Q924X6 · LRP8_MOUSE
- ProteinLow-density lipoprotein receptor-related protein 8
- GeneLrp8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids996 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
LRP8 participates in transmitting the extracellular Reelin signal to intracellular signaling processes, by binding to DAB1 on its cytoplasmic tail (PubMed:10380922).
Reelin acts via both the VLDL receptor (VLDLR) and LRP8 to regulate DAB1 tyrosine phosphorylation and microtubule function in neurons (PubMed:10380922).
LRP8 has higher affinity for Reelin than VLDLR (PubMed:10380922, PubMed:11294845).
LRP8 is thus a key component of the Reelin pathway which governs neuronal layering of the forebrain during embryonic brain development (PubMed:10380922, PubMed:11294845, PubMed:18778775).
Binds the endoplasmic reticulum resident receptor-associated protein (RAP) (PubMed:12899622).
Binds dimers of beta 2-glycoprotein I and may be involved in the suppression of platelet aggregation in the vasculature. Highly expressed in the initial segment of the epididymis, where it affects the functional expression of clusterin and phospholipid hydroperoxide glutathione peroxidase (PHGPx), two proteins required for sperm maturation (PubMed:12695510).
May also function as an endocytic receptor (PubMed:12169628).
Not required for endocytic uptake of SEPP1 in the kidney which is mediated by LRP2 (PubMed:18174160).
Together with its ligand, apolipoprotein E (apoE), may indirectly play a role in the suppression of the innate immune response by controlling the survival of myeloid-derived suppressor cells (PubMed:29336888).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 58 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 61 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 63 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 65 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 71 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 72 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: E |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameLow-density lipoprotein receptor-related protein 8
- Short namesLRP-8
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ924X6
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 29-858 | Extracellular | ||||
Sequence: DPLPGGQGPVKECEEDQFRCRNERCIPLVWRCDEDNDCSDNSDEDDCPKRTCADSDFTCDNGHCIPERWKCDGEEECPDGSDESKATCSSEECPAEKLSCGPTSHKCVPASWRCDGEKDCEGGADEAGCPTLCAPHEFQCSNRSCLASVFVCDGDDDCGDGSDERGCSDPACPPREFRCGGGGTCIPERWVCDRQFDCEDRSDEAAELCGRAGQGTTATPAACAPTAQFTCRSGECIHLGWRCDGDRDCKDKSDEADCSPGPCRENEFQCGDGTCVLAIKRCNQERDCPDGSDEAGCLQESTCEGPRRFQCKSGECVDGGKVCDDQRDCRDWSDEPQKVCGLNECLHNNGGCSHICTDLKIGFECTCPAGFQLLDQKTCGDIDECQDPDACSQICVNYKGYFKCECHPGYEMDTLTKNCKAVAGKSPSLIFTNRHEVRRIDLVKRDYSRLIPMLKNVVALDVEVATNRIYWCDLSYRKIYSAHMDKASIPDEQVVLIDEQLHSPEGLAVDWVHKHIYWTDSGNKTISVATTDGRRRCTLFSRELSEPRAIAVDPLRGFMYWSDWGFQAKIEKAGLNGADRQTLVSDNIEWPNGITLDLLSQRLYWVDSKLHQLSSIDFNGGNRKMLIFSTDFLSHPFGVAVFEDKVFWTDLENEAIFSANRLNGLEIAILAENLNNPHDIVIFHELKQPKAADACDLSAQPNGGCEYLCLPAPQISSHSPKYTCACPDTMWLGPDMKRCYRAPQSTSTTTLASAMTRTVPATTRAPGTTIHDPTYQNHSTETPSQTAAAPHSVNVPRAPSTSPSTPSPATSNHSQHYGNEGSQMGSTVTA | ||||||
Transmembrane | 859-881 | Helical | ||||
Sequence: AVIGVIVPIVVIALLCMSGYLIW | ||||||
Topological domain | 882-996 | Cytoplasmic | ||||
Sequence: RNWKRKNTKSMNFDNPVYRKTTEEEEEDELHIGRTAQIGHVYPAAISNYDRPLWAEPCLGETRDLEDPAPALKELFVLPGEPRSQLHQLPKNPLSELPVVKCKRVALSLEDDGLP |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Targeted disruption of LRP8 and VLVLR together results in a phenotype virtually indistinguishable from that seen in 'reeler' and 'scrambler' mice (PubMed:10380922).
Subtle effects of VLDLR deletion are found mainly in the cerebellum, whereas lack of LRP8 predominantly affects the positioning of the neurons in the neocortex (PubMed:10380922).
