Protein detail

LRP6

Low-density lipoprotein receptor-related protein 6 (LRP-6)

Protein symbol LRP6	UniProt ID O75581	EVMP score 0.38
Frequency	Transmembrane count 1	Protein classification Cancer-related genesDisease related genesHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins

Basic Information

Protein Names

Low-density lipoprotein receptor-related protein 6 (LRP-6)

Protein Class

Cancer-related genesDisease related genesHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins

Protein Function

Human disease related genes:Cardiovascular diseases:Vascular diseases
Predicted intracellular proteins
Human disease related genes:Cancers:Cancers of the breast and female genital organs
Human disease related genes:Digestive system diseases:Mouth and dental diseases
Cancer-related genes:Candidate cancer biomarkers
Disease related genes

Transmembrane

1371..1393; Helical

Transmembrane Count

Ensembl

ENSG00000070018

Entrez Gene Symbol

LRP6

Gene Synonym

ADCAD2

Gene Description

LDL receptor related protein 6

Chromosome

Position

12116025-12267044

EVMP Score

0.38

Fluorescence & Localization

Function & Pathway

Protein Function

Human disease related genes:Cardiovascular diseases:Vascular diseases
Predicted intracellular proteins
Human disease related genes:Cancers:Cancers of the breast and female genital organs
Human disease related genes:Digestive system diseases:Mouth and dental diseases
Cancer-related genes:Candidate cancer biomarkers
Disease related genes

Cellular Component

Molecular Function

Biological Process

KEGG

Reactome

Canonical Pathways

M5880 Naba ecm affiliated
M5885 Naba matrisome associated
M5889 Naba matrisome

Mediation Categories

Clinical-translation mediationFusion and delivery mediationReceptor-signaling mediation

Relations & Evidence

Enzyme-Mediated Modification

40 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
LRP6	CDK14	O94921	S	1,490	phosphorylation	SIGNORProtMapperdbPTMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	dbPTM:16341017 ProtMapper:20059949 dbPTM:20059949 dbPTM:19801552 SIGNOR:20059949 dbPTM:17698587
LRP6	CSNK1E	P49674	S	1,420	phosphorylation	PhosphoSite_MIMPMIMPSIGNORProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	SIGNOR:16513652 ProtMapper:16513652
LRP6	CSNK1E	P49674	S	1,430	phosphorylation	SIGNOR_ProtMapperSIGNORProtMapper	SIGNOR:16513652 ProtMapper:16513652
LRP6	CSNK1E	P49674	S	1,431	phosphorylation	PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper
LRP6	CSNK1E	P49674	S	1,490	phosphorylation	PhosphoSite
LRP6	CSNK1G1	Q9HCP0	T	1,479	phosphorylation	PhosphoSite_MIMPMIMPNCI-PID_ProtMapperSIGNORProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:19107203 ProtMapper:16341016 ProtMapper:19309792 SIGNOR:16341016
LRP6	CSNK1G1	Q9HCP0	T	1,493	phosphorylation	NCI-PID_ProtMapperProtMapper	ProtMapper:19107203 ProtMapper:19309792 ProtMapper:16341016 ProtMapper:16341017 ProtMapper:18077588
LRP6	GSK3B	P49841	S	1,490	phosphorylation	Sparser_ProtMapperPhosphoSite_MIMPMIMPHPRD_MIMPSIGNORProtMapperKEASIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:22357953 KEA:16365045 ProtMapper:16341017 ProtMapper:16890161 SIGNOR:16341017
LRP6	GSK3B	P49841	T	1,572	phosphorylation	MIMPHPRD_MIMPKEAPhosphoSite_MIMP	KEA:16365045
LRP6	GSK3B	P49841	S	1,607	phosphorylation	MIMPHPRD_MIMPKEAPhosphoSite_MIMP	KEA:16365045

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Ligand-Receptor Signaling

52 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
receptor	receptor	CellPhoneDB	No	Yes	No	Yes	No
receptor	receptor	GO_Intercell	No	Yes	No	Yes	No
receptor	receptor	ICELLNET	No	Yes	No	Yes	No
receptor	receptor	CellTalkDB	No	Yes	No	Yes	No
receptor	receptor	Surfaceome	No	Yes	No	Yes	No
receptor	receptor	Ramilowski2015	No	Yes	No	Yes	No
receptor	receptor	LRdb	No	Yes	No	Yes	No
receptor	receptor	SignaLink_function	No	Yes	No	Yes	No
low_density_lipoprotein	receptor	Almen2009	No	Yes	No	Yes	No
ldlr	receptor	Surfaceome	No	Yes	No	Yes	No

