Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Reviewed UniProtKB entry for human LRP11 (Q86VZ4)
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Human LRP11 is curated as a single-pass type-I membrane protein.
"CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}."
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The reviewed record describes two splice isoforms; isoform 2 replaces residues 205-237 and lacks the remainder of the canonical sequence.
"CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86VZ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86VZ4-2; Sequence=VSP_017535, VSP_017536;"
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The extracellular region contains MANSC, PKD and one LDL-receptor class-A domain, but domain membership alone does not establish a lipoprotein ligand.
"FT DOMAIN 99..184
FT /note="MANSC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00341"
FT DOMAIN 210..305
FT /note="PKD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00151"
FT DOMAIN 309..345
FT /note="LDL-receptor class A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124""
PANTHER PTHR46876 family member table
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Human LRP11 Q86VZ4 belongs to the LRP11-specific PTHR46876:SF1 subfamily.
"Q86VZ4,Low-density lipoprotein receptor-related protein 11,protein,9606,Homo sapiens,Homo sapiens (Human),LRP11,500,PTHR46876:SF1,LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 11,True"
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Mouse Lrp11 Q8CB67 belongs to the same LRP11-specific PTHR46876:SF1 subfamily.
"Q8CB67,Low-density lipoprotein receptor-related protein 11,protein,10090,Mus musculus,Mus musculus (Mouse),Lrp11,483,PTHR46876:SF1,LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 11,True"
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
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The MGC generated high-quality full-open-reading-frame human and mouse cDNA clones; UniProt uses LRP11 clones from this resource to define its two isoforms.
"The National Institutes of Health's Mammalian Gene Collection (MGC) project was
designed to generate and sequence a publicly accessible cDNA resource containing
a complete open reading frame (ORF) for every human and mouse gene."
Functional specialization of beta-arrestin interactions revealed by proteomic analysis.
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The study was a broad beta-arrestin interactome screen, not an LRP11-focused functional analysis; the cached abstract does not name LRP11.
"As
determined by LC tandem MS, 71 proteins interacted with beta-arrestin 1, 164
interacted with beta-arrestin 2, and 102 interacted with both beta-arrestins."
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Only 16 randomly selected new partners were validated by coimmunoprecipitation, and the cache does not show whether LRP11 was among them.
"The binding of 16 randomly selected newly identified beta-arrestin
partners was validated by coimmunoprecipitation assays in HEK293 cells."
Genetic regulatory network analysis reveals that low density lipoprotein receptor-related protein 11 is involved in stress responses in mice.
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In mouse amygdala, Lrp11 abundance was measured after stress and was higher in stressed animals; this is expression-response evidence, not a causal test of each transferred stress process.
"Western blotting, qPCR and immunohistochemistry were used to
investigate the expression variation of Lrp11 in amygdala tissue after exposure
to stress. We found the quantity of Lrp11 was more obvious in stress models than
that in normal mice (P<0.05) which suggests Lrp11 might participate in the
process of stress response."
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Lrp11 depletion altered four transcript-level network members in human cell lines, but did not directly test heat, cold, deprivation or immobilization.
"we transfected HEK 293T cells and SH-SY5Y cells with Lrp11 siRNA
leading to down-regulation of Lrp11mRNA and were able to confirm a significant
influence of Lrp11 depletion on the expression of Xpnpep1, Maneal, Pgap1 and
Uprt."
The role of low density lipoprotein receptor-related protein 11 as a tumor promoter in cervical cancer.
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Human cervical cancer cell-line LRP11 silencing reduced proliferation, migration and invasion, and slowed xenograft growth.
"The silencing of LRP11 in SiHa
and CaSki cell lines inhibited cell proliferation, reduced migration and
invasion and suppressed cell growth in nude mice, which possibly related to cell
cycle protein regulation of CDK 2/4, cyclin D1/E1, MMP-2/9, and VEGF."
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The paper explicitly confines these phenotypes to HSIL/cervical-cancer context and does not establish LRP11's normal physiological role.
"LRP11 plays important roles in proliferation, migration and
invasion, with the potential to be a useful prognostic marker and therapeutic
target for patients with HSIL and cervical cancer."
LRP11 activates β-catenin to induce PD-L1 expression in prostate cancer.
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LRP11 gain- and loss-of-function in two human prostate-cancer cell lines placed LRP11 upstream of beta-catenin-dependent PD-L1 expression.
"Further experiments
in two PRAD cell lines with LRP11 over-expression and knockdown showed that
LRP11 induced PD-L1 expression through β-catenin signalling."
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LRP11 overexpression suppressed Jurkat-cell activity in coculture, and blocking LRP11 or PD-L1 reversed the effect.
"In addition, LRP11
over-expression in PRAD cell line induced immunosuppression of Jurkat cell in
in-vitro co-culture system. The effects of LRP11 could be blocked by
neutralising LRP11 or PD-L1 antibody."
LRP11 promotes stem-like T cells via MAPK13-mediated TCF1 phosphorylation, enhancing anti-PD1 immunotherapy.
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A chimeric-receptor assay identified LDL as an LRP11-interacting stimulus and linked receptor activation to TCF1 in a tumor-bearing mouse/T-cell system.
"Using a cell-based chimeric receptor
screening system, we showed that LRP11 interacted with LDL and activated TCF1."
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The proposed proximal pathway is LRP11-dependent MAPK13 activation followed by MAPK13 phosphorylation of TCF1 and expansion of stem-like CD8 T cells.
"Mechanistically, LRP11
activation induces MAPK13 activation. Then, MAPK13 phosphorylates TCF1, leading
to increase of stem-like T cells."