ID LRP8_CHICK Reviewed; 917 AA.
AC Q98931; Q90883;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 27-MAR-2024, entry version 143.
DE RecName: Full=Low-density lipoprotein receptor-related protein 8;
DE Short=LRP-8;
DE AltName: Full=Apolipoprotein E receptor 2;
DE AltName: Full=Protein LR8B;
DE Flags: Precursor;
GN Name=LRP8; Synonyms=LR8B;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=White leghorn; TISSUE=Brain;
RX PubMed=8662771; DOI=10.1074/jbc.271.20.11732;
RA Novak S., Hiesberger T., Schneider W.J., Nimpf J.;
RT "A new LDL receptor homologue with 8 ligand binding repeats in brain of
RT chicken and mouse.";
RL J. Biol. Chem. 271:11732-11736(1996).
RN [2]
RP ALTERNATIVE SPLICING, AND INTERACTION WITH ALPHA2-MACROGLOBULIN.
RX PubMed=11294845; DOI=10.1074/jbc.m102662200;
RA Brandes C., Kahr L., Stockinger W., Hiesberger T., Schneider W.J.,
RA Nimpf J.;
RT "Alternative splicing in the ligand binding domain of mouse ApoE receptor-2
RT produces receptor variants binding reelin but not alpha2-macroglobulin.";
RL J. Biol. Chem. 276:22160-22169(2001).
CC -!- FUNCTION: Cell surface receptor for Reelin (RELN) and apolipoprotein E
CC (apoE)-containing ligands. Also binds alpha2-macroglobulin. LRP8
CC participates in transmitting the extracellular Reelin signal to
CC intracellular signaling processes, by binding to DAB1 on its
CC cytoplasmic tail. Reelin acts via both the VLDL receptor (VLDLR) and
CC LRP8 to regulate DAB1 tyrosine phosphorylation and microtubule function
CC in neurons. LRP8 has higher affinity for Reelin than VLDLR. LRP8 is
CC thus a key component of the Reelin pathway which governs neuronal
CC layering of the forebrain during embryonic brain development. Not
CC required for endocytic uptake of SEPP1 in the kidney which is mediated
CC by LRP2 (By similarity). {ECO:0000250|UniProtKB:Q14114,
CC ECO:0000250|UniProtKB:Q924X6}.
CC -!- SUBUNIT: Homooligomer. Interacts with VLDLR. Reelin associates with two
CC or more receptor molecules (By similarity). Interacts with DAB1 and
CC JNK-interacting proteins. Interacts with SNX17 (By similarity).
CC Interacts with PCSK9. Interacts with MDK; this interaction is calcium
CC dependent (By similarity). Interacts with CLU (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:Q14114,
CC ECO:0000250|UniProtKB:Q924X6}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=A number of isoforms are produced.;
CC Name=1;
CC IsoId=Q98931-1; Sequence=Displayed;
CC -!- TISSUE SPECIFICITY: Mainly in brain.
CC -!- PTM: O-glycosylated. {ECO:0000250}.
CC -!- PTM: Tyrosine phosphorylated upon apoE binding. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
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DR EMBL; X97001; CAA65729.1; -; mRNA.
DR RefSeq; NP_990517.1; NM_205186.2.
DR AlphaFoldDB; Q98931; -.
DR SMR; Q98931; -.
DR BioGRID; 676368; 2.
DR STRING; 9031.ENSGALP00000017370; -.
DR GlyCosmos; Q98931; 6 sites, No reported glycans.
DR PaxDb; 9031-ENSGALP00000017370; -.
DR GeneID; 396102; -.
DR KEGG; gga:396102; -.
DR CTD; 7804; -.
DR VEuPathDB; HostDB:geneid_396102; -.
DR eggNOG; KOG1215; Eukaryota.
DR InParanoid; Q98931; -.
DR PhylomeDB; Q98931; -.
DR PRO; PR:Q98931; -.
DR Proteomes; UP000000539; Unassembled WGS sequence.
DR GO; GO:0005901; C:caveola; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0021517; P:ventral spinal cord development; IEP:UniProtKB.
DR CDD; cd00054; EGF_CA; 2.
DR CDD; cd00112; LDLa; 8.
DR Gene3D; 2.10.25.10; Laminin; 3.
DR Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 8.
DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
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 PANTHER; PTHR24270; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED; 1.
DR PANTHER; PTHR24270:SF3; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 8; 1.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF14670; FXa_inhibition; 1.
DR Pfam; PF00057; Ldl_recept_a; 8.
DR Pfam; PF00058; Ldl_recept_b; 5.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 5.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00192; LDLa; 8.
DR SMART; SM00135; LY; 5.
DR SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR SUPFAM; SSF57424; LDL receptor-like module; 7.
DR SUPFAM; SSF63825; YWTD domain; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 2.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS01209; LDLRA_1; 7.
DR PROSITE; PS50068; LDLRA_2; 8.
