FLAD1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003919 FMN adenylyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT inference identifies the conserved FMN adenylyltransferase activity of human FLAD1. Reason: The exact human Q8NFF5 leaf PTN002510965 descends from the positive GO:0003919 IBD at PTN000591373 in the retrieved PTHR23293 tree. The target MSA sequence is identical to the 587-residue UniProt sequence. Human biochemical assays independently establish the reaction. The target appearing among the descendant evidence is expected and is not circular evidence. API release 19 and the original PAINT GAF are separately identified in the evidence guide. Supporting Evidence: PMID:16643857 FAD synthetase (FADS) (EC 2.7.7.2) is a key enzyme in the metabolic pathway that converts riboflavin into the redox cofactor FAD.
GO:0006747 FAD biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: FLAD1 directly performs the terminal FAD biosynthetic reaction. Reason: The GO:0006747 IBD at PTN000591373 lies on the verified human target path. Human FADS converts FMN and ATP to FAD and diphosphate, so the protein catalyzes a step of this process rather than merely being necessary for its downstream consequences. Supporting Evidence: PMID:25954742 the enzyme responsible for FMN adenylation to FAD.
GO:0003824 catalytic activity	IEA GO_REF:0000002	MODIFY	Summary: The InterPro catalytic-activity mapping is correct but less informative than the demonstrated FAD synthase activity. Reason: IPR002500 denotes the PAPS-reductase-family domain, whose human FLAD1 construct comprising residues 329-587 directly synthesizes FAD from FMN and ATP. Replace this broad term with FMN adenylyltransferase activity. Generality alone is not biological overannotation, and a PAPS-family fold does not establish PAPS reductase chemistry in FLAD1. Proposed replacements: FMN adenylyltransferase activity Supporting Evidence: PMID:23443125 the PAPS reductase domain, per se, is able to catalyze the typical reactions of the FADS: FAD synthesis and its cleavage.
GO:0003919 FMN adenylyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: The combined electronic sources correctly identify FMN adenylyltransferase activity. Reason: The current source context combines rat D4A4P4, mouse Q8R123, InterPro, Rhea and EC mappings. Donor identities were verified as Flad1 orthologs; the reaction is also established directly for human recombinant isoforms, so its support does not rest on reciprocal electronic transfers. Supporting Evidence: PMID:16643857 Both isoforms possessed FADS activity and had a strict requirement for MgCl(2)
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic subcellular-location mapping to nucleus. Nuclear localization of FADS is experimentally supported (a nuclear flavin pool supplying LSD1/KDM1A), so this is acceptable but non-core relative to the enzyme's cytosolic/mitochondrial catalytic roles. Supporting Evidence: PMID:25954742 a novel FADS localisation was found to be the nucleus of mammalian cells
GO:0005737 cytoplasm	IEA GO_REF:0000117	MODIFY	Summary: Cytoplasm is correct but can be refined to the experimentally supported cytosolic and mitochondrial-matrix pools. Reason: The ARBA location is biologically compatible with FLAD1, but it is less informative than the measured locations. Replace it with cytosol for the human isoform-2 pool and mitochondrial matrix for the longer isoform-1 pool, preserving those product and assay limits. Neither replacement requires all natural products to share a location, and the broad original is not rejected as false. Human localization and import evidence support both replacements independently of the electronic rule. Proposed replacements: cytosol mitochondrial matrix Supporting Evidence: PMID:25954742 Isoform 1 and 2 are located in mitochondria and cytosol, respectively
GO:0005759 mitochondrial matrix	IEA GO_REF:0000120	ACCEPT	Summary: The mitochondrial-matrix mapping is consistent with the mitochondrial FLAD1 isoform. Reason: The current combined source includes rat D4A4P4 and UniProt subcellular-location mapping. Human isoform 1 import and mitochondrial localization independently support this compartment of the core FAD synthase function. Acceptance is product-scoped and does not require all five human products to enter mitochondria. Import processing was observed, whereas the precise 17-residue targeting-peptide cleavage boundary was predicted in the accessible source. Supporting Evidence: PMID:20060505 hFADS1, but not hFADS2, localizes in mitochondria
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Electronic subcellular-location mapping to cytosol. Cytosol is the location of the abundant isoform 2 and is directly supported experimentally; redundant with the IDA cytosol annotations. Supporting Evidence: PMID:25954742 Isoform 1 and 2 are located in mitochondria and cytosol, respectively
GO:0006747 FAD biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: The combined electronic annotation correctly places FLAD1 in FAD biosynthesis. Reason: Rhea/EC-linked activity, domain and pathway assignments agree with direct human formation of FAD from FMN and ATP. Rat donor identity is verified; the human enzyme itself performs the biosynthetic step. Supporting Evidence: PMID:21951714 the enzyme catalyzes FAD assembly from ATP and FMN
