UniProtKB - O75096 (LRP4_HUMAN)
Low-density lipoprotein receptor-related protein 4
LRP4
Functioni
Mediates SOST-dependent inhibition of bone formation. Functions as a specific facilitator of SOST-mediated inhibition of Wnt signaling. Plays a key role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between motor neuron and skeletal muscle. Directly binds AGRIN and recruits it to the MUSK signaling complex. Mediates the AGRIN-induced phosphorylation of MUSK, the kinase of the complex. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Alternatively, may be involved in the negative regulation of the canonical Wnt signaling pathway, being able to antagonize the LRP6-mediated activation of this pathway. More generally, has been proposed to function as a cell surface endocytic receptor binding and internalizing extracellular ligands for degradation by lysosomes. May play an essential role in the process of digit differentiation (By similarity).
By similarity2 PublicationsGO - Molecular functioni
- apolipoprotein binding Source: Ensembl
- calcium ion binding Source: InterPro
- protein homodimerization activity Source: Ensembl
- receptor tyrosine kinase binding Source: UniProtKB
- scaffold protein binding Source: UniProtKB
GO - Biological processi
- amyloid-beta clearance by cellular catabolic process Source: ARUK-UCL
- dendrite morphogenesis Source: UniProtKB
- dorsal/ventral pattern formation Source: Ensembl
- embryonic digit morphogenesis Source: Ensembl
- endocytosis Source: UniProtKB-KW
- generation of neurons Source: GO_Central
- hair follicle development Source: Ensembl
- kidney development Source: UniProtKB
- limb development Source: UniProtKB
- negative regulation of axonogenesis Source: UniProtKB
- negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
- negative regulation of ossification Source: UniProtKB
- odontogenesis of dentin-containing tooth Source: Ensembl
- positive regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
- positive regulation of presynaptic membrane organization Source: UniProtKB
- positive regulation of skeletal muscle acetylcholine-gated channel clustering Source: Ensembl
- postsynaptic membrane assembly Source: UniProtKB
- presynaptic membrane assembly Source: UniProtKB
- proximal/distal pattern formation Source: Ensembl
- skeletal muscle acetylcholine-gated channel clustering Source: UniProtKB
- synapse organization Source: UniProtKB
- synaptic assembly at neuromuscular junction Source: UniProtKB
- Wnt signaling pathway Source: UniProtKB-KW
Keywordsi
Molecular function | Developmental protein, Receptor |
Biological process | Differentiation, Endocytosis, Wnt signaling pathway |
Ligand | Calcium |
Enzyme and pathway databases
PathwayCommonsi | O75096 |
Reactomei | R-HSA-3000178, ECM proteoglycans |
SignaLinki | O75096 |
SIGNORi | O75096 |
Protein family/group databases
TCDBi | 9.B.87.1.24, the selenoprotein p receptor (selp-receptor) family |
Names & Taxonomyi
Protein namesi | Recommended name: Low-density lipoprotein receptor-related protein 4Short name: LRP-4 Alternative name(s): Multiple epidermal growth factor-like domains 7 |
Gene namesi | Name:LRP4 Synonyms:KIAA0816, LRP10, MEGF7 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6696, LRP4 |
MIMi | 604270, gene |
neXtProti | NX_O75096 |
VEuPathDBi | HostDB:ENSG00000134569 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Single-pass type I membrane protein Sequence analysis
Plasma Membrane
- plasma membrane Source: UniProtKB
- plasma membrane raft Source: UniProtKB
- synaptic membrane Source: UniProtKB
Other locations
- cell surface Source: UniProtKB
- dendrite Source: UniProtKB