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Regulatory Interaction Network

55 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
GSK3B	P49841	LRP6	O75581	Yes	Yes	No	HPRD_MIMPSIGNORProtMapperHINTPhosphoSite_KEASignaLink3Lit-BM-17HPRDIntActWangPhosphoSite_ProtMapperPhosphoSite_MIMPMIMPiPTMnetPhosphoPointKEAHPRD_KEASIGNOR_ProtMapperREACH_ProtMapperSparser_ProtMapperACSN	HINT:24642411 ProtMapper:16365045 ProtMapper:22357953 ProtMapper:33388549 HINT:19107203 HINT:16365045 SignaLink3:16365045 ACSN:19366350 ProtMapper:16890161 ACSN:21709260 SIGNOR:16341017 ACSN:21406690 ACSN:21606194 ACSN:17318175 HINT:16890161 KEA:16365045 SignaLink3:23331499 Lit-BM-17:16890161 IntAct:16365045 Lit-BM-17:19107203 SignaLink3:16340998 HPRD:16365045 ProtMapper:16341017
DKK1	O94907	LRP6	O75581	Yes	Yes	Yes	iTALKSIGNORHINTSignaLink3DIPHPMR_talklrHPRD_LRdbtalklrHPRDCui2007IntActLMPIDCancerCellMapWangRamilowski2015HPMR_LRdbCellPhoneDBELMHPRD_talklrCellinkerSTRING_talklrCellCallCellTalkDBFantom5_LRdbHPMR_CellinkerNetPathconnectomeDB2020SPIKE_LCLRdbSPIKE	LMPID:21944579 HINT:22000856 SignaLink3:11448771 Cellinker:12527209 SignaLink3:11357136 SPIKE_LC:11516963 HPRD:11357136 HINT:28052259 IntAct:11448771 CancerCellMap:11448771 HINT:11448771LRdb:11NetPath:19339249 HINT:11357136 DIP:21984209 SignaLink3:18988627 SPIKE:11516963 SIGNOR:11448771 connectomeDB2020:11357136 SignaLink3:23331499 Cellinker:11448771 HINT:27524201 IntAct:21984209 HINT:33961781 SignaLink3:21071413 HPRD:11448771 DIP:21944579 NetPath:11448771 HINT:21984209 ELM:21944579 LRdb:11357136 Cellinker:29925589 CellTalkDB:11516963 IntAct:21944579 HINT:21944579 Cellinker:11357136 connectomeDB2020:11448771
GSK3A	P49840	LRP6	O75581	Yes	Yes	No	SPIKEWangPhosphoSite_MIMPMIMPPhosphoSite_norefSIGNORiPTMnetProtMapperELMHINTACSNIntActSPIKE_LCPhosphoSitePhosphoSite_ProtMapper	ACSN:21406690 ELM:24642411 IntAct:16365045 ELM:14731402 ACSN:21606194 ACSN:17318175 SPIKE:20229235 SPIKE_LC:20229235 SPIKE:14731402 SIGNOR:35487243 SPIKE_LC:14731402 IntAct:30824926 HINT:16365045 PhosphoSite:21406690 ACSN:19366350 HINT:30824926 ACSN:21709260
FZD8	Q9H461	LRP6	O75581	Yes	Yes	No	WangNetPathSIGNORHPRDHINTSPIKE_LCSPIKE	HPRD:11448771 HPRD:11029007 NetPath:11448771 SPIKE:11448771 SPIKE_LC:11448771 HINT:11448771 SIGNOR:21078818 HINT:11029007 NetPath:20093360
WNT1	P04628	LRP6	O75581	Yes	Yes	No	iTALKSIGNORProtMapperHINTSignaLink3HPRD_LRdbtalklrHPRDCancerCellMapWangRamilowski2015HPRD_talklrREACH_ProtMapperSTRING_talklrCellCallFantom5_LRdbCellTalkDBNetPathconnectomeDB2020SPIKE_LCLRdbSPIKE	CancerCellMap:11029007 SignaLink3:11448771 CancerCellMap:11448771 HINT:11448771LRdb:11SIGNOR:21078818 SPIKE:10557084 SPIKE_LC:10557084 SignaLink3:18988627 LRdb:11029007 connectomeDB2020:11029007 ProtMapper:29444668 SignaLink3:23331499 NetPath:11029007 SignaLink3:21071413 HPRD:11448771 HPRD:11029007 CellTalkDB:11029007 SignaLink3:11029007 HINT:11029007 connectomeDB2020:11448771
WNT3A	P56704	LRP6	O75581	Yes	Yes	No	iTALKSIGNORProtMapperHINTDIPHPRD_LRdbtalklrHPRDIntActWangRamilowski2015HPRD_talklrBioGRIDREACH_ProtMapperSTRING_talklrCellCallFantom5_LRdbCellTalkDBSparser_ProtMapperNetPathconnectomeDB2020SPIKE_LCLRdbSPIKE	connectomeDB2020:14739301 ProtMapper:24265322LRdb:13NetPath:20093360 ProtMapper:16890161 BioGRID:19910923 HINT:22726442 SPIKE:12897152 HPRD:14739301 ProtMapper:23400998 ProtMapper:18772438 SIGNOR:21078818 SIGNOR:16890161 NetPath:12897152 NetPath:19339249 SIGNOR:15578921 SPIKE_LC:12897152 HPRD:12897152 LRdb:14739301 HINT:33961781 DIP:21944579 connectomeDB2020:12897152 ProtMapper:22491013 CellTalkDB:14739301 IntAct:21944579 IntAct:22726442 ProtMapper:25336320
LRP6	O75581	AXIN1	O15169	Yes	Yes	Yes	WangNetPathSIGNORHPRDHINTSignaLink3ACSNCancerCellMapSPIKE_LCLit-BM-17SPIKE	HINT:24976009 HINT:22682247 HINT:19107203 SIGNOR:12897152 Lit-BM-17:22682247 ACSN:10428961 SPIKE:12897152 ACSN:8666229 SIGNOR:16890161 CancerCellMap:12897152 NetPath:12897152 SignaLink3:12897152 Lit-BM-17:23959799 SignaLink3:18988627 SPIKE_LC:12897152 HPRD:12897152 SignaLink3:23331499 Lit-BM-17:16890161 Lit-BM-17:24976009 SIGNOR:18632848 Lit-BM-17:19107203 Lit-BM-17:20128690 SignaLink3:16340998 HINT:23892894
TDGF1	P13385	LRP6	O75581	Yes	Yes	No	SignaLink3	SignaLink3:23022962
KREM1	Q96MU8	LRP6	O75581	Yes	Yes	No	CellinkerHINTSignaLink3	HINT:27524201 Cellinker:29925589 SignaLink3:23331499 SignaLink3:12050670
KREM2	Q8NCW0	LRP6	O75581	Yes	Yes	Yes	CellinkerWangSIGNORSignaLink3	Cellinker:29925589 SignaLink3:23331499 SignaLink3:12050670 SIGNOR:12050670