Besides brain formation defects, LRP8-deficient mice also exhibit male infertility (PubMed:10380922).
Does not affect endocytosis of SEPP1 in the kidney proximal tubule (PubMed:18174160).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 61 | Lower affinity for RAP. Abolishes binding to Reelin. | ||||
Sequence: D → N | ||||||
Mutagenesis | 102 | Same affinity for RAP. Same affinity for Reelin. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 145 | Same affinity for RAP. Lower affinity for Reelin. | ||||
Sequence: E → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 41 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-28 | |||||
Sequence: MGRPELGALRPLALLLLLLLQLQHLSAA | ||||||
Chain | PRO_0000017333 | 29-996 | Low-density lipoprotein receptor-related protein 8 | |||
Sequence: DPLPGGQGPVKECEEDQFRCRNERCIPLVWRCDEDNDCSDNSDEDDCPKRTCADSDFTCDNGHCIPERWKCDGEEECPDGSDESKATCSSEECPAEKLSCGPTSHKCVPASWRCDGEKDCEGGADEAGCPTLCAPHEFQCSNRSCLASVFVCDGDDDCGDGSDERGCSDPACPPREFRCGGGGTCIPERWVCDRQFDCEDRSDEAAELCGRAGQGTTATPAACAPTAQFTCRSGECIHLGWRCDGDRDCKDKSDEADCSPGPCRENEFQCGDGTCVLAIKRCNQERDCPDGSDEAGCLQESTCEGPRRFQCKSGECVDGGKVCDDQRDCRDWSDEPQKVCGLNECLHNNGGCSHICTDLKIGFECTCPAGFQLLDQKTCGDIDECQDPDACSQICVNYKGYFKCECHPGYEMDTLTKNCKAVAGKSPSLIFTNRHEVRRIDLVKRDYSRLIPMLKNVVALDVEVATNRIYWCDLSYRKIYSAHMDKASIPDEQVVLIDEQLHSPEGLAVDWVHKHIYWTDSGNKTISVATTDGRRRCTLFSRELSEPRAIAVDPLRGFMYWSDWGFQAKIEKAGLNGADRQTLVSDNIEWPNGITLDLLSQRLYWVDSKLHQLSSIDFNGGNRKMLIFSTDFLSHPFGVAVFEDKVFWTDLENEAIFSANRLNGLEIAILAENLNNPHDIVIFHELKQPKAADACDLSAQPNGGCEYLCLPAPQISSHSPKYTCACPDTMWLGPDMKRCYRAPQSTSTTTLASAMTRTVPATTRAPGTTIHDPTYQNHSTETPSQTAAAPHSVNVPRAPSTSPSTPSPATSNHSQHYGNEGSQMGSTVTAAVIGVIVPIVVIALLCMSGYLIWRNWKRKNTKSMNFDNPVYRKTTEEEEEDELHIGRTAQIGHVYPAAISNYDRPLWAEPCLGETRDLEDPAPALKELFVLPGEPRSQLHQLPKNPLSELPVVKCKRVALSLEDDGLP | ||||||
Disulfide bond | 41↔53 | |||||
Sequence: CEEDQFRCRNERC | ||||||
Disulfide bond | 48↔66 | |||||
Sequence: CRNERCIPLVWRCDEDNDC | ||||||
Disulfide bond | 60↔75 | |||||
Sequence: CDEDNDCSDNSDEDDC | ||||||
Disulfide bond | 80↔92 | |||||
Sequence: CADSDFTCDNGHC | ||||||
Disulfide bond | 87↔105 | |||||
Sequence: CDNGHCIPERWKCDGEEEC | ||||||
Disulfide bond | 99↔116 | |||||
Sequence: CDGEEECPDGSDESKATC | ||||||
Disulfide bond | 121↔135 | |||||
Sequence: CPAEKLSCGPTSHKC | ||||||
Disulfide bond | 128↔148 | |||||
Sequence: CGPTSHKCVPASWRCDGEKDC | ||||||
Disulfide bond | 142↔157 | |||||
Sequence: CDGEKDCEGGADEAGC | ||||||
Disulfide bond | 161↔173 | |||||
Sequence: CAPHEFQCSNRSC | ||||||
Disulfide bond | 168↔186 | |||||
Sequence: CSNRSCLASVFVCDGDDDC | ||||||
Glycosylation | 170 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 180↔195 | |||||
Sequence: CDGDDDCGDGSDERGC | ||||||
Disulfide bond | 200↔213 | |||||
Sequence: CPPREFRCGGGGTC | ||||||
Disulfide bond | 207↔226 | |||||
Sequence: CGGGGTCIPERWVCDRQFDC | ||||||
Disulfide bond | 220↔237 | |||||
Sequence: CDRQFDCEDRSDEAAELC | ||||||
Disulfide bond | 251↔264 | |||||
Sequence: CAPTAQFTCRSGEC | ||||||