- integral component of membrane Source: UniProtKB-KW
- neuromuscular junction Source: UniProtKB
- neuronal cell body Source: UniProtKB
- postsynaptic density Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 21 – 1725 | ExtracellularSequence analysisAdd BLAST | 1705 | |
Transmembranei | 1726 – 1746 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1747 – 1905 | CytoplasmicSequence analysisAdd BLAST | 159 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Involvement in diseasei
Cenani-Lenz syndactyly syndrome (CLSS)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_063776 | 137 | D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs267607222EnsemblClinVar. | 1 | |
Natural variantiVAR_063777 | 160 | C → Y in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs267607221EnsemblClinVar. | 1 | |
Natural variantiVAR_063778 | 449 | D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs267607224EnsemblClinVar. | 1 | |
Natural variantiVAR_063779 | 461 | T → P in CLSS. 1 PublicationCorresponds to variant dbSNP:rs267607223EnsemblClinVar. | 1 | |
Natural variantiVAR_063780 | 473 | L → F in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 Publication | 1 | |
Natural variantiVAR_063781 | 529 | D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs267607220EnsemblClinVar. | 1 | |
Natural variantiVAR_063782 | 1017 | C → R in CLSS. 1 Publication | 1 |
Sclerosteosis 2 (SOST2)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_066630 | 1170 | R → W in SOST2; impairs the interaction with SOST; loss of function as facilitator of SOST-mediated inhibition of Wnt signaling; has no effect on AGRN-mediated MUSK signaling; retains the ability to bind AGRN and MUSK. 2 PublicationsCorresponds to variant dbSNP:rs387906884EnsemblClinVar. | 1 | |
Natural variantiVAR_066631 | 1186 | W → S in SOST2; impairs the interaction with SOST; loss of function as facilitator of SOST-mediated inhibition of Wnt signaling; has no effect on AGRN-mediated MUSK signaling; retains the ability to bind AGRN and MUSK. 2 PublicationsCorresponds to variant dbSNP:rs387906883EnsemblClinVar. | 1 |
Myasthenic syndrome, congenital, 17 (CMS17)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_073695 | 1233 | E → K in CMS17; decreases binding affinity for AGRN and MUSK proteins; does not enhance downstream activation of the MUSK signaling pathway thus impairing clustering of AChRs. 1 PublicationCorresponds to variant dbSNP:rs786205153EnsemblClinVar. | 1 | |
Natural variantiVAR_073696 | 1277 | R → H in CMS17; decreases binding affinity for AGRN and MUSK proteins; does not enhance downstream activation of the MUSK signaling pathway thus impairing clustering of AChRs. 1 PublicationCorresponds to variant dbSNP:rs746136135EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1214 | N → A: Compromises Wnt-suppressive activity. 1 Publication | 1 | |
Mutagenesisi | 1252 | V → A: Compromises AGRN-mediated up-regulation of MUSK signaling. 1 Publication | 1 | |
Mutagenesisi | 1256 | Y → A: Compromises Wnt-suppressive activity. 1 Publication | 1 | |
Mutagenesisi | 1287 | I → A: Compromises AGRN-mediated up-regulation of MUSK signaling. 1 Publication | 1 |
Keywords - Diseasei
Congenital myasthenic syndrome, Disease variantOrganism-specific databases
DisGeNETi | 4038 |
GeneReviewsi | LRP4 |
MalaCardsi | LRP4 |
MIMi | 212780, phenotype 614305, phenotype 616304, phenotype |
OpenTargetsi | ENSG00000134569 |
Orphaneti | 3258, Cenani-Lenz syndrome 98913, Postsynaptic congenital myasthenic syndromes 3152, Sclerosteosis |
PharmGKBi | PA30454 |
Miscellaneous databases
Pharosi | O75096, Tbio |
Genetic variation databases
