ID LRP4_HUMAN Reviewed; 1905 AA. AC O75096; B2RN39; Q4AC85; Q5KTZ5; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 24-NOV-2009, sequence version 4. DT 13-SEP-2023, entry version 188. DE RecName: Full=Low-density lipoprotein receptor-related protein 4; DE Short=LRP-4; DE AltName: Full=Multiple epidermal growth factor-like domains 7; DE Flags: Precursor; GN Name=LRP4; Synonyms=KIAA0816, LRP10, MEGF7; 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 VARIANTS VAL-1086; GLY-1554 AND GLN-1646. RC TISSUE=Brain; RA Ishikawa K., Fujimoto H., Kim D., Saeki S.; RT "Low density lipoprotein receptor-related protein 10."; RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-1086; GLY-1554 AND RP GLN-1646. RC TISSUE=Brain; RX PubMed=9693030; DOI=10.1006/geno.1998.5341; RA Nakayama M., Nakajima D., Nagase T., Nomura N., Seki N., Ohara O.; RT "Identification of high-molecular-weight proteins with multiple EGF-like RT motifs by motif-trap screening."; RL Genomics 51:27-34(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-1086; GLY-1554 AND RP GLN-1646. RC TISSUE=Muscle; 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 [5] RP FUNCTION IN THE REGULATION OF CANONICAL WTN SIGNALING, VARIANTS CLSS RP ASN-137; TYR-160; ASN-449; PRO-461; PHE-473; ASN-529 AND ARG-1017, AND RP CHARACTERIZATION OF VARIANTS CLSS ASN-137; TYR-160; ASN-449; PHE-473 AND RP ASN-529. RX PubMed=20381006; DOI=10.1016/j.ajhg.2010.03.004; RA Li Y., Pawlik B., Elcioglu N., Aglan M., Kayserili H., Yigit G., Percin F., RA Goodman F., Nurnberg G., Cenani A., Urquhart J., Chung B.D., Ismail S., RA Amr K., Aslanger A.D., Becker C., Netzer C., Scambler P., Eyaid W., RA Hamamy H., Clayton-Smith J., Hennekam R., Nurnberg P., Herz J., RA Temtamy S.A., Wollnik B.; RT "LRP4 mutations alter Wnt/beta-catenin signaling and cause limb and kidney RT malformations in Cenani-Lenz syndrome."; RL Am. J. Hum. Genet. 86:696-706(2010). RN [6] RP FUNCTION, INTERACTION WITH SOST, TISSUE SPECIFICITY, VARIANTS SOST2 RP TRP-1170 AND SER-1186, CHARACTERIZATION OF VARIANTS SOST2 TRP-1170 AND RP SER-1186, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=21471202; DOI=10.1074/jbc.m110.190330; RA Leupin O., Piters E., Halleux C., Hu S., Kramer I., Morvan F., RA Bouwmeester T., Schirle M., Bueno-Lozano M., Fuentes F.J., Itin P.H., RA Boudin E., de Freitas F., Jennes K., Brannetti B., Charara N., RA Ebersbach H., Geisse S., Lu C.X., Bauer A., Van Hul W., Kneissel M.; RT "Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin RT facilitator function."; RL J. Biol. Chem. 286:19489-19500(2011). RN [7] RP INVOLVEMENT IN CMS17, VARIANTS SOST2 TRP-1170 AND SER-1186, VARIANTS CMS17 RP LYS-1233 AND HIS-1277, CHARACTERIZATION OF VARIANTS SOST2 TRP-1170 AND RP SER-1186, CHARACTERIZATION OF VARIANTS CMS17 LYS-1233 AND HIS-1277, AND RP MUTAGENESIS OF ASN-1214; VAL-1252; TYR-1256 AND ILE-1287. RX PubMed=24234652; DOI=10.1093/hmg/ddt578; RA Ohkawara B., Cabrera-Serrano M., Nakata T., Milone M., Asai N., Ito K., RA Ito M., Masuda A., Ito Y., Engel A.G., Ohno K.; RT "LRP4 third beta-propeller domain mutations cause novel congenital RT myasthenia by compromising agrin-mediated MuSK signaling in a position- RT specific manner."; RL Hum. Mol. Genet. 23:1856-1868(2014). CC -!