Reactome | UniProt:O75197 LRP5

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UniProt:O75197 LRP5 Show undefined attributes

chain	signal peptide:1-31 chain:32-1615
checksum	8BA25D07F51E02CA
comment	FUNCTION Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins (PubMed:11336703, PubMed:11448771, PubMed:11719191, PubMed:15778503, PubMed:15908424, PubMed:16252235). Activates the canonical Wnt signaling pathway that controls cell fate determination and self-renewal during embryonic development and adult tissue regeneration (PubMed:11336703, PubMed:11719191). In particular, may play an important role in the development of the posterior patterning of the epiblast during gastrulation (By similarity). During bone development, regulates osteoblast proliferation and differentiation thus determining bone mass (PubMed:11719191). Mechanistically, the formation of the signaling complex between Wnt ligand, frizzled receptor and LRP5 coreceptor promotes the recruitment of AXIN1 to LRP5, stabilizing beta-catenin/CTNNB1 and activating TCF/LEF-mediated transcriptional programs (PubMed:11336703, PubMed:14731402, PubMed:24706814, PubMed:25920554). Acts as a coreceptor for non-Wnt proteins, such as norrin/NDP. Binding of norrin/NDP to frizzled 4/FZD4-LRP5 receptor complex triggers beta-catenin/CTNNB1-dependent signaling known to be required for retinal vascular development (PubMed:16252235, PubMed:27228167). Plays a role in controlling postnatal vascular regression in retina via macrophage-induced endothelial cell apoptosis (By similarity).SUBUNIT Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling (By similarity). Component of a Wnt-signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts with FZD8; the interaction is formed on WNT-binding and signaling (PubMed:11448771). Interacts (via the phosphorylated PPPSP motif domains) with AXIN1; the interaction prevents inhibition of beta-catenin phosphorylation and signaling and is enhanced in the presence of GSK3B and WNT1 or WNT3A (PubMed:11336703, PubMed:14731402). Interacts (via beta-propeller regions 3 and 4) with DKK1; the interaction, enhanced by MESD and/or KREMEN, inhibits beta-catenin signaling by preventing GSK3-mediated phosphorylation of the PPPSP motifs and subsequent, AXIN1 binding (PubMed:11448771, PubMed:15778503, PubMed:19746449). Interacts with MESD; the interaction prevents the formation of LRP5 aggregates, targets LRP5 to the plasma membrane and, when complexed with KREMEN2, increases DKK1 binding (PubMed:15143163, PubMed:17488095, PubMed:19746449). Interacts with CSNK1E (PubMed:16513652). Interacts with SOST; the interaction antagonizes canonical Wnt signaling (PubMed:15778503, PubMed:15908424). Interacts with APCDD1 (PubMed:20393562). Interacts with CAPRIN2 (PubMed:18762581).INTERACTION Chaperoned to the plasma membrane by MESD.TISSUE SPECIFICITY Widely expressed, with the highest level of expression in the liver and in aorta.PTM Phosphorylation of cytoplasmic PPPSP motifs regulates the signal transduction of the Wnt signaling pathway through acting as a docking site for AXIN1.POLYMORPHISM Genetic variations in LRP5 define the bone mineral density quantitative trait locus 1 (BMND1) [MIM:601884]. Variance in bone mineral density influences bone mass and contributes to size determination in the general population.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE LRP5 variations may act as a disease modifier in autosomal dominant polycystic kidney disease (ADPKD) in patients who have causative mutations in PKD1. May contribute to the disease phenotype heterogeneity and hepatic cystogenesis.SIMILARITY Belongs to the LDLR family.