BioMutai | LRP4 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Sequence analysisAdd BLAST | 20 | |
ChainiPRO_0000017325 | 21 – 1905 | Low-density lipoprotein receptor-related protein 4Add BLAST | 1885 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 27 ↔ 44 | PROSITE-ProRule annotation | ||
Disulfide bondi | 34 ↔ 57 | PROSITE-ProRule annotation | ||
Disulfide bondi | 51 ↔ 66 | PROSITE-ProRule annotation | ||
Disulfide bondi | 71 ↔ 83 | PROSITE-ProRule annotation | ||
Disulfide bondi | 78 ↔ 96 | PROSITE-ProRule annotation | ||
Disulfide bondi | 90 ↔ 105 | PROSITE-ProRule annotation | ||
Disulfide bondi | 110 ↔ 122 | PROSITE-ProRule annotation | ||
Disulfide bondi | 117 ↔ 135 | PROSITE-ProRule annotation | ||
Disulfide bondi | 129 ↔ 143 | PROSITE-ProRule annotation | ||
Disulfide bondi | 148 ↔ 160 | PROSITE-ProRule annotation | ||
Disulfide bondi | 155 ↔ 173 | PROSITE-ProRule annotation | ||
Disulfide bondi | 167 ↔ 182 | PROSITE-ProRule annotation | ||
Disulfide bondi | 191 ↔ 203 | PROSITE-ProRule annotation | ||
Disulfide bondi | 198 ↔ 216 | PROSITE-ProRule annotation | ||
Disulfide bondi | 210 ↔ 225 | PROSITE-ProRule annotation | ||
Disulfide bondi | 231 ↔ 243 | PROSITE-ProRule annotation | ||
Disulfide bondi | 238 ↔ 256 | PROSITE-ProRule annotation | ||
Disulfide bondi | 250 ↔ 265 | PROSITE-ProRule annotation | ||
Glycosylationi | 264 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 270 ↔ 282 | PROSITE-ProRule annotation | ||
Disulfide bondi | 277 ↔ 295 | PROSITE-ProRule annotation | ||
Disulfide bondi | 289 ↔ 304 | PROSITE-ProRule annotation | ||
Disulfide bondi | 312 ↔ 324 | PROSITE-ProRule annotation | ||
Disulfide bondi | 319 ↔ 337 | PROSITE-ProRule annotation | ||
Disulfide bondi | 331 ↔ 349 | PROSITE-ProRule annotation | ||
Disulfide bondi | 358 ↔ 369 | PROSITE-ProRule annotation | ||
Disulfide bondi | 365 ↔ 378 | PROSITE-ProRule annotation | ||
Disulfide bondi | 380 ↔ 393 | PROSITE-ProRule annotation | ||
Disulfide bondi | 399 ↔ 409 | PROSITE-ProRule annotation | ||
Disulfide bondi | 405 ↔ 418 | PROSITE-ProRule annotation | ||
Disulfide bondi | 420 ↔ 433 | PROSITE-ProRule annotation | ||
Glycosylationi | 498 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 702 ↔ 713 | PROSITE-ProRule annotation | ||
Disulfide bondi | 709 ↔ 722 | PROSITE-ProRule annotation | ||
Glycosylationi | 719 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 724 ↔ 736 | PROSITE-ProRule annotation | ||
Glycosylationi | 901 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 1077 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 1415 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 1467 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | O75096 |
jPOSTi | O75096 |
MassIVEi | O75096 |
MaxQBi | O75096 |
PaxDbi | O75096 |
PeptideAtlasi | O75096 |
PRIDEi | O75096 |
ProteomicsDBi | 49760 |
TopDownProteomicsi | O75096 |
PTM databases
GlyGeni | O75096, 12 sites, 2 O-linked glycans (3 sites) |
iPTMneti | O75096 |
PhosphoSitePlusi | O75096 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000134569, Expressed in ventricular zone and 199 other tissues |
ExpressionAtlasi | O75096, baseline and differential |
Genevisiblei | O75096, HS |
Organism-specific databases
HPAi | ENSG00000134569, Group enriched (brain, skin) |
Interactioni
Subunit structurei
Homooligomer.
Interacts with MUSK; the heterodimer forms an AGRIN receptor complex that binds AGRIN resulting in activation of MUSK (By similarity).
Interacts (via the extracellular domain) with SOST; the interaction facilitates the inhibition of Wnt signaling (PubMed:21471202).
Interacts with MESD; the interaction promotes glycosylation of LRP4 and its cell-surface expression (By similarity).
