##gff-version 3 O75096 UniProtKB Signal peptide 1 20 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Chain 21 1905 . . . ID=PRO_0000017325;Note=Low-density lipoprotein receptor-related protein 4 O75096 UniProtKB Topological domain 21 1725 . . . Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Transmembrane 1726 1746 . . . Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Topological domain 1747 1905 . . . Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Domain 26 67 . . . Note=LDL-receptor class A 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Domain 70 106 . . . Note=LDL-receptor class A 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Domain 109 144 . . . Note=LDL-receptor class A 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Domain 147 183 . . . Note=LDL-receptor class A 4;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Domain 190 226 . . . Note=LDL-receptor class A 5;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Domain 230 266 . . . Note=LDL-receptor class A 6;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Domain 269 305 . . . Note=LDL-receptor class A 7;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Domain 311 350 . . . Note=LDL-receptor class A 8;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Domain 354 394 . . . Note=EGF-like 1%3B calcium-binding;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Domain 395 434 . . . Note=EGF-like 2%3B calcium-binding;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Repeat 480 522 . . . Note=LDL-receptor class B 1 O75096 UniProtKB Repeat 523 565 . . . Note=LDL-receptor class B 2 O75096 UniProtKB Repeat 566 609 . . . Note=LDL-receptor class B 3 O75096 UniProtKB Repeat 610 652 . . . Note=LDL-receptor class B 4 O75096 UniProtKB Repeat 653 693 . . . Note=LDL-receptor class B 5 O75096 UniProtKB Domain 698 737 . . . Note=EGF-like 3 O75096 UniProtKB Repeat 785 827 . . . Note=LDL-receptor class B 6 O75096 UniProtKB Repeat 828 870 . . . Note=LDL-receptor class B 7 O75096 UniProtKB Repeat 871 914 . . . Note=LDL-receptor class B 8 O75096 UniProtKB Repeat 915 956 . . . Note=LDL-receptor class B 9 O75096 UniProtKB Repeat 957 998 . . . Note=LDL-receptor class B 10 O75096 UniProtKB Repeat 1093 1135 . . . Note=LDL-receptor class B 11 O75096 UniProtKB Repeat 1136 1178 . . . Note=LDL-receptor class B 12 O75096 UniProtKB Repeat 1179 1222 . . . Note=LDL-receptor class B 13 O75096 UniProtKB Repeat 1223 1263 . . . Note=LDL-receptor class B 14 O75096 UniProtKB Repeat 1264 1306 . . . Note=LDL-receptor class B 15 O75096 UniProtKB Repeat 1397 1439 . . . Note=LDL-receptor class B 16 O75096 UniProtKB Repeat 1440 1482 . . . Note=LDL-receptor class B 17 O75096 UniProtKB Repeat 1483 1526 . . . Note=LDL-receptor class B 18 O75096 UniProtKB Repeat 1527 1568 . . . Note=LDL-receptor class B 19 O75096 UniProtKB Repeat 1569 1610 . . . Note=LDL-receptor class B 20 O75096 UniProtKB Region 1659 1686 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite O75096 UniProtKB Region 1852 1905 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite O75096 UniProtKB Motif 1766 1769 . . . Note=Endocytosis signal;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Compositional bias 1667 1686 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite O75096 UniProtKB Compositional bias 1852 1881 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite O75096 UniProtKB Compositional bias 1888 1905 . . . Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite O75096 UniProtKB Glycosylation 264 264 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Glycosylation 498 498 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Glycosylation 719 719 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Glycosylation 901 901 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Glycosylation 1077 1077 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Glycosylation 1415 1415 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Glycosylation 1467 1467 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255 O75096 UniProtKB Disulfide bond 27 44 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 34 57 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 51 66 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 71 83 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 78 96 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 90 105 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 110 122 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 117 135 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 129 143 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 148 160 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 155 173 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 167 182 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 191 203 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 198 216 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 210 225 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 231 243 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 238 256 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 250 265 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 270 282 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 277 295 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 289 304 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 312 324 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 319 337 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 331 349 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 358 369 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 365 378 