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 13-FEB-2019, entry version 172. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT density 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., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA 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., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA 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., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., 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 RT project: 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: RT interaction with A FZD5 x LRP6 receptor complex and modulation by RT 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., RA 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 RP INTERACTION 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 RP THR-1493, 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 RT Wnt signaling pathway."; RL Genes Dev. 20:1933-1945(2006). RN [11] RP PHOSPHORYLATION AT SER-1420 AND SER-1430, FUNCTION, INTERACTION WITH RP CSNKIE AND AXIN1, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS RP OF SER-1420 AND SER-1430. RX PubMed=16513652; DOI=10.1074/jbc.M510580200; RA Swiatek W., Kang H., Garcia B.A., Shabanowitz J., Coombs G.S., RA Hunt D.F., 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 RT mechanism by 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., RA 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., RA Bienz M., 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 RT of 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., RA Lee J., Oh S., Han J.K., Park B.J., Weis W.I., Ha N.C.; RT "Direct inhibition of GSK3beta by the phosphorylated cytoplasmic RT domain of 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., RA Bartscherer K., 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 RP 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, RP AND 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., RA Costa M., 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 RT signaling 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 RT LRP6 and 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., RA Bouwmeester T., Finan P.M., Kirschner M.W., Porter J.A., Serluca F.C., RA Cong F.; RT "ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive RT 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 RP BY 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 RT constitutive 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 RT ternary complex formation with LRP6 and Dickkopf."; RL Structure 24:1599-1605(2016). RN [33] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 630-1246 IN COMPLEX WITH RP DKK1, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-692; ASN-859; RP ASN-865; 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 [34] RP VARIANT ADCAD2 CYS-611, AND CHARACTERIZATION OF VARIANT ADCAD2 RP 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., RA Lifton R.P.; RT "LRP6 mutation in a family with early coronary disease and metabolic RT risk factors."; RL Science 315:1278-1282(2007). RN [35] 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 [36] RP INVOLVEMENT IN STHAG7, VARIANT STHAG7 VAL-19, CHARACTERIZATION OF RP VARIANT 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 RT Autosomal-Dominant Oligodontia."; RL Am. J. Hum. Genet. 97:621-626(2015). CC -!- FUNCTION: Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers CC beta-catenin signaling through inducing aggregation of receptor- CC ligand complexes into ribosome-sized signalsomes. Cell-surface CC coreceptor of Wnt/beta-catenin signaling, which plays a pivotal CC role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor CC complex recruits DVL1 polymers to the plasma membrane which, in CC turn, recruits the AXIN1/GSK3B-complex to the cell surface CC promoting the formation of signalsomes and inhibiting AXIN1/GSK3- CC mediated phosphorylation and destruction of beta-catenin. Required CC for posterior patterning of the epiblast during gastrulation (By CC similarity). {ECO:0000250, ECO:0000269|PubMed:11357136, CC ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:15778503, CC ECO:0000269|PubMed:16341017, ECO:0000269|PubMed:16513652, CC ECO:0000269|PubMed:17326769, ECO:0000269|PubMed:17400545, CC ECO:0000269|PubMed:19107203, ECO:0000269|PubMed:19293931, CC ECO:0000269|PubMed:19801552}. CC -!