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Protein

Low-density lipoprotein receptor-related protein 4

Gene

LRP4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Differentiation, Endocytosis, Wnt signaling pathway

Keywords - Ligandi

Calcium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134569-MONOMER.
ReactomeiR-HSA-3000178. ECM proteoglycans.
SIGNORiO75096.

Names & Taxonomyi

Protein namesi
Recommended name:
Low-density lipoprotein receptor-related protein 4
Short name:
LRP-4
Alternative name(s):
Multiple epidermal growth factor-like domains 7
Gene namesi
Name:LRP4
Synonyms:KIAA0816, LRP10, MEGF7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:6696. LRP4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 1725ExtracellularSequence analysisAdd BLAST1705
Transmembranei1726 – 1746HelicalSequence analysisAdd BLAST21
Topological domaini1747 – 1905CytoplasmicSequence analysisAdd BLAST159

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Cenani-Lenz syndactyly syndrome (CLSS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA congenital malformation syndrome defined as complete and complex syndactyly of the hands combined with malformations of the forearm bones and similar manifestations in the lower limbs. It is characterized by fusion and disorganization of metacarpal and phalangeal bones, radius and ulnar shortening, radioulnar synostosis, and severe syndactyly of hands and feet.
See also OMIM:212780
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063776137D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant rs267607222dbSNPEnsembl.1
Natural variantiVAR_063777160C → Y in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant rs267607221dbSNPEnsembl.1
Natural variantiVAR_063778449D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant rs267607224dbSNPEnsembl.1
Natural variantiVAR_063779461T → P in CLSS. 1 PublicationCorresponds to variant rs267607223dbSNPEnsembl.1
Natural variantiVAR_063780473L → F in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 Publication1
Natural variantiVAR_063781529D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant rs267607220dbSNPEnsembl.1
Natural variantiVAR_0637821017C → R in CLSS. 1 Publication1
Sclerosteosis 2 (SOST2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA sclerosing bone dysplasia characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients.
See also OMIM:614305
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0666301170R → 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 rs387906884dbSNPEnsembl.1
Natural variantiVAR_0666311186W → 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 rs387906883dbSNPEnsembl.1
Myasthenic syndrome, congenital, 17 (CMS17)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort.
See also OMIM:616304
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0736951233E → 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 rs786205153dbSNPEnsembl.1
Natural variantiVAR_0736961277R → 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 rs746136135dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1214N → A: Compromises Wnt-suppressive activity. 1 Publication1
Mutagenesisi1252V → A: Compromises AGRN-mediated up-regulation of MUSK signaling. 1 Publication1
Mutagenesisi1256Y → A: Compromises Wnt-suppressive activity. 1 Publication1
Mutagenesisi1287I → A: Compromises AGRN-mediated up-regulation of MUSK signaling. 1 Publication1

Keywords - Diseasei

Congenital myasthenic syndrome, Disease mutation

Organism-specific databases

DisGeNETi4038.
MalaCardsiLRP4.
MIMi212780. phenotype.
614305. phenotype.
616304. phenotype.
OpenTargetsiENSG00000134569.
Orphaneti3258. Cenani-Lenz syndrome.
98913. Postsynaptic congenital myasthenic syndromes.
3152. Sclerosteosis.
PharmGKBiPA30454.

Polymorphism and mutation databases

BioMutaiLRP4.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001732521 – 1905Low-density lipoprotein receptor-related protein 4Add BLAST1885