created	[InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
crossReference	[DatabaseIdentifier:11451142] ENSEMBL:ENSG00000162337 [DatabaseIdentifier:12322482] RefSeq:NP_001278831.1 [DatabaseIdentifier:12322483] RefSeq:NP_002326.2 [DatabaseIdentifier:12285978] Pharos - Targets:O75197 [DatabaseIdentifier:12245755] PRO:O75197 [DatabaseIdentifier:12137095] Orphanet:LRP5 [DatabaseIdentifier:12125701] OpenTargets:ENSG00000162337 [DatabaseIdentifier:11540451] ENSEMBL:ENSP00000294304 [DatabaseIdentifier:11663150] ENSEMBL:ENST00000294304 [DatabaseIdentifier:11788085] GeneCards:LRP5 [DatabaseIdentifier:11832705] HMDB Protein:HMDBP07786 [DatabaseIdentifier:11841148] HPA:ENSG00000162337-LRP5
databaseName	UniProt
dbId	149847
description	recommendedName: fullName evidence="47"Low-density lipoprotein receptor-related protein 5 shortName evidence="46"LRP-5 alternativeName: fullName evidence="1"Low-density lipoprotein receptor-related protein 7 shortName: LRP-7
displayName	UniProt:O75197 LRP5
geneName	LRP5 LR3 LRP7
identifier	O75197
isSequenceChanged	false
keyword	Developmental protein Disease variant Disulfide bond EGF-like domain Endocytosis Endoplasmic reticulum Glycoprotein Membrane Osteogenesis imperfecta Osteopetrosis Osteoporosis Phosphoprotein Proteomics identification Receptor Reference proteome Repeat Signal Transmembrane Transmembrane helix Wnt signaling pathway
modified	[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	LRP5
otherIdentifier	11727159_a_at 16728066 209468_PM_at 209468_at 3337517 3337518 3337539 3337548 3337549 3337550 3337561 3337565 3337574 3337575 3337576 3337577 3337578 3337579 3337580 3337581 3337582 3337588 3337589 3337590 3337592 3337595 3337598 3337599 3337600 3337601 3337602 3337603 3337606 3337607 3337609 3337610 3337611 3337613 3955653 3955654 4041 41831_at 7942007 A_14_P104736 A_23_P1505 GE54706 GO:0001702 GO:0001944 GO:0002053 GO:0002076 GO:0005515 GO:0005783 GO:0005886 GO:0005975 GO:0006007 GO:0006355 GO:0006629 GO:0006865 GO:0006897 GO:0007399 GO:0008078 GO:0008203 GO:0008217 GO:0008284 GO:0009887 GO:0009888 GO:0009952 GO:0010467 GO:0015026 GO:0016020 GO:0016055 GO:0016192 GO:0017147 GO:0023052 GO:0030879 GO:0033687 GO:0033690 GO:0035019 GO:0035108 GO:0035426 GO:0042074 GO:0042632 GO:0042733 GO:0042813 GO:0042981 GO:0043235 GO:0043434 GO:0044281 GO:0045597 GO:0045600 GO:0045667 GO:0045668 GO:0045669 GO:0045787 GO:0045840 GO:0045893 GO:0045944 GO:0046849 GO:0048514 GO:0048539 GO:0048856 GO:0048870 GO:0060033 GO:0060042 GO:0060070 GO:0060348 GO:0060349 GO:0060444 GO:0060603 GO:0060612 GO:0060764 GO:0060856 GO:0061178 GO:0061298 GO:0061299 GO:0061304 GO:0065008 GO:0098609 GO:0110135 GO:1902262 GO:1990851 GO:1990909 GO:1990963 HMNXSV003010807 ILMN_1702775 ILMN_2075892 PH_hs_0000640 TC11000707.hg g3582144_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-201671] LRP5 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-1458893] p-5S,5T-LRP5 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-1458905] p-3S,2T-LRP5 [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5368479] LRP5 [early endosome membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5339694] LRP5 D666_L809del [plasma membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:11859835] KEGG:hsa:4041 LRP5 [ReferenceDNASequence:12725609] UCSC:O75197 LRP5 [ReferenceDNASequence:12110934] OMIM:603506 LRP5 [ReferenceDNASequence:12030442] NCBI Gene:4041 LRP5 [ReferenceDNASequence:11946349] Monarch:4041 LRP5 [ReferenceDNASequence:ensembl:ENSG00000162337] ENSEMBL:ENSG00000162337 LRP5 [ReferenceDNASequence:11316560] BioGPS Gene:4041 LRP5 [ReferenceDNASequence:11397863] COSMIC - genes:LRP5 LRP5 [ReferenceDNASequence:11414181] CTD Gene:4041 LRP5 [ReferenceDNASequence:11434616] dbSNP Gene:4041 LRP5 [ReferenceDNASequence:11819734] HGNC:6697 LRP5