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Protein Complex Composition

21 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
Kremen1_LRP6	KREMEN1 LRP6	O75581 Q96MU8	1:1	CellPhoneDBICELLNET	CellPhoneDB:Kremen1_LRP6	17804805
Kremen2_LRP6	KREMEN2 LRP6	O75581 Q8NCW0	1:1	CellPhoneDB	CellPhoneDB:Kremen2_LRP6
	AXIN1 GSK3B LRP6	O15169 O75581 P49841	1:1:1	PDB	PDB:4nm7PDB:4nm5
	LGR5 LRP6	O75473 O75581	0:0	Cellinker
	LRP6	O75581	2	PDB	PDB:6h15PDB:3s94
	DKK1 LRP6	O75581 O94907	2:1	PDB	PDB:3soqPDB:3s2kPDB:3s8vPDB:5gje
	CSH2 GH1 LRP6 SCG5 SOST	O75581 P01241 P05408 P0DML3 Q9BQB4	0:0:0:0:0	hu.MAP2
	LRP6 OGFR SOST TGIF2LX TGIF2LY	O75581 Q8IUE0 Q8IUE1 Q9BQB4 Q9NZT2	0:0:0:0:0	hu.MAP2
	LRP6 OGFR TGIF2LX TGIF2LY	O75581 Q8IUE0 Q8IUE1 Q9NZT2	0:0:0:0	hu.MAP2
	LRP6 SOST	O75581 Q9BQB4	2:2	PDB	PDB:3sovPDB:6l6r

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Isolation & Detection Technology

