ID   F5H7J9_HUMAN            Unreviewed;      1568 AA.
AC   F5H7J9;
DT   28-JUN-2011, integrated into UniProtKB/TrEMBL.
DT   28-JUN-2011, sequence version 1.
DT   16-JAN-2019, entry version 70.
DE   RecName: Full=Low-density lipoprotein receptor-related protein {ECO:0000256|PIRNR:PIRNR036314};
GN   Name=LRP6 {ECO:0000313|Ensembl:ENSP00000442472};
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 {ECO:0000313|Ensembl:ENSP00000442472, ECO:0000313|Proteomes:UP000005640};
RN   [1] {ECO:0000313|Proteomes:UP000005640}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [2] {ECO:0000313|Ensembl:ENSP00000442472, ECO:0000313|Proteomes:UP000005640}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16541075; DOI=10.1038/nature04569;
RG   Baylor College of Medicine Human Genome Sequencing Center Sequence Production Team;
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., 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., null.;
RT   "The finished DNA sequence of human chromosome 12.";
RL   Nature 440:346-351(2006).
RN   [3] {ECO:0000313|Ensembl:ENSP00000442472}
RP   IDENTIFICATION.
RG   Ensembl;
RL   Submitted (JUL-2011) to UniProtKB.
RN   [4] {ECO:0000213|PubMed:23186163}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=23186163;
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   [5] {ECO:0000313|Ensembl:ENSP00000486524}
RP   IDENTIFICATION.
RG   Ensembl;
RL   Submitted (JUN-2015) to UniProtKB.
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.
CC       {ECO:0000256|PIRNR:PIRNR036314}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. Forms phosphorylated
CC       oligomer aggregates on Wnt-signaling.
CC       {ECO:0000256|PIRNR:PIRNR036314}.
CC   -!- SIMILARITY: Belongs to the LDLR family.
CC       {ECO:0000256|PIRNR:PIRNR036314}.
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DR   EMBL; AC007537; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC007621; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; KF455603; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EPD; F5H7J9; -.
DR   jPOST; F5H7J9; -.
DR   MaxQB; F5H7J9; -.
DR   PRIDE; F5H7J9; -.
DR   Ensembl; ENST00000543091; ENSP00000442472; ENSG00000070018.
DR   Ensembl; ENST00000626698; ENSP00000486524; ENSG00000281324.
DR   UCSC; uc010shl.2; human.
DR   EuPathDB; HostDB:ENSG00000070018.8; -.
DR   HGNC; HGNC:6698; LRP6.
DR   OpenTargets; ENSG00000070018; -.
DR   eggNOG; ENOG410IPT4; Eukaryota.
DR   eggNOG; ENOG410XSY5; LUCA.
DR   GeneTree; ENSGT00940000158990; -.
DR   ChiTaRS; LRP6; human.
DR   Proteomes; UP000005640; Chromosome 12.
DR   Bgee; ENSG00000070018; Expressed in 234 organ(s), highest expression level in metanephros.
DR   ExpressionAtlas; F5H7J9; baseline and differential.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0071936; F:coreceptor activity involved in Wnt signaling pathway; IEA:UniProtKB-UniRule.
DR   GO; GO:0042813; F:Wnt-activated receptor activity; IEA:InterPro.
DR   GO; GO:0017147; F:Wnt-protein binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:InterPro.
DR   GO; GO:0007275; P:multicellular organism development; IEA:UniProtKB-KW.
DR   CDD; cd00112; LDLa; 2.
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; 2.
DR   Pfam; PF00058; Ldl_recept_b; 11.
DR   PIRSF; PIRSF036314; LDL_recpt-rel_p5/6; 2.
DR   PRINTS; PR00261; LDLRECEPTOR.
DR   SMART; SM00181; EGF; 4.
DR   SMART; SM00192; LDLa; 2.
DR   SMART; SM00135; LY; 20.
DR   SUPFAM; SSF57424; SSF57424; 2.
DR   PROSITE; PS01209; LDLRA_1; 2.