- SUBUNIT: Homodimer; disulfide-linked. Forms phosphorylated CC oligomer aggregates on Wnt-signaling. Forms a WNT-signaling CC complex formed of a WNT protein, a FZD protein and LRP5 or LRP6. CC Interacts (via the extracellular domain) with WNT1; the CC interaction is enhanced by prior formation of the Wnt/Fzd complex. CC Interacts (via the beta-propeller regions 3 and 4) with WNT3A. CC Interacts (via the beta-propeller regions 1 and 2) with WNT9B. CC Interacts with FZD5; the interaction forms a coreceptor complex CC for Wnt signaling and is inhibited by DKK1 and DRAXIN. Interacts CC (via beta propeller region) with DKK1; the interaction inhibits CC FZD5/LRP6 complex formation. Interacts with DKK2. Interacts with CC C1orf187/DRAXIN; the interaction inhibits Wnt signaling (By CC similarity). Interacts (via the phosphorylated PPPSP motifs) with CC AXIN1; the interaction recruits the AXIN1/GSK3B complex to cell CC surface LRP6 signalsomes. Interacts with GRB10; the interaction CC prevents AXIN1 binding, thus negatively regulating the Wnt CC signaling pathway (By similarity). Interacts (via the CC extracellular domain) with RSPO1; the interaction activates CC Wnt/beta-catenin signaling. Interacts (via the extracellular CC domain) with RSPO3 (via the cysteine rich domain); the interaction CC activates Wnt/beta-catenin signaling. Interacts (via the beta- CC propeller regions 1 and 2) with SOST; the interaction competes CC with DKK1 for binding for inhibiting beta-catenin signaling. CC Interacts with MESD; the interaction prevents the formation of CC LRP6 aggregates and targets LRP6 to the plasma membrane (By CC similarity). Interacts (via the cytoplasmic domain) with CSNKIE; CC the interaction phosphorylates LRP6, binds AXIN1 and inhibits CC AXIN1/GSK3B-mediated phosphorylation of beta-catenin. Interacts CC with MACF1. Interacts with DAB2; the interaction involves LRP6 CC phosphorylation by CK2 and sequesters LRP6 towards clathrin- CC mediated endocytosis. Interacts with TMEM198. Interacts with CC CAPRIN2; the interaction promotes LRP6 phosphorylation at Ser-1490 CC (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 CC to CDK14 via its C terminus (PubMed:27821587). Interacts with CC LYPD6 (PubMed:23987510). Forms a ternary complex with DKK1 and CC KREM1 (PubMed:27524201). Interacts with KREM1 in a DKK1-dependent CC manner (PubMed:17804805). {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}. CC -!- INTERACTION: CC Self; NbExp=4; IntAct=EBI-910915, EBI-910915; CC Q9Y4X0:AMMECR1; NbExp=5; IntAct=EBI-910915, EBI-8583355; CC Q9H6X2:ANTXR1; NbExp=3; IntAct=EBI-910915, EBI-905643; CC O15169-2:AXIN1; NbExp=3; IntAct=EBI-910915, EBI-10987526; CC O35625:Axin1 (xeno); NbExp=2; IntAct=EBI-910915, EBI-2365912; CC O70239:Axin1 (xeno); NbExp=12; IntAct=EBI-910915, EBI-6857773; CC Q03135:CAV1; NbExp=3; IntAct=EBI-910915, EBI-603614; CC P98082:DAB2; NbExp=20; IntAct=EBI-910915, EBI-1171238; CC O94907:DKK1; NbExp=14; IntAct=EBI-910915, EBI-742864; CC Q61091:Fzd8 (xeno); NbExp=4; IntAct=EBI-910915, EBI-6171689; CC P49840:GSK3A; NbExp=2; IntAct=EBI-910915, EBI-1044067; CC P49841:GSK3B; NbExp=4; IntAct=EBI-910915, EBI-373586; CC P47879:Igfbp4 (xeno); NbExp=4; IntAct=EBI-910915, EBI-15706768; CC Q5S007:LRRK2; NbExp=4; IntAct=EBI-910915, EBI-5323863; CC Q9ERE7:Mesd (xeno); NbExp=2; IntAct=EBI-910915, EBI-6662606; CC P09619:PDGFRB; NbExp=3; IntAct=EBI-910915, EBI-641237; CC Q9BQB4:SOST; NbExp=6; IntAct=EBI-910915, EBI-5746563; CC P04426:Wnt1 (xeno); NbExp=2; IntAct=EBI-910915, EBI-1570911; CC P56704:WNT3A; NbExp=2; IntAct=EBI-910915, EBI-6173037; CC P27467:Wnt3a (xeno); NbExp=4; IntAct=EBI-910915, EBI-2899665; CC Q9ULT6:ZNRF3; NbExp=2; IntAct=EBI-910915, EBI-949772; 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 CC cycle of caveolin- or clathrin-mediated endocytosis and plasma CC membrane location. Released from the endoplasmic reticulum on CC palmitoylation. Mono-ubiquitination retains it in the endoplasmic CC reticulum in the absence of palmitoylation. On Wnt signaling, CC phosphorylated, aggregates and colocalizes with AXIN1 and GSK3B at CC the plasma membrane in LRP6-signalsomes. Chaperoned to the plasma CC membrane by MESD (By similarity). {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Widely coexpressed with LRP5 during CC embryogenesis 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 CC and 4 are required for the interaction with DKK1. CC {ECO:0000269|PubMed:20059949}. CC -!