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationDensity Gradient CentrifugationSize Exclusion Chromatography	Western blottingFACS\|Western blottingMass spectrometryMass spectrometry\|Western blottingMass spectrometry [LTQ-FT Ultra]R Sequencing	2	14602237 38627767

Sequence, Structure & Domains

Sequences

Length

1,613

Mass

180,429

Sequence

MGAVLRSLLACSFCVLLRAAPLLLYANRRDLRLVDATNGKENATIVVGGLEDAAAVDFVFSHGLIYWSDVSEEAIKRTEFNKTESVQNVVVSGLLSPDGLACDWLGEKLYWTDSETNRIEVSNLDGSLRKVLFWQELDQPRAIALDPSSGFMYWTDWGEVPKIERAGMDGSSRFIIINSEIYWPNGLTLDYEEQKLYWADAKLNFIHKSNLDGTNRQAVVKGSLPHPFALTLFEDILYWTDWSTHSILACNKYTGEGLREIHSDIFSPMDIHAFSQQRQPNATNPCGIDNGGCSHLCLMSPVKPFYQCACPTGVKLLENGKTCKDGATELLLLARRTDLRRISLDTPDFTDIVLQLEDIRHAIAIDYDPVEGYIYWTDDEVRAIRRSFIDGSGSQFVVTAQIAHPDGIAVDWVARNLYWTDTGTDRIEVTRLNGTMRKILISEDLEEPRAIVLDPMVGYMYWTDWGEIPKIERAALDGSDRVVLVNTSLGWPNGLALDYDEGKIYWGDAKTDKIEVMNTDGTGRRVLVEDKIPHIFGFTLLGDYVYWTDWQRRSIERVHKRSAEREVIIDQLPDLMGLKATNVHRVIGSNPCAEENGGCSHLCLYRPQGLRCACPIGFELISDMKTCIVPEAFLLFSRRADIRRISLETNNNNVAIPLTGVKEASALDFDVTDNRIYWTDISLKTISRAFMNGSALEHVVEFGLDYPEGMAVDWLGKNLYWADTGTNRIEVSKLDGQHRQVLVWKDLDSPRALALDPAEGFMYWTEWGGKPKIDRAAMDGSERTTLVPNVGRANGLTIDYAKRRLYWTDLDTNLIESSNMLGLNREVIADDLPHPFGLTQYQDYIYWTDWSRRSIERANKTSGQNRTIIQGHLDYVMDILVFHSSRQSGWNECASSNGHCSHLCLAVPVGGFVCGCPAHYSLNADNRTCSAPTTFLLFSQKSAINRMVIDEQQSPDIILPIHSLRNVRAIDYDPLDKQLYWIDSRQNMIRKAQEDGSQGFTVVVSSVPSQNLEIQPYDLSIDIYSRYIYWTCEATNVINVTRLDGRSVGVVLKGEQDRPRAVVVNPEKGYMYFTNLQERSPKIERAALDGTEREVLFFSGLSKPIALALDSRLGKLFWADSDLRRIESSDLSGANRIVLEDSNILQPVGLTVFENWLYWIDKQQQMIEKIDMTGREGRTKVQARIAQLSDIHAVKELNLQEYRQHPCAQDNGGCSHICLVKGDGTTRCSCPMHLVLLQDELSCGEPPTCSPQQFTCFTGEIDCIPVAWRCDGFTECEDHSDELNCPVCSESQFQCASGQCIDGALRCNGDANCQDKSDEKNCEVLCLIDQFRCANGQCIGKHKKCDHNVDCSDKSDELDCYPTEEPAPQATNTVGSVIGVIVTIFVSGTVYFICQRMLCPRMKGDGETMTNDYVVHGPASVPLGYVPHPSSLSGSLPGMSRGKSMISSLSIMGGSSGPPYDRAHVTGASSSSSSSTKGTYFPAILNPPPSPATERSHYTMEFGYSSNSPSTHRSYSYRPYSYRHFAPPTTPCSTDVCDSDYAPSRRMTSVATAKGYTSDLNYDSEPVPPPPTPRSQYLSAEENYESCPPSPYTERSYSHHLYPPPPSPCTDSS

3D Structural Models

Turn

37..40; 70..73; 104..107; 114..117; 191..194; 201..204; 242..245; 252..254; 285..289; 369..372; 379..382; 412..415; 422..425; 455..458; 499..502; 509..512; 550..553; 560..562; 671..674; 681..684; 714..717; 724..727; 757..760; 800..803; 810..813; 850..853; 860..862; 892..896; 908..910; 974..977; 984..987; 1023..1026; 1033..1036; 1066..1069; 1111..1114; 1121..1124; 1162..1165; 1206..1209

