Full-length FLVCR1a facilitates plasma-membrane transport of choline and ethanolamine. Two substrate-specific functions capture this principal activity. Cellular heme export, mitochondrial heme distribution and erythroid maturation are retained as contextual functions with the original experimental and natural-product boundaries.
Human-cell knockout and complementation establish choline uptake and changes in downstream phosphocholine. Measured choline-kinase activity is unchanged, distinguishing precursor delivery from phosphorylation. The full-length product restores phosphocholine; paired tagged-product localization Methods do not amount to an independent audit of supplementary image pixels. PMID:37100056(https://pmc.ncbi.nlm.nih.gov/articles/PMC10367582/)
The final structural study reconstitutes purified human FLVCR1 into lipid vesicles and measures radiolabeled choline uptake against protein-free controls. Its ethanolamine evidence instead uses human-cell knockout/rescue, uptake, substrate-selective mutants and substrate-bound structure. Q214A strongly reduces ethanolamine uptake while preserving choline uptake in the tested system. Isotope tracing measures phosphocholine and phosphoethanolamine, not direct mature phosphatidylcholine/phosphatidylethanolamine synthesis. FLVCR1 supplies pathway precursors; downstream enzymes phosphorylate and assemble them. The original phospholipid-biosynthesis annotation and two part_of extensions retain this pathway-entry context without assigning catalytic lipid synthesis. The final article is now genuinely available in the normal cache; selected Results and protein-expression, reconstitution and uptake Methods were read. PMID:38693265(https://pmc.ncbi.nlm.nih.gov/articles/PMC11188936/)
Independent human FLVCR1a experiments combine cellular uptake, membrane imaging, substrate-bound structures and mutagenesis. CHKA or ETNK1 enhances accumulation by trapping imported substrate, so cell-based kinetic endpoints are not purified turnover rates. FLVCR1 ethanolamine washout and FLVCR2 choline washout are separate experiments. These observations support facilitative, gradient-dependent transport rather than an ATP-driven pump or obligatory one-way importer. The final human variant study uses kinase-only controls and corroborates transport without establishing universal variant effects or severity. Unresolved termini in atomic models are not naturally deleted products. PMID:38778100(https://pmc.ncbi.nlm.nih.gov/articles/PMC11168923/), PMID:39306721(https://pubmed.ncbi.nlm.nih.gov/39306721/)
The exact FLVCR1 assay in the later sixteen-transporter comparison remains unverified beyond authentic metadata and abstract. Independent target evidence supports the existing choline assertions, while the reference assessment retains UNVERIFIED for the source-specific claim. Kinetics or inhibitor responses reported for other SLC proteins are not transferred to FLVCR1. PMID:40972734(https://pubmed.ncbi.nlm.nih.gov/40972734/)
The original heme-export paper expresses human AF118637 FLVCR in rat NRK cells, with empty-vector and paralog controls. It measures fluorescent-analog and radiolabeled-hemin washout and extracellular HPLC-detected heme; separate human K562 interference/antibody experiments support the physiological context. Thus its evidence is more than a steady-state heme-content phenotype. These are cellular assays, not purified full-length translocation or experiments on the shorter natural product. Selected original PDF Methods/Results were read in addition to the authentic abstract cache. PMID:15369674(https://pubmed.ncbi.nlm.nih.gov/15369674/)
The acceptor study measures cellular export in human-FLVCR-expressing rat cells, with macrophage and FLVCR-null mouse fibroblast experiments as distinct models. A GST-tagged FLVCR fragment spanning residues 132–201 binds heme and purified rabbit apohemopexin with GST/competition controls; its insert species is not separately specified in the inspected Methods. The original human HPX accession is preserved. This supports the generic interaction but does not establish purified full-length human-human affinity, every histidine mechanism step or every natural product's behavior. The interaction stays non-core under the explicit campaign exception. PMID:20610401(https://pmc.ncbi.nlm.nih.gov/articles/PMC2937914/)
The mitochondrial study detects an endogenous human C-terminal-reactive protein of the short-product size in purified mitochondrial fractions with compartment controls. Human transcript depletion links this pool to mitochondrial heme accumulation. Tagged a/b overexpression constructs are murine even when expressed in human HeLa or K562 cells. Differentiation, heme-content and hemin-rescue endpoints support contextual physiology; they are not purified short-product transport or a b-specific K562 knockout/rescue. The inspected Methods do not distinguish inner from outer mitochondrial membrane. Accordingly, two inner-membrane assignments are generalized to mitochondrial membrane, and heme-biosynthesis annotations are over-annotated because no synthetic reaction, scaffold or cofactor step performed by FLVCR1 has been established. This does not deny the observed effects on heme synthesis or export. PMID:23187127(https://pmc.ncbi.nlm.nih.gov/articles/PMC3533534/)