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi27 ↔ 44PROSITE-ProRule annotation
Disulfide bondi34 ↔ 57PROSITE-ProRule annotation
Disulfide bondi51 ↔ 66PROSITE-ProRule annotation
Disulfide bondi71 ↔ 83PROSITE-ProRule annotation
Disulfide bondi78 ↔ 96PROSITE-ProRule annotation
Disulfide bondi90 ↔ 105PROSITE-ProRule annotation
Disulfide bondi110 ↔ 122PROSITE-ProRule annotation
Disulfide bondi117 ↔ 135PROSITE-ProRule annotation
Disulfide bondi129 ↔ 143PROSITE-ProRule annotation
Disulfide bondi148 ↔ 160PROSITE-ProRule annotation
Disulfide bondi155 ↔ 173PROSITE-ProRule annotation
Disulfide bondi167 ↔ 182PROSITE-ProRule annotation
Disulfide bondi191 ↔ 203PROSITE-ProRule annotation
Disulfide bondi198 ↔ 216PROSITE-ProRule annotation
Disulfide bondi210 ↔ 225PROSITE-ProRule annotation
Disulfide bondi231 ↔ 243PROSITE-ProRule annotation
Disulfide bondi238 ↔ 256PROSITE-ProRule annotation
Disulfide bondi250 ↔ 265PROSITE-ProRule annotation
Glycosylationi264N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi270 ↔ 282PROSITE-ProRule annotation
Disulfide bondi277 ↔ 295PROSITE-ProRule annotation
Disulfide bondi289 ↔ 304PROSITE-ProRule annotation
Disulfide bondi312 ↔ 324PROSITE-ProRule annotation
Disulfide bondi319 ↔ 337PROSITE-ProRule annotation
Disulfide bondi331 ↔ 349PROSITE-ProRule annotation
Disulfide bondi358 ↔ 369PROSITE-ProRule annotation
Disulfide bondi365 ↔ 378PROSITE-ProRule annotation
Disulfide bondi380 ↔ 393PROSITE-ProRule annotation
Disulfide bondi399 ↔ 409PROSITE-ProRule annotation
Disulfide bondi405 ↔ 418PROSITE-ProRule annotation
Disulfide bondi420 ↔ 433PROSITE-ProRule annotation
Glycosylationi498N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi702 ↔ 713PROSITE-ProRule annotation
Disulfide bondi709 ↔ 722PROSITE-ProRule annotation
Glycosylationi719N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi724 ↔ 736PROSITE-ProRule annotation
Glycosylationi901N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1077N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1415N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1467N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO75096.
PaxDbiO75096.
PeptideAtlasiO75096.
PRIDEiO75096.
TopDownProteomicsiO75096.

PTM databases

iPTMnetiO75096.
PhosphoSitePlusiO75096.

Expressioni

Tissue specificityi

Expressed in bone; present in osteoblasts and osteocytes. No expression is observed in osteoclast. Expressed in several regions of the brain.1 Publication

Gene expression databases

BgeeiENSG00000134569.
CleanExiHS_LRP4.
ExpressionAtlasiO75096. baseline and differential.
GenevisibleiO75096. HS.

Organism-specific databases

HPAiHPA011934.
HPA012300.

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.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
SOSTQ9BQB44EBI-310873,EBI-5746563

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110218. 25 interactors.
IntActiO75096. 5 interactors.
STRINGi9606.ENSP00000367888.

Structurei

3D structure databases

ProteinModelPortaliO75096.
SMRiO75096.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 67LDL-receptor class A 1PROSITE-ProRule annotationAdd BLAST42
Domaini70 – 106LDL-receptor class A 2PROSITE-ProRule annotationAdd BLAST37
Domaini109 – 144LDL-receptor class A 3PROSITE-ProRule annotationAdd BLAST36
Domaini147 – 183LDL-receptor class A 4PROSITE-ProRule annotationAdd BLAST37
Domaini190 – 226LDL-receptor class A 5PROSITE-ProRule annotationAdd BLAST37
Domaini230 – 266LDL-receptor class A 6PROSITE-ProRule annotationAdd BLAST37
Domaini269 – 305LDL-receptor class A 7PROSITE-ProRule annotationAdd BLAST37
Domaini311 – 350LDL-receptor class A 8PROSITE-ProRule annotationAdd BLAST40
Domaini354 – 394EGF-like 1; calcium-bindingSequence analysisAdd BLAST41
Domaini395 – 434EGF-like 2; calcium-bindingSequence analysisAdd BLAST40
Repeati480 – 522LDL-receptor class B 1Add BLAST43
Repeati523 – 565LDL-receptor class B 2Add BLAST43
Repeati566 – 609LDL-receptor class B 3Add BLAST44
Repeati610 – 652LDL-receptor class B 4Add BLAST43
Repeati653 – 693LDL-receptor class B 5Add BLAST41
Domaini698 – 737EGF-like 3Add BLAST40
Repeati785 – 827LDL-receptor class B 6Add BLAST43
Repeati828 – 870LDL-receptor class B 7Add BLAST43
Repeati871 – 914LDL-receptor class B 8Add BLAST44
Repeati915 – 956LDL-receptor class B 9Add BLAST42
Repeati957 – 998LDL-receptor class B 10Add BLAST42
Repeati1093 – 1135LDL-receptor class B 11Add BLAST43
Repeati1136 – 1178LDL-receptor class B 12Add BLAST43
Repeati1179 – 1222LDL-receptor class B 13Add BLAST44
Repeati1223 – 1263LDL-receptor class B 14Add BLAST41
Repeati1264 – 1306LDL-receptor class B 15Add BLAST43
Repeati1397 – 1439LDL-receptor class B 16Add BLAST43
Repeati1440 – 1482LDL-receptor class B 17Add BLAST43
Repeati1483 – 1526LDL-receptor class B 18Add BLAST44
Repeati1527 – 1568LDL-receptor class B 19Add BLAST42
Repeati1569 – 1610LDL-receptor class B 20Add BLAST42