- DOMAIN: The PPPSP motifs play a central role in signal CC transduction by being phosphorylated, leading to activate the Wnt CC signaling pathway. {ECO:0000269|PubMed:20059949}. CC -!- PTM: Dual phosphorylation of cytoplasmic PPPSP motifs sequentially CC by 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 CC vitro, by GRK5/6 within and outside the PPPSP motifs. CC Phosphorylation at Ser-1490 by CDK14 during G2/M phase leads to CC regulation of the Wnt signaling pathway during the cell cycle. CC Phosphorylation by GSK3B is induced by RPSO1 binding and inhibited CC by DKK1. Phosphorylated, in vitro, by casein kinase I on Thr-1479. CC {ECO:0000269|PubMed:16341017, ECO:0000269|PubMed:16513652, CC ECO:0000269|PubMed:17400545, ECO:0000269|PubMed:17569865, CC ECO:0000269|PubMed:17698587, ECO:0000269|PubMed:18362152, CC ECO:0000269|PubMed:19107203, ECO:0000269|PubMed:19293931, CC ECO:0000269|PubMed:19801552, 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 CC is 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 CC the proteasome. {ECO:0000269|PubMed:18378904, CC 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 CC absent blood flow in one or more of the arteries that encircle and CC supply the heart. Its most important complication is acute CC myocardial infarction. {ECO:0000269|PubMed:17332414, CC ECO:0000269|PubMed:23703864}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Tooth agenesis, selective, 7 (STHAG7) [MIM:616724]: An CC autosomal dominant form of selective tooth agenesis, a common CC anomaly characterized by the congenital absence of one or more CC teeth. Selective tooth agenesis without associated systemic CC disorders has sometimes been divided into 2 types: oligodontia, CC defined as agenesis of 6 or more permanent teeth, and hypodontia, CC defined as agenesis of less than 6 teeth. The number in both cases CC does not include absence of third molars (wisdom teeth). CC {ECO:0000269|PubMed:26387593}. Note=The disease is caused by CC mutations 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 UniGene; Hs.584775; -. DR UniGene; Hs.658913; -. 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 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 ProteinModelPortal; O75581; -. DR SMR; O75581; -. DR BioGrid; 110219; 54. DR CORUM; O75581; -. DR DIP; DIP-29884N; -. DR IntAct; O75581; 39. DR MINT; O75581; -. DR STRING; 9606.ENSP00000261349; -. DR BindingDB; O75581; -. DR ChEMBL; CHEMBL3745588; -. DR iPTMnet; O75581; -. DR PhosphoSitePlus; O75581; -. DR SwissPalm; O75581; -. DR BioMuta; LRP6; -. DR EPD; O75581; -. DR jPOST; O75581; -. DR MaxQB; O75581; -. DR PaxDb; O75581; -. DR PeptideAtlas; O75581; -. DR PRIDE; O75581; -. DR ProteomicsDB; 50097; -. DR Ensembl; ENST00000261349; ENSP00000261349; ENSG00000070018. DR Ensembl; ENST00000628182; ENSP00000486315; ENSG00000281324. DR GeneID; 4040; -. DR KEGG; hsa:4040; -. DR UCSC; uc001rah.6; human. DR CTD; 4040; -. DR DisGeNET; 4040; -. DR EuPathDB; HostDB:ENSG00000070018.8; -. DR GeneCards; LRP6; -. DR H-InvDB; HIX0036693; -. DR HGNC; HGNC:6698; LRP6. DR HPA; CAB004490; -. DR HPA; HPA029925; -. 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 eggNOG; ENOG410IPT4; Eukaryota. DR eggNOG; ENOG410XSY5; LUCA. DR GeneTree; ENSGT00940000158990; -. DR HOGENOM; HOG000230697; -. DR HOVERGEN; HBG049167; -. DR InParanoid; O75581; -. DR KO; K03068; -. DR OMA; WQELDQP; -. DR OrthoDB; 121310at2759; -. DR PhylomeDB; O75581; -. DR TreeFam; TF315253; -. 