LRP8

Protein identityUniProt · HPA

UniProt accession

Q14114

Gene

LRP8

Ensembl

ENSG00000157193

Chromosome

1

Canonical length

963 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins

Secretome location

Secreted in other tissues

Quaternary structure

Homooligomer

OverviewNCBI Gene

This gene encodes a member of the low density lipoprotein receptor (LDLR) family. Low density lipoprotein receptors are cell surface proteins that play roles in both signal transduction and receptor-mediated endocytosis of specific ligands for lysosomal degradation. The encoded protein plays a critical role in the migration of neurons during development by mediating Reelin signaling, and also functions as a receptor for the cholesterol transport protein apolipoprotein E. Expression of this gene may be a marker for major depressive disorder. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2011]

Canonical amino-acid sequenceUniProt

963 residues, UniProt reviewed canonical sequence.

>Q14114|LRP8
     1  MGLPEPGPLR LLALLLLLLL LLLLQLQHLA AAAADPLLGG QGPAKDCEKD QFQCRNERCI
    61  PSVWRCDEDD DCLDHSDEDD CPKKTCADSD FTCDNGHCIH ERWKCDGEEE CPDGSDESEA
   121  TCTKQVCPAE KLSCGPTSHK CVPASWRCDG EKDCEGGADE AGCATLCAPH EFQCGNRSCL
   181  AAVFVCDGDD DCGDGSDERG CADPACGPRE FRCGGDGGGA CIPERWVCDR QFDCEDRSDE
   241  AAELCGRPGP GATSAPAACA TASQFACRSG ECVHLGWRCD GDRDCKDKSD EADCPLGTCR
   301  GDEFQCGDGT CVLAIKHCNQ EQDCPDGSDE AGCLQGLNEC LHNNGGCSHI CTDLKIGFEC
   361  TCPAGFQLLD QKTCGDIDEC KDPDACSQIC VNYKGYFKCE CYPGYEMDLL TKNCKAAAGK
   421  SPSLIFTNRH EVRRIDLVKR NYSRLIPMLK NVVALDVEVA TNRIYWCDLS YRKIYSAYMD
   481  KASDPKEQEV LIDEQLHSPE GLAVDWVHKH IYWTDSGNKT ISVATVDGGR RRTLFSRNLS
   541  EPRAIAVDPL RGFMYWSDWG DQAKIEKSGL NGVDRQTLVS DNIEWPNGIT LDLLSQRLYW
   601  VDSKLHQLSS IDFSGGNRKT LISSTDFLSH PFGIAVFEDK VFWTDLENEA IFSANRLNGL
   661  EISILAENLN NPHDIVIFHE LKQPRAPDAC ELSVQPNGGC EYLCLPAPQI SSHSPKYTCA
   721  CPDTMWLGPD MKRCYRAPQS TSTTTLASTM TRTVPATTRA PGTTVHRSTY QNHSTETPSL
   781  TAAVPSSVSV PRAPSISPST LSPATSNHSQ HYANEDSKMG STVTAAVIGI IVPIVVIALL
   841  CMSGYLIWRN WKRKNTKSMN FDNPVYRKTT EEEDEDELHI GRTAQIGHVY PAAISSFDRP
   901  LWAEPCLGET REPEDPAPAL KELFVLPGEP RSQLHQLPKN PLSELPVVKS KRVALSLEDD
   961  GLP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LRP8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.42

Highest tissue expression

39 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LRP8.

Disease | AllUniProt

Conditions LRP8 is implicated in, by any mechanism.

• Myocardial infarction 1 (MCI1) MIM:608446

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.22

gnomAD pLI

1

gnomAD missense Z

2.52

DepMap mean gene effect

-0.15

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to cholesterol
• cellular response to growth factor stimulus
• chemical synaptic transmission
• cytokine-mediated signaling pathway
• dendrite morphogenesis
• endocytosis
• layer formation in cerebral cortex
• lipid metabolic process
• modulation of chemical synaptic transmission
• positive regulation of dendrite development
• positive regulation of dendritic spine morphogenesis
• proteolysis
• reelin-mediated signaling pathway
• regulation of apoptotic process
• regulation of innate immune response
• response to xenobiotic stimulus
• retinoid metabolic process
• signal transduction
• ventral spinal cord development
• ammon gyrus development

Molecular functions

• amyloid-beta binding
• apolipoprotein binding
• calcium ion binding
• calcium-dependent protein binding
• cargo receptor activity
• high-density lipoprotein particle binding
• kinesin binding
• low-density lipoprotein particle receptor activity
• reelin receptor activity
• transmembrane signaling receptor activity
• very-low-density lipoprotein particle receptor activity

Cellular components

• axon
• caveola
• cell surface
• dendrite
• extracellular space
• glutamatergic synapse
• membrane
• microtubule associated complex
• neuronal cell body
• plasma membrane
• postsynaptic density membrane
• receptor complex
• Schaffer collateral - CA1 synapse

Protein domainsUniProt · Pfam · InterPro

• LDLR class B repeat
• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• EGF-like calcium-binding domain
• Low-density lipoprotein (LDL) receptor class A repeat
• Six-bladed beta-propeller, TolB-like
• EGF-like calcium-binding, conserved site
• Low-density lipoprotein (LDL) receptor class A, conserved site
• LDL receptor-like superfamily
• NOTCH1, EGF-like calcium-binding domain
• Low-density lipoprotein receptor-related
• Low-density lipoprotein receptor domain class A
• Low-density lipoprotein receptor repeat class B
• Calcium-binding EGF domain
• Coagulation Factor Xa inhibitory site

KeywordsUniProt

• Calcium
• Cell membrane
• Disulfide bond
• EGF-like domain
• Endocytosis
• Glycoprotein
• Host-virus interaction
• Membrane
• Metal-binding
• Phosphoprotein
• Receptor
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of LRP8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CLU
• DAB1
• MDK
• PCSK9
• SNX17
• VLDLR
• LRPAP1