Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
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
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression.
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LOXL2 interacts and cooperates with SNAI1 to repress E-cadherin and promote epithelial-to-mesenchymal transition in carcinoma models.
"Here we show that lysyl-oxidase-like 2 and 3 (LOXL2 and LOXL3), two members of the lysyl-oxidase gene family, interact and cooperate with Snail to downregulate E-cadherin expression."
Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane.
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LOXL2 accumulates in endothelial extracellular matrix and is required for collagen-IV assembly and sprouting angiogenesis.
"Further investigation in vitro by loss and gain of function experiments confirmed that LOXL2 was required for tubulogenesis in 3D fibrin gels and demonstrated that this enzyme was required for collagen IV assembly in the ECM."
Reduced nuclear and ectopic cytoplasmic expression of lysyl oxidase-like 2 is associated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma.
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LOXL2 protein was detected in nuclear and cytoplasmic compartments of human esophageal carcinoma samples, with altered distribution associated with progression.
"The protein manifested decreased nuclear expression and increased cytoplasmic expression."
Post-translational modifications of recombinant human lysyl oxidase-like 2 (rhLOXL2) secreted from Drosophila S2 cells.
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Recombinant human LOXL2 contains LTQ at Lys653/Tyr689, oxidizes tropoelastin, and requires N-glycosylation for efficient secretion from Drosophila S2 cells.
"The recombinant proteins also show activity in tropoelastin oxidation. After phenylhydrazine derivatization and trypsin digestion, we used mass spectrometry to identify peptides containing the derivatized lysine tyrosylquinone cross-link at Lys-653 and Tyr-689, as well as N-linked glycans at Asn-455 and Asn-644."
Elastic fibres in health and disease.
SILAC-based proteomics of human primary endothelial cell morphogenesis unveils tumor angiogenic markers.
Regulation of heterochromatin transcription by Snail1/LOXL2 during epithelial-to-mesenchymal transition.
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The paper attributes repression of mouse pericentromeric transcription during EMT to a SNAI1/LOXL2 pathway, but its H3K4-deaminase mechanism is disputed.
"Here, we show that the Snail1 transcription factor represses mouse pericentromeric transcription, acting through the H3K4 deaminase LOXL2."
LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition.
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Catalytically inactive LOXL2 mutants can cooperate with SNAI1 and activate FAK/Src signaling to drive EMT.
"Here we show that LOXL2 catalytic inactive mutants collaborate with Snail1 in E-cadherin gene repression to trigger EMT and, in addition, promote FAK/Src pathway activation to support EMT."
Lysyl oxidase-like 2 (LOXL2) controls tumor-associated cell proliferation through the interaction with MARCKSL1.
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The LOXL2 SRCR region interacts with MARCKSL1 in human breast carcinoma cells and modulates proliferation/apoptosis signaling.
"The scavenger-receptor domain of LOXL2 was shown to interact with the N-terminal domain of MARCKSL1."
LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation.
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Methylated TAF10 was reported as an intracellular LOXL2 substrate whose oxidation changes TFIID-dependent transcription during neural differentiation.
"Using an unbiased proteomic approach, we have identified methylated TAF10, a member of the TFIID complex, as a LOXL2 substrate."
Functional consequence of fibulin-4 missense mutations associated with vascular and skeletal abnormalities and cutis laxa.
Lysyl oxidase-like 2 (LOXL2) oxidizes trimethylated lysine 4 in histone H3.
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The authors report recombinant LOXL2 oxidation of H3K4me3, but this claim is disputed and unsuitable as secure annotation evidence.
"Infrared spectroscopy and mass spectrometry analyses demonstrated that recombinant LOXL2 specifically deaminates trimethylated H3K4."
Comprehensive proteomic characterization of stem cell-derived extracellular matrices.
LOXL2 drives epithelial-mesenchymal transition via activation of IRE1-XBP1 signalling pathway.
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Overexpressed LOXL2 accumulates in the endoplasmic reticulum and activates IRE1-XBP1 signaling in carcinoma-cell EMT models independently of catalytic activity.
"We demonstrate that overexpression of LOXL2 promotes its accumulation in the Endoplasmic Reticulum (ER), inducing ER stress and activating the IRE1-XBP1 signalling pathway of the ER-stress response."
Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor state.
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Copper loading activates human LOXL2 and supports LTQ formation, whereas zinc occupancy traps an inactive precursor state.