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; RNF mutants show enhanced WNT signaling and proliferation. DR SignaLink; O75581; -. DR SIGNOR; O75581; -. DR ChiTaRS; LRP6; human. DR EvolutionaryTrace; O75581; -. DR GeneWiki; LRP6; -. DR GenomeRNAi; 4040; -. DR PRO; PR:O75581; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; ENSG00000070018; Expressed in 234 organ(s), highest expression level in metanephros. DR ExpressionAtlas; O75581; baseline and differential. DR Genevisible; O75581; HS. DR GO; GO:0005901; C:caveola; IBA:GO_Central. 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:0043025; C:neuronal cell body; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0045202; C:synapse; IBA:GO_Central. 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:0034185; F:apolipoprotein binding; IBA:GO_Central. 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-activated receptor activity; IEA:InterPro. DR GO; GO:0017147; F:Wnt-protein binding; IPI:BHF-UCL. DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central. DR GO; GO:0090245; P:axis elongation involved in somitogenesis; IBA:GO_Central. DR GO; GO:1904886; P:beta-catenin destruction complex disassembly; TAS:Reactome. DR GO; GO:0060349; P:bone morphogenesis; IBA:GO_Central. DR GO; GO:0046849; P:bone remodeling; IBA:GO_Central. DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IBA:GO_Central. 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:0021587; P:cerebellum morphogenesis; IBA:GO_Central. DR GO; GO:0021987; P:cerebral cortex development; IBA:GO_Central. DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central. DR GO; GO:0060026; P:convergent extension; IBA:GO_Central. DR GO; GO:0071542; P:dopaminergic neuron differentiation; ISS:ParkinsonsUK-UCL. DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IBA:GO_Central. DR GO; GO:0030326; P:embryonic limb morphogenesis; IBA:GO_Central. DR GO; GO:0009880; P:embryonic pattern specification; IBA:GO_Central. DR GO; GO:0060059; P:embryonic retina morphogenesis in camera-type eye; IBA:GO_Central. DR GO; GO:0035261; P:external genitalia morphogenesis; IBA:GO_Central. DR GO; GO:0060325; P:face morphogenesis; IBA:GO_Central. DR GO; GO:0001702; P:gastrulation with mouth forming second; IBA:GO_Central. DR GO; GO:0030901; P:midbrain development; IBA:GO_Central. DR GO; GO:1904948; P:midbrain dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL. DR GO; GO:0030917; P:midbrain-hindbrain boundary development; IBA:GO_Central. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; TAS:Reactome. 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:0001843; P:neural tube closure; IBA:GO_Central. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IBA:GO_Central. DR GO; GO:0003344; P:pericardium morphogenesis; IBA:GO_Central. 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:0090009; P:primitive streak formation; IBA:GO_Central. 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:0060021; P:roof of mouth development; IBA:GO_Central. DR GO; GO:0021794; P:thalamus development; IBA:GO_Central. DR GO; GO:0060535; P:trachea cartilage morphogenesis; IBA:GO_Central. 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 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; Complete proteome; Developmental protein; KW Disease mutation; Disulfide bond; EGF-like domain; Endocytosis; KW Endoplasmic reticulum; Glycoprotein; Isopeptide bond; Lipoprotein; KW Membrane; Palmitate; Phosphoprotein; Polymorphism; Receptor; KW Reference proteome; Repeat; Signal; Transmembrane; KW Transmembrane helix; Ubl conjugation; Wnt signaling pathway. FT SIGNAL 1 19 {ECO:0000255}. FT CHAIN 20 1613 Low-density lipoprotein receptor-related FT protein 6. FT /FTId=PRO_0000017330. FT TOPO_DOM 20 1370 Extracellular. {ECO:0000255}. FT TRANSMEM 1371 1393 Helical. {ECO:0000255}. FT TOPO_DOM 1394 1613 Cytoplasmic. {ECO:0000255}. FT REPEAT 63 106 LDL-receptor class B 1. FT REPEAT 107 149 LDL-receptor class B 2. FT REPEAT 150 193 LDL-receptor class B 3. FT REPEAT 194 236 LDL-receptor class B 4. FT REPEAT 237 276 LDL-receptor class B 5. FT DOMAIN 282 324 EGF-like 1. FT REPEAT 372 414 LDL-receptor class B 6. FT REPEAT 415 457 LDL-receptor class B 7. FT REPEAT 458 501 