LRP4_HUMAN
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 03-AUG-2022, entry version 182.
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};
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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 AlphaFoldDB; O75096; -.
DR SMR; O75096; -.
DR BioGRID; 110218; 81.
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 GlyGen; O75096; 12 sites, 2 O-linked glycans (3 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 PRIDE; O75096; -.
DR ProteomicsDB; 49760; -.
DR TopDownProteomics; O75096; -.
DR Antibodypedia; 1985; 366 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 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; 121310at2759; -.
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 1068 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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; cd00112; LDLa; 7.
DR Gene3D; 2.120.10.30; -; 4.
DR Gene3D; 4.10.400.10; -; 8.
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 Pfam; PF12662; cEGF; 1.
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; SSF57184; SSF57184; 1.
DR SUPFAM; SSF57424; SSF57424; 8.
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 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
