Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Defining the membrane proteome of NK cells.
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The study surveyed a membrane-enriched preparation from the human NK-like YTS cell line; the accessible abstract does not expose the LRP10-specific peptide evidence behind the HDA annotation.
"proteome of the Natural Killer (NK) like cell line YTS."
A reference map of the human binary protein interactome.
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HuRI used repeated yeast-two-hybrid screens followed by pairwise retesting and sequence confirmation to construct a human binary-interaction map.
"To map the reference interactome, we performed nine screens of Space III, followed by pairwise verification by quadruplicate retesting and sequence confirmation."
A novel low-density lipoprotein receptor-related protein mediating cellular uptake of apolipoprotein E-enriched beta-VLDL in vitro.
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The original study characterized the mouse LRP10 ortholog, then called LRP9, rather than directly assaying human Q7Z4F1.
"screening of a mouse lymphocyte cDNA library. The protein was termed LDL
receptor-related protein 9 (LRP9)."
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Expression of mouse LRP9 in ldl-A7 cells supported uptake-related handling of apoE-enriched beta-VLDL, specifically bounding the tested lipoprotein cargo to beta-VLDL.
"Apolipoprotein E (apoE)-enriched beta-VLDL stimulated cellular
cholesteryl ester formation in ldl-A7/LRP9."
LDLR-related protein 10 (LRP10) regulates amyloid precursor protein (APP) trafficking and processing: evidence for a role in Alzheimer's disease.
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Human LRP10 binds APP primarily through their ectodomains in the reported biochemical assays.
"These results indicated that LRP10 interacts directly and predominantly with the ectodomain of APP in vitro."
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Surface-exposed LRP10 is rapidly internalized into early endosomes and recycled to the Golgi through a cytoplasmic-tail DXXLL-dependent step.
"These results suggested that LRP10 moves through the secretory pathway to the cell surface. After rapid internalization in early endosomes, LRP10 is recycled back to the Golgi, a step that requires the DXXLL motifs in the cytoplasmic tail of LRP10 ."
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In human neuroblastoma cells, increasing LRP10 retained mature APP in the Golgi and reduced amyloidogenic processing, whereas LRP10 depletion increased Aβ production.
"Increased
expression of LRP10 in human neuroblastoma SH-SY5Y cells induces the
accumulation of mature APP in the Golgi and reduces its presence at the cell
surface and its processing into Aβ, while knockdown of LRP10 expression
increases Aβ production."
LRP10 genetic variants in familial Parkinson's disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study.
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Rare LRP10 variants showed limited familial co-segregation across the reported Parkinson disease and Lewy-body-disease cohorts.
"The LRP10 variants were present in nine of these ten relatives,
providing independent-albeit limited-evidence of co-segregation with disease."
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Different reported variants affected mRNA abundance, protein stability, or subcellular localization in the study's cell-based assays.
"severe Lewy body pathology. Of nine variants identified in total (one in the
initial family and eight in stage 2), three severely affected LRP10 expression
and mRNA stability (1424+5delG, 1424+5G→A, and Ala212Serfs*17, shown by cDNA
analysis), four affected protein stability (Tyr307Asn, Gly603Arg, Arg235Cys, and
Pro699Ser, shown by cycloheximide-chase experiments), and two affected protein
localisation (Asn517del and Arg533Leu; shown by immunocytochemistry), pointing
to loss of LRP10 function as a common pathogenic mechanism."
LRP10 interacts with SORL1 in the intracellular vesicle trafficking pathway in non-neuronal brain cells and localises to Lewy bodies in Parkinson's disease and dementia with Lewy bodies.
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Endogenous LRP10 was detected mainly in astrocytes and neurovasculature in adult human brain and in iPSC-derived astrocytes, but not in the examined neurons.
"In adult human brain, LRP10 is mainly expressed in astrocytes and
neurovasculature but undetectable in neurons. Similarly, LRP10 is highly
expressed in iPSC-derived astrocytes but cannot be observed in iPSC-derived
neurons."
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In astrocytes, endogenous LRP10 occupies TGN, plasma-membrane, retromer, and early-endosome compartments and partially colocalizes and interacts with SORL1.
"In astrocytes, LRP10 is present at trans-Golgi network, plasma
membrane, retromer, and early endosomes. Interestingly, LRP10 also partially
co-localises and interacts with sortilin-related receptor 1 (SORL1)."
LRP10 and α-synuclein transmission in Lewy body diseases.
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In the reported cell and organoid systems, wild-type LRP10 was released in extracellular vesicles and could be internalized by clathrin-dependent endocytosis.
"Here, we demonstrate that
wild-type LRP10 is secreted via extracellular vesicles (EVs) and can be
internalised via clathrin-dependent endocytosis."
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The α-synuclein experiments provide initial model-dependent evidence and are explicitly limited by overexpression, non-neural cell lines, and lack of aging context.
"our model to study LRP10 and α-synuclein has important limitations, including overexpression, the use of non-neural cell lines, and the lack of the aging component of LBDs"
UniProtKB/Swiss-Prot record for human LRP10 (Q7Z4F1)
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The reviewed human reference product is a 713-residue LRP10 precursor.
"ID LRP10_HUMAN Reviewed; 713 AA."
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UniProt predicts a type-I topology with residues 17-440 extracellular, a transmembrane helix at 441-461, and residues 462-713 cytoplasmic.
"FT TOPO_DOM 17..440
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 441..461
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 462..713
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255""
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Domain resources on the record support two CUB domains and four LDLRA repeats.
"DR SMART; SM00042; CUB; 2.
DR SMART; SM00192; LDLa; 4."
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Isoform 2 is recorded as lacking residues 557-713 of the long cytoplasmic tail.
"FT VAR_SEQ 557..713
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_009820""
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The exact PANTHER subfamily assignment is LRP10-specific SF17, whereas the parent family is the broad LDL-receptor-related family.
"DR PANTHER; PTHR24270; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED; 1.
DR PANTHER; PTHR24270:SF17; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 10; 1."
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The structure cross-reference on the record is an AlphaFold prediction.
"DR AlphaFoldDB; Q7Z4F1; -."