ID A0A8C3ADD3_CYCLU Unreviewed; 1608 AA.
AC A0A8C3ADD3;
DT 19-JAN-2022, integrated into UniProtKB/TrEMBL.
DT 19-JAN-2022, sequence version 1.
DT 28-JAN-2026, entry version 19.
DE RecName: Full=Low-density lipoprotein receptor-related protein {ECO:0000256|PIRNR:PIRNR036314};
GN Name=lrp6 {ECO:0000313|Ensembl:ENSCLMP00005039543.1};
OS Cyclopterus lumpus (Lumpsucker).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Eupercaria; Perciformes; Cottioidei; Cottales; Cyclopteridae; Cyclopterus.
OX NCBI_TaxID=8103 {ECO:0000313|Ensembl:ENSCLMP00005039543.1, ECO:0000313|Proteomes:UP000694565};
RN [1] {ECO:0000313|Ensembl:ENSCLMP00005039543.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (AUG-2025) to UniProtKB.
RN [2] {ECO:0000313|Ensembl:ENSCLMP00005039543.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2025) to UniProtKB.
CC -!- FUNCTION: Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers
CC beta-catenin signaling through inducing aggregation of receptor-ligand
CC complexes into ribosome-sized signalosomes. Cell-surface coreceptor of
CC Wnt/beta-catenin signaling, which plays a pivotal role in bone
CC formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1
CC polymers to the plasma membrane which, in turn, recruits the
CC AXIN1/GSK3B-complex to the cell surface promoting the formation of
CC signalosomes and inhibiting AXIN1/GSK3-mediated phosphorylation and
CC destruction of beta-catenin. Required for posterior patterning of the
CC epiblast during gastrulation. {ECO:0000256|ARBA:ARBA00057392}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Forms phosphorylated oligomer
CC aggregates on Wnt-signaling. {ECO:0000256|PIRNR:PIRNR036314}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004251};
CC Single-pass type I membrane protein {ECO:0000256|ARBA:ARBA00004251}.
CC Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00004240}. Membrane raft
CC {ECO:0000256|ARBA:ARBA00004285}.
CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000256|ARBA:ARBA00009939,
CC ECO:0000256|PIRNR:PIRNR036314}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|PROSITE-ProRule:PRU00124}.
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DR Ensembl; ENSCLMT00005041025.1; ENSCLMP00005039543.1; ENSCLMG00005015932.1.
DR GeneTree; ENSGT00940000158990; -.
DR Proteomes; UP000694565; Unplaced.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-ARBA.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019534; F:toxin transmembrane transporter activity; IEA:UniProtKB-ARBA.
DR GO; GO:0042813; F:Wnt receptor activity; IEA:InterPro.
DR GO; GO:0017147; F:Wnt-protein binding; IEA:UniProtKB-UniRule.
DR GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IEA:UniProtKB-ARBA.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:InterPro.
DR GO; GO:0043009; P:chordate embryonic development; IEA:UniProtKB-ARBA.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IEA:UniProtKB-ARBA.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0030901; P:midbrain development; IEA:UniProtKB-ARBA.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:UniProtKB-ARBA.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:UniProtKB-ARBA.
DR GO; GO:0009888; P:tissue development; IEA:UniProtKB-ARBA.
DR CDD; cd00112; LDLa; 3.
DR FunFam; 2.10.25.10:FF:000381; Low-density lipoprotein receptor-related protein 6; 1.
DR FunFam; 2.120.10.30:FF:000001; Low-density lipoprotein receptor-related protein 6; 2.
DR FunFam; 2.120.10.30:FF:000017; Low-density lipoprotein receptor-related protein 6; 1.
DR FunFam; 2.120.10.30:FF:000241; Low-density lipoprotein receptor-related protein 6; 1.
DR FunFam; 4.10.400.10:FF:000016; Low-density lipoprotein receptor-related protein 6; 1.
DR FunFam; 4.10.400.10:FF:000074; low-density lipoprotein receptor-related protein 6; 1.
DR Gene3D; 2.10.25.10; Laminin; 1.
DR Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 3.
DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 4.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR050778; Cueball_EGF_LRP_Nidogen.
DR InterPro; IPR000742; EGF.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR000033; LDLR_classB_rpt.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR017049; LRP5/6.
DR PANTHER; PTHR46513:SF40; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 6; 1.
DR PANTHER; PTHR46513; VITELLOGENIN RECEPTOR-LIKE PROTEIN-RELATED-RELATED; 1.
DR Pfam; PF14670; FXa_inhibition; 4.
DR Pfam; PF00057; Ldl_recept_a; 3.
DR Pfam; PF00058; Ldl_recept_b; 12.
DR PIRSF; PIRSF036314; LDL_recpt-rel_p5/6; 1.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 4.
DR SMART; SM00192; LDLa; 3.
DR SMART; SM00135; LY; 20.
DR SUPFAM; SSF57196; EGF/Laminin; 4.
DR SUPFAM; SSF57424; LDL receptor-like module; 3.
DR SUPFAM; SSF63825; YWTD domain; 4.
DR PROSITE; PS01209; LDLRA_1; 1.
DR PROSITE; PS50068; LDLRA_2; 3.
DR PROSITE; PS51120; LDLRB; 15.
PE 3: Inferred from homology;
KW Cell membrane {ECO:0000256|ARBA:ARBA00022475};
KW Developmental protein {ECO:0000256|ARBA:ARBA00022473,
KW ECO:0000256|PIRNR:PIRNR036314};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157, ECO:0000256|PROSITE-
KW ProRule:PRU00124}; EGF-like domain {ECO:0000256|ARBA:ARBA00022536};
KW Endocytosis {ECO:0000256|ARBA:ARBA00022583};
KW Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824};
KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW Isopeptide bond {ECO:0000256|ARBA:ARBA00022499};
KW Lipoprotein {ECO:0000256|ARBA:ARBA00023288};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|PIRNR:PIRNR036314};
KW Palmitate {ECO:0000256|ARBA:ARBA00023139};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW Receptor {ECO:0000256|ARBA:ARBA00023170, ECO:0000256|PIRNR:PIRNR036314};
KW Reference proteome {ECO:0000313|Proteomes:UP000694565};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Signal {ECO:0000256|ARBA:ARBA00022729};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692,
KW ECO:0000256|PIRNR:PIRNR036314};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW ECO:0000256|PIRNR:PIRNR036314};
KW Ubl conjugation {ECO:0000256|ARBA:ARBA00022843};
KW Wnt signaling pathway {ECO:0000256|ARBA:ARBA00022687,
KW ECO:0000256|PIRNR:PIRNR036314}.
FT TRANSMEM 1368..1388
FT /note="Helical"
FT /evidence="ECO:0000256|PIRNR:PIRNR036314"
FT REPEAT 100..142
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT REPEAT 143..186
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT REPEAT 187..229
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT DOMAIN 279..318
FT /note="EGF-like"
FT /evidence="ECO:0000259|SMART:SM00181"
FT REPEAT 366..408
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT REPEAT 409..451
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT REPEAT 452..495
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT REPEAT 496..538
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT DOMAIN 585..622
FT /note="EGF-like"
FT /evidence="ECO:0000259|SMART:SM00181"
FT REPEAT 668..710
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT REPEAT 711..753
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT REPEAT 754..796