By similarity1 PublicationBinary interactionsi
O75096
With | #Exp. | IntAct |
---|---|---|
SOST [Q9BQB4] | 5 | EBI-310873,EBI-5746563 |
GO - Molecular functioni
- apolipoprotein binding Source: Ensembl
- protein homodimerization activity Source: Ensembl
- receptor tyrosine kinase binding Source: UniProtKB
- scaffold protein binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 110218, 72 interactors |
IntActi | O75096, 102 interactors |
MINTi | O75096 |
STRINGi | 9606.ENSP00000367888 |
Miscellaneous databases
RNActi | O75096, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 26 – 67 | LDL-receptor class A 1PROSITE-ProRule annotationAdd BLAST | 42 | |
Domaini | 70 – 106 | LDL-receptor class A 2PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 109 – 144 | LDL-receptor class A 3PROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 147 – 183 | LDL-receptor class A 4PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 190 – 226 | LDL-receptor class A 5PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 230 – 266 | LDL-receptor class A 6PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 269 – 305 | LDL-receptor class A 7PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 311 – 350 | LDL-receptor class A 8PROSITE-ProRule annotationAdd BLAST | 40 | |
Domaini | 354 – 394 | EGF-like 1; calcium-bindingSequence analysisAdd BLAST | 41 | |
Domaini | 395 – 434 | EGF-like 2; calcium-bindingSequence analysisAdd BLAST | 40 | |
Repeati | 480 – 522 | LDL-receptor class B 1Add BLAST | 43 | |
Repeati | 523 – 565 | LDL-receptor class B 2Add BLAST | 43 | |
Repeati | 566 – 609 | LDL-receptor class B 3Add BLAST | 44 | |
Repeati | 610 – 652 | LDL-receptor class B 4Add BLAST | 43 | |
Repeati | 653 – 693 | LDL-receptor class B 5Add BLAST | 41 | |
Domaini | 698 – 737 | EGF-like 3Add BLAST | 40 | |
Repeati | 785 – 827 | LDL-receptor class B 6Add BLAST | 43 | |
Repeati | 828 – 870 | LDL-receptor class B 7Add BLAST | 43 | |
Repeati | 871 – 914 | LDL-receptor class B 8Add BLAST | 44 | |
Repeati | 915 – 956 | LDL-receptor class B 9Add BLAST | 42 | |
Repeati | 957 – 998 | LDL-receptor class B 10Add BLAST | 42 | |
Repeati | 1093 – 1135 | LDL-receptor class B 11Add BLAST | 43 | |
Repeati | 1136 – 1178 | LDL-receptor class B 12Add BLAST | 43 | |
Repeati | 1179 – 1222 | LDL-receptor class B 13Add BLAST | 44 | |
Repeati | 1223 – 1263 | LDL-receptor class B 14Add BLAST | 41 | |
Repeati | 1264 – 1306 | LDL-receptor class B 15Add BLAST | 43 | |
Repeati | 1397 – 1439 | LDL-receptor class B 16Add BLAST | 43 | |
Repeati | 1440 – 1482 | LDL-receptor class B 17Add BLAST | 43 | |
Repeati | 1483 – 1526 | LDL-receptor class B 18Add BLAST | 44 | |
Repeati | 1527 – 1568 | LDL-receptor class B 19Add BLAST | 42 | |
Repeati | 1569 – 1610 | LDL-receptor class B 20Add BLAST | 42 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1659 – 1686 | DisorderedSequence analysisAdd BLAST | 28 | |
Regioni | 1852 – 1905 | DisorderedSequence analysisAdd BLAST | 54 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 1766 – 1769 | Endocytosis signalSequence analysis | 4 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1667 – 1686 | Polar residuesSequence analysisAdd BLAST | 20 | |