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 380 393 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 399 409 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 405 418 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 420 433 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 702 713 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 709 722 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Disulfide bond 724 736 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00124 O75096 UniProtKB Natural variant 137 137 . . . ID=VAR_063776;Note=In CLSS%3B abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. D->N;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20381006;Dbxref=dbSNP:rs267607222,PMID:20381006 O75096 UniProtKB Natural variant 160 160 . . . ID=VAR_063777;Note=In CLSS%3B abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. C->Y;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20381006;Dbxref=dbSNP:rs267607221,PMID:20381006 O75096 UniProtKB Natural variant 314 314 . . . ID=VAR_058290;Note=L->S;Dbxref=dbSNP:rs7926667 O75096 UniProtKB Natural variant 449 449 . . . ID=VAR_063778;Note=In CLSS%3B abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. D->N;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20381006;Dbxref=dbSNP:rs267607224,PMID:20381006 O75096 UniProtKB Natural variant 461 461 . . . ID=VAR_063779;Note=In CLSS. T->P;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20381006;Dbxref=dbSNP:rs267607223,PMID:20381006 O75096 UniProtKB Natural variant 473 473 . . . ID=VAR_063780;Note=In CLSS%3B abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. L->F;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20381006;Dbxref=PMID:20381006 O75096 UniProtKB Natural variant 529 529 . . . ID=VAR_063781;Note=In CLSS%3B abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. D->N;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20381006;Dbxref=dbSNP:rs267607220,PMID:20381006 O75096 UniProtKB Natural variant 1017 1017 . . . ID=VAR_063782;Note=In CLSS. C->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:20381006;Dbxref=PMID:20381006 O75096 UniProtKB Natural variant 1086 1086 . . . ID=VAR_057955;Note=I->V;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:15489334,ECO:0000269|PubMed:9693030,ECO:0000269|Ref.1;Dbxref=dbSNP:rs6485702,PMID:15489334,PMID:9693030 O75096 UniProtKB Natural variant 1170 1170 . . . ID=VAR_066630;Note=In SOST2%3B impairs the interaction with SOST%3B loss of function as facilitator of SOST-mediated inhibition of Wnt signaling%3B has no effect on AGRN-mediated MUSK signaling%3B retains the ability to bind AGRN and MUSK. R->W;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:21471202,ECO:0000269|PubMed:24234652;Dbxref=dbSNP:rs387906884,PMID:21471202,PMID:24234652 O75096 UniProtKB Natural variant 1186 1186 . . . ID=VAR_066631;Note=In SOST2%3B impairs the interaction with SOST%3B loss of function as facilitator of SOST-mediated inhibition of Wnt signaling%3B has no effect on AGRN-mediated MUSK signaling%3B retains the ability to bind AGRN and MUSK. W->S;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:21471202,ECO:0000269|PubMed:24234652;Dbxref=dbSNP:rs387906883,PMID:21471202,PMID:24234652 O75096 UniProtKB Natural variant 1203 1203 . . . ID=VAR_058291;Note=A->V;Dbxref=dbSNP:rs2306033 O75096 UniProtKB Natural variant 1233 1233 . . . ID=VAR_073695;Note=In CMS17%3B decreases binding affinity for AGRN and MUSK proteins%3B does not enhance downstream activation of the MUSK signaling pathway thus impairing clustering of AChRs. E->K;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24234652;Dbxref=dbSNP:rs786205153,PMID:24234652 O75096 UniProtKB Natural variant 1238 1238 . . . ID=VAR_058292;Note=A->T;Dbxref=dbSNP:rs2306031 O75096 UniProtKB Natural variant 1277 1277 . . . ID=VAR_073696;Note=In CMS17%3B decreases binding affinity for AGRN and MUSK proteins%3B does not enhance downstream activation of the MUSK signaling pathway thus impairing clustering of AChRs. R->H;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24234652;Dbxref=dbSNP:rs746136135,PMID:24234652 O75096 UniProtKB Natural variant 1554 1554 . . . ID=VAR_057956;Note=S->G;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:15489334,ECO:0000269|PubMed:9693030,ECO:0000269|Ref.1;Dbxref=dbSNP:rs2306029,PMID:15489334,PMID:9693030 O75096 UniProtKB Natural variant 1646 1646 . . . ID=VAR_057957;Note=R->Q;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:15489334,ECO:0000269|PubMed:9693030,ECO:0000269|Ref.1;Dbxref=dbSNP:rs3816614,PMID:15489334,PMID:9693030 O75096 UniProtKB Mutagenesis 1214 1214 . . . Note=Compromises Wnt-suppressive activity. N->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24234652;Dbxref=PMID:24234652 O75096 UniProtKB Mutagenesis 1252 1252 . . . Note=Compromises AGRN-mediated up-regulation of MUSK signaling. V->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24234652;Dbxref=PMID:24234652 O75096 UniProtKB Mutagenesis 1256 1256 . . . Note=Compromises Wnt-suppressive activity. Y->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24234652;Dbxref=PMID:24234652 O75096 UniProtKB Mutagenesis 1287 1287 . . . Note=Compromises AGRN-mediated up-regulation of MUSK signaling. I->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24234652;Dbxref=PMID:24234652 O75096 UniProtKB Sequence conflict 1472 1475 . . . Note=EPRA->D;Ontology_term=ECO:0000305;evidence=ECO:0000305 O75096 UniProtKB Sequence conflict 1478 1478 . . . Note=V->A;Ontology_term=ECO:0000305;evidence=ECO:0000305 O75096 UniProtKB Sequence conflict 1862 1862 . . . Note=T->M;Ontology_term=ECO:0000305;evidence=ECO:0000305