LDL-receptor class B 8. FT REPEAT 502 542 LDL-receptor class B 9. FT REPEAT 543 584 LDL-receptor class B 10. FT DOMAIN 588 628 EGF-like 2. FT REPEAT 674 716 LDL-receptor class B 11. FT REPEAT 717 759 LDL-receptor class B 12. FT REPEAT 760 802 LDL-receptor class B 13. FT REPEAT 803 842 LDL-receptor class B 14. FT REPEAT 843 885 LDL-receptor class B 15. FT DOMAIN 889 930 EGF-like 3. FT REPEAT 977 1025 LDL-receptor class B 16. FT REPEAT 1026 1068 LDL-receptor class B 17. FT REPEAT 1069 1113 LDL-receptor class B 18. FT REPEAT 1114 1156 LDL-receptor class B 19. FT REPEAT 1157 1198 LDL-receptor class B 20. FT DOMAIN 1203 1244 EGF-like 4. FT DOMAIN 1248 1286 LDL-receptor class A 1. FT {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DOMAIN 1287 1323 LDL-receptor class A 2. FT {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DOMAIN 1325 1361 LDL-receptor class A 3. FT {ECO:0000255|PROSITE-ProRule:PRU00124}. FT REGION 20 275 Beta-propeller 1. FT REGION 328 589 Beta-propeller 2. FT REGION 631 890 Beta-propeller 3. FT REGION 933 1202 Beta-propeller 4. FT MOTIF 1487 1493 PPPSP motif A. FT MOTIF 1527 1534 PPPSP motif B. FT MOTIF 1568 1575 PPPSP motif C. FT MOTIF 1588 1593 PPPSP motif D. FT MOTIF 1603 1610 PPPSP motif E. FT MOD_RES 1420 1420 Phosphoserine; by CK1. FT {ECO:0000269|PubMed:16513652}. FT MOD_RES 1430 1430 Phosphoserine; by CK1. FT {ECO:0000269|PubMed:16513652}. FT MOD_RES 1479 1479 Phosphothreonine. FT {ECO:0000269|PubMed:17569865}. FT MOD_RES 1490 1490 Phosphoserine; by CDK14, GRK5 and GRK6. FT {ECO:0000244|PubMed:23186163, FT ECO:0000269|PubMed:16341017, FT ECO:0000269|PubMed:17698587, FT ECO:0000269|PubMed:18762581, FT ECO:0000269|PubMed:19801552, FT ECO:0000269|PubMed:20059949, FT ECO:0000269|PubMed:25331957, FT ECO:0000269|PubMed:27821587}. FT MOD_RES 1493 1493 Phosphothreonine; by CK1. FT {ECO:0000269|PubMed:16341017}. FT LIPID 1394 1394 S-palmitoyl cysteine. FT {ECO:0000269|PubMed:18378904}. FT LIPID 1399 1399 S-palmitoyl cysteine. FT {ECO:0000269|PubMed:18378904}. FT CARBOHYD 42 42 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 81 81 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 281 281 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 433 433 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 486 486 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 692 692 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22000856}. FT CARBOHYD 859 859 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22000856}. FT CARBOHYD 865 865 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22000856}. FT CARBOHYD 926 926 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22000856}. FT CARBOHYD 1039 1039 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22000856}. FT DISULFID 286 297 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 293 308 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 310 323 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 592 603 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 599 612 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 614 627 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 893 904 {ECO:0000255|PROSITE-ProRule:PRU00124, FT ECO:0000269|PubMed:22000856}. FT DISULFID 900 914 {ECO:0000255|PROSITE-ProRule:PRU00124, FT ECO:0000269|PubMed:22000856}. FT DISULFID 916 929 {ECO:0000255|PROSITE-ProRule:PRU00124, FT ECO:0000269|PubMed:22000856}. FT DISULFID 1207 1218 {ECO:0000255|PROSITE-ProRule:PRU00124, FT ECO:0000269|PubMed:22000856}. FT DISULFID 1214 1228 {ECO:0000255|PROSITE-ProRule:PRU00124, FT ECO:0000269|PubMed:22000856}. FT DISULFID 1230 1243 {ECO:0000255|PROSITE-ProRule:PRU00124, FT ECO:0000269|PubMed:22000856}. FT DISULFID 1249 1263 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 1256 1276 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 1270 1285 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 1288 1300 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 1295 1313 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 1307 1322 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 1326 1338 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 1333 1351 