. DR ChEMBL; CHEMBL3745588; -. DR GlyCosmos; O75581; 10 sites, No reported glycans. 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; 9606-ENSP00000261349; -. DR PeptideAtlas; O75581; -. DR ProteomicsDB; 50097; -. DR Pumba; O75581; -. DR ABCD; O75581; 6 sequenced antibodies. DR Antibodypedia; 3851; 713 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 AGR; HGNC:6698; -. 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; VNPCKVN; -. DR OrthoDB; 3107655at2759; -. 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; 13 hits in 1161 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 106 other cell types or tissues. DR ExpressionAtlas; O75581; baseline and differential. 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: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:MGI. DR GO; GO:0045202; C:synapse; IEA:GOC. 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:0015026; F:coreceptor activity; 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; IBA:GO_Central. 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: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: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:0045893; P:positive regulation of DNA-templated transcription; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA: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:0090244; P:Wnt signaling pathway involved in somitogenesis; IBA:GO_Central. DR CDD; cd00112; LDLa; 3. DR Gene3D; 2.10.25.10; Laminin; 1. DR Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 3. DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 4. 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 PANTHER; PTHR46513:SF40; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 6; 1. DR PANTHER; PTHR46513; VITELLOGENIN RECEPTOR-LIKE PROTEIN-RELATED-RELATED; 1. DR Pfam; PF14670; FXa_inhibition; 4. 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; SSF57196; EGF/Laminin; 4. DR SUPFAM; SSF57424; LDL receptor-like module; 3. DR SUPFAM; SSF63825; YWTD domain; 4. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS01209; LDLRA_1; 3. DR PROSITE; PS50068; LDLRA_2; 3. DR PROSITE; PS51120; LDLRB; 19. DR Genevisible; O75581; HS. 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; uncertain 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 FT beta-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 TURN 37..40 FT /evidence="ECO:0007829|PDB:8FFE" 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:8FFE" FT STRAND 339..346 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 351..353 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 362..368 FT /evidence="ECO:0007829|PDB:8FFE" FT TURN 369..372 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 373..378 FT /evidence="ECO:0007829|PDB:8FFE" FT TURN 379..382 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 383..387 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 389..391 FT /evidence="ECO:0007829|PDB:4DG6" FT STRAND 395..398 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 407..411 FT /evidence="ECO:0007829|PDB:8FFE" FT TURN 412..415 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 416..421 FT /evidence="ECO:0007829|PDB:8FFE" FT TURN 422..425 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 426..431 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 438..441 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 446..454 FT /evidence="ECO:0007829|PDB:8FFE" FT TURN 455..458 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 459..464 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 466..468 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 470..475 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 482..485 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 492..498 FT /evidence="ECO:0007829|PDB:8FFE" FT TURN 499..502 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 503..508 FT /evidence="ECO:0007829|PDB:8FFE" FT TURN 509..512 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 513..518 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 525..528 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 535..541 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 544..549 FT /evidence="ECO:0007829|PDB:8FFE" FT TURN 550..553 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 554..559 FT /evidence="ECO:0007829|PDB:8FFE" FT TURN 560..562 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 565..569 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 575..584 FT /evidence="ECO:0007829|PDB:8FFE" FT HELIX 591..593 FT /evidence="ECO:0007829|PDB:8FFE" FT HELIX 595..598 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 600..604 FT /evidence="ECO:0007829|PDB:8FFE" FT STRAND 611..613 FT /evidence="ECO:0007829|PDB:8FFE" 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 STRAND 1222..1224 FT /evidence="ECO:0007829|PDB:8DVM" FT STRAND 1226..1229 FT /evidence="ECO:0007829|PDB:4A0P" FT STRAND 1234..1236 FT /evidence="ECO:0007829|PDB:4A0P" FT STRAND 1240..1244 FT /evidence="ECO:0007829|PDB:8DVN" 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 //