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT REPEAT 837..879
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT DOMAIN 886..924
FT /note="EGF-like"
FT /evidence="ECO:0000259|SMART:SM00181"
FT REPEAT 971..1014
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT REPEAT 1020..1062
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT REPEAT 1063..1107
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT REPEAT 1108..1150
FT /note="LDL-receptor class B"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00461"
FT DOMAIN 1200..1244
FT /note="EGF-like"
FT /evidence="ECO:0000259|SMART:SM00181"
FT REGION 1454..1482
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1554..1585
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 1264..1279
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00124"
FT DISULFID 1282..1294
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00124"
FT DISULFID 1289..1307
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00124"
FT DISULFID 1301..1316
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00124"
FT DISULFID 1320..1332
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00124"
FT DISULFID 1327..1345
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00124"
FT DISULFID 1339..1354
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00124"
SQ SEQUENCE 1608 AA; 179440 MW; EC677C42634AB3AE CRC64;
QNSACRSSVG CVPLLLYANR RDLRLVDAAH EKANATVVVG GLEDAAAVDY VYSQGLIYWS
DVSEEAIKRT VFNQSGASAV QTVVPGLASP DGLACDWLGS KLYWTDSETN RIEVAELDGS
LRKVLFWQEL DQPRAIALDP ERGYMYWTDW GEVPKIERAG MDGTNRSMII DKEIYWPNGL
TLDYSLEKLY WADAKHNFIH RSNLDGSSRE VVVKGELPHP FALTLYEDTL FWTDWNTHSI
HSCRKQTGAE QRIVHSDIFS PMDIHVFSAK RQDILVTCPC SVDNGGCSHL CLLSPMKPFY
QCACPTGVQL LEDGKTCRDG ATQMLLLARR TDLRRISLDT PDFTDVVLQL DDVRHAIAID
YDPVDGFVYW TDDDVKAVRR SRLDGSDSQF VVTSQVNHPD GIAVDWIARN LYWTDTGTDR
IEVTRLNGTM RKILISEDLD EPRAIVLDPV AGYMYWTDWG EVPKIERADL DGLERLVLVN
TSLGWPNGLA LDYEDRRLYW GDAKTDKIEV MDMDGTGRRV LVEDKLPHIF GFTLLGDFIY
WTDWQRRSIE RVHKRTAERE FIIDQLPDLM GLKAAYVHKS FGTNPCAESN GGCSHLCLYK
PQGVQCGCPI GLELVADMRT CIVPEAFLLF SRHTDIRRIS LETNNNNVAI PLTGVKEASA
LDFDVTDNRI YWTDITLKTI SRAFMNGSAL EHVVEFGLDY PEGMAVDWLG KNLYWADTGT
NRIEVAKLDG QHRQVLVWKD LDSPRALALD PAEGYMYWTE WGGKPKIDRA AMDGTGRITL
VADVGRANGL TIDYAERRLY WTDLDTTLIE SSNMLGQDRE VIADDLPHPF GLTQYQDYIY
WTDWSQRSIE RANKTSGQNR TVIQGHLDYV MDILVFHSSR QGGWNACAAT NGHCSHLCLA
VPISGFVCGC PAHFSLNIDN KTCSAPTSFL LFSQKSAINR MVMDEQQSPD IILPIHSLRN
VRALDYDPLD KQLYWIDSKQ NVIRRAQEDG NQSVTVVSGT LGGPSQGLQL YDLSIDIYSR
FIYWTSELTN AINVTRSDGS RVGVVLRGEH DKPRAIVVNP ERGYMYFTNL LERSPKIERA
ALDGTEREVL FFSGLGKPVA LAIDNELGKL FWVDSDLRRI ESSDLSGANR IVIADSNILQ
PVGLTVFGDH LYWIDKQQQM IERIDKTTRE GRTKIQARIA YLSDIHAVHE LDMREYSKHP
CTWDNGGCSH ICIVKGDGTT RCSCPVHLVL LQDELSCGEP PTCSPEQFSC TSGEVDCIPQ
AWRCDGFAEC DDSSDEEDCP VCSEAEFQCD SRQCVQLLLR CNGEADCQDR SDESKCEVRC
PPDQFTCSNG QCIGKHKKCD HNTDCTDNSD EIGCYPTEEP PPPSNNTIGS IVGVVMALFV
VGAVYFVCQR VLCPQMKDDG ETVANDFVVH GPSAVPLGYV PQPSSLSSSL PGMSRGKSVI
GSLSIVGGSS GPPYDRAHVT GASSSSSSST KGTYFPPILN PPPSPATVRS QYTMEFGYSS
NSPSTHRSYS YRPYSYRHFA PPTTPCSTDV CDSDYTPGRR VPLKPGVAKG YASDLQYDSE
PFPPPPTPRS QYLSAEENCE SCPPSPFTER SYAHHLYPPP PSPCTDSS
//
