Gene Ontology annotation through association of InterPro records with GO terms
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
Electronic Gene Ontology annotations created by ARBA machine learning models
Characterization of a novel gene product (mammalian tolloid-like) with high sequence similarity to mammalian tolloid/bone morphogenetic protein-1.
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Mouse mTll was cloned; it shares 76% identity with mTld in the protease and downstream domains and is additionally expressed in brain.
"mTll shows additional strong expression in structures of the developing, neonatal, and adult brain in which expression of BMP-1 and mTld has not been observed"
Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis.
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TLL-1 specifically removes procollagen C-propeptides at the physiological site and cleaves chordin; TLL-2 lacks procollagen C-proteinase activity. Reactome states that the human enzyme was tested on human procollagens I and II.
"mTLL-1 is shown to specifically process procollagen C-propeptides at the physiologically relevant site, while mTLL-2 is shown to lack this activity"
The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart.
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Tll1-null mice die at mid-gestation with incomplete muscular interventricular septum and abnormal heart positioning.
"Constant features were incomplete formation of the muscular interventricular septum and an abnormal and novel positioning of the heart and aorta."
Bone morphogenetic protein-1 processes probiglycan.
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mTLL-1 has low probiglycan-cleaving activity, and Bmp1/Tll1 double-null fibroblasts produce only unprocessed probiglycan.
"MEFs homozygous null for both the Bmp1 gene and the mTLL-1 gene Tll1 produce only unprocessed probiglycan"
Multiple bone morphogenetic protein 1-related mammalian metalloproteinases process pro-lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures.
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mTLL-1 cleaves pro-lysyl oxidase at the physiological site and, with BMP-1/mTLD, accounts for most lysyl oxidase activation in fibroblasts.
"all four proteinases productively cleave pro-lysyl oxidase at the correct physiological site"
Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen.
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mTLL-1 processes procollagen VII at the BMP-1 consensus site in vitro.
"Mammalian tolloid-like (mTLL)-1 and -2, two other proteases of the astacin enzyme family, were able to process procollagen VII at the same site in vitro."
Use of Bmp1/Tll1 doubly homozygous null mice and proteomics to identify and validate in vivo substrates of bone morphogenetic protein 1/tolloid-like metalloproteinases.
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mTLL-1 is an in vivo procollagen C-proteinase, and Bmp1 and Tll1 products account for chordin cleavage in mammals.
"mTLL-1 is an in vivo pCP that provides residual activity observed in Bmp1(-/-) embryos"
Activation of latent myostatin by the BMP-1/tolloid family of metalloproteinases.
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mTLL-1 cleaves the myostatin propeptide in the latent complex about as efficiently as BMP-1 and mTLL-2.
"Three of the proteinases, BMP-1, mTLL-1, and mTLL-2, were approximately equally effective in cleaving the propeptide"
Mammalian tolloid-like 1 binds procollagen C-proteinase enhancer protein 1 and differs from bone morphogenetic protein 1 in the functional roles of homologous protein domains.
Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases.
Mutations in mammalian tolloid-like 1 gene detected in adult patients with ASD.
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TLL1 missense variants were found in atrial septal defect patients.
"In four nonrelated patients, three missense mutations in coding sequence, and one single base change in the 5'UTR have been detected."
Structural and functional evidence for a substrate exclusion mechanism in mammalian tolloid like-1 (TLL-1) proteinase.
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Full-length TLL-1 forms a calcium-dependent dimer; truncated monomeric TLL-1 has higher chordinase activity.
"truncated TLL-1 molecules having the same shorter structure as BMP-1 are monomers and have improved activity towards their substrate chordin"
Induced ablation of Bmp1 and Tll1 produces osteogenesis imperfecta in mice.
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Postnatal combined ablation of Bmp1 and Tll1 produces brittle bones with reduced procollagen processing.
"Bones of the conditionally null mice are dramatically weakened and brittle, with spontaneous fractures-defining features of OI."
Diversity between mammalian tolloid proteinases: Oligomerisation and non-catalytic domains influence activity and specificity.
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TLL-2 can cleave chordin in vitro, so the chordinase difference between TLL1 and TLL2 is assay-dependent.
"we show that TLL-2 can cleave chordin in vitro"
Functional and structural studies of tolloid-like 1 mutants associated with atrial-septal defect 6.
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Recombinant human TLL1 (cloned from NTERA-2 cells) cleaves chordin and procollagen I; ASD6 variants reduce activity and chordin binding.
"in comparison with the native TLL1, mutants cleaved chordin and procollagen I at significantly lower rates"
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The TLL1 construct was of human origin.
"human TLL1 was derived from NTERA-2 cells"
Mitral Valve Prolapse Caused by TLL1 Gain-of-Function Mutation.
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A TLL1 p.T253A catalytic-domain variant segregates with dominant mitral valve prolapse and increases extracellular TLL1 activity.
"the enzymatic activity of the mutated TLL1 protein was 3.4-fold higher than that of the wild-type"
SLIT2 repellent is cleaved by TLL1 protease and promotes sensory axon fasciculation.
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TLL1 cleaves SLIT2 in cultured cells after furin-type activation.
"The Tolloid-related protease TLL1 cleaved SLIT2 in cultured cells, with TLL1 requiring activation by furin/prohormone convertases."
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The cleavage assays used human TLL1 and human SLIT2.
"human TLL1 and human SLIT2 in Drosophila S2 cells."
Collagen biosynthesis and modifying enzymes
Removal of fibrillar collagen C-propeptides
Prolysyl oxidase activation
Anchoring fibril formation
Cleavage of collagen VII NC2 region by BMP1
Crosslinking of collagen fibrils
HSPG2 (perlecan) is cleaved by BMP1, TLL1, TLL2, Cathepsin L1
UniProt entry O43897 (TLL1_HUMAN)