GO:0035529 NADH pyrophosphatase activity	IEA GO_REF:0000116	KEEP AS NON CORE	Summary: Rhea maps the reported NADH pyrophosphatase substrate activity of FLAD1. Reason: GO:0035529 denotes NADH hydrolysis to AMP and NMNH. Retention defers to the original UniProt EXP curation of PMID:31351152 and the current UniProt/Rhea assignment; the isolated NADH turnover assay was not independently recovered. The accessible PMID:31351152 abstract describes FAD turnover and NADH inhibition, which neither demonstrates nor disproves NADH substrate hydrolysis. The separately read PMID:38688286 body discusses earlier NADH hydrolysis, but its displayed NADH experiments measure binding and docking. A general statement about ADP-containing dinucleotides does not identify an assayed NADH substrate. Keep this reported activity outside the defining FAD-synthesis core without asserting a turnover rate, relative efficiency or physiological NADH flux. The inherited snippet has been relocated unchanged to its source finding, where its actual meaning is stated; it is no longer presented as support for this activity. Supporting Evidence: file:human/FLAD1/FLAD1-uniprot.txt Reaction=NADH + H2O = reduced beta-nicotinamide D-ribonucleotide + AMP PMID:31351152 PMID:38688286
GO:0047884 FAD diphosphatase activity	IEA GO_REF:0000120	ACCEPT	Summary: The FAD diphosphatase mapping represents a demonstrated second catalytic activity. Reason: RHEA:13889 and EC:3.6.1.18 describe hydrolytic conversion of FAD to FMN and AMP. Recombinant human FADS exhibits this activity under cobalt-dependent conditions; structural and truncation results assign the minimal functional unit to MPTb plus KH, rather than the isolated MPTb domain. Biochemical capacity is established while its physiological flux remains uncertain. Supporting Evidence: PMID:26277395 The recombinant hFADS2 was able to hydrolyse added FAD in a Co(2+) and mersalyl dependent reaction.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: The 2014 interactome records an association between FLAD1 and O00560. Reason: Exact IntAct records match Q8NFF5, O00560 and PMID:25416956 in validated, pooled and array two-hybrid assays. This physical association does not establish a specific catalytic, adaptor or regulatory function. Under the user campaign policy, retain supported generic binding as non-core; no interaction-derived core activity is proposed. This source is the 2014 interactome study, not the later HuRI resource. Supporting Evidence: file:human/FLAD1/FLAD1-uniprot.txt Q8NFF5; O00560: SDCBP; NbExp=4;
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	KEEP AS NON CORE	Summary: The interaction-variation study supports the FLAD1/O00560 association. Reason: An exact IntAct two-hybrid-array record matches this pair and PMID:31515488; its annotated variant feature is recorded in the evidence guide. The experiment supports the association in its assay context without defining the physiological role of the pair or a specific binding-function subtype. Supported generic binding is retained as non-core under the user campaign policy. Supporting Evidence: file:human/FLAD1/FLAD1-uniprot.txt Q8NFF5; O00560: SDCBP; NbExp=4;
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: BioPlex supports an association between FLAD1 and Q5T6F2. Reason: An exact IntAct record links the pair to PMID:33961781 by anti-tag coimmunoprecipitation in HEK293T cells. This supports assay association, not necessarily direct physical contact or a defined catalytic complex. Retain generic binding as non-core under the user campaign policy without inferring a specific function from co-purification. Supporting Evidence: file:human/FLAD1/FLAD1-uniprot.txt Q8NFF5; Q5T6F2: UBAP2; NbExp=2;
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	KEEP AS NON CORE	Summary: The FLAD1/Q5T6F2 pair is independently supported, with a source-specific limit for the cell-map annotation. Reason: The accessible PMID:40205054 body describes multimodal cell maps and comparisons with BioPlex, but the exact FLAD1 pair was not recovered from that publication or the bounded IntAct response. The identical Q8NFF5/Q5T6F2 pair is independently recorded by anti-tag coimmunoprecipitation in PMID:33961781. Retain the corroborated generic association as non-core under the user campaign policy while explicitly withholding claims about the newer paper-specific assay, cell context or directness. Supporting Evidence: file:human/FLAD1/FLAD1-uniprot.txt Q8NFF5; Q5T6F2: UBAP2; NbExp=2;
GO:0042802 identical protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	KEEP AS NON CORE	Summary: FLAD1 self-association is supported in the cited interaction assay. Reason: An exact Q8NFF5/Q8NFF5 IntAct record joins PMID:16189514 to two-hybrid pooling. Self-association is independently compatible with the dimeric structure and interprotomer hydrolase site in PMID:38688286. Keep the binding annotation as structural context rather than a third catalytic core; the screening construct is not assumed to represent every natural product. Supporting Evidence: PMID:38688286 hFADS2 associates in a stable C2-symmetric dimer