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1766 – 1769Endocytosis signalSequence analysis4

Sequence similaritiesi

Belongs to the LDLR family.Curated
Contains 3 EGF-like domains.Curated
Contains 8 LDL-receptor class A domains.PROSITE-ProRule annotation
Contains 20 LDL-receptor class B repeats.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1215. Eukaryota.
ENOG410XPR2. LUCA.
GeneTreeiENSGT00760000118968.
HOGENOMiHOG000047507.
HOVERGENiHBG049163.
InParanoidiO75096.
KOiK20051.
OMAiGSQLLWA.
OrthoDBiEOG091G0178.
PhylomeDBiO75096.
TreeFamiTF315253.

Family and domain databases

Gene3Di2.120.10.30. 4 hits.
4.10.400.10. 8 hits.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR026823. cEGF.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
IPR030799. LRP4.
[Graphical view]
PANTHERiPTHR10529:SF249. PTHR10529:SF249. 4 hits.
PfamiPF12662. cEGF. 1 hit.
PF00057. Ldl_recept_a. 8 hits.
PF00058. Ldl_recept_b. 16 hits.
[Graphical view]
PRINTSiPR00261. LDLRECEPTOR.
SMARTiSM00181. EGF. 7 hits.
SM00179. EGF_CA. 3 hits.
SM00192. LDLa. 8 hits.
SM00135. LY. 20 hits.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 2 hits.
SSF57424. SSF57424. 8 hits.
PROSITEiPS00010. 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.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O75096-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:1,905
Mass (Da):212,045
Last modified:November 24, 2009 - v4
Checksum:iA39117C18279F9AA
GO

Sequence cautioni

The sequence BAE19679 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1472 – 1475EPRA → D in BAE19679 (PubMed:9693030).Curated4
Sequence conflicti1478V → A in BAE19679 (PubMed:9693030).Curated1
Sequence conflicti1862T → M in BAD83615 (Ref. 1) Curated1
Sequence conflicti1862T → M in BAA32468 (PubMed:9693030).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063776137D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant rs267607222dbSNPEnsembl.1
Natural variantiVAR_063777160C → Y in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant rs267607221dbSNPEnsembl.1
Natural variantiVAR_058290314L → S.Corresponds to variant rs7926667dbSNPEnsembl.1
Natural variantiVAR_063778449D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant rs267607224dbSNPEnsembl.1
Natural variantiVAR_063779461T → P in CLSS. 1 PublicationCorresponds to variant rs267607223dbSNPEnsembl.1
Natural variantiVAR_063780473L → F in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 Publication1
Natural variantiVAR_063781529D → N in CLSS; abolishes the antagonistic effect of LRP4 on LRP6-mediated activation of Wnt signaling. 1 PublicationCorresponds to variant rs267607220dbSNPEnsembl.1
Natural variantiVAR_0637821017C → R in CLSS. 1 Publication1
Natural variantiVAR_0579551086I → V.3 PublicationsCorresponds to variant rs6485702dbSNPEnsembl.1
Natural variantiVAR_0666301170R → 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 rs387906884dbSNPEnsembl.1
Natural variantiVAR_0666311186W → 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 rs387906883dbSNPEnsembl.1
Natural variantiVAR_0582911203A → V.Corresponds to variant rs2306033dbSNPEnsembl.1
Natural variantiVAR_0736951233E → 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 rs786205153dbSNPEnsembl.1
Natural variantiVAR_0582921238A → T.Corresponds to variant rs2306031dbSNPEnsembl.1
Natural variantiVAR_0736961277R → 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 rs746136135dbSNPEnsembl.1
Natural variantiVAR_0579561554S → G.3 PublicationsCorresponds to variant rs2306029dbSNPEnsembl.1
Natural variantiVAR_0579571646R → Q.3 PublicationsCorresponds to variant rs3816614dbSNPEnsembl.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.
CCDSiCCDS31478.1.
RefSeqiNP_002325.2. NM_002334.3.
UniGeneiHs.4930.