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT DISULFID 1345 1360 {ECO:0000255|PROSITE-ProRule:PRU00124}. FT CROSSLNK 1403 1403 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000269|PubMed:18378904}. FT VARIANT 19 19 A -> V (in STHAG7; impairs Wnt signaling; FT prevents transport to plasma membrane FT location; dbSNP:rs864309648). FT {ECO:0000269|PubMed:26387593}. FT /FTId=VAR_076207. FT VARIANT 360 360 R -> H (in ADCAD2; dbSNP:rs141212743). FT {ECO:0000269|PubMed:23703864}. FT /FTId=VAR_076208. FT VARIANT 433 433 N -> S (in ADCAD2; dbSNP:rs397515473). FT {ECO:0000269|PubMed:23703864}. FT /FTId=VAR_076209. FT VARIANT 473 473 R -> Q (in ADCAD2; impairs Wnt signaling; FT dbSNP:rs397515474). FT {ECO:0000269|PubMed:23703864}. FT /FTId=VAR_076210. FT VARIANT 483 483 V -> I (in dbSNP:rs7975614). FT /FTId=VAR_030349. FT VARIANT 611 611 R -> C (in ADCAD2; impairs Wnt signaling FT in vitro; dbSNP:rs121918313). FT {ECO:0000269|PubMed:17332414}. FT /FTId=VAR_034701. FT VARIANT 817 817 S -> C (in dbSNP:rs2302686). FT /FTId=VAR_030350. FT VARIANT 1062 1062 V -> I (in dbSNP:rs2302685). FT {ECO:0000269|PubMed:9704021}. FT /FTId=VAR_024520. FT VARIANT 1401 1401 R -> H (in dbSNP:rs34815107). FT /FTId=VAR_034702. FT MUTAGEN 1394 1394 C->A: Some reduction of palmitoylation, FT little change in plasma membrane location FT in the presence of MESD nor in Wnt- FT signaling activity. Completely abolishes FT palmitoylation, no plasma membrane FT location, greatly reduced Wnt-signaling FT activity but no effect on ubiquitination; FT when associated with A-1399. Exhibits FT full Wnt-signaling activity and no change FT in plasma membrane location; when FT associated with A-1399 and R-1403. FT {ECO:0000269|PubMed:18378904}. FT MUTAGEN 1399 1399 C->A: Some reduction of palmitoylation, FT and little change in plasma membrane FT location in the presence of MESD nor in FT Wnt-signaling activity. Completely FT abolishes palmitoylation, no plasma FT membrane location, greatly reduced Wnt- FT signaling activity but no effect on FT ubiquitination; when associated with A- FT 1394. Exhibits full Wnt-signaling FT activity and no change in plasma membrane FT location in the in presence of MESD; when FT associated with A-1394 and R-1403. FT {ECO:0000269|PubMed:18378904}. FT MUTAGEN 1403 1403 K->R: Abolishes ubiquitination, no change FT in plasma membrane location in the FT presence of MESD but greatly reduced Wnt- FT signaling activity. Exhibits full Wnt- FT signaling activity and no change in FT plasma membrane location; when associated FT with A-1394 and A-1399. FT MUTAGEN 1420 1420 S->A: Enhanced AXIN1 binding and FT increased beta-catenin activity by 2.2- FT fold. Further enhanced AXIN1 binding and FT increases beta-catenin activity by 3.3- FT fold; when associated with A-1430. FT {ECO:0000269|PubMed:16513652}. FT MUTAGEN 1430 1430 S->A: Enhanced AXIN1 binding. Further FT enhanced AXIN1 binding and increases FT beta-catenin activity by 3.3-fold; when FT associated with A-1420. FT {ECO:0000269|PubMed:16513652}. FT MUTAGEN 1485 1485 L->A: No change in the phosphorylation FT state of PPPSP motif. Some reduction in FT Wnt/beta-catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1486 1486 N->A: No change in the phosphorylation FT state of PPPSP motif. Increased Wnt/beta- FT catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1487 1487 P->A: No change in the phosphorylation FT state of PPPSP motif A. Greatly reduced FT Wnt/beta-catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1487 1487 P->C: No change in the phosphorylation FT state of PPPSP motif A. Greatly reduced FT Wnt/beta-catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1488 1488 P->A: No change in the phosphorylation FT state of PPPSP motif A. Greatly reduced FT Wnt/beta-catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1489 1489 P->A: No change in the phosphorylation FT state of PPPSP motif A. Greatly reduced FT Wnt/beta-catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1490 1490 S->A: Greatly reduced phosphorylation of FT PPPSP motif A. Greatly reduced Wnt/beta- FT catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1490 