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
Elastic fibres in health and disease.
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Elastic fibers are extracellular-matrix fibers that provide recoil and resilience to dynamic connective tissues.
"Elastic fibres are a major class of extracellular matrix fibres that are abundant in dynamic connective tissues such as arteries, lungs, skin and ligaments. Their structural role is to endow tissues with elastic recoil and resilience."
Proteomics characterization of extracellular space components in the human aorta.
Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins.
Functional consequence of fibulin-4 missense mutations associated with vascular and skeletal abnormalities and cutis laxa.
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Recombinant interaction studies found that human fibulin-4 binds LOXL1 as well as canonical LOX.
"We show that fibulin-4 binds stronger than fibulin-3 and -5 to LTBP1s, 3, and 4s, and to the lysyl oxidases LOX and LOXL1"
Comprehensive proteomic characterization of stem cell-derived extracellular matrices.
Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics.
HELZ2: a new, interferon-regulated, human 3'-5' exoribonuclease of the RNB family is expressed from a non-canonical initiation codon.
A novel human cDNA with a predicted protein similar to lysyl oxidase maps to chromosome 15q24-q25.
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The defining human LOXL1 cDNA encoded a protein homologous to the C-terminal region of lysyl oxidase and mapped to chromosome 15q24-q25.
"A novel human cDNA with a predicted protein homologous to the carboxyl end of lysyl oxidase, an extracellular enzyme involved in the maturation of collagen and elastin, has been isolated."
Elastic fiber homeostasis requires lysyl oxidase-like 1 protein.
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Loxl1-deficient mice have defective postpartum uterine elastic-fiber deposition and abnormalities in lung, skin, and vasculature with tropoelastin accumulation.
"Here we show that mice lacking the protein lysyl oxidase-like 1 (LOXL1) do not deposit normal elastic fibers in the uterine tract post partum and develop pelvic organ prolapse, enlarged airspaces of the lung, loose skin and vascular abnormalities with concomitant tropoelastin accumulation."
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Unlike canonical LOX, LOXL1 localizes to sites of elastogenesis, interacts with fibulin-5, and supports spatially defined elastin deposition as both cross-linking enzyme and scaffold-associated component.
"Distinct from the prototypic lysyl oxidase (LOX), LOXL1 localizes specifically to sites of elastogenesis and interacts with fibulin-5. Thus elastin polymer deposition is a crucial aspect of elastic fiber maintenance and is dependent on LOXL1, which serves both as a cross-linking enzyme and an element of the scaffold to ensure spatially defined deposition of elastin."
Cleavage of LOXL1 by BMP1 and ADAMTS14 Proteases Suggests a Role for Proteolytic Processing in the Regulation of LOXL1 Function.
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Human LOXL1 is secreted into extracellular medium as multiple processed species.
"The presence of this complex array of LOXL1 species in the extracellular medium suggests that LOXL1 protein is the subject of specific post-translational modifications, likely including proteolysis by endogenous proteases."
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BMP1 cleaves LOXL1 once within its propeptide, whereas ADAMTS14 cleaves at multiple sites spanning the propeptide and beginning of the catalytic domain.
"Our data show that BMP1 cleaves LOXL1 in a unique location within the pro-peptide region, whereas ADAMTS14 processes LOXL1 in at least three different sites located within the pro-peptide and in the first residues of the catalytic domain."
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Proteomics mapped the human LOXL1 BMP1 site to residues 151-152 and ADAMTS14 sites to residues 216-217, 292-293, and 375-376.
"The analysis resulted in one single processing site at 151–152 (RH/GG) for BMP1 and three distinct cleavage sites for ADAMTS14 at positions 216–217 (GA/AA), 292–293 (PD/PG), and 375–376 (PD/PN)"
Fibulin-5/DANCE has an elastogenic organizer activity that is abrogated by proteolytic cleavage in vivo.
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In vitro binding assays with human proteins found specific LOXL1-fibulin-5 interaction, primarily through the fibulin-5 C-terminal domain, and showed that N-terminal fibulin-5 cleavage diminishes LOXL1 binding.
"As shown in Fig. 7 B, we detected the specific interaction of LOXL1, 2, and 4 proteins with fibulin-5 protein (top, lanes 1, 7, and 13). The interaction of fibulin-5 and these LOXL proteins was eliminated or considerably diminished by the C-terminal deletion of fibulin-5 (Fig. 7 B, top, lanes 5, 11, and 17)."
Lysyl oxidase-like protein from bovine aorta. Isolation and maturation to an active form by bone morphogenetic protein-1.
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Purified bovine LOXL1 precursor was largely inactive, while further BMP1 processing produced enzyme active on elastin and collagen substrates.
"The immunopurified protein was largely inactive, but further processing in vitro by bone morphogenetic protein-1 led to an enzyme that was active on elastin and collagen substrates."
Ancestral LOXL1 variants are associated with pseudoexfoliation in Caucasian Australians but with markedly lower penetrance than in Nordic people.
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Human LOXL1 RNA and protein were detected broadly in ocular tissues, with a 42-kDa mature form detected in iris and ciliary body.
"LOXL1 was found to be expressed by reverse transcription-polymerase chain reaction in all ocular tissues examined except retina. The presence of LOXL1 protein in ocular tissues of interest was demonstrated by western blotting."
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The reported human ocular LOXL1 immunoreactive species included higher apparent-mass forms and a mature 42-kDa form.
"Specific bands of approximately 130 and 80 kDa, representing polymerized protein forms, were detected in the cornea, iris, ciliary body, lens capsule and optic nerve. The 42 kDa mature form of LOXL1 was detected in the iris and ciliary body."
UniProtKB/Swiss-Prot record for human LOXL1 (Q08397)
Formation of allysine by LOX
Prolysyl oxidase activation
Elastin cross-linking by lysyl oxidase
Formation of hydroxyallysine by LOX