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 Gene Ontology annotation based on Rhea mapping
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Peroxisomal fatty acid oxidation disorders and 58 kDa sterol carrier protein X (SCPx). Activity measurements in liver and fibroblasts using a newly developed method.
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SCPx plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids; a specific assay measuring choloyl-CoA production from a bile-acid intermediate was developed and shown deficient in SCPx-knockout mouse fibroblasts.
"Sterol carrier protein X (SCPx) plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids."
Identification of the peroxisomal beta-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid.
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Both the conventional 3-ketoacyl-CoA thiolase and SCPx are among the main peroxisomal enzymes catalyzing beta-oxidation of C24:6n-3 to DHA (C22:6n-3).
"the main enzymes involved in beta-oxidation of C24:6n-3 to C22:6n-3 are SCOX, DBP, and both 3-ketoacyl-CoA thiolase and SCPx"
Subcellular localisation and processing of non-specific lipid transfer protein are not aberrant in Rhizomelic Chondrodysplasia Punctata fibroblasts.
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nsLTP (the SCP2 product) is localised to peroxisomes and present as its mature processed form, even in RCDP fibroblasts.
"non-specific lipid transfer protein (nsLTP), another peroxisomal protein synthesised as a larger precursor, is localised in peroxisomes and is present as the mature protein in RCDP fibroblasts"
Sterol carrier protein-2 directly interacts with caveolin-1 in vitro and in vivo.
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SCP-2 binds both cholesterol and phosphatidylinositol and directly interacts with caveolin-1, implicating it in trafficking these lipids to caveolae/lipid rafts.
"SCP-2 (but not PITP) selectively interacted with caveolin-1, both within the cytoplasm and at the plasma membrane"
Sterol carrier protein-2-facilitated intermembrane transfer of cholesterol- and phospholipid-derived hydroperoxides.
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SCP-2 facilitates intermembrane transfer/exchange of cholesterol and phospholipids and can also traffic their hydroperoxide (LOOH) derivatives, accelerating peroxidative damage.
"Sterol carrier protein-2 (SCP-2) facilitates cholesterol (Ch) and phospholipid (PL) transfer/exchange between membranes and appears to play a key role in intracellular lipid trafficking"
Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy.
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The first SCPx-deficient patient shows leukoencephalopathy with dystonia and motor neuropathy, pristanic-acid accumulation and abnormal bile-alcohol glucuronides; fibroblasts lack SCPx thiolytic activity and SCPx protein.
"In cultured skin fibroblasts, the thiolytic activity of SCPx was deficient, and no SCPx protein could be detected by western blotting"
Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p.
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The SCP2 gene yields two products (58 kDa SCPx thiolase-SCP2 fusion, and ~15 kDa preSCP2 processed to mature SCP2); SCP2 is a folded PTS1 cargo recognized by PEX5, and its lipid binding is retained when receptor-bound.
"The SCP2 gene is translated into two protein products: SCPx, a 58 kDa fusion protein comprising an N-terminal thiolase domain and a C-terminal SCP2 domain, and preSCP2, a protein with a molecular mass of about 15 kDa"
Investigation of the ligand spectrum of human sterol carrier protein 2 using a direct mass spectrometry assay.
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Native mass spectrometry confirmed that long-chain fatty acyl-CoAs are high-affinity SCP2 ligands, whereas the equivalent LCFA-carnitines do not bind.
"The observation that LCFA-CoAs are high affinity ligands for SCP2 was confirmed, while LCFA-carnitines were demonstrated for the first time not to interact with SCP2"
Structure and function of the sterol carrier protein-2 N-terminal presequence.
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The 20-residue N-terminal presequence of proSCP-2 modulates SCP-2 structure, cholesterol localization in the ligand-binding site, membrane association and intracellular targeting; SCP-2 binds cholesterol and fatty acyl-CoAs.
"membrane association, and, potentially, intracellular targeting"
Solution structure of human Pex5.Pex14.PTS1 protein complexes obtained by small angle X-ray scattering.
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SAXS/SLS analysis of the human PEX5.PEX14 complex loaded with SCP2 (PTS1 cargo); SCP2 is a transient cargo within the peroxisomal import machinery, not a stable functional complex partner.
"the interaction of the cargo-loaded Pex5p receptor and the peroxisomal membrane protein Pex14p is the essential primary docking step"
Defining the membrane proteome of NK cells.
The Peroxisomal Targeting Signal 1 in sterol carrier protein 2 is autonomous and essential for receptor recognition.
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SCP2 import into peroxisomes is absolutely dependent on its C-terminal PTS1; the ancillary secondary Pex5p interface is dispensable for import.
"receptor-cargo binding and SCP2 transfer into the peroxisome are absolutely dependent on the presence of the PTS1"
Next-generation sequencing to generate interactome datasets.
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A next-generation-sequencing yeast-two-hybrid interactome-mapping pipeline (Stitch-seq) that generated a human binary interactome dataset including an SCP2 interaction.
"used it to generate a new human"
A proteome-scale map of the human interactome network.
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A systematic proteome-scale map of ~14,000 high-quality human binary protein-protein interactions, one of which involves SCP2.
"we describe a systematic map of ?14,000 high-quality human"
Sterol carrier protein X (SCPx) is a peroxisomal branched-chain beta-ketothiolase specifically reacting with 3-oxo-pristanoyl-CoA: a new, unique role for SCPx in branched-chain fatty acid metabolism in peroxisomes.
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SCPx is the peroxisomal branched-chain beta-ketothiolase that readily cleaves 3-oxopristanoyl-CoA, a reaction the conventional peroxisomal thiolase performs poorly; SCPx is thus central to branched-chain fatty acid beta-oxidation.
"SCPx, a 58 kDa protein with both thiolase and sterol carrier protein activity but unknown function so far, readily reacts with 3-oxopristanoyl-CoA"
Thiolysis of 3alpha,7alpha,12alpha-trihydroxy-5beta-cholan-24-one-CoA yields choloyl-CoA (3alpha,7alpha,12alpha-trihydroxy-5beta-cholan-24-one-CoA) and propionyl CoA
Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
Thiolysis of 3alpha,7alpha-dihydroxy-5beta-cholan-24-one-CoA yields chenodeoxycholoyl-CoA (3alpha,7alpha-dihydroxy-5beta-cholan-24-one-CoA) and propionyl CoA
alpha-linolenic acid (ALA) metabolism
Formation of DHA-CoA catalysed by sterol carrier protein X (SCPx)
Beta-oxidation of pristanoyl-CoA
3-ketopristanoyl-CoA + CoASH => 4,8,12-trimethyltridecanoyl-CoA + propionyl-CoA
Cargo of PEX5S,L translocates from the cytosol to the peroxisomal matrix
PEX5S,L:Cargo binds PEX13:PEX14:PEX2:PEX10:PEX12 (Docking and Translocation Module)