GO:0042802 identical protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: FLAD1 self-association is supported in the cited interaction assay. Reason: An exact Q8NFF5/Q8NFF5 IntAct record joins PMID:25416956 to two-hybrid array. Self-association is independently compatible with the dimeric structure and interprotomer hydrolase site in PMID:38688286. Keep the binding annotation as structural context rather than a third catalytic core; the screening construct is not assumed to represent every natural product. Supporting Evidence: PMID:38688286 hFADS2 associates in a stable C2-symmetric dimer
GO:0042802 identical protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	KEEP AS NON CORE	Summary: FLAD1 self-association is supported in the cited interaction assay. Reason: An exact Q8NFF5/Q8NFF5 IntAct record joins PMID:31515488 to two-hybrid array. Self-association is independently compatible with the dimeric structure and interprotomer hydrolase site in PMID:38688286. Keep the binding annotation as structural context rather than a third catalytic core; the screening construct is not assumed to represent every natural product. Supporting Evidence: PMID:38688286 hFADS2 associates in a stable C2-symmetric dimer
GO:0006771 riboflavin metabolic process	TAS Reactome:R-HSA-196843	KEEP AS NON CORE	Summary: FLAD1 participates in the broader riboflavin-derived cofactor pathway. Reason: The Reactome pathway encompasses vitamin B2 metabolism; FLAD1 directly adenylates FMN in the FAD-producing portion. Retain this broader process without assigning riboflavin uptake or the riboflavin-kinase step to FLAD1. The specific FAD biosynthetic process expresses its catalytic role more precisely. Supporting Evidence: Reactome:R-HSA-196843 Riboflavin (vitamin B2, E101) is an essential component for the cofactors FAD (flavin-adenine dinucleotide) and FMN (flavin mononucleotide). Reactome:R-HSA-196929 The enzyme responsible , FMN adenylyltransferase (FLAD1 aka FAD synthase), is cytosolic and transfers a phosphate and an adenyl group from ATP to form FAD.
GO:0003919 FMN adenylyltransferase activity	TAS Reactome:R-HSA-196929	ACCEPT	Summary: The Reactome reaction assigns the correct FMN adenylyltransferase activity. Reason: Despite the cached reaction title using phosphorylates, the human FLAD1 reaction is ATP-dependent adenylylation of FMN to FAD and diphosphate. The activity and cytosolic context agree with purified human enzyme studies; this does not make FLAD1 a riboflavin kinase. Supporting Evidence: Reactome:R-HSA-196929 The enzyme responsible , FMN adenylyltransferase (FLAD1 aka FAD synthase), is cytosolic and transfers a phosphate and an adenyl group from ATP to form FAD.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: The immunofluorescence-derived cytosol annotation agrees with direct human FLAD1 localization. Reason: GO_REF:0000052 identifies a curated immunofluorescence source. Cytosolic localization is independently supported for human isoform 2 and by human HepG2 FADS staining. No antibody-specific image or exact natural-product assignment is claimed for the GO_REF assay itself. Supporting Evidence: PMID:25954742 Isoform 1 and 2 are located in mitochondria and cytosol, respectively
GO:0003919 FMN adenylyltransferase activity	EXP PMID:16643857 Over-expression in Escherichia coli and characterization of ...	ACCEPT	Summary: Both recombinant human isoforms tested possess FAD synthase activity. Reason: The PMID:16643857 abstract reports recombinant human isoforms 1 and 2 produced in E. coli and activity requiring MgCl2. Their expression tags are assay constructs, not additional natural products. This directly supports the core FMN adenylyltransferase activity. Supporting Evidence: PMID:16643857 Both isoforms possessed FADS activity and had a strict requirement for MgCl(2)
GO:0003919 FMN adenylyltransferase activity	EXP PMID:21924249 The antibiotics roseoflavin and 8-demethyl-8-amino-riboflavi...	ACCEPT	Summary: Human FAD synthase adenylates flavin mononucleotide substrates, including RoFMN. Reason: The accessible PMID:21924249 abstract explicitly assays human FAD synthetase: it converts RoFMN to RoFAD but does not accept AFMN. The bacterial producer named in the title does not make this a wrong-organism annotation. Retain the established human adenylyltransferase function without assigning the preceding flavokinase reaction. Supporting Evidence: PMID:21924249 Consequently, roseoflavin adenine dinucleotide (RoFAD) was synthesized by the latter enzyme
GO:0003919 FMN adenylyltransferase activity	EXP PMID:23443125 Bacterial over-expression and purification of the 3'phosphoa...	ACCEPT	Summary: The isolated human C-terminal domain catalyzes FMN adenylylation. Reason: Actual Results and Methods of PMID:23443125 describe a His-tagged human 329-587 construct, expression in E. coli, and FMN/ATP-dependent FAD synthesis measured fluorimetrically. The reported reverse cleavage uses added pyrophosphate and is pyrophosphorolysis, not evidence that this isolated C-terminal domain possesses the distinct water-dependent FAD diphosphatase reaction. Supporting Evidence: PMID:23443125 the PAPS reductase domain, per se, is able to catalyze the typical reactions of the FADS: FAD synthesis and its cleavage.