Compositional biasi | 1852 – 1881 | Polar residuesSequence analysisAdd BLAST | 30 | |
Compositional biasi | 1888 – 1905 | Basic and acidic residuesSequence analysisAdd BLAST | 18 |
Sequence similaritiesi
Keywords - Domaini
EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1215, Eukaryota |
GeneTreei | ENSGT00940000158287 |
HOGENOMi | CLU_000085_4_1_1 |
InParanoidi | O75096 |
OMAi | NNRYTAI |
OrthoDBi | 121310at2759 |
PhylomeDBi | O75096 |
TreeFami | TF315253 |
Family and domain databases
CDDi | cd00112, LDLa, 7 hits |
Gene3Di | 2.120.10.30, 4 hits 4.10.400.10, 8 hits |
InterProi | View protein in InterPro IPR011042, 6-blade_b-propeller_TolB-like IPR026823, cEGF IPR001881, EGF-like_Ca-bd_dom IPR000742, EGF-like_dom IPR018097, EGF_Ca-bd_CS IPR009030, Growth_fac_rcpt_cys_sf IPR036055, LDL_receptor-like_sf IPR023415, LDLR_class-A_CS IPR000033, LDLR_classB_rpt IPR002172, LDrepeatLR_classA_rpt |
Pfami | View protein in Pfam PF12662, cEGF, 1 hit PF00057, Ldl_recept_a, 8 hits PF00058, Ldl_recept_b, 16 hits |
PRINTSi | PR00261, LDLRECEPTOR |
SMARTi | View protein in SMART SM00181, EGF, 7 hits SM00179, EGF_CA, 3 hits SM00192, LDLa, 8 hits SM00135, LY, 20 hits |
SUPFAMi | SSF57184, SSF57184, 1 hit SSF57424, SSF57424, 8 hits |
PROSITEi | View protein in PROSITE PS00010, ASX_HYDROXYL, 1 hit PS01186, EGF_2, 3 hits PS01187, EGF_CA, 1 hit PS01209, LDLRA_1, 8 hits PS50068, LDLRA_2, 8 hits PS51120, LDLRB, 20 hits |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MRRQWGALLL GALLCAHGLA SSPECACGRS HFTCAVSALG ECTCIPAQWQ
60 70 80 90 100
CDGDNDCGDH SDEDGCILPT CSPLDFHCDN GKCIRRSWVC DGDNDCEDDS
110 120 130 140 150
DEQDCPPREC EEDEFPCQNG YCIRSLWHCD GDNDCGDNSD EQCDMRKCSD
160 170 180 190 200
KEFRCSDGSC IAEHWYCDGD TDCKDGSDEE NCPSAVPAPP CNLEEFQCAY
210 220 230 240 250
GRCILDIYHC DGDDDCGDWS DESDCSSHQP CRSGEFMCDS GLCINAGWRC
260 270 280 290 300
DGDADCDDQS DERNCTTSMC TAEQFRCHSG RCVRLSWRCD GEDDCADNSD
310 320 330 340 350
EENCENTGSP QCALDQFLCW NGRCIGQRKL CNGVNDCGDN SDESPQQNCR
360 370 380 390 400
PRTGEENCNV NNGGCAQKCQ MVRGAVQCTC HTGYRLTEDG HTCQDVNECA
410 420 430 440 450
EEGYCSQGCT NSEGAFQCWC ETGYELRPDR RSCKALGPEP VLLFANRIDI
460 470 480 490 500
RQVLPHRSEY TLLLNNLENA IALDFHHRRE LVFWSDVTLD RILRANLNGS
510 520 530 540 550
NVEEVVSTGL ESPGGLAVDW VHDKLYWTDS GTSRIEVANL DGAHRKVLLW
560 570 580 590 600
QNLEKPRAIA LHPMEGTIYW TDWGNTPRIE ASSMDGSGRR IIADTHLFWP
610 620 630 640 650
NGLTIDYAGR RMYWVDAKHH VIERANLDGS HRKAVISQGL PHPFAITVFE
660 670 680 690 700
DSLYWTDWHT KSINSANKFT GKNQEIIRNK LHFPMDIHTL HPQRQPAGKN
710 720 730 740 750
RCGDNNGGCT HLCLPSGQNY TCACPTGFRK ISSHACAQSL DKFLLFARRM
760 770 780 790 800
DIRRISFDTE DLSDDVIPLA DVRSAVALDW DSRDDHVYWT DVSTDTISRA
810 820 830 840 850
KWDGTGQEVV VDTSLESPAG LAIDWVTNKL YWTDAGTDRI EVANTDGSMR
860 870 880 890 900
TVLIWENLDR PRDIVVEPMG GYMYWTDWGA SPKIERAGMD ASGRQVIISS
910 920 930 940 950
NLTWPNGLAI DYGSQRLYWA DAGMKTIEFA GLDGSKRKVL IGSQLPHPFG
960 970 980 990 1000
LTLYGERIYW TDWQTKSIQS ADRLTGLDRE TLQENLENLM DIHVFHRRRP
1010 1020 1030 1040 1050
PVSTPCAMEN GGCSHLCLRS PNPSGFSCTC PTGINLLSDG KTCSPGMNSF
1060 1070 1080 1090 1100
