Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
LRP-DIT, a putative endocytic receptor gene, is frequently inactivated in non-small cell lung cancer cell lines.
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The original human LRP1B/LRP-DIT study predicted a 4,599-residue product with extensive homology to the multiligand endocytic receptor LRP1.
"The predicted LRP-DIT
product of 4599 amino acids has extensive homology to a gigantic receptor, LRP1,
which mediates endocytosis of multiple proteins from the cell surface."
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Homozygous deletions and abnormal LRP-DIT transcripts were frequent in the tested human NSCLC cell-line panel.
"Homozygous deletions in LRP-DIT were detected in 17% (4 of 23) of non-small cell
lung cancer (NSCLC) cell lines. The expression of only abnormal transcripts
missing portions of the LRP-DIT sequence was demonstrated in an additional 30%
(11 of 36) of NSCLC lines."
Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.
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The study defines general SNX17 recognition of NPxY/NxxY cargo motifs and reports a broad putative-cargo screen, but the cached main text does not identify an LRP1B-specific functional assay.
"We further show that the PX-FERM proteins share a promiscuous ability to bind a wide array of putative cargo molecules, including receptor tyrosine kinases, and propose a model for their coordinated molecular interactions with membrane, cargo, and regulatory proteins."
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein.
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A human LRP1B domain-IV minireceptor bound, internalized, and degraded RAP, uPA, tPA, and PAI-1.
"Ligands
of LRP including receptor-associated protein, urokinase plasminogen activator,
tissue-type plasminogen activator, and plasminogen activator inhibitor type-1
each demonstrate binding, internalization, and degradation via mLRP1B4."
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LRP1B ligand endocytosis was markedly slower than LRP1 endocytosis.
"Interestingly, the kinetics of ligand endocytosis is distinctly different from
that of LRP, with LRP1B exhibiting a markedly diminished internalization rate."
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Human LRP1B transcript expression was detected in brain, thyroid, and salivary gland in this study.
"In addition, tissue expression analysis reveals that the LRP1B gene is expressed
in brain, thyroid, and salivary gland."
The low density lipoprotein receptor-related protein 1B retains beta-amyloid precursor protein at the cell surface and reduces amyloid-beta peptide production.
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A human LRP1B region-IV minireceptor formed an immunoprecipitable complex with APP.
"Using an LRP1B minireceptor (mLRP1B4) generated
to study the trafficking of LRP1B, we found that mLRP1B4 and APP form an
immunoprecipitable complex."
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Soluble APP containing a Kunitz protease-inhibitor domain, but not the tested APP form lacking that domain, was bound and degraded by mLRP1B4.
"Furthermore mLRP1B4 bound and facilitated the
degradation of a soluble isoform of APP containing a Kunitz proteinase inhibitor
domain but not soluble APP lacking a Kunitz proteinase inhibitor domain."
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mLRP1B4 increased cell-surface APP, reduced A-beta production, and increased soluble APP secretion in the experimental cell system.
"A
functional consequence of mLRP1B4 expression was a significant accumulation of
APP at the cell surface, which is likely related to the slow endocytosis rate of
LRP1B. More importantly, mLRP1B4-expressing cells that accumulated cell surface
APP produced less Abeta and secreted more soluble APP."
Normal development and fertility of knockout mice lacking the tumor suppressor gene LRP1b suggest functional compensation by LRP1.
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Mice lacking membrane-inserted Lrp1b developed and reproduced normally, with Lrp1 or other receptors proposed as compensators.
"In contrast to LRP1, LRP1b-deficient mice develop
normally, most likely due to its restricted expression pattern and functional
compensation by LRP1 or other receptors."
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Mouse Lrp1b was expressed predominantly in brain, with a differentially spliced form reported in adrenal gland and testis.
"LRP1b is expressed predominantly in the
brain, and a differentially spliced form is present in the adrenal gland and in
the testis."
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Mouse Lrp1b remained a single 600-kDa polypeptide rather than undergoing LRP1-like furin processing; yeast two-hybrid assays identified PSD95 and AIP as intracellular-tail partners.
"Despite the presence of a potential furin cleavage site and in
contrast to LRP1, immunoblotting for LRP1b reveals the presence of a single
600-kDa polypeptide species. Using a yeast two-hybrid approach, we have
identified two intracellular proteins, the postsynaptic density protein 95 and
the aryl hydrocarbon receptor-interacting protein, that bind to the
intracellular domain of LRP1b."
Slow endocytosis of the LDL receptor-related protein 1B: implications for a novel cytoplasmic tail conformation.
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In the minireceptor comparison, LRP1B internalized approximately 15-fold more slowly than LRP1.
"Although the positions of these endocytic motifs
are similar in both receptors, LRP1B is internalized at a 15-fold slower rate
than LRP1."
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Either cytoplasmic NPXY motif could support LRP1B internalization; only the double mutation abolished it.
"Only mutation of both NPXY motifs together abolished LRP1B
endocytosis, suggesting that LRP1B can use either of these motifs for
internalization."
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Both halves of the LRP1B cytoplasmic tail contribute to a conformation that is inefficiently recognized by endocytic adaptors.
"From these
data, we propose that both halves of the LRP1B cytoplasmic tail contribute to a
unique global conformation, which results in less efficient recognition by
endocytic adaptors and a slow endocytosis rate."
LRP1b shows restricted expression in human tissues and binds to several extracellular ligands, including fibrinogen and apoE-carrying lipoproteins.
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Human LRP1B transcript was consistently detected in brain, thyroid, and skeletal muscle, with lower and inconsistent testis detection in the tested tissue panels.
"Using two independent RT-PCR assays, LRP1b mRNA was
detected in human brain, thyroid gland, skeletal muscle, and to a lesser amount
in testis but absent in other tissues, including heart, kidney, liver, lung, and
placenta."
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Direct binding of recombinant LRP1B ectodomains to fibrinogen was verified by co-immunoprecipitation.
"Direct binding of LRP1b ectodomains to
fibrinogen was verified by co-immunoprecipitation."
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ApoE-carrying lipoproteins bound recombinant LRP1B ectodomains.
"ApoE-carrying lipoproteins
were shown to bind to LRP1b ectodomains in a lipoprotein binding assay."
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A human LRP1B region-IV minireceptor supported both VLDL binding and internalization in cultured cells.
"Furthermore, binding as well as internalization of very low density lipoproteins
by cells expressing an LRP1b minireceptor was demonstrated."
Expression of a recombinant full-length LRP1B receptor in human non-small cell lung cancer cells confirms the postulated growth-suppressing function of this large LDL receptor family member.
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Full-length mouse Lrp1b expression reduced proliferation in human NSCLC cell lines with little endogenous LRP1B.
"Overexpression of Lrp1b in non-small cell lung cancer cells with low
or absent endogenous LRP1B expression significantly reduced cellular
proliferation compared to empty vector-transfected control cells."
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Knockdown of endogenous human LRP1B increased proliferation of Calu-1 NSCLC cells.
"Conversely, in
Calu-1 cells, which express higher endogenous levels of the receptor,
siRNA-mediated LRP1B knockdown significantly enhanced cellular proliferation."
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In the same human NSCLC-cell assays, LRP1 overexpression did not reproduce the antiproliferative effect of mouse full-length Lrp1b or the human LRP1B minireceptor.
"However, in contrast to full-length mLrp1b or the hLRP1B minireceptor, LRP1 overexpression did not significantly affect cellular proliferation of A549 (Supplementary Figure S1) and A427 cells (data not shown), respectively."
UniProtKB/Swiss-Prot record for human LRP1B (Q9NZR2)