Genome annotation databases

EnsembliENST00000378623; ENSP00000367888; ENSG00000134569.
GeneIDi4038.
KEGGihsa:4038.
UCSCiuc001ndn.5. human.

Keywords - Coding sequence diversityi

Polymorphism

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.
CCDSiCCDS31478.1.
RefSeqiNP_002325.2. NM_002334.3.
UniGeneiHs.4930.

3D structure databases

ProteinModelPortaliO75096.
SMRiO75096.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110218. 25 interactors.
IntActiO75096. 5 interactors.
STRINGi9606.ENSP00000367888.

PTM databases

iPTMnetiO75096.
PhosphoSitePlusiO75096.

Polymorphism and mutation databases

BioMutaiLRP4.

Proteomic databases

MaxQBiO75096.
PaxDbiO75096.
PeptideAtlasiO75096.
PRIDEiO75096.
TopDownProteomicsiO75096.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000378623; ENSP00000367888; ENSG00000134569.
GeneIDi4038.
KEGGihsa:4038.
UCSCiuc001ndn.5. human.

Organism-specific databases

CTDi4038.
DisGeNETi4038.
GeneCardsiLRP4.
H-InvDBHIX0009607.
HGNCiHGNC:6696. LRP4.
HPAiHPA011934.
HPA012300.
MalaCardsiLRP4.
MIMi212780. phenotype.
604270. gene.
614305. phenotype.
616304. phenotype.
neXtProtiNX_O75096.
OpenTargetsiENSG00000134569.
Orphaneti3258. Cenani-Lenz syndrome.
98913. Postsynaptic congenital myasthenic syndromes.
3152. Sclerosteosis.
PharmGKBiPA30454.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1215. Eukaryota.
ENOG410XPR2. LUCA.
GeneTreeiENSGT00760000118968.
HOGENOMiHOG000047507.
HOVERGENiHBG049163.
InParanoidiO75096.
KOiK20051.
OMAiGSQLLWA.
OrthoDBiEOG091G0178.
PhylomeDBiO75096.
TreeFamiTF315253.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000134569-MONOMER.
ReactomeiR-HSA-3000178. ECM proteoglycans.
SIGNORiO75096.

Miscellaneous databases

ChiTaRSiLRP4. human.
GeneWikiiLow_density_lipoprotein_receptor-related_protein_4.
GenomeRNAii4038.
PROiO75096.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134569.
CleanExiHS_LRP4.
ExpressionAtlasiO75096. baseline and differential.
GenevisibleiO75096. HS.

Family and domain databases

Gene3Di2.120.10.30. 4 hits.
4.10.400.10. 8 hits.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR026823. cEGF.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
IPR030799. LRP4.
[Graphical view]
PANTHERiPTHR10529:SF249. PTHR10529:SF249. 4 hits.
PfamiPF12662. cEGF. 1 hit.
PF00057. Ldl_recept_a. 8 hits.
PF00058. Ldl_recept_b. 16 hits.
[Graphical view]
PRINTSiPR00261. LDLRECEPTOR.
SMARTiSM00181. EGF. 7 hits.
SM00179. EGF_CA. 3 hits.
SM00192. LDLa. 8 hits.
SM00135. LY. 20 hits.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 2 hits.
SSF57424. SSF57424. 8 hits.
PROSITEiPS00010. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLRP4_HUMAN
AccessioniPrimary (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: November 2, 2016
This is version 148 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.