LIFARRIDIR MVSLDIPYFA DVVVPINITM KNTIAIGVDP QEGKVYWSDS
1110 1120 1130 1140 1150
TLHRISRANL DGSQHEDIIT TGLQTTDGLA VDAIGRKVYW TDTGTNRIEV
1160 1170 1180 1190 1200
GNLDGSMRKV LVWQNLDSPR AIVLYHEMGF MYWTDWGENA KLERSGMDGS
1210 1220 1230 1240 1250
DRAVLINNNL GWPNGLTVDK ASSQLLWADA HTERIEAADL NGANRHTLVS
1260 1270 1280 1290 1300
PVQHPYGLTL LDSYIYWTDW QTRSIHRADK GTGSNVILVR SNLPGLMDMQ
1310 1320 1330 1340 1350
AVDRAQPLGF NKCGSRNGGC SHLCLPRPSG FSCACPTGIQ LKGDGKTCDP
1360 1370 1380 1390 1400
SPETYLLFSS RGSIRRISLD TSDHTDVHVP VPELNNVISL DYDSVDGKVY
1410 1420 1430 1440 1450
YTDVFLDVIR RADLNGSNME TVIGRGLKTT DGLAVDWVAR NLYWTDTGRN
1460 1470 1480 1490 1500
TIEASRLDGS CRKVLINNSL DEPRAIAVFP RKGYLFWTDW GHIAKIERAN
1510 1520 1530 1540 1550
LDGSERKVLI NTDLGWPNGL TLDYDTRRIY WVDAHLDRIE SADLNGKLRQ
1560 1570 1580 1590 1600
VLVSHVSHPF ALTQQDRWIY WTDWQTKSIQ RVDKYSGRNK ETVLANVEGL
1610 1620 1630 1640 1650
MDIIVVSPQR QTGTNACGVN NGGCTHLCFA RASDFVCACP DEPDSRPCSL
1660 1670 1680 1690 1700
VPGLVPPAPR ATGMSEKSPV LPNTPPTTLY SSTTRTRTSL EEVEGRCSER
1710 1720 1730 1740 1750
DARLGLCARS NDAVPAAPGE GLHISYAIGG LLSILLILVV IAALMLYRHK
1760 1770 1780 1790 1800
KSKFTDPGMG NLTYSNPSYR TSTQEVKIEA IPKPAMYNQL CYKKEGGPDH
1810 1820 1830 1840 1850
NYTKEKIKIV EGICLLSGDD AEWDDLKQLR SSRGGLLRDH VCMKTDTVSI
1860 1870 1880 1890 1900
QASSGSLDDT ETEQLLQEEQ SECSSVHTAA TPERRGSLPD TGWKHERKLS
SESQV
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketE9PNJ5 | E9PNJ5_HUMAN | Low-density lipoprotein receptor-re... | LRP4 | 133 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 1472 – 1475 | EPRA → D in BAE19679 (PubMed:9693030).Curated | 4 | |
Sequence conflicti | 1478 | V → A in BAE19679 (PubMed:9693030).Curated | 1 | |
Sequence conflicti | 1862 | T → M in BAD83615 (Ref. 1) Curated | 1 | |
Sequence conflicti | 1862 | T → M in BAA32468 (PubMed:9693030).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_063776 | 137 | D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs267607222EnsemblClinVar. | 1 | |
Natural variantiVAR_063777 | 160 | C → Y in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs267607221EnsemblClinVar. | 1 | |
Natural variantiVAR_058290 | 314 | L → S. Corresponds to variant dbSNP:rs7926667EnsemblClinVar. | 1 | |
Natural variantiVAR_063778 | 449 | D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs267607224EnsemblClinVar. | 1 | |
Natural variantiVAR_063779 | 461 | T → P in CLSS. 1 PublicationCorresponds to variant dbSNP:rs267607223EnsemblClinVar. | 1 | |
Natural variantiVAR_063780 | 473 | L → F in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 Publication | 1 | |
Natural variantiVAR_063781 | 529 | D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs267607220EnsemblClinVar. | 1 | |
Natural variantiVAR_063782 | 1017 | C → R in CLSS. 1 Publication | 1 | |
Natural variantiVAR_057955 | 1086 | I → V3 PublicationsCorresponds to variant dbSNP:rs6485702EnsemblClinVar. | 1 | |
Natural variantiVAR_066630 | 1170 | R → W in SOST2; impairs the interaction with SOST; loss of function as facilitator of SOST-mediated inhibition of Wnt signaling; has no effect on AGRN-mediated MUSK signaling; retains the ability to bind AGRN and MUSK. 2 PublicationsCorresponds to variant dbSNP:rs387906884EnsemblClinVar. | 1 | |