Disulfide bond | 259↔277 | |||||
Sequence: CRSGECIHLGWRCDGDRDC | ||||||
Disulfide bond | 271↔286 | |||||
Sequence: CDGDRDCKDKSDEADC | ||||||
Disulfide bond | 291↔303 | |||||
Sequence: CRENEFQCGDGTC | ||||||
Disulfide bond | 298↔316 | |||||
Sequence: CGDGTCVLAIKRCNQERDC | ||||||
Disulfide bond | 310↔325 | |||||
Sequence: CNQERDCPDGSDEAGC | ||||||
Disulfide bond | 331↔344 | |||||
Sequence: CEGPRRFQCKSGEC | ||||||
Disulfide bond | 339↔357 | |||||
Sequence: CKSGECVDGGKVCDDQRDC | ||||||
Disulfide bond | 351↔368 | |||||
Sequence: CDDQRDCRDWSDEPQKVC | ||||||
Disulfide bond | 373↔384 | |||||
Sequence: CLHNNGGCSHIC | ||||||
Disulfide bond | 380↔393 | |||||
Sequence: CSHICTDLKIGFEC | ||||||
Disulfide bond | 395↔407 | |||||
Sequence: CPAGFQLLDQKTC | ||||||
Disulfide bond | 413↔423 | |||||
Sequence: CQDPDACSQIC | ||||||
Disulfide bond | 419↔432 | |||||
Sequence: CSQICVNYKGYFKC | ||||||
Disulfide bond | 434↔447 | |||||
Sequence: CHPGYEMDTLTKNC | ||||||
Glycosylation | 551 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 805 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 840 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Interaction
Subunit
Interacts with VLDLR (By similarity).
Reelin associates with two or more receptor molecules. Interacts with DAB1 and JNK-interacting proteins. Interacts with SNX17. Interacts with PCSK9 (By similarity).
Interacts with MDK; this interaction is calcium dependent (PubMed:12573468).
Interacts with CLU (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | Q924X6 | APOH P02749 | 2 | EBI-432319, EBI-2114682 | |
BINARY | Q924X6 | Dlg4 Q62108 | 3 | EBI-432319, EBI-300895 | |
BINARY | Q924X6 | Grin1 P35438 | 4 | EBI-432319, EBI-400084 | |
XENO | Q924X6 | Lrpap1 Q99068 | 2 | EBI-432319, EBI-919734 | |
BINARY | Q924X6 | Reln Q60841 | 4 | EBI-432319, EBI-9248666 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, repeat, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 40-76 | LDL-receptor class A 1 | ||||
Sequence: ECEEDQFRCRNERCIPLVWRCDEDNDCSDNSDEDDCP | ||||||
Domain | 79-117 | LDL-receptor class A 2 | ||||
Sequence: TCADSDFTCDNGHCIPERWKCDGEEECPDGSDESKATCS | ||||||
Domain | 120-158 | LDL-receptor class A 3 | ||||
Sequence: ECPAEKLSCGPTSHKCVPASWRCDGEKDCEGGADEAGCP | ||||||
Domain | 160-196 | LDL-receptor class A 4 | ||||
Sequence: LCAPHEFQCSNRSCLASVFVCDGDDDCGDGSDERGCS | ||||||
Domain | 199-238 | LDL-receptor class A 5 | ||||
Sequence: ACPPREFRCGGGGTCIPERWVCDRQFDCEDRSDEAAELCG | ||||||
Domain | 250-287 | LDL-receptor class A 6 | ||||
Sequence: ACAPTAQFTCRSGECIHLGWRCDGDRDCKDKSDEADCS | ||||||
Domain | 290-326 | LDL-receptor class A 7 | ||||
Sequence: PCRENEFQCGDGTCVLAIKRCNQERDCPDGSDEAGCL | ||||||
Domain | 330-369 | LDL-receptor class A 8 | ||||
Sequence: TCEGPRRFQCKSGECVDGGKVCDDQRDCRDWSDEPQKVCG | ||||||
Domain | 364-408 | EGF-like 1 | ||||
Sequence: PQKVCGLNECLHNNGGCSHICTDLKIGFECTCPAGFQLLDQKTCG | ||||||
Domain | 409-448 | EGF-like 2; calcium-binding | ||||
