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
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Leupaxin is a critical adaptor protein in the adhesion zone of the osteoclast.
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In murine osteoclasts, LPXN is a component of the podosomal signaling complex and associates with PYK2/PTK2B, FAK1/PTK2, PTP-PEST, and p95PKL.
"We have identified leupaxin to be a component of the osteoclast podosomal signaling complex. We have found that leupaxin in murine osteoclasts is associated with both PYK2 and pp125FAK in the osteoclast."
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Reducing LPXN in osteoclasts decreases their in-vitro resorptive capacity.
"Finally, in vitro inhibition of leupaxin expression in the osteoclast led to a decrease in resorptive capacity."
Leupaxin negatively regulates B cell receptor signaling.
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BCR stimulation recruits and tyrosine-phosphorylates LPXN at the plasma membrane of human BJAB lymphoma cells and induces LPXN binding to Lyn through its LD3 region.
"We show here that leupaxin (LPXN), a member of this family, was tyrosine-phosphorylated and recruited to the plasma membrane of human BJAB lymphoma cells upon BCR stimulation and that it interacted with Lyn (a critical Src family tyrosine kinase in BCR signaling) in a BCR-induced manner."
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In mouse A20 B lymphoma cells, LPXN overexpression selectively suppresses BCR signaling, and Tyr72 is required for inhibition of IL-2 secretion.
"The overexpression of LPXN in mouse A20 B lymphoma cells led to the suppression of BCR-induced activation of JNK, p38 MAPK, and, to a lesser extent, Akt, but not ERK and NFkappaB, suggesting that LPXN can selectively repress BCR signaling."
Leupaxin, a novel coactivator of the androgen receptor, is expressed in prostate cancer and plays a role in adhesion and invasion of prostate carcinoma cells.
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In prostate-cancer cells, LPXN shuttles between focal adhesions and the nucleus and binds ligand-activated androgen receptor as a transcriptional coactivator.
"We could also demonstrate for the first time that leupaxin interacts with the androgen receptor in a ligand-dependent manner and serves as a transcriptional activator of this hormone receptor in PCa cells."
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LPXN depletion reduces motility and invasion of androgen-independent PC-3 and DU145 prostate-cancer cells.
"In contrast, knockdown of leupaxin expression in androgen-independent PC-3 and DU 145 cells induced a significant decrease of both the invasive capacity and motility."
The LIM protein leupaxin is enriched in smooth muscle and functions as an serum response factor cofactor to induce smooth muscle cell gene transcription.
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LPXN is enriched in human and mouse vascular smooth muscle, localizes to focal adhesions and nucleus, and functions as an SRF cofactor.
"Herein, we identified leupaxin in a screen for focal adhesion kinase binding partners in aortic smooth muscle, and we show that leupaxin is enriched in human and mouse vascular smooth muscle and that leupaxin expression is dynamically regulated during development."
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LPXN forms a complex with SRF, occupies CArG-containing smooth-muscle promoters, and promotes smooth-muscle marker transcription in mouse and rat cell systems.
"We found that leupaxin forms a complex with serum response factor and associates with CArG-containing regions of smooth muscle promoters and that ectopic expression of leupaxin induces smooth muscle marker gene expression in both 10T1/2 cells and rat aortic smooth muscle cells."
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Increased FAK activity retains LPXN outside the nucleus and limits its SRF-dependent transcriptional effect.
"Subsequent studies indicated that enhanced focal adhesion kinase activity (induced by fibronectin or expression of constitutively active focal adhesion kinase) attenuates the nuclear accumulation of leupaxin and limits the ability of leupaxin to enhance serum response factor-dependent gene transcription."
Defining the membrane proteome of NK cells.
Leupaxin is similar to paxillin in focal adhesion targeting and tyrosine phosphorylation but has distinct roles in cell adhesion and spreading.
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LPXN LIM3 is the main focal-adhesion targeting domain, and focal-adhesion recruitment precedes stimulus-dependent tyrosine phosphorylation.
"Using mutagenesis, we identified LIM3 as the primary FA targeting domain for LPXN and showed BN-induced LPXN tyrosine phosphorylation on residues 22, 62 and 72."
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In MDA-MB-231 cells, LPXN opposes collagen-I adhesion and regulates spreading in a substrate-specific manner distinct from paxillin.
"LPXN siRNA stimulated whereas paxillin siRNA inhibited cell adhesion."
A directed protein interaction network for investigating intracellular signal transduction.
Protein interactions of the transcription factor Hoxa1.
A proteome-scale map of the human interactome network.
Architecture of the human interactome defines protein communities and disease networks.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Quantitative fragmentomics allow affinity mapping of interactomes.
Multimodal cell maps as a foundation for structural and functional genomics.
Leupaxin is a novel LIM domain protein that forms a complex with PYK2.
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Human LPXN is a hematopoietic-enriched paxillin-family adaptor with three N-terminal LD motifs and four C-terminal LIM domains.
"We have identified a novel cytoplasmic protein, leupaxin, that is preferentially expressed in hematopoietic cells and is most homologous to the focal adhesion protein, paxillin."
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LPXN associates with PYK2/PTK2B and is tyrosine phosphorylated in lymphoid cells.
"We demonstrate here that leupaxin associates with a second FAK family member, PYK2."
Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses.
Association of leupaxin with Src in osteoclasts.
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LPXN overexpression increases adhesion and bone-resorptive activity in murine osteoclasts.
"In the current study, overexpression of LPXN in murine osteoclasts resulted in both enhanced resorptive activity and cell adhesion, as assessed by in vitro resorption assays."
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Src co-immunoprecipitates with LPXN in osteoclasts, and TNF-alpha increases this association.
"After exposure to the pro-inflammatory and osteoclastogenic cytokine TNF-alpha, there was an increase in the level of Src that coimmunoprecipitated with LPXN."
Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells.
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In human PC-3 prostate-cancer cells, LPXN associates with PYK2/PTK2B, Src, and PTP-PEST in a migration-regulating signaling complex.
"In PC-3 cells, LPXN was also found to associate with Pyk2, c-Src, and PTP-PEST."
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LPXN gain and loss have reciprocal effects on PC-3 migration, whereas PTP-PEST overexpression reduces LPXN-associated PYK2/PTK2B and Src and migration.
"A siRNA-mediated inhibition of LPXN resulted in decreased in vitro PC-3 cell migration."
Structural Basis for the Interaction between Pyk2-FAT Domain and Leupaxin LD Repeats.
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LPXN LD1 and LD3 preferentially occupy the two binding sites of the PYK2/PTK2B FAT domain.
"The first and third LD motifs of leupaxin preferably target the two LD-binding sites on the Pyk2-FAT domain, respectively."
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Full-length LPXN and PYK2/PTK2B FAT form a stable one-to-one complex in vitro.
"Moreover, the full-length leupaxin binds to Pyk2-FAT as a stable one-to-one complex."
Regulation of β-catenin transcription activity by leupaxin in hepatocellular carcinoma.
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In human hepatocellular-carcinoma models, LPXN binds beta-catenin and enhances its transcriptional activity through recruitment of SRC-1 and p300.
"We show that leupaxin could interact with β-catenin and enhance its transcriptional activity through recruitment of coactivator complex, including steroid receptor coactivator 1 (SRC-1) and P300."