- FUNCTION: Mediates SOST-dependent inhibition of bone formation. CC Functions as a specific facilitator of SOST-mediated inhibition of Wnt CC signaling. Plays a key role in the formation and the maintenance of the CC neuromuscular junction (NMJ), the synapse between motor neuron and CC skeletal muscle. Directly binds AGRIN and recruits it to the MUSK CC signaling complex. Mediates the AGRIN-induced phosphorylation of MUSK, CC the kinase of the complex. The activation of MUSK in myotubes induces CC the formation of NMJ by regulating different processes including the CC transcription of specific genes and the clustering of AChR in the CC postsynaptic membrane. Alternatively, may be involved in the negative CC regulation of the canonical Wnt signaling pathway, being able to CC antagonize the LRP6-mediated activation of this pathway. More CC generally, has been proposed to function as a cell surface endocytic CC receptor binding and internalizing extracellular ligands for CC degradation by lysosomes. May play an essential role in the process of CC digit differentiation (By similarity). {ECO:0000250|UniProtKB:Q8VI56, CC ECO:0000269|PubMed:20381006, ECO:0000269|PubMed:21471202}. CC -!- SUBUNIT: Homooligomer. Interacts with MUSK; the heterodimer forms an CC AGRIN receptor complex that binds AGRIN resulting in activation of MUSK CC (By similarity). Interacts (via the extracellular domain) with SOST; CC the interaction facilitates the inhibition of Wnt signaling CC (PubMed:21471202). Interacts with MESD; the interaction promotes CC glycosylation of LRP4 and its cell-surface expression (By similarity). CC {ECO:0000250|UniProtKB:Q8VI56, ECO:0000269|PubMed:21471202}. CC -!- INTERACTION: CC O75096; Q9BQB4: SOST; NbExp=5; IntAct=EBI-310873, EBI-5746563; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8VI56}; CC Single-pass type I membrane protein {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Expressed in bone; present in osteoblasts and CC osteocytes. No expression is observed in osteoclast. Expressed in CC several regions of the brain. {ECO:0000269|PubMed:21471202}. CC -!- DISEASE: Cenani-Lenz syndactyly syndrome (CLSS) [MIM:212780]: A CC congenital malformation syndrome defined as complete and complex CC syndactyly of the hands combined with malformations of the forearm CC bones and similar manifestations in the lower limbs. It is CC characterized by fusion and disorganization of metacarpal and CC phalangeal bones, radius and ulnar shortening, radioulnar synostosis, CC and severe syndactyly of hands and feet. {ECO:0000269|PubMed:20381006}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Sclerosteosis 2 (SOST2) [MIM:614305]: A sclerosing bone CC dysplasia characterized by a generalized hyperostosis and sclerosis CC leading to a markedly thickened skull, with mandible, ribs, clavicles CC and all long bones also being affected. Due to narrowing of the CC foramina of the cranial nerves, facial nerve palsy, hearing loss and CC atrophy of the optic nerves can occur. Sclerosteosis is clinically and CC radiologically very similar to van Buchem disease, mainly CC differentiated by hand malformations and a large stature in CC sclerosteosis patients. {ECO:0000269|PubMed:21471202, CC ECO:0000269|PubMed:24234652}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Myasthenic syndrome, congenital, 17 (CMS17) [MIM:616304]: A CC form of congenital myasthenic syndrome, a group of disorders CC characterized by failure of neuromuscular transmission, including pre- CC synaptic, synaptic, and post-synaptic disorders that are not of CC autoimmune origin. Clinical features are easy fatigability and muscle CC weakness affecting the axial and limb muscles (with hypotonia in early- CC onset forms), the ocular muscles (leading to ptosis and CC ophthalmoplegia), and the facial and bulbar musculature (affecting CC sucking and swallowing, and leading to dysphonia). The symptoms CC fluctuate and worsen with physical effort. CC {ECO:0000269|PubMed:24234652}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAE19679.