low density lipoprotein (LDL) receptor related protein (LRP) 6

Function: - involved in Wnt1 signaling pathway - probably coreceptor with frizzled for wnt - receptor for DKK1 & DKK2 but not DKK3 - interacts with frizzled 5 - component of wnt7 receptor complex - Wnt7A interacts with the LRP6/FZD5 complex which is antagonized by DKK1 & DKK3 - interacts with RSPO1 & RSPO3 - interacts with FZD5 Structure: - YWTD-EGF-like domains 1 & 2 are required for the interaction with Wnt-frizzled complex - YWTD-EGF-like domains 3 & 4 are required for the interaction with DKK1 - belongs to the LDLR family - contains 4 EGF-like domains - contains 3 LDL-receptor class A domains - contains 20 LDL-receptor class B repeats Compartment: membrane Expression: - widely expressed - co-expressed with LRP5 during embryogenesis & in adult tissues Pathology: - defects in LRP6 are the cause of autosomal dominant coronary artery disease 2 (ADCAD2)

Properties

SIZE: MW = 180 kD entity length = 1613 aa COMPARTMENT: cellular membrane MOTIF: signal sequence {1-19} N-glycosylation site {N42} LDL-receptor class B {63-105} MOTIF: N-glycosylation site {N81} LDL-receptor class B {107-148} LDL-receptor class B {150-192} LDL-receptor class B {194-235} LDL-receptor class B {237-276} N-glycosylation site {N281} EGF domain {282-324} MOTIF: cysteine residue {C286} MODIFICATION: cysteine residue {C297} cysteine residue {C293} MODIFICATION: cysteine residue {C308} cysteine residue {C297} MODIFICATION: cysteine residue {C286} cysteine residue {C308} MODIFICATION: cysteine residue {C293} cysteine residue {C310} MODIFICATION: cysteine residue {C323} cysteine residue {C323} MODIFICATION: cysteine residue {C310} LDL-receptor class B {372-413} LDL-receptor class B {415-456} MOTIF: N-glycosylation site {N433} LDL-receptor class B {458-500} MOTIF: N-glycosylation site {N486} LDL-receptor class B {502-540} LDL-receptor class B {543-586} EGF domain {588-628} MOTIF: cysteine residue {C592} MODIFICATION: cysteine residue {C603} cysteine residue {C599} MODIFICATION: cysteine residue {C612} cysteine residue {C603} MODIFICATION: cysteine residue {C592} cysteine residue {C612} MODIFICATION: cysteine residue {C599} cysteine residue {C614} MODIFICATION: cysteine residue {C627} cysteine residue {C627} MODIFICATION: cysteine residue {C614} LDL-receptor class B {674-715} MOTIF: N-glycosylation site {N692} LDL-receptor class B {717-758} LDL-receptor class B {760-801} LDL-receptor class B {803-840} LDL-receptor class B {843-884} MOTIF: N-glycosylation site {N859} N-glycosylation site {N865} EGF domain {889-930} MOTIF: cysteine residue {C893} MODIFICATION: cysteine residue {C904} cysteine residue {C900} MODIFICATION: cysteine residue {C914} cysteine residue {C904} MODIFICATION: cysteine residue {C893} cysteine residue {C914} MODIFICATION: cysteine residue {C900} cysteine residue {C916} MODIFICATION: cysteine residue {C929} N-glycosylation site {N926} cysteine residue {C929} MODIFICATION: cysteine residue {C916} LDL-receptor class B {977-1024} LDL-receptor class B {1026-1067} MOTIF: N-glycosylation site {N1039} LDL-receptor class B {1069-1112} LDL-receptor class B {1114-1155} LDL-receptor class B {1157-1197} EGF domain {1203-1244} MOTIF: cysteine residue {C1207} MODIFICATION: cysteine residue {C1218} cysteine residue {C1214} MODIFICATION: cysteine residue {C1228} cysteine residue {C1218} MODIFICATION: cysteine residue {C1207} cysteine residue {C1228} MODIFICATION: cysteine residue {C1214} cysteine residue {C1230} MODIFICATION: cysteine residue {C1243} cysteine residue {C1243} MODIFICATION: cysteine residue {C1230} LDL-receptor class A {1248-1286} MOTIF: cysteine residue {C1249} MODIFICATION: cysteine residue {C1263} cysteine residue {C1256} MODIFICATION: cysteine residue {C1276} cysteine residue {C1263} MODIFICATION: cysteine residue {C1249} cysteine residue {C1270} MODIFICATION: cysteine residue {C1285} cysteine residue {C1276} MODIFICATION: cysteine residue {C1256} cysteine residue {C1285} MODIFICATION: cysteine residue {C1270} LDL-receptor class A {1287-1323} MOTIF: cysteine residue {C1288} MODIFICATION: cysteine residue {C1300} cysteine residue {C1295} MODIFICATION: cysteine residue {C1313} cysteine residue {C1300} MODIFICATION: cysteine residue {C1288} cysteine residue {C1307} MODIFICATION: cysteine residue {C1322} cysteine residue {C1313} MODIFICATION: cysteine residue {C1295} cysteine residue {C1322} MODIFICATION: cysteine residue {C1307} LDL-receptor class A {1325-1361} MOTIF: cysteine residue {C1326} MODIFICATION: cysteine residue {C1338} cysteine residue {C1333} MODIFICATION: cysteine residue {C1351} cysteine residue {C1338} MODIFICATION: cysteine residue {C1326} cysteine residue {C1345} MODIFICATION: cysteine residue {C1360} cysteine residue {C1351} MODIFICATION: cysteine residue {C1333} cysteine residue {C1360} MODIFICATION: cysteine residue {C1345} transmembrane domain {1371-1393}

Database Correlations

OMIM 603507 MORBIDMAP 603507 UniProt O75581 PFAM correlations Entrez Gene 4040

References

UniProt :accession O75581