referenceTranscript	[ReferenceRNASequence:12504457] RefSeq:NM_001291902.1 LRP5 [ReferenceRNASequence:12504458] RefSeq:NM_002335.4 LRP5
schemaClass	ReferenceGeneProduct
secondaryIdentifier	LRP5_HUMAN Q96TD6 Q9UES7 Q9UP66
sequenceLength	1615
species	[Species:48887] Homo sapiens
stId	uniprot:O75197
url	http://purl.uniprot.org/uniprot/O75197

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-201671] LRP5 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-1458893] p-5S,5T-LRP5 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-1458905] p-3S,2T-LRP5 [plasma membrane] [EntityWithAccessionedSequence:R-HSA-5368479] LRP5 [early endosome membrane] [EntityWithAccessionedSequence:R-HSA-5339694] LRP5 D666_L809del [plasma membrane]
(referenceSequence)	[ModifiedResidue:1458886] O-phospho-L-threonine at unknown position [ModifiedResidue:1458882] O-phospho-L-serine at unknown position [FragmentDeletionModification:5339680] Deletion of residues 666 to 809
(interactor)	[UndirectedInteraction:11129955] UniProt:Q9BQB4 <-> UniProt:O75197 (IntAct) [UndirectedInteraction:11248603] UniProt:O75197 <-> UniProt:O94907 (IntAct) [UndirectedInteraction:11248605] UniProt:O75197 <-> UniProt:P41212 (IntAct) [UndirectedInteraction:11248607] UniProt:O75197 <-> UniProt:Q9H5K3 (IntAct) [UndirectedInteraction:11248609] UniProt:O75197 <-> UniProt:Q8IUE0 (IntAct) [UndirectedInteraction:11248611] UniProt:O75197 <-> UniProt:Q9HCJ2 (IntAct) [UndirectedInteraction:11248613] UniProt:O75197 <-> UniProt:Q9UBM8 (IntAct) [UndirectedInteraction:11248615] UniProt:O75197 <-> UniProt:P55899 (IntAct) [UndirectedInteraction:11248617] UniProt:O75197 <-> UniProt:Q17RF5 (IntAct) [UndirectedInteraction:11248619] UniProt:O75197 <-> UniProt:P00740 (IntAct) [UndirectedInteraction:11248621] UniProt:O75197 <-> UniProt:Q9UBT3 (IntAct) [UndirectedInteraction:11248623] UniProt:O75197 <-> UniProt:O00744 (IntAct) [UndirectedInteraction:11248625] UniProt:O75197 <-> UniProt:O95156 (IntAct) [UndirectedInteraction:11248627] UniProt:O75197 <-> UniProt:Q8WWY8 (IntAct) [UndirectedInteraction:11248629] UniProt:O75197 <-> UniProt:P58499 (IntAct) [UndirectedInteraction:11248631] UniProt:O75197 <-> UniProt:A4D1T9 (IntAct) [UndirectedInteraction:11248633] UniProt:O75197 <-> UniProt:Q96D21 (IntAct) [UndirectedInteraction:11248635] UniProt:O75197 <-> UniProt:Q9BZ11 (IntAct) [UndirectedInteraction:11248637] UniProt:O75197 <-> UniProt:Q8IW75 (IntAct) [UndirectedInteraction:11248639] UniProt:O75197 <-> UniProt:O95968 (IntAct) [UndirectedInteraction:11248641] UniProt:O75197 <-> UniProt:Q7L1S5 (IntAct) [UndirectedInteraction:11248643] UniProt:O75197 <-> UniProt:Q76B58 (IntAct) [UndirectedInteraction:11248645] UniProt:O75197 <-> UniProt:Q9UK85 (IntAct) [UndirectedInteraction:11248647] UniProt:O75197 <-> UniProt:Q92187 (IntAct) [UndirectedInteraction:11248649] UniProt:O75197 <-> UniProt:Q6IMN6 (IntAct) [UndirectedInteraction:11248651] UniProt:O75197 <-> UniProt:Q8J025 (IntAct)

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