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AB084910; BAD83615.1; -; mRNA. DR EMBL; AB011540; BAA32468.1; -; mRNA. DR EMBL; AB231861; BAE19679.1; ALT_INIT; mRNA. DR EMBL; AC021573; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC037360; AAH37360.1; -; mRNA. DR EMBL; BC041048; AAH41048.1; -; mRNA. DR EMBL; BC136667; AAI36668.1; -; mRNA. DR EMBL; BC136668; AAI36669.1; -; mRNA. DR CCDS; CCDS31478.1; -. DR RefSeq; NP_002325.2; NM_002334.3. DR PDB; 8S9P; EM; 3.80 A; B=1-1905. DR PDBsum; 8S9P; -. DR AlphaFoldDB; O75096; -. DR SMR; O75096; -. DR BioGRID; 110218; 82. DR IntAct; O75096; 102. DR MINT; O75096; -. DR STRING; 9606.ENSP00000367888; -. DR TCDB; 9.B.87.1.24; the selenoprotein p receptor (selp-receptor) family. DR GlyCosmos; O75096; 10 sites, 2 glycans. DR GlyGen; O75096; 15 sites, 3 O-linked glycans (6 sites). DR iPTMnet; O75096; -. DR PhosphoSitePlus; O75096; -. DR BioMuta; LRP4; -. DR EPD; O75096; -. DR jPOST; O75096; -. DR MassIVE; O75096; -. DR MaxQB; O75096; -. DR PaxDb; O75096; -. DR PeptideAtlas; O75096; -. DR ProteomicsDB; 49760; -. DR TopDownProteomics; O75096; -. DR Antibodypedia; 1985; 381 antibodies from 38 providers. DR DNASU; 4038; -. DR Ensembl; ENST00000378623.6; ENSP00000367888.1; ENSG00000134569.10. DR GeneID; 4038; -. DR KEGG; hsa:4038; -. DR MANE-Select; ENST00000378623.6; ENSP00000367888.1; NM_002334.4; NP_002325.2. DR UCSC; uc001ndn.5; human. DR AGR; HGNC:6696; -. DR CTD; 4038; -. DR DisGeNET; 4038; -. DR GeneCards; LRP4; -. DR GeneReviews; LRP4; -. DR HGNC; HGNC:6696; LRP4. DR HPA; ENSG00000134569; Group enriched (brain, skin). DR MalaCards; LRP4; -. DR MIM; 212780; phenotype. DR MIM; 604270; gene. DR MIM; 614305; phenotype. DR MIM; 616304; phenotype. DR neXtProt; NX_O75096; -. DR OpenTargets; ENSG00000134569; -. DR Orphanet; 3258; Cenani-Lenz syndrome. DR Orphanet; 98913; Postsynaptic congenital myasthenic syndromes. DR Orphanet; 3152; Sclerosteosis. DR PharmGKB; PA30454; -. DR VEuPathDB; HostDB:ENSG00000134569; -. DR eggNOG; KOG1215; Eukaryota. DR GeneTree; ENSGT00940000158287; -. DR HOGENOM; CLU_000085_4_1_1; -. DR InParanoid; O75096; -. DR OMA; NNRYTAI; -. DR OrthoDB; 3107655at2759; -. DR PhylomeDB; O75096; -. DR TreeFam; TF315253; -. DR PathwayCommons; O75096; -. DR Reactome; R-HSA-3000178; ECM proteoglycans. DR SignaLink; O75096; -. DR SIGNOR; O75096; -. DR BioGRID-ORCS; 4038; 15 hits in 1146 CRISPR screens. DR ChiTaRS; LRP4; human. DR GeneWiki; Low_density_lipoprotein_receptor-related_protein_4; -. DR GenomeRNAi; 4038; -. DR Pharos; O75096; Tbio. DR PRO; PR:O75096; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; O75096; Protein. DR Bgee; ENSG00000134569; Expressed in ventricular zone and 161 other tissues. DR ExpressionAtlas; O75096; baseline and differential. DR Genevisible; O75096; HS. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0031594; C:neuromuscular junction; ISS:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0044853; C:plasma membrane raft; ISS:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB. DR GO; GO:0097060; C:synaptic membrane; ISS:UniProtKB. DR GO; GO:0034185; F:apolipoprotein binding; IEA:Ensembl. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl. DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISS:UniProtKB. DR GO; GO:0097110; F:scaffold protein binding; ISS:UniProtKB. DR GO; GO:0150094; P:amyloid-beta clearance by cellular catabolic process; IMP:ARUK-UCL. DR GO; GO:0048813; P:dendrite morphogenesis; ISS:UniProtKB. DR GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:Ensembl. DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl. DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW. DR GO; GO:0048699; P:generation of neurons; IBA:GO_Central. DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl. DR GO; GO:0001822; P:kidney development; IDA:UniProtKB. DR GO; GO:0060173; P:limb development; IDA:UniProtKB. DR GO; GO:0050771; P:negative regulation of axonogenesis; ISS:UniProtKB. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:BHF-UCL. DR GO; GO:0030279; P:negative regulation of ossification; IMP:UniProtKB. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl. DR GO; GO:1901631; P:positive regulation of presynaptic membrane organization; ISS:UniProtKB. DR GO; GO:1904395; P:positive regulation of skeletal muscle acetylcholine-gated channel clustering; IEA:Ensembl. DR GO; GO:0097104; P:postsynaptic membrane assembly; ISS:UniProtKB. DR GO; GO:0097105; P:presynaptic membrane assembly; ISS:UniProtKB. DR GO; GO:0009954; P:proximal/distal pattern formation; IEA:Ensembl. DR GO; GO:0071340; P:skeletal muscle acetylcholine-gated channel clustering; ISS:UniProtKB. DR GO; GO:0050808; P:synapse organization; ISS:UniProtKB. DR GO; GO:0051124; P:synaptic assembly at neuromuscular junction; ISS:UniProtKB. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR CDD; cd00054; EGF_CA; 1. DR CDD; cd00112; LDLa; 7. DR Gene3D; 2.10.25.10; Laminin; 2. DR Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 8. DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 4. DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like. DR InterPro; IPR026823; cEGF. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. 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 PANTHER; PTHR22722; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 2-RELATED; 1. DR Pfam; PF12662; cEGF; 1. DR Pfam; PF14670; FXa_inhibition; 2. DR Pfam; PF00057; Ldl_recept_a; 8. DR Pfam; PF00058; Ldl_recept_b; 16. DR PRINTS; PR00261; LDLRECEPTOR. DR SMART; SM00181; EGF; 7. DR SMART; SM00179; EGF_CA; 3. DR SMART; SM00192; LDLa; 8. DR SMART; SM00135; LY; 20. DR SUPFAM; SSF57196; EGF/Laminin; 2. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF57424; LDL receptor-like module; 8. DR SUPFAM; SSF63825; YWTD domain; 4. DR PROSITE; PS00010; ASX_HYDROXYL; 1. DR PROSITE; PS01186; EGF_2; 3. DR PROSITE; PS01187; EGF_CA; 1. DR PROSITE; PS01209; LDLRA_1; 8. DR PROSITE; PS50068; LDLRA_2; 8. DR PROSITE; PS51120; LDLRB; 20. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Cell membrane; Congenital myasthenic syndrome; KW Developmental protein; Differentiation; Disease variant; Disulfide bond; KW EGF-like domain; Endocytosis; Glycoprotein; Membrane; Receptor; KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix; KW Wnt signaling pathway. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT CHAIN 21..1905 FT /note="Low-density lipoprotein receptor-related protein 4" FT /id="PRO_0000017325" FT TOPO_DOM 21..1725 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1726..1746 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1747..1905 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 26..67 FT /note="LDL-receptor class A 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 70..106 FT /note="LDL-receptor class A 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 109..144 FT /note="LDL-receptor class A 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 147..183 FT /note="LDL-receptor class A 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 190..226 FT /note="LDL-receptor