DR   PROSITE; PS50068; LDLRA_2; 2.
DR   PROSITE; PS51120; LDLRB; 19.
PE   1: Evidence at protein level;
KW   Complete proteome {ECO:0000313|Proteomes:UP000005640};
KW   Developmental protein {ECO:0000256|PIRNR:PIRNR036314};
KW   Disulfide bond {ECO:0000256|PROSITE-ProRule:PRU00124,
KW   ECO:0000256|SAAS:SAAS01050632};
KW   EGF-like domain {ECO:0000256|SAAS:SAAS00063520};
KW   Membrane {ECO:0000256|PIRNR:PIRNR036314,
KW   ECO:0000256|SAAS:SAAS00492819};
KW   Proteomics identification {ECO:0000213|MaxQB:F5H7J9,
KW   ECO:0000213|PeptideAtlas:F5H7J9};
KW   Receptor {ECO:0000256|PIRNR:PIRNR036314};
KW   Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW   Repeat {ECO:0000256|SAAS:SAAS00998998};
KW   Signal {ECO:0000256|PIRNR:PIRNR036314};
KW   Transmembrane {ECO:0000256|PIRNR:PIRNR036314,
KW   ECO:0000256|SAAS:SAAS00492819};
KW   Transmembrane helix {ECO:0000256|PIRNR:PIRNR036314,
KW   ECO:0000256|SAAS:SAAS00492819};
KW   Wnt signaling pathway {ECO:0000256|PIRNR:PIRNR036314}.
FT   SIGNAL        1     19       {ECO:0000256|PIRNR:PIRNR036314}.
FT   CHAIN        20   1568       Low-density lipoprotein receptor-related
FT                                protein. {ECO:0000256|PIRNR:PIRNR036314}.
FT                                /FTId=PRO_5013989095.
FT   TRANSMEM   1329   1349       Helical. {ECO:0000256|PIRNR:PIRNR036314}.
FT   REPEAT       63    106       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT      107    149       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT      150    193       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT      194    236       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   DOMAIN      285    324       EGF-like. {ECO:0000259|SMART:SM00181}.
FT   REPEAT      372    414       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT      415    457       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT      458    501       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT      502    544       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT      545    584       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   DOMAIN      591    628       EGF-like. {ECO:0000259|SMART:SM00181}.
FT   REPEAT      674    716       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT      717    759       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT      760    802       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT      803    839       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT      843    885       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   DOMAIN      892    930       EGF-like. {ECO:0000259|SMART:SM00181}.
FT   REPEAT      977   1025       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1026   1068       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1069   1113       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1114   1156       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1157   1198       LDL-receptor class B.
FT                                {ECO:0000256|PROSITE-ProRule:PRU00461}.
FT   DOMAIN     1206   1244       EGF-like. {ECO:0000259|SMART:SM00181}.
FT   DISULFID   1243   1255       {ECO:0000256|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1250   1268       {ECO:0000256|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1262   1277       {ECO:0000256|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1281   1293       {ECO:0000256|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1288   1306       {ECO:0000256|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1300   1315       {ECO:0000256|PROSITE-ProRule:PRU00124}.
SQ   SEQUENCE   1568 AA;  175436 MW;  2E1599CDED75E590 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 LSCGESQFQC ASGQCIDGAL
     RCNGDANCQD KSDEKNCEVL CLIDQFRCAN GQCIGKHKKC DHNVDCSDKS DELDCYPTEE
     PAPQATNTVG SVIGVIVTIF VSGTVYFICQ RMLCPRMKGD GETMTNDYVV HGPASVPLGY
     VPHPSSLSGS LPGMSRGKSM ISSLSIMGGS SGPPYDRAHV TGASSSSSSS TKGTYFPAIL
     NPPPSPATER SHYTMEFGYS SNSPSTHRSY SYRPYSYRHF APPTTPCSTD VCDSDYAPSR
     RMTSVATAKG YTSDLNYDSE PVPPPPTPRS QYLSAEENYE SCPPSPYTER SYSHHLYPPP
     PSPCTDSS
//