Natural variantiVAR_066631 | 1186 | W → S in SOST2; impairs the interaction with SOST; loss of function as facilitator of SOST-mediated inhibition of Wnt signaling; has no effect on AGRN-mediated MUSK signaling; retains the ability to bind AGRN and MUSK. 2 PublicationsCorresponds to variant dbSNP:rs387906883EnsemblClinVar. | 1 | |
Natural variantiVAR_058291 | 1203 | A → V. Corresponds to variant dbSNP:rs2306033EnsemblClinVar. | 1 | |
Natural variantiVAR_073695 | 1233 | E → K in CMS17; decreases binding affinity for AGRN and MUSK proteins; does not enhance downstream activation of the MUSK signaling pathway thus impairing clustering of AChRs. 1 PublicationCorresponds to variant dbSNP:rs786205153EnsemblClinVar. | 1 | |
Natural variantiVAR_058292 | 1238 | A → T. Corresponds to variant dbSNP:rs2306031Ensembl. | 1 | |
Natural variantiVAR_073696 | 1277 | R → H in CMS17; decreases binding affinity for AGRN and MUSK proteins; does not enhance downstream activation of the MUSK signaling pathway thus impairing clustering of AChRs. 1 PublicationCorresponds to variant dbSNP:rs746136135EnsemblClinVar. | 1 | |
Natural variantiVAR_057956 | 1554 | S → G3 PublicationsCorresponds to variant dbSNP:rs2306029EnsemblClinVar. | 1 | |
Natural variantiVAR_057957 | 1646 | R → Q3 PublicationsCorresponds to variant dbSNP:rs3816614EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB084910 mRNA Translation: BAD83615.1 AB011540 mRNA Translation: BAA32468.1 AB231861 mRNA Translation: BAE19679.1 Different initiation. AC021573 Genomic DNA No translation available. BC037360 mRNA Translation: AAH37360.1 BC041048 mRNA Translation: AAH41048.1 BC136667 mRNA Translation: AAI36668.1 BC136668 mRNA Translation: AAI36669.1 |
CCDSi | CCDS31478.1 |
RefSeqi | NP_002325.2, NM_002334.3 |
Genome annotation databases
Ensembli | ENST00000378623; ENSP00000367888; ENSG00000134569 |
GeneIDi | 4038 |
KEGGi | hsa:4038 |
MANE-Selecti | ENST00000378623.6; ENSP00000367888.1; NM_002334.4; NP_002325.2 |
UCSCi | uc001ndn.5, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB084910 mRNA Translation: BAD83615.1 AB011540 mRNA Translation: BAA32468.1 AB231861 mRNA Translation: BAE19679.1 Different initiation. AC021573 Genomic DNA No translation available. BC037360 mRNA Translation: AAH37360.1 BC041048 mRNA Translation: AAH41048.1 BC136667 mRNA Translation: AAI36668.1 BC136668 mRNA Translation: AAI36669.1 |
CCDSi | CCDS31478.1 |
RefSeqi | NP_002325.2, NM_002334.3 |
3D structure databases
SMRi | O75096 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 110218, 72 interactors |
IntActi | O75096, 102 interactors |
MINTi | O75096 |
STRINGi | 9606.ENSP00000367888 |
Protein family/group databases
TCDBi | 9.B.87.1.24, the selenoprotein p receptor (selp-receptor) family |
PTM databases
GlyGeni | O75096, 12 sites, 2 O-linked glycans (3 sites) |
iPTMneti | O75096 |
PhosphoSitePlusi | O75096 |
Genetic variation databases
BioMutai | LRP4 |
Proteomic databases
EPDi | O75096 |
jPOSTi | O75096 |
MassIVEi | O75096 |
MaxQBi | O75096 |
PaxDbi | O75096 |
PeptideAtlasi | O75096 |