class A 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 230..266 FT /note="LDL-receptor class A 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 269..305 FT /note="LDL-receptor class A 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 311..350 FT /note="LDL-receptor class A 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 354..394 FT /note="EGF-like 1; calcium-binding" FT /evidence="ECO:0000255" FT DOMAIN 395..434 FT /note="EGF-like 2; calcium-binding" FT /evidence="ECO:0000255" FT REPEAT 480..522 FT /note="LDL-receptor class B 1" FT REPEAT 523..565 FT /note="LDL-receptor class B 2" FT REPEAT 566..609 FT /note="LDL-receptor class B 3" FT REPEAT 610..652 FT /note="LDL-receptor class B 4" FT REPEAT 653..693 FT /note="LDL-receptor class B 5" FT DOMAIN 698..737 FT /note="EGF-like 3" FT REPEAT 785..827 FT /note="LDL-receptor class B 6" FT REPEAT 828..870 FT /note="LDL-receptor class B 7" FT REPEAT 871..914 FT /note="LDL-receptor class B 8" FT REPEAT 915..956 FT /note="LDL-receptor class B 9" FT REPEAT 957..998 FT /note="LDL-receptor class B 10" FT REPEAT 1093..1135 FT /note="LDL-receptor class B 11" FT REPEAT 1136..1178 FT /note="LDL-receptor class B 12" FT REPEAT 1179..1222 FT /note="LDL-receptor class B 13" FT REPEAT 1223..1263 FT /note="LDL-receptor class B 14" FT REPEAT 1264..1306 FT /note="LDL-receptor class B 15" FT REPEAT 1397..1439 FT /note="LDL-receptor class B 16" FT REPEAT 1440..1482 FT /note="LDL-receptor class B 17" FT REPEAT 1483..1526 FT /note="LDL-receptor class B 18" FT REPEAT 1527..1568 FT /note="LDL-receptor class B 19" FT REPEAT 1569..1610 FT /note="LDL-receptor class B 20" FT REGION 1659..1686 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1852..1905 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 1766..1769 FT /note="Endocytosis signal" FT /evidence="ECO:0000255" FT COMPBIAS 1667..1686 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1852..1881 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1888..1905 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 264 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 498 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 719 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 901 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1077 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1415 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1467 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 27..44 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 34..57 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 51..66 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 71..83 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 78..96 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 90..105 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 110..122 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 117..135 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 129..143 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 148..160 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 155..173 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 167..182 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 191..203 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 198..216 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 210..225 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 231..243 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 238..256 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 250..265 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 270..282 