Sequence: DIDECQDPDACSQICVNYKGYFKCECHPGYEMDTLTKNCK | ||||||
Repeat | 495-541 | LDL-receptor class B 1 | ||||
Sequence: NRIYWCDLSYRKIYSAHMDKASIPDEQVVLIDEQLHSPEGLAVDWVH | ||||||
Repeat | 542-584 | LDL-receptor class B 2 | ||||
Sequence: KHIYWTDSGNKTISVATTDGRRRCTLFSRELSEPRAIAVDPLR | ||||||
Repeat | 585-628 | LDL-receptor class B 3 | ||||
Sequence: GFMYWSDWGFQAKIEKAGLNGADRQTLVSDNIEWPNGITLDLLS | ||||||
Repeat | 629-671 | LDL-receptor class B 4 | ||||
Sequence: QRLYWVDSKLHQLSSIDFNGGNRKMLIFSTDFLSHPFGVAVFE | ||||||
Repeat | 672-714 | LDL-receptor class B 5 | ||||
Sequence: DKVFWTDLENEAIFSANRLNGLEIAILAENLNNPHDIVIFHEL | ||||||
Region | 773-831 | Clustered O-linked oligosaccharides | ||||
Sequence: STSTTTLASAMTRTVPATTRAPGTTIHDPTYQNHSTETPSQTAAAPHSVNVPRAPSTSP | ||||||
Region | 778-851 | Disordered | ||||
Sequence: TLASAMTRTVPATTRAPGTTIHDPTYQNHSTETPSQTAAAPHSVNVPRAPSTSPSTPSPATSNHSQHYGNEGSQ |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
Q924X6-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length996
- Mass (Da)109,818
- Last updated2004-05-10 v2
- ChecksumBA1AF0132A964EBA
Q924X6-2
- Name2
- Differences from canonical
- 160-285: Missing
Q924X6-5
- Name3
- SynonymsApoER2delta4-6,8-F
- NoteContains a 18 aa insert in the extracellular part which carries a furin cleavage site.
Computationally mapped potential isoform sequences
There are 12 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
B1AXJ3 | B1AXJ3_MOUSE | Lrp8 | 832 | ||
B1AXJ4 | B1AXJ4_MOUSE | Lrp8 | 955 | ||
B1AXJ5 | B1AXJ5_MOUSE | Lrp8 | 896 | ||
B1AXJ6 | B1AXJ6_MOUSE | Lrp8 | 694 | ||
F6YZZ8 | F6YZZ8_MOUSE | Lrp8 | 870 | ||
A0A571BEC8 | A0A571BEC8_MOUSE | Lrp8 | 726 | ||
A0A571BE80 | A0A571BE80_MOUSE | Lrp8 | 787 | ||
A0A571BE60 | A0A571BE60_MOUSE | Lrp8 | 828 | ||
A0A571BDQ2 | A0A571BDQ2_MOUSE | Lrp8 | 135 | ||
A0A571BDC7 | A0A571BDC7_MOUSE | Lrp8 | 189 | ||
A0A571BGD2 | A0A571BGD2_MOUSE | Lrp8 | 157 | ||
A0A571BEF2 | A0A571BEF2_MOUSE | Lrp8 | 124 |
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 32 | in Ref. 1; BAB46965 | ||||
Sequence: P → L | ||||||
Alternative sequence | VSP_010309 | 160-285 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 286-287 | in Ref. 2 | ||||
Sequence: CS → SA | ||||||
Sequence conflict | 610 | in Ref. 2; CAC38356 | ||||
Sequence: T → P | ||||||
Sequence conflict | 672-673 | in Ref. 2; CAC38356 | ||||
Sequence: DK → VQ | ||||||
Sequence conflict | 715-716 | in Ref. 2; CAC38356 | ||||
Sequence: KQ → NE | ||||||
Sequence conflict | 750 | in Ref. 2; CAC38356 | ||||
Sequence: Y → F | ||||||
Sequence conflict | 766 | in Ref. 2; CAC38356 | ||||
Sequence: R → K | ||||||
Sequence conflict | 802 | in Ref. 2; CAC38356 | ||||
Sequence: T → A | ||||||
Sequence conflict | 815-817 | in Ref. 2; CAC38356 | ||||
Sequence: AAA → VAV |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D85463 EMBL· GenBank· DDBJ | BAB46965.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ312058 EMBL· GenBank· DDBJ | CAC38356.1 EMBL· GenBank· DDBJ | mRNA |