Helix

60..62; 147..149; 276..278; 290..292; 591..593; 595..598; 884..886; 897..899; 1199..1204; 1210..1213

Beta Strand

22..26; 28..35; 44..59; 64..69; 74..79; 82..84; 88..92; 99..103; 108..113; 118..123; 130..133; 138..146; 151..156; 158..160; 162..167; 174..177; 184..190; 195..200; 205..210; 217..220; 227..233; 236..241; 246..251; 259..262; 271..274; 294..299; 305..309; 328..337; 339..346; 351..353; 362..368; 373..378; 383..387; 389..391; 395..398; 407..411; 416..421; 426..431; 438..441; 446..454; 459..464; 466..468; 470..475; 482..485; 492..498; 503..508; 513..518; 525..528; 535..541; 544..549; 554..559; 565..569; 575..584; 600..604; 611..613; 633..638; 641..648; 653..655; 664..670; 675..680; 685..690; 697..700; 709..713; 718..723; 728..733; 740..743; 750..756; 761..766; 768..770; 772..777; 784..787; 791..799; 804..809; 814..819; 826..830; 835..841; 844..849; 854..859; 867..870; 878..882; 901..907; 911..915; 933..940; 943..947; 967..973; 978..983; 988..993; 1000..1003; 1016..1022; 1027..1032; 1037..1042; 1047..1052; 1059..1065; 1070..1077; 1080..1087; 1094..1097; 1104..1110; 1115..1120; 1125..1130; 1137..1140; 1147..1153; 1156..1161; 1166..1171; 1174..1176; 1179..1182; 1188..1194; 1215..1220; 1222..1224; 1226..1229; 1234..1236; 1240..1244

3D Structure

Electron microscopy (2); X-ray crystallography (25)

Domain & Motif Annotations

Compositional Bias

1602..1613; Pro residues

Repeat

63..106; LDL-receptor class B 1; 107..149; LDL-receptor class B 2; 150..193; LDL-receptor class B 3; 194..236; LDL-receptor class B 4; 237..276; LDL-receptor class B 5; 372..414; LDL-receptor class B 6; 415..457; LDL-receptor class B 7; 458..501; LDL-receptor class B 8; 502..542; LDL-receptor class B 9; 543..584; LDL-receptor class B 10; 674..716; LDL-receptor class B 11; 717..759; LDL-receptor class B 12; 760..802; LDL-receptor class B 13; 803..842; LDL-receptor class B 14; 843..885; LDL-receptor class B 15; 977..1025; LDL-receptor class B 16; 1026..1068; LDL-receptor class B 17; 1069..1113; LDL-receptor class B 18; 1114..1156; LDL-receptor class B 19; 1157..1198; LDL-receptor class B 20

Motif

1487..1493; PPPSP motif A; 1527..1534; PPPSP motif B; 1568..1575; PPPSP motif C; 1588..1593; PPPSP motif D; 1603..1610; PPPSP motif E

Domain (CC)

The YWTD-EGF-like domains 1 and 2 are required for the interaction with Wnt-frizzled complex. The YWTD-EGF-like domains 3 and 4 are required for the interaction with DKK1..; DOMAIN: The PPPSP motifs play a central role in signal transduction by being phosphorylated, leading to activate the Wnt signaling pathway.

Domain (FT)

282..324; EGF-like 1; 588..628; EGF-like 2; 889..930; EGF-like 3; 1203..1244; EGF-like 4; 1248..1286; LDL-receptor class A 1; 1287..1323; LDL-receptor class A 2; 1325..1361; LDL-receptor class A 3

Region

20..275; Beta-propeller 1; 328..589; Beta-propeller 2; 631..890; Beta-propeller 3; 933..1202; Beta-propeller 4; 1556..1613; Disordered

Protein Families

LDLR family

Sequence Similarities

Belongs to the LDLR family.

Clinical Relevance

Disease Involvement

Cancer-related genesDisease variant

Antibody

CAB004490 HPA029925

Interaction Protein

ENSG00000082701ENSG00000105723ENSG00000105974ENSG00000107984ENSG00000154342ENSG00000167941ENSG00000185900ENSG00000188906

Interaction Count

Interaction Dataset

intact_biogridintact_biogrid_bioplexbiogrid_bioplex