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 277..295 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 289..304 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 312..324 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 319..337 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 331..349 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 358..369 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 365..378 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 380..393 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 399..409 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 405..418 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 420..433 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 702..713 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 709..722 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 724..736 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT VARIANT 137 FT /note="D -> N (in CLSS; abolishes the antagonistic effect FT of LRP4 on LRP6-mediated activation of Wnt signaling; FT dbSNP:rs267607222)" FT /evidence="ECO:0000269|PubMed:20381006" FT /id="VAR_063776" FT VARIANT 160 FT /note="C -> Y (in CLSS; abolishes the antagonistic effect FT of LRP4 on LRP6-mediated activation of Wnt signaling; FT dbSNP:rs267607221)" FT /evidence="ECO:0000269|PubMed:20381006" FT /id="VAR_063777" FT VARIANT 314 FT /note="L -> S (in dbSNP:rs7926667)" FT /id="VAR_058290" FT VARIANT 449 FT /note="D -> N (in CLSS; abolishes the antagonistic effect FT of LRP4 on LRP6-mediated activation of Wnt signaling; FT dbSNP:rs267607224)" FT /evidence="ECO:0000269|PubMed:20381006" FT /id="VAR_063778" FT VARIANT 461 FT /note="T -> P (in CLSS; dbSNP:rs267607223)" FT /evidence="ECO:0000269|PubMed:20381006" FT /id="VAR_063779" FT VARIANT 473 FT /note="L -> F (in CLSS; abolishes the antagonistic effect FT of LRP4 on LRP6-mediated activation of Wnt signaling)" FT /evidence="ECO:0000269|PubMed:20381006" FT /id="VAR_063780" FT VARIANT 529 FT /note="D -> N (in CLSS; abolishes the antagonistic effect FT of LRP4 on LRP6-mediated activation of Wnt signaling; FT dbSNP:rs267607220)" FT /evidence="ECO:0000269|PubMed:20381006" FT /id="VAR_063781" FT VARIANT 1017 FT /note="C -> R (in CLSS)" FT /evidence="ECO:0000269|PubMed:20381006" FT /id="VAR_063782" FT VARIANT 1086 FT /note="I -> V (in dbSNP:rs6485702)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9693030, ECO:0000269|Ref.1" FT /id="VAR_057955" FT VARIANT 1170 FT /note="R -> W (in SOST2; impairs the interaction with SOST; FT loss of function as facilitator of SOST-mediated inhibition FT of Wnt signaling; has no effect on AGRN-mediated MUSK FT signaling; retains the ability to bind AGRN and MUSK; FT dbSNP:rs387906884)" FT /evidence="ECO:0000269|PubMed:21471202, FT ECO:0000269|PubMed:24234652" FT /id="VAR_066630" FT VARIANT 1186 FT /note="W -> S (in SOST2; impairs the interaction with SOST; FT loss of function as facilitator of SOST-mediated inhibition FT of Wnt signaling; has no effect on AGRN-mediated MUSK FT signaling; retains the ability to bind AGRN and MUSK; FT dbSNP:rs387906883)" FT /evidence="ECO:0000269|PubMed:21471202, FT ECO:0000269|PubMed:24234652" FT /id="VAR_066631" FT VARIANT 1203 FT /note="A -> V (in dbSNP:rs2306033)" FT /id="VAR_058291" FT VARIANT 1233 FT /note="E -> K (in CMS17; decreases binding affinity for FT AGRN and MUSK proteins; does not enhance downstream FT activation of the MUSK signaling pathway thus impairing FT clustering of AChRs; dbSNP:rs786205153)" FT /evidence="ECO:0000269|PubMed:24234652" FT /id="VAR_073695" FT VARIANT 1238 FT /note="A -> T (in dbSNP:rs2306031)" FT /id="VAR_058292" FT VARIANT 1277 FT /note="R -> H (in CMS17; decreases binding affinity for FT AGRN and MUSK proteins; does not enhance downstream FT activation of the MUSK signaling pathway thus impairing FT clustering of AChRs; dbSNP:rs746136135)" FT /evidence="ECO:0000269|PubMed:24234652" FT /id="VAR_073696" FT VARIANT 1554 FT /note="S -> G (in dbSNP:rs2306029)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9693030, ECO:0000269|Ref.1" FT /id="VAR_057956" FT VARIANT 1646 FT /note="R -> Q (in dbSNP:rs3816614)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9693030, ECO:0000269|Ref.1" FT /id="VAR_057957" FT MUTAGEN 1214 FT /note="N->A: Compromises Wnt-suppressive activity." FT /evidence="ECO:0000269|PubMed:24234652" FT MUTAGEN 1252 FT /note="V->A: Compromises AGRN-mediated up-regulation of FT MUSK signaling." FT /evidence="ECO:0000269|PubMed:24234652" FT MUTAGEN 1256 FT /note="Y->A: Compromises Wnt-suppressive activity." FT /evidence="ECO:0000269|PubMed:24234652" FT MUTAGEN 1287 FT /note="I->A: Compromises AGRN-mediated up-regulation of FT MUSK signaling." FT /evidence="ECO:0000269|PubMed:24234652" FT CONFLICT 1472..1475 FT /note="EPRA -> D (in Ref. 2; BAE19679)" FT /evidence="ECO:0000305" FT CONFLICT 1478 FT /note="V -> A (in Ref. 2; BAE19679)" FT /evidence="ECO:0000305" FT CONFLICT 1862 FT /note="T -> M (in Ref. 1; BAD83615 and 2; BAA32468)" FT /evidence="ECO:0000305" SQ SEQUENCE 1905 AA; 212045 MW; A39117C18279F9AA CRC64; MRRQWGALLL GALLCAHGLA SSPECACGRS HFTCAVSALG ECTCIPAQWQ CDGDNDCGDH SDEDGCILPT CSPLDFHCDN GKCIRRSWVC DGDNDCEDDS DEQDCPPREC EEDEFPCQNG YCIRSLWHCD GDNDCGDNSD EQCDMRKCSD KEFRCSDGSC IAEHWYCDGD TDCKDGSDEE NCPSAVPAPP CNLEEFQCAY GRCILDIYHC DGDDDCGDWS DESDCSSHQP CRSGEFMCDS GLCINAGWRC DGDADCDDQS DERNCTTSMC TAEQFRCHSG RCVRLSWRCD GEDDCADNSD EENCENTGSP QCALDQFLCW NGRCIGQRKL CNGVNDCGDN SDESPQQNCR PRTGEENCNV NNGGCAQKCQ MVRGAVQCTC HTGYRLTEDG HTCQDVNECA EEGYCSQGCT NSEGAFQCWC ETGYELRPDR RSCKALGPEP VLLFANRIDI RQVLPHRSEY TLLLNNLENA IALDFHHRRE LVFWSDVTLD RILRANLNGS NVEEVVSTGL ESPGGLAVDW VHDKLYWTDS GTSRIEVANL DGAHRKVLLW QNLEKPRAIA LHPMEGTIYW TDWGNTPRIE ASSMDGSGRR IIADTHLFWP NGLTIDYAGR RMYWVDAKHH VIERANLDGS HRKAVISQGL PHPFAITVFE DSLYWTDWHT KSINSANKFT GKNQEIIRNK LHFPMDIHTL HPQRQPAGKN RCGDNNGGCT HLCLPSGQNY TCACPTGFRK ISSHACAQSL DKFLLFARRM DIRRISFDTE DLSDDVIPLA DVRSAVALDW DSRDDHVYWT DVSTDTISRA KWDGTGQEVV VDTSLESPAG LAIDWVTNKL YWTDAGTDRI EVANTDGSMR TVLIWENLDR PRDIVVEPMG GYMYWTDWGA SPKIERAGMD ASGRQVIISS NLTWPNGLAI DYGSQRLYWA DAGMKTIEFA GLDGSKRKVL IGSQLPHPFG LTLYGERIYW TDWQTKSIQS ADRLTGLDRE TLQENLENLM DIHVFHRRRP PVSTPCAMEN GGCSHLCLRS PNPSGFSCTC PTGINLLSDG KTCSPGMNSF LIFARRIDIR MVSLDIPYFA DVVVPINITM KNTIAIGVDP QEGKVYWSDS TLHRISRANL DGSQHEDIIT TGLQTTDGLA VDAIGRKVYW TDTGTNRIEV GNLDGSMRKV LVWQNLDSPR AIVLYHEMGF MYWTDWGENA KLERSGMDGS DRAVLINNNL GWPNGLTVDK ASSQLLWADA HTERIEAADL NGANRHTLVS PVQHPYGLTL LDSYIYWTDW QTRSIHRADK GTGSNVILVR SNLPGLMDMQ AVDRAQPLGF NKCGSRNGGC SHLCLPRPSG FSCACPTGIQ LKGDGKTCDP SPETYLLFSS RGSIRRISLD TSDHTDVHVP VPELNNVISL DYDSVDGKVY YTDVFLDVIR RADLNGSNME TVIGRGLKTT DGLAVDWVAR NLYWTDTGRN TIEASRLDGS CRKVLINNSL DEPRAIAVFP RKGYLFWTDW GHIAKIERAN LDGSERKVLI NTDLGWPNGL TLDYDTRRIY WVDAHLDRIE SADLNGKLRQ VLVSHVSHPF ALTQQDRWIY WTDWQTKSIQ RVDKYSGRNK ETVLANVEGL MDIIVVSPQR QTGTNACGVN NGGCTHLCFA RASDFVCACP DEPDSRPCSL VPGLVPPAPR ATGMSEKSPV LPNTPPTTLY SSTTRTRTSL EEVEGRCSER DARLGLCARS NDAVPAAPGE GLHISYAIGG LLSILLILVV IAALMLYRHK KSKFTDPGMG NLTYSNPSYR TSTQEVKIEA IPKPAMYNQL CYKKEGGPDH NYTKEKIKIV EGICLLSGDD AEWDDLKQLR SSRGGLLRDH VCMKTDTVSI QASSGSLDDT ETEQLLQEEQ SECSSVHTAA TPERRGSLPD TGWKHERKLS SESQV //