The variant study's authentic abstract reports export, trafficking and stability defects; original detailed Methods remain inaccessible. Host species and unreported assay details are not invented. Independent target studies support the retained activity/location without claiming that this individual assay was fully reproduced. PMID:22483575(https://pubmed.ncbi.nlm.nih.gov/22483575/)
Official UniProt identifies Q9Y5Y0-1/FLVCR1a (555 residues) and Q9Y5Y0-2/FLVCR1b (279 residues). Independent official FASTAs reconstruct the shorter product by deletion of residues 1–276 (VSP_047866). Sequence identity does not assign the full-length plasma-membrane substrate repertoire to the mitochondrial product. The broader mitochondrial location does not demonstrate a cleaved targeting peptide, inner-bilayer topology or a particular oligomer. UniProt Q9Y5Y0
The original fragmentomics study tests human PDZ domains against a biotinylated ten-residue FLVCR1 C-terminal peptide, MLSKQSESAI. Exact original supplementary-data joins support above-threshold DAPF holdup measurements for eight source partners: DLG4, SCRIB, PDZK1, MAGI2, NHERF4, LNX1, DLG3 and WHRN. These eight existing rows are refined to PDZ domain binding. They are domain-peptide experiments, not endogenous full-length complexes. Each relevant measurement is a single observation converted using an estimated peptide concentration, without FLVCR1-specific fluorescence-polarization replication. LNX1_1 normalized binding intensity 0.05565566 is only slightly above the 0.05 detection threshold and is not characterized as robust or high-affinity binding. PMID:36115835(https://pmc.ncbi.nlm.nih.gov/articles/PMC9482650/), IntAct Q9Y5Y0, PDZ domain binding
For the other thirteen source partners, all tested target domains fall below the authors' quantification threshold and composite pKd is coded zero. Their original positive GOA/IntAct assertions remain UNDECIDED pending source reconciliation. A below-threshold value is not proof of biological nonbinding; the original assertions are not removed. IntAct's negative=false flag and malformed affinity parameter do not establish a measured positive affinity. The source identifier and original measurements are verified, while the structured reference assessment records unresolved claim support. No partner activity or transport regulation is assigned from these interactions.
The original eight-row PTHR10924 PAINT slice matches the complete original IBD GAF. Its 359-node tree and 359-record alignment contain the exact 555-residue human target PTN002475065. Seven incoming IBA contexts arise at verified on-path nodes: PTN000858905 for heme activity/binding/export, PTN002589204 for mitochondrial transport/location and erythroid differentiation, and PTN000858822 for membrane. The first six are retained non-core; the true but generic membrane assertion is TOO_GENERAL. Target self-evidence and donor count are not objections to this considered phylogenetic placement. Node inheritance establishes provenance, not an independent substrate assay. PANTHER PTHR10924, Original IBD GAF
Official term relationships support the two distinct substrate activities and their part_of transport processes. Specific activity ancestry entails the generic transmembrane-transport process across aspects; this is not a false is_a claim between biological-process terms. Plasma membrane entails membrane, while mitochondrial inner membrane is a child of mitochondrial membrane. The three original singleton extensions are serialized in the YAML without changing their meaning: raw 26 and39 part_of phospholipid biosynthetic process, raw 34 part_of heme export. These come from original QuickGO JSON, not the misprojected TSV extension column. Choline activity, Ethanolamine activity, Mitochondrial membrane
Reactome's plasma-membrane and mitochondrial export events support contextual model placement, not independent experiments or resolved inner-membrane topology. Heme synthesis concerns precursor conversion, whereas FLVCR1 handles completed heme; the broad iron-homeostasis context includes iron carried by heme without establishing free-ion transport. The source guide preserves all four reaction/pathway identities. R-HSA-917892, R-HSA-9661408, R-HSA-189451, R-HSA-917937
Actual reading scope, normal source hashes and every original context are recorded in the source guide. No new publication quotation or annotation was authored.
The auditable PDZ table reproduces the original normalized DAPF measurements for every tested domain of the 21 existing partner accessions. The thirteen unresolved source pairs are explicitly marked as suspected checks for IntAct, without asserting nonbinding, an incorrect IPI code or a missing NOT qualifier. Domain/peptide singlicates and estimated-concentration affinity conversion do not establish full-length physiological complexes.
FLVCR1 supplies the experimentally linked precursor-entry operation for cellular choline/ethanolamine metabolism, and the original transporter assertions carry part_of phospholipid-biosynthesis extensions. This supports the retained contextual pathway association while downstream enzymes perform phosphorylation and lipid assembly. Export or redistribution of already completed heme does not identify a heme-forming step; its observed feedback effects remain real but do not establish biosynthetic participation. These distinctions preserve the existing actions and both transport cores. The original hemopexin paper's conflicting fragment ranges are now also recorded directly beside both affected YAML claims and its reference assessment.