Annotation inferences using phylogenetic trees
-
PAN-GO uses curator-selected GO terms on PANTHER phylogenetic trees to make traceable IBA annotations from biological ancestors.
"The GO terms are manually selected by a curator and used to annotate ancestral genes in the phylogenetic tree using the evidence code IBA (Inferred from Biological Ancestor)."
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
-
This pipeline maps UniProtKB/Swiss-Prot Subcellular Location vocabulary terms to corresponding GO cellular-component terms.
"When a UniProtKB Subcellular Location term describes a concept that is within the scope of the Gene Ontology, a mapping is made to the corresponding GO term."
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
-
Ensembl Compara transfers selected experimentally supported annotations between orthologs while retaining the source identifier in WITH/FROM.
"GO terms from a source species are projected onto one or more target species based on gene orthology obtained from Ensembl Compara."
Characterization and tissue-specific expression of human LRIG2.
-
Human LRIG2 is a 1065-residue type-I single-pass protein predicted to contain a signal peptide, 15 extracellular LRRs, three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic tail.
"the same domain organization as LRIG1"
-
Heterologously expressed human LRIG2 is N-glycosylated and occurs at both the cell surface and in the cytoplasm.
"the cell surface and in the cytoplasm."
LRIG2 mutations cause urofacial syndrome.
-
Biallelic LRIG2 variants cause a subset of human urofacial syndrome, providing human genetic evidence for a developmental role.
"individuals have biallelic mutations in LRIG2"
-
LRIG2 protein was detected in nerve fascicles in the human fetal bladder, supporting a lower-urinary-tract neural-development context.
"heparanase-2 were immunodetected in nerve fascicles"
In vivo analysis of Lrig genes reveals redundant and independent functions in the inner ear.
-
In mice, Lrig2 is broadly expressed in the developing inner ear and becomes enriched in neurons and sensory epithelia at later stages.
"Lrig2 levels are enhanced in neurons"
-
Mouse Lrig2 loss preserves sound-detection sensitivity but attenuates the later auditory neuronal response.
"Specifically, although mutant animals can detect sounds with normal sensitivity, the subsequent neuronal response is attenuated, as evidenced by significantly decreased ABR amplitudes across multiple frequencies."
-
Mouse genetics distinguishes Lrig2 from Lrig1 and Lrig3 while revealing limited redundancy with Lrig1 in vestibular and cochlear-innervation phenotypes.
"emerging as the most functionally distinct family member."
Soluble LRIG2 ectodomain is released from glioblastoma cells and promotes the proliferation and inhibits the apoptosis of glioblastoma cells in vitro and in vivo in a similar manner to the full-length LRIG2.
-
Soluble LRIG2 ectodomain is released from human glioblastoma cells, although the release mechanism was not established.
"that soluble LRIG2 ectodomain was capable of being released from glioblastoma"
-
In engineered U87 and U251 glioblastoma cells, both full-length LRIG2 and its ectodomain physically interact with EGFR.
"Consistent with the immunofluorescence results, this analysis revealed that LRIG2 physically interacted with EGFR (Figure 7B). Most strikingly, we found that the LRIG2 ectodomain was also capable of interacting physically with EGFR (Figure 7B), which indicates that the full-length LRIG2 interacts with EGFR through the recognition of the ectodomain of LRIG2 and EGFR."
-
LRIG2 and its ectodomain increased EGFR abundance and activation and downstream PI3K/Akt signaling in the glioblastoma models.
"Remarkably, in the present study we for the first time demonstrated that full-length LRIG2 and LRIG2 ectodomain both could physically interact with EGFR, increase the level of EGFR and enhance the activation of EGFR and its downstream PI3K/Akt pathway, resulting in increment of pro-proliferative and anti-apoptotic proteins and attenuation of pro-apoptotic proteins."
-
Overexpressed full-length LRIG2 or ectodomain promoted glioblastoma-cell proliferation and inhibited apoptosis in culture and xenograft models.
"promoted the proliferation and inhibited the apoptosis of glioblastoma cells in"
Lrig2 Negatively Regulates Ectodomain Shedding of Axon Guidance Receptors by ADAM Proteases.
-
Neuronal Lrig2 binds Neogenin and restrains its premature ADAM17-mediated ectodomain shedding.
"repulsive guidance molecules (RGMs), and prevents premature Neogenin shedding by
ADAM17 (TACE)."
-
RGMa weakens the Lrig2-Neogenin interaction, permitting ADAM17 cleavage; this regulation is required for neurite-growth inhibition in vitro and cortical-neuron migration in vivo.
"of ADAM17-mediated Neogenin cleavage by Lrig2 is required"
LRIG2 promotes the proliferation and cell cycle progression of glioblastoma cells in vitro and in vivo through enhancing PDGFRβ signaling.
-
Reciprocal co-immunoprecipitation in engineered U87 glioblastoma cells supports a physical association between LRIG2 and PDGFRB.
"Coprecipitation of PDGFRβ was observed by probing the resulting blot with anti-PDGFRβ, and when PDGFRβ was immunoprecipitated from the cell lysates, coprecipitation of the Flag-LRIG2 was also detected by western blotting with the anti-Flag antibody (Fig. 8B), indicating that LRIG2 physically associates with PDGFRβ."
-
In the U87 glioblastoma model, LRIG2 increased PDGFRB abundance and ligand-induced activation together with downstream Akt and STAT3 signaling.
"progression. Mechanistically, LRIG2 has the ability to physically interact with"
-
LRIG2 enhanced PDGF-BB-dependent glioblastoma-cell proliferation and cell-cycle progression in culture and U87 xenografts.
"demonstrate that LRIG2 promoted the PDGF‑BB‑induced proliferation"
-
The glioblastoma result conflicts with a prior mouse embryonic-fibroblast result, in which Lrig2 did not alter PDGFR abundance or PDGFR/Akt phosphorylation.
"However, Rondahl et al (20) reported that Lrig2 exerted no effects on PDGFR protein levels or the phosphorylation events of PDGFR and Akt in mouse embryonic fibroblasts (MEFs), which was distinct from the results of the present study."
[Corrigendum] LRIG2 promotes the proliferation and cell cycle progression of glioblastoma cells in vitro and in vivo through enhancing PDGFRβ signaling.
[Corrigendum] LRIG2 promotes the proliferation and cell cycle progression of glioblastoma cells in vitro and in vivo through enhancing PDGFRβ signaling.
-
The 2022 corrigendum replaces duplicated p-Akt and Cyclin D1 panels in Figure 7 after re-examination and repetition; Figure 8 interaction data are not changed.
"The corrected version of Fig. 7, showing replacement data for the p-Akt and Cyclin D1 experiments"