"Unexpectedly, the copper-binding site of hLOXL2 is occupied by zinc, which blocks LTQ generation and the enzymatic activity of hLOXL2 in our in vitro assay. Biochemical analysis confirms that copper loading robustly activates hLOXL2 and supports LTQ formation."
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The crystallized human LOXL2 fragment is monomeric in solution and contains a structurally coordinated calcium ion.
"Despite the observation of two molecules in a single ASU, hLOXL2 is revealed as being in a monomeric state in solution."
Lysyl oxidase-like 2 (LOXL2)-mediated cross-linking of tropoelastin.
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Full-length recombinant human LOXL2 directly binds and deaminates tropoelastin and creates allysines and cross-linked tropoelastin peptides in vitro.
"We detected direct interaction between LOXL2 and tropoelastin (TE) and also LOXL2-mediated deamination of TE. Using proteomics, we identified several allysines together with cross-linked TE peptides."
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LOXL2 N-terminal processing is not required for catalytic activation, unlike propeptide cleavage of LOX and LOXL1.
"Our data suggest that SRCR domains 1 and 2 are located away from the catalytic domain, supporting the notion that LOXL2 processing is not associated with enzyme activation, as recently proposed in López-Jiménez et al. (4)."
Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Like2 regulate endothelial ECM and angiogenesis through non-catalytic scaffolding mechanisms.
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LOXL2 SRCR domains directly bind collagen IV and support endothelial collagen-IV deposition and angiogenesis independently of the catalytic domain.
"Neither enzyme activity nor catalytic domain were necessary for collagen IV deposition and angiogenesis, whereas the SRCR domains were effective for these processes."
LOXL2 promotes oncogenic progression in alveolar rhabdomyosarcoma independently of its catalytic activity.
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LOXL2 promotes rhabdomyosarcoma motility and metastasis independently of catalytic activity and was reported to interact with vimentin.
"The intermediated filament protein vimentin was validated as a LOXL2-interactor."
The lysyl oxidases LOX and LOXL2 are necessary and sufficient to repress E-cadherin in hypoxia: insights into cellular transformation processes mediated by HIF-1.
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LOXL2 is induced as a direct HIF-1 target and contributes to hypoxia-driven E-cadherin repression and EMT in cell models.
"In addition to the previously demonstrated LOX, we characterize LOXL2 as a direct transcriptional target of HIF-1."
The human lysyl oxidase-like 2 protein functions as an amine oxidase toward collagen and elastin.
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Recombinant human LOXL2 oxidizes multiple collagen types and elastin in vitro, and its N-terminal SRCR domains are dispensable for this catalytic activity.
"All of the purified recombinant LOXL2 proteins, with or without the SRCR domains in the N-terminus, showed significant amine oxidase activity toward several different types of collagen and elastin in in vitro amine oxidase assays."
Modulation of lysyl oxidase-like 2 enzymatic activity by an allosteric antibody inhibitor.
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LOXL2 oxidizes diamine substrates and fibrillar type-I collagen and is inhibited allosterically by an antibody binding SRCR4.
"In this report, we assessed the steady-state enzymatic activity of lysyl oxidase-like 2 (LOXL2) against the substrates 1,5-diaminopentane (DAP), spermine, and fibrillar type I collagen."
Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment.
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LOXL2 inhibition reduces fibrotic and tumor-associated stromal remodeling in animal models.
"Targeting LOXL2 with an inhibitory monoclonal antibody (AB0023) was efficacious in both primary and metastatic xenograft models of cancer, as well as in liver and lung fibrosis models."
Lysyl oxidase-like 2 deaminates lysine 4 in histone H3.
Retraction Notice to: Lysyl Oxidase-like 2 Deaminates Lysine 4 in Histone H3.
UniProtKB record for human LOXL2 (Q9Y4K0)
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UniProt curates LOXL2 as a precursor with extracellular matrix, basement-membrane, nuclear, chromosome, and endoplasmic-reticulum localizations.
"CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix, basement membrane {ECO:0000269|PubMed:23319596}. Nucleus CC {ECO:0000269|PubMed:22204712, ECO:0000269|PubMed:24414204}. Chromosome CC {ECO:0000269|PubMed:27735137}. Endoplasmic reticulum CC {ECO:0000269|PubMed:28332555}."
Falcon deep-research report for human LOXL2
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The provider report prioritizes LOXL2 extracellular protein-lysine oxidation and collagen/elastin cross-link initiation as the most defensible core function.
"The most defensible functional annotation of human LOXL2 is **a secreted copper/LTQ-dependent protein-lysine oxidase that initiates collagen and elastin cross-linking in the extracellular matrix**."