1490 S->T: Some loss of phosphorylation of FT PPPSP motif A. Little reduction in FT Wnt/beta-catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1491 1491 P->A: Greatly reduced phosphorylation of FT PPPSP motif A. Greatly reduced Wnt/beta- FT catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1492 1492 A->G: No change in the phosphorylation FT state of PPPSP motif A. Greatly reduced FT Wnt/beta-catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1493 1493 T->A: No change in the phosphorylation FT state of PPPSP motif A. Greatly reduced FT Wnt/beta-catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1494 1494 E->A: No change in the phosphorylation FT state of PPPSP motif A. Little reduction FT of Wnt/beta-catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1495 1495 R->A: No change in the phosphorylation FT state of PPPSP motif. No reduction of FT Wnt/beta-catenin signaling. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1529 1529 T->A: No effect on the phosphorylation FT state of PPPSP motif B. FT {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1530 1530 T->A: Abolishes phosphorylation of PPPSP FT motif B. Reduced Wnt/beta-catenin FT signaling. {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1531 1531 P->A: Abolishes phosphorylation of PPPSP FT motif B. Reduced Wnt/beta-catenin FT signaling. {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1572 1572 T->A: Abolishes Wnt/beta-catenin FT signaling. {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1590 1590 S->A: Abolishes Wnt/beta-catenin FT signaling. {ECO:0000269|PubMed:18362152}. FT MUTAGEN 1607 1607 S->A: Abolishes Wnt/beta-catenin FT signaling. {ECO:0000269|PubMed:18362152}. FT STRAND 22 26 {ECO:0000244|PDB:3SOV}. FT STRAND 28 35 {ECO:0000244|PDB:3SOV}. FT HELIX 36 38 {ECO:0000244|PDB:3SOB}. FT STRAND 44 59 {ECO:0000244|PDB:3SOV}. FT HELIX 60 62 {ECO:0000244|PDB:3SOV}. FT STRAND 64 69 {ECO:0000244|PDB:3SOV}. FT TURN 70 73 {ECO:0000244|PDB:3SOV}. FT STRAND 74 79 {ECO:0000244|PDB:3SOV}. FT STRAND 82 84 {ECO:0000244|PDB:3SOV}. FT STRAND 88 92 {ECO:0000244|PDB:3SOV}. FT STRAND 99 103 {ECO:0000244|PDB:3SOV}. FT TURN 104 107 {ECO:0000244|PDB:3SOV}. FT STRAND 108 113 {ECO:0000244|PDB:3SOV}. FT TURN 114 117 {ECO:0000244|PDB:3SOV}. FT STRAND 118 123 {ECO:0000244|PDB:3SOV}. FT STRAND 130 133 {ECO:0000244|PDB:3SOV}. FT STRAND 138 146 {ECO:0000244|PDB:3SOV}. FT HELIX 147 149 {ECO:0000244|PDB:3SOV}. FT STRAND 151 156 {ECO:0000244|PDB:3SOV}. FT STRAND 158 160 {ECO:0000244|PDB:3SOV}. FT STRAND 162 167 {ECO:0000244|PDB:3SOV}. FT STRAND 174 177 {ECO:0000244|PDB:3SOV}. FT STRAND 184 190 {ECO:0000244|PDB:3SOV}. FT TURN 191 194 {ECO:0000244|PDB:3SOV}. FT STRAND 195 200 {ECO:0000244|PDB:3SOV}. FT TURN 201 204 {ECO:0000244|PDB:3SOV}. FT STRAND 205 210 {ECO:0000244|PDB:3SOV}. FT STRAND 217 220 {ECO:0000244|PDB:3SOV}. FT STRAND 227 233 {ECO:0000244|PDB:3SOV}. FT STRAND 236 241 {ECO:0000244|PDB:3SOV}. FT TURN 242 245 {ECO:0000244|PDB:3SOV}. FT STRAND 246 251 {ECO:0000244|PDB:3SOV}. FT TURN 252 254 {ECO:0000244|PDB:3SOV}. FT STRAND 259 262 {ECO:0000244|PDB:3SOV}. FT STRAND 271 274 {ECO:0000244|PDB:3SOV}. FT HELIX 276 278 {ECO:0000244|PDB:3SOV}. FT TURN 285 289 {ECO:0000244|PDB:3SOV}. FT HELIX 290 292 {ECO:0000244|PDB:3SOV}. FT STRAND 294 299 {ECO:0000244|PDB:3SOV}. FT STRAND 305 309 {ECO:0000244|PDB:3SOV}. FT STRAND 328 337 {ECO:0000244|PDB:3S94}. FT STRAND 339 346 {ECO:0000244|PDB:3S94}. FT STRAND 360 368 {ECO:0000244|PDB:3S94}. FT TURN 369 372 {ECO:0000244|PDB:3S94}. FT STRAND 373 378 {ECO:0000244|PDB:3S94}. FT TURN 379 382 {ECO:0000244|PDB:3S94}. FT STRAND 383 388 {ECO:0000244|PDB:3S94}. FT STRAND 389 391 {ECO:0000244|PDB:4DG6}. FT STRAND 395 398 {ECO:0000244|PDB:3S94}. FT STRAND 407 411 {ECO:0000244|PDB:3S94}. FT TURN 412 415 {ECO:0000244|PDB:3S94}. FT STRAND 416 421 {ECO:0000244|PDB:3S94}. FT TURN 422 425 {ECO:0000244|PDB:3S94}. FT STRAND 426 431 {ECO:0000244|PDB:3S94}. FT STRAND 438 441 {ECO:0000244|PDB:3S94}. FT STRAND 447 454 {ECO:0000244|PDB:3S94}. FT TURN 455 458 {ECO:0000244|PDB:3S94}. FT STRAND 459 464 {ECO:0000244|PDB:3S94}. FT STRAND 466 468 {ECO:0000244|PDB:3S94}. FT