GO:0003919 FMN adenylyltransferase activity	EXP PMID:25135855 Significance of redox-active cysteines in human FAD synthase...	ACCEPT	Summary: Human isoform 2 synthase activity is altered by cysteine substitutions and thiol reagents. Reason: PMID:25135855 reports reduced FAD synthesis for tested hFADS2 mutants and inhibition by thiol-blocking reagents. This supports the measured FMN adenylyltransferase activity. Its proposed redox switch is not treated as a separately established physiological process, and isoform-2 residue numbering is not silently transferred to the 587-residue canonical product. Supporting Evidence: PMID:25135855 FAD synthase (FMN:ATP adenylyl transferase, FMNAT or FADS, EC 2.7.7.2) is the last enzyme in the pathway converting riboflavin into FAD.
GO:0035529 NADH pyrophosphatase activity	EXP PMID:31351152 The hidden side of the human FAD synthase 2.	KEEP AS NON CORE	Summary: NADH pyrophosphatase is retained as a reported substrate activity with explicit assay-access limits. Reason: GO:0035529 denotes NADH hydrolysis to AMP and NMNH. Retention defers to the original UniProt EXP curation of PMID:31351152 and the current UniProt/Rhea assignment; the isolated NADH turnover assay was not independently recovered. The accessible PMID:31351152 abstract describes FAD turnover and NADH inhibition, which neither demonstrates nor disproves NADH substrate hydrolysis. The separately read PMID:38688286 body discusses earlier NADH hydrolysis, but its displayed NADH experiments measure binding and docking. A general statement about ADP-containing dinucleotides does not identify an assayed NADH substrate. Keep this reported activity outside the defining FAD-synthesis core without asserting a turnover rate, relative efficiency or physiological NADH flux. The inherited snippet has been relocated unchanged to its source finding, where its actual meaning is stated; it is no longer presented as support for this activity. Supporting Evidence: file:human/FLAD1/FLAD1-uniprot.txt Reaction=NADH + H2O = reduced beta-nicotinamide D-ribonucleotide + AMP PMID:31351152 PMID:38688286
GO:0047884 FAD diphosphatase activity	IDA PMID:26277395 Human FAD synthase is a bi-functional enzyme with a FAD hydr...	ACCEPT	Summary: Purified human hFADS2 hydrolyzes FAD under the tested cobalt/mersalyl conditions. Reason: The PMID:26277395 abstract directly reports hydrolysis of added FAD by recombinant hFADS2 and lack of this activity in the C-terminal synthase fragment. Later structural work refines the minimal active substructure to MPTb plus KH; the title does not prove that isolated MPTb is sufficient. Do not equate this assay with constitutive intracellular FAD degradation. Supporting Evidence: PMID:26277395 The recombinant hFADS2 was able to hydrolyse added FAD in a Co(2+) and mersalyl dependent reaction.
