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
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
Cloning and characterization of a fourth human lysyl oxidase isoenzyme.
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Recombinant human LOXL3 expressed in HT-1080 cells was secreted into the culture medium and was not detected in nuclei by immunofluorescence.
"Recombinant LOXL3, expressed in HT-1080 cells, was secreted into the culture medium but was not detected by immunofluorescence staining in nuclei."
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The cloned 753-residue human precursor has a 25-residue signal peptide, four N-terminal SRCR domains, and a C-terminal lysyl-oxidase domain containing predicted copper- and LTQ-forming residues.
"The predicted polypeptide is 753 amino acids in length, including a signal peptide of 25 residues."
Cloning and characterization of a human lysyl oxidase-like 3 gene (hLOXL3).
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Human LOXL3 cDNA was cloned from fetal-brain mRNA and was predicted to encode a signal-peptide-containing SRCR-family protein.
"Using the PCR primers generated from human expressed sequence tag (EST), the cDNA of lysyl oxidase-like gene 3 (LOXL3), a new member of human lysyl oxidases gene family, was cloned from the human fetal brain mRNA."
Central nervous system, uterus, heart, and leukocyte expression of the LOXL3 gene, encoding a novel lysyl oxidase-like protein.
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Human ESTs predicted an alternative LOXL3 form lacking exons 5 and 8; the predicted product retains the amine-oxidase region but truncates SRCR domains 2 and 4 and lacks the potential BMP-1 cleavage site.
"The putative resulting protein retained the region encoding the structural and functional elements of the amine oxidase but the second and fourth SRCR domains were truncated and the potential BMP-1 cleavage site was not present."
A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression.
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In epithelial/carcinoma models, LOXL3 interacted and cooperated with Snail to repress E-cadherin, and LOXL3 overexpression induced an EMT phenotype.
"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."
Elastic fibres in health and disease.
A tissue-specific variant of the human lysyl oxidase-like protein 3 (LOXL3) functions as an amine oxidase with substrate specificity.
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Human LOXL3-sv1 lacks sequences corresponding to exons 1, 2, 3, and 5, encodes a 392-residue protein lacking SRCR domains 1-3, and retains the C-terminal catalytic region.
"LOXL3-sv1 was predicted to encode a polypeptide of 392 amino acids that contains the C-terminal domains required for amine oxidase activity but lacks the N-terminal SRCR domains 1, 2, and 3."
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Recombinant human LOXL3-sv1 has BAPN-inhibitable amine-oxidase activity toward elastin and collagen, with substrate specificity distinct from full-length LOXL3.
"The recombinant LOXL3-sv1 protein showed a beta-aminopropionitrile-inhibitable amine oxidase activity toward elastin and collagen with substrate specificity."
Lysyl oxidase-like 3b is critical for cartilage maturation during zebrafish craniofacial development.
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Zebrafish loxl3b loss-of-function disrupts craniofacial cartilage maturation and chondrogenic progenitor proliferation/differentiation.
"We now demonstrate that loxl3b is abundantly expressed within the head mesenchyme of the zebrafish and is critically important for maturation of neural crest derived cartilage elements."
Elastic fibres in health and disease.
LOXL3, encoding lysyl oxidase-like 3, is mutated in a family with autosomal recessive Stickler syndrome.
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A LOXL3 missense variant identified by combined autozygome/exome analysis was proposed as the likely candidate cause of autosomal-recessive Stickler syndrome in one family.
"we combined autozygome and exome analysis to identify a novel missense variant in LOXL3 as the likely candidate cause."
The presence of lysyl oxidase-like enzymes in human control and keratoconic corneas.
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Immunohistochemistry detected LOXL3 throughout control human corneal layers, limbus, and conjunctiva, with reduced stromal staining in keratoconus.
"All four LOX-like enzymes were present in all layers of control corneas as well as in the limbus and conjunctiva."
Loss of lysyl oxidase-like 3 causes cleft palate and spinal deformity in mice.
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Loxl3-null mice die perinatally with cleft palate and spinal deformity; loss lowers collagen content/cross-links in affected tissues without a detected elastin-cross-link change.
"In our study, a significant decrease in collagen-links from the lack of LOXL3 caused cleft palate and spinal deformity, while no obvious difference was observed in the elastin cross-links in the palate and spine."
Localized LoxL3-Dependent Fibronectin Oxidation Regulates Myofiber Stretch and Integrin-Mediated Adhesion.
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In non-human developmental models, locally secreted LoxL3 complexes with and oxidizes fibronectin at the myotendinous junction, enhancing integrin activation and myofiber positioning/anchoring.
"We find that LoxL3 complexes with and directly oxidizes Fibronectin (FN), an ECM scaffold protein and integrin ligand enriched at the MTJ."
Exome sequencing identified null mutations in LOXL3 associated with early-onset high myopia.
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Biallelic LOXL3 frameshift variants were found in two singleton human early-onset high-myopia cases; the authors explicitly classified LOXL3 as a candidate requiring confirmation.
"LOXL3 is a potential candidate gene for high myopia, but this possibility should be confirmed in additional studies."
Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.
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The study reports nuclear LOXL3 association with STAT3 and both deacetylation and deacetylimination/oxidation of multiple acetyl-lysine sites, suppressing STAT3 dimerization and transcriptional activity.
"LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites."
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The reported STAT3 deacetylation/deacetylimination activity maps mainly to the N-terminal SRCR repeats rather than the canonical C-terminal amine-oxidase domain.
"Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity."
LOXL3-sv2, a novel variant of human lysyl oxidase-like 3 (LOXL3), functions as an amine oxidase.
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Human LOXL3-sv2 lacks exons 4 and 5, encodes a 608-residue protein missing SRCR domain 2, and retains the C-terminal catalytic apparatus.
"The deletion of exons 4 and 5 do not change the open-reading frame of LOXL3 but results in deletion of the SRCR domain 2."
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Recombinant LOXL3-sv2 has BAPN-inhibitable amine-oxidase activity toward collagen type I.
"The recombinant LOXL3-sv2 protein showed a β-aminopropionitrile-inhibitable amine oxidase activity toward collagen type I."
Lysyl oxidase-like 3 is required for melanoma cell survival by maintaining genomic stability.
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Canonical LOXL3 and LOXL3ΔE4E5 (probably sv2) are expressed in human melanoma cells; LOXL3 depletion impairs proliferation and DNA-damage responses and induces apoptosis.
"Both LOXL3 isoforms were found similarly expressed in most melanoma cells tested (Fig. 1f). LOXL3Δ isoform probably corresponds to the recently identified splice variant LOXL3-sv2 [27]."
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Proteomics and follow-up assays identified associations with genome-integrity proteins including BRCA2 and MSH2, but did not define a stoichiometric stable LOXL3 complex or a catalytic substrate relationship.
"Consistent with these findings, LOXL3 binds to proteins involved in the maintenance of genome integrity, in particular BRCA2 and MSH2, whose levels dramatically decrease upon LOXL3 depletion."
Interactions between lysyl oxidases and ADAMTS proteins suggest a novel crosstalk between two extracellular matrix families.
Exploiting the Autozygome to Support Previously Published Mendelian Gene-Disease Associations: An Update.
UniProtKB reviewed entry P58215 (LOXL3_HUMAN)