DR PROSITE; PS51120; LDLRB; 5.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Disulfide bond; EGF-like domain;
KW Endocytosis; Glycoprotein; Membrane; Metal-binding; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..917
FT /note="Low-density lipoprotein receptor-related protein 8"
FT /id="PRO_0000017334"
FT TOPO_DOM 25..838
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 839..861
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 862..917
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..64
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 67..105
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 108..146
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 148..184
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 187..225
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 272..308
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 312..351
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 346..390
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 391..430
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 476..522
FT /note="LDL-receptor class B 1"
FT REPEAT 523..565
FT /note="LDL-receptor class B 2"
FT REPEAT 566..609
FT /note="LDL-receptor class B 3"
FT REPEAT 610..652
FT /note="LDL-receptor class B 4"
FT REPEAT 653..695
FT /note="LDL-receptor class B 5"
FT REGION 754..813
FT /note="Clustered O-linked oligosaccharides"
FT BINDING 46
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q14114"
FT BINDING 49
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q14114"
FT BINDING 51
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q14114"
FT BINDING 53
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q14114"
FT BINDING 59
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q14114"
FT BINDING 60
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q14114"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 532
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 628
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 782
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 820
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..41
FT /evidence="ECO:0000250|UniProtKB:Q14114"
FT DISULFID 36..54
FT /evidence="ECO:0000250|UniProtKB:Q14114"
FT DISULFID 48..63
FT /evidence="ECO:0000250|UniProtKB:Q14114"
FT DISULFID 68..80
FT /evidence="ECO:0000250"
FT DISULFID 75..93
FT /evidence="ECO:0000250"
FT DISULFID 87..104
FT /evidence="ECO:0000250"
FT DISULFID 109..123
FT /evidence="ECO:0000250"
FT DISULFID 116..136
FT /evidence="ECO:0000250"
FT DISULFID 130..145
FT /evidence="ECO:0000250"
FT DISULFID 149..161
FT /evidence="ECO:0000250"
FT DISULFID 156..174
FT /evidence="ECO:0000250"
FT DISULFID 168..183
FT /evidence="ECO:0000250"
FT DISULFID 188..200
FT /evidence="ECO:0000250"
FT DISULFID 195..213
FT /evidence="ECO:0000250"
FT DISULFID 207..224
FT /evidence="ECO:0000250"
FT DISULFID 234..246
FT /evidence="ECO:0000250"
FT DISULFID 241..259
FT /evidence="ECO:0000250"
FT DISULFID 253..268
FT /evidence="ECO:0000250"
FT DISULFID 273..285
FT /evidence="ECO:0000250"
FT DISULFID 280..298
FT /evidence="ECO:0000250"
FT DISULFID 292..307
FT /evidence="ECO:0000250"
FT DISULFID 313..326
FT /evidence="ECO:0000250"
FT DISULFID 321..339
FT /evidence="ECO:0000250"
FT DISULFID 333..350
FT /evidence="ECO:0000250"
FT DISULFID 355..366
FT /evidence="ECO:0000250"
FT DISULFID 362..375
FT /evidence="ECO:0000250"
FT DISULFID 377..389
FT /evidence="ECO:0000250"
FT DISULFID 395..405
FT /evidence="ECO:0000250"
FT DISULFID 401..414
FT /evidence="ECO:0000250"
FT DISULFID 416..429
FT /evidence="ECO:0000250"
SQ SEQUENCE 917 AA; 101379 MW; EF85E4D49441436A CRC64;
MCRPALARLL LLQLLLLKLY LGKGAMKECD KDQFQCRNER CIPAVWACDE DNDCSDNSDE
ADCPKKTCAE TDFACDNGHC IPDRWKCDGE EECSDGSDES EAACTKQVCP AEKISCGDLS
NKCIPSSWRC DGQKDCESGI DEAGCAPACS PDEFQCSNKT CISINFVCDG YNNCGDGSDE
KKCSPLTCSP NEFQCNNSVC IPQLWVCDNQ ADCEDHSDES IERCGYDAKA FNTCAAHEFQ
CGNGECILLN WKCDGDEDCK DKSDEQDCPL VTCRPDEFQC GDGTCIHGAK QCDKVHDCPD
NSDEAGCVQE SACESPSKFQ CKSGECIDGG KVCDLHRDCR DWSDEPLKEC GINECSLNNG
GCSHICKDLK IGYECECPPG YKLLDKKTCG DIDECENPDA CSQICINYKG DYKCECYEGY
EMDTLSKNCK AVGKSPYLIF TNRHEVRKID LVKRDYSRII PMLKNVVALD VEVATNRIYW
CDLFYRKIYS AYIDKASDTA EQVILIDSQL NSPEGVAIDW VHKNIYWTDS GNKTISVATA
DGSRRRTVFN SDLSEPRAIA VDPTRRFMYW SDWGDKAKIE KAGLNGVGRQ VLVSDNIEWP
NGITLDLLNQ RLYWVDSKLH SLSCIDFNGS NREVLISSID DLSHPFGLAV FEDRVFWTDL
ENEAIFSANR LSGLDISVLA ENLNNPHDIV VFHELKQPKA PDSCELSPQP NGGCEYLCLP
APHISPRSPK FTCACPDNMW LGPDMKKCYK ELPTTPATVE VPTTTTSHPA ATSTVTVTGS
ANTTTAVIPR AVSEATTAIP SSHSTTSLLI DSEMTTGNSN LSQHYSNNGQ GFDSTVTAAV
IGIVIPVVVI GLLCMGGYLI WRNWKRKNTK SMNFDNPVYR KTTEEEDEDE IHIGRTAQIG
HVYPARVALS LEDDGLP
//