STRAND 470 475 {ECO:0000244|PDB:3S94}. FT STRAND 482 485 {ECO:0000244|PDB:3S94}. FT STRAND 492 498 {ECO:0000244|PDB:3S94}. FT TURN 499 502 {ECO:0000244|PDB:3S94}. FT STRAND 503 508 {ECO:0000244|PDB:3S94}. FT TURN 509 512 {ECO:0000244|PDB:3S94}. FT STRAND 513 521 {ECO:0000244|PDB:3S94}. FT STRAND 525 529 {ECO:0000244|PDB:3S94}. FT STRAND 538 541 {ECO:0000244|PDB:3S94}. FT STRAND 544 548 {ECO:0000244|PDB:3S94}. FT STRAND 555 562 {ECO:0000244|PDB:3S94}. FT STRAND 565 569 {ECO:0000244|PDB:3S94}. FT STRAND 575 584 {ECO:0000244|PDB:3S94}. FT HELIX 591 593 {ECO:0000244|PDB:3S94}. FT HELIX 595 598 {ECO:0000244|PDB:3S94}. FT STRAND 600 606 {ECO:0000244|PDB:3S94}. FT STRAND 609 613 {ECO:0000244|PDB:3S94}. FT STRAND 633 638 {ECO:0000244|PDB:4A0P}. FT STRAND 641 648 {ECO:0000244|PDB:4A0P}. FT STRAND 653 655 {ECO:0000244|PDB:4A0P}. FT STRAND 664 670 {ECO:0000244|PDB:4A0P}. FT TURN 671 674 {ECO:0000244|PDB:4A0P}. FT STRAND 675 680 {ECO:0000244|PDB:4A0P}. FT TURN 681 684 {ECO:0000244|PDB:4A0P}. FT STRAND 685 690 {ECO:0000244|PDB:4A0P}. FT STRAND 697 700 {ECO:0000244|PDB:4A0P}. FT STRAND 709 713 {ECO:0000244|PDB:4A0P}. FT TURN 714 717 {ECO:0000244|PDB:4A0P}. FT STRAND 718 723 {ECO:0000244|PDB:4A0P}. FT TURN 724 727 {ECO:0000244|PDB:4A0P}. FT STRAND 728 733 {ECO:0000244|PDB:4A0P}. FT STRAND 740 743 {ECO:0000244|PDB:4A0P}. FT STRAND 750 756 {ECO:0000244|PDB:4A0P}. FT TURN 757 760 {ECO:0000244|PDB:4A0P}. FT STRAND 761 766 {ECO:0000244|PDB:4A0P}. FT STRAND 768 770 {ECO:0000244|PDB:4A0P}. FT STRAND 772 777 {ECO:0000244|PDB:4A0P}. FT STRAND 784 787 {ECO:0000244|PDB:4A0P}. FT STRAND 791 799 {ECO:0000244|PDB:4A0P}. FT TURN 800 803 {ECO:0000244|PDB:4A0P}. FT STRAND 804 809 {ECO:0000244|PDB:4A0P}. FT TURN 810 813 {ECO:0000244|PDB:4A0P}. FT STRAND 814 819 {ECO:0000244|PDB:4A0P}. FT STRAND 826 830 {ECO:0000244|PDB:4A0P}. FT STRAND 835 841 {ECO:0000244|PDB:4A0P}. FT STRAND 844 849 {ECO:0000244|PDB:4A0P}. FT TURN 850 853 {ECO:0000244|PDB:4A0P}. FT STRAND 854 859 {ECO:0000244|PDB:4A0P}. FT TURN 860 862 {ECO:0000244|PDB:4A0P}. FT STRAND 867 870 {ECO:0000244|PDB:4A0P}. FT STRAND 878 882 {ECO:0000244|PDB:4A0P}. FT HELIX 884 886 {ECO:0000244|PDB:4A0P}. FT TURN 892 896 {ECO:0000244|PDB:4A0P}. FT HELIX 897 899 {ECO:0000244|PDB:4A0P}. FT STRAND 901 907 {ECO:0000244|PDB:4A0P}. FT TURN 908 910 {ECO:0000244|PDB:4A0P}. FT STRAND 911 915 {ECO:0000244|PDB:4A0P}. FT STRAND 933 940 {ECO:0000244|PDB:4A0P}. FT STRAND 943 947 {ECO:0000244|PDB:4A0P}. FT STRAND 967 973 {ECO:0000244|PDB:4A0P}. FT TURN 974 977 {ECO:0000244|PDB:4A0P}. FT STRAND 978 983 {ECO:0000244|PDB:4A0P}. FT TURN 984 987 {ECO:0000244|PDB:4A0P}. FT STRAND 988 993 {ECO:0000244|PDB:4A0P}. FT STRAND 1000 1003 {ECO:0000244|PDB:4A0P}. FT STRAND 1016 1022 {ECO:0000244|PDB:4A0P}. FT TURN 1023 1026 {ECO:0000244|PDB:4A0P}. FT STRAND 1027 1032 {ECO:0000244|PDB:4A0P}. FT TURN 1033 1036 {ECO:0000244|PDB:4A0P}. FT STRAND 1037 1042 {ECO:0000244|PDB:4A0P}. FT STRAND 1047 1052 {ECO:0000244|PDB:4A0P}. FT STRAND 1059 1065 {ECO:0000244|PDB:4A0P}. FT TURN 1066 1069 {ECO:0000244|PDB:4A0P}. FT STRAND 1070 1077 {ECO:0000244|PDB:4A0P}. FT STRAND 1080 1087 {ECO:0000244|PDB:4A0P}. FT STRAND 1094 1097 {ECO:0000244|PDB:4A0P}. FT STRAND 1104 1110 {ECO:0000244|PDB:4A0P}. FT TURN 1111 1114 {ECO:0000244|PDB:4A0P}. FT STRAND 1115 1120 {ECO:0000244|PDB:4A0P}. FT TURN 1121 1124 {ECO:0000244|PDB:4A0P}. FT STRAND 1125 1130 {ECO:0000244|PDB:4A0P}. FT STRAND 1137 1140 {ECO:0000244|PDB:4A0P}. FT STRAND 1147 1153 {ECO:0000244|PDB:4A0P}. FT STRAND 1156 1161 {ECO:0000244|PDB:4A0P}. FT TURN 1162 1165 {ECO:0000244|PDB:4A0P}. FT STRAND 1166 1171 {ECO:0000244|PDB:4A0P}. FT STRAND 1174 1176 {ECO:0000244|PDB:4A0P}. FT STRAND 1179 1182 {ECO:0000244|PDB:4A0P}. FT STRAND 1188 1194 {ECO:0000244|PDB:4A0P}. FT HELIX 1199 1204 {ECO:0000244|PDB:4A0P}. FT TURN 1206 1209 {ECO:0000244|PDB:4A0P}. FT HELIX 1210 1213 {ECO:0000244|PDB:4A0P}. FT STRAND 1215 1220 {ECO:0000244|PDB:4A0P}. FT TURN 1222 1224 {ECO:0000244|PDB:3S8Z}. FT STRAND 1226 1229 {ECO:0000244|PDB:4A0P}. FT STRAND 1234 1236 {ECO:0000244|PDB:4A0P}. FT STRAND 1238 1241 {ECO:0000244|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 //