PRIDEi | O75096 |
ProteomicsDBi | 49760 |
TopDownProteomicsi | O75096 |
Protocols and materials databases
Antibodypediai | 1985, 363 antibodies from 37 providers |
DNASUi | 4038 |
Genome annotation databases
Ensembli | ENST00000378623; ENSP00000367888; ENSG00000134569 |
GeneIDi | 4038 |
KEGGi | hsa:4038 |
MANE-Selecti | ENST00000378623.6; ENSP00000367888.1; NM_002334.4; NP_002325.2 |
UCSCi | uc001ndn.5, human |
Organism-specific databases
CTDi | 4038 |
DisGeNETi | 4038 |
GeneCardsi | LRP4 |
GeneReviewsi | LRP4 |
HGNCi | HGNC:6696, LRP4 |
HPAi | ENSG00000134569, Group enriched (brain, skin) |
MalaCardsi | LRP4 |
MIMi | 212780, phenotype 604270, gene 614305, phenotype 616304, phenotype |
neXtProti | NX_O75096 |
OpenTargetsi | ENSG00000134569 |
Orphaneti | 3258, Cenani-Lenz syndrome 98913, Postsynaptic congenital myasthenic syndromes 3152, Sclerosteosis |
PharmGKBi | PA30454 |
VEuPathDBi | HostDB:ENSG00000134569 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1215, Eukaryota |
GeneTreei | ENSGT00940000158287 |
HOGENOMi | CLU_000085_4_1_1 |
InParanoidi | O75096 |
OMAi | NNRYTAI |
OrthoDBi | 121310at2759 |
PhylomeDBi | O75096 |
TreeFami | TF315253 |
Enzyme and pathway databases
PathwayCommonsi | O75096 |
Reactomei | R-HSA-3000178, ECM proteoglycans |
SignaLinki | O75096 |
SIGNORi | O75096 |
Miscellaneous databases
BioGRID-ORCSi | 4038, 11 hits in 1037 CRISPR screens |
ChiTaRSi | LRP4, human |
GeneWikii | Low_density_lipoprotein_receptor-related_protein_4 |
GenomeRNAii | 4038 |
Pharosi | O75096, Tbio |
PROi | PR:O75096 |
RNActi | O75096, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000134569, Expressed in ventricular zone and 199 other tissues |
ExpressionAtlasi | O75096, baseline and differential |
Genevisiblei | O75096, HS |
Family and domain databases
CDDi | cd00112, LDLa, 7 hits |
Gene3Di | 2.120.10.30, 4 hits 4.10.400.10, 8 hits |
InterProi | View protein in InterPro IPR011042, 6-blade_b-propeller_TolB-like IPR026823, cEGF IPR001881, EGF-like_Ca-bd_dom IPR000742, EGF-like_dom IPR018097, EGF_Ca-bd_CS IPR009030, Growth_fac_rcpt_cys_sf IPR036055, LDL_receptor-like_sf IPR023415, LDLR_class-A_CS IPR000033, LDLR_classB_rpt IPR002172, LDrepeatLR_classA_rpt |
Pfami | View protein in Pfam PF12662, cEGF, 1 hit PF00057, Ldl_recept_a, 8 hits PF00058, Ldl_recept_b, 16 hits |
PRINTSi | PR00261, LDLRECEPTOR |
SMARTi | View protein in SMART SM00181, EGF, 7 hits SM00179, EGF_CA, 3 hits SM00192, LDLa, 8 hits SM00135, LY, 20 hits |
SUPFAMi | SSF57184, SSF57184, 1 hit SSF57424, SSF57424, 8 hits |
PROSITEi | View protein in PROSITE PS00010, ASX_HYDROXYL, 1 hit PS01186, EGF_2, 3 hits PS01187, EGF_CA, 1 hit PS01209, LDLRA_1, 8 hits PS50068, LDLRA_2, 8 hits PS51120, LDLRB, 20 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | LRP4_HUMAN | |
Accessioni | O75096Primary (citable) accession number: O75096 Secondary accession number(s): B2RN39, Q4AC85, Q5KTZ5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 13, 2004 |
Last sequence update: | November 24, 2009 | |
Last modified: | February 23, 2022 | |
This is version 180 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families