GO:0047884 FAD diphosphatase activity	IDA PMID:31351152 The hidden side of the human FAD synthase 2.	ACCEPT	Summary: Human FADS2 has cobalt-dependent, potassium-stimulated FAD hydrolytic activity. Reason: The PMID:31351152 abstract reports FAD turnover stimulated by K+ and Co2+, with NADH inhibition and glutathione stimulation. These are direct biochemical properties of the hydrolase reaction. The physiological importance of cobalt-supported turnover remains unresolved; NADH inhibition is distinct from its reported substrate activity. Supporting Evidence: PMID:31351152 Co2+ induced FAD hydrolysis was strongly stimulated in the presence of K+, reaching a Vmax higher than that of FAD synthesis.
GO:0003919 FMN adenylyltransferase activity	IDA PMID:25954742 Remaining challenges in cellular flavin cofactor homeostasis...	ACCEPT	Summary: Recombinant human isoform 2 catalyzes FAD synthesis through an ordered substrate-binding mechanism. Reason: Actual PMID:25954742 assays support ATP binding before FMN and product release of diphosphate before FAD. Direct cofactor delivery was tested from human hFADS2 to recombinant rat apo-DMGDH; the separate LSD1 association experiments used rat nuclear material and do not establish purified-human-LSD1 transfer. These scope limits do not weaken the directly measured synthase reaction. Supporting Evidence: PMID:25954742 FAD synthesis catalyzed by recombinant isoform 2 of FADS occurs via an ordered bi-bi mechanism in which ATP binds prior to FMN, and pyrophosphate is released before FAD.
GO:0006747 FAD biosynthetic process	IDA PMID:25954742 Remaining challenges in cellular flavin cofactor homeostasis...	ACCEPT	Summary: The experimentally characterized synthase directly produces FAD. Reason: The FAD-forming reaction studied in PMID:25954742 is the terminal biosynthetic step. This process assignment rests on the enzyme carrying out the reaction, not on indirect effects of FLAD1 deficiency on client oxidoreductases or chromatin. Supporting Evidence: PMID:25954742 the enzyme responsible for FMN adenylation to FAD.
GO:0005634 nucleus	IDA PMID:25954742 Remaining challenges in cellular flavin cofactor homeostasis...	KEEP AS NON CORE	Summary: FADS immunoreactivity is observed in human HepG2 nuclei. Reason: The actual localization experiments in PMID:25954742 use anti-FADS staining in human HepG2 cells and show nuclear as well as cytoplasmic signal. Other nuclear binding experiments in that article use rat liver material. Retain nuclear localization without claiming every human isoform is nuclear, or assigning FLAD1 the catalytic activity of nuclear client enzymes. Supporting Evidence: PMID:25954742 a novel FADS localisation was found to be the nucleus of mammalian cells
GO:0005829 cytosol	IDA PMID:25954742 Remaining challenges in cellular flavin cofactor homeostasis...	ACCEPT	Summary: Human cellular observations support a cytosolic FLAD1 pool. Reason: Human HepG2 FADS staining in PMID:25954742 complements the isoform-specific cytosolic localization reported for hFADS2 in PMID:20060505. The staining experiment is not resolved to all natural products, so the cytosolic core location is product-scoped rather than universal. Supporting Evidence: PMID:25954742 Isoform 1 and 2 are located in mitochondria and cytosol, respectively
GO:0003919 FMN adenylyltransferase activity	IDA PMID:21951714 Human FAD synthase (isoform 2): a component of the machinery...	ACCEPT	Summary: Purified recombinant human isoform 2 catalyzes FAD assembly from ATP and FMN. Reason: PMID:21951714 directly reports FAD synthesis and tight product retention by purified His-tagged hFADS2. Its slower reverse reaction requires pyrophosphate; this is distinct from the separately established N-terminal FAD hydrolase. Product retention and release kinetics support a delivery mechanism without demonstrating all possible client interactions. Supporting Evidence: PMID:21951714 the enzyme catalyzes FAD assembly from ATP and FMN
GO:0003919 FMN adenylyltransferase activity	IDA PMID:38688286 Structural insights into the bifunctional enzyme human FAD s...	ACCEPT	Summary: The structural study supports C-terminal FAD synthase activity. Reason: The separately accessed PMID:38688286 primary text establishes C-terminal FAD binding and synthesis. Its crystallized human 110-587 construct lacks twelve residues present in natural isoform 2 and must not be described as literal full-length hFADS2. Structural assays refine domain mechanism while the independent earlier human synthase experiments establish the same activity. Supporting Evidence: PMID:38688286 the C-terminal domain tightly binds FAD and catalyzes its synthesis
GO:0047884 FAD diphosphatase activity	IDA PMID:38688286 Structural insights into the bifunctional enzyme human FAD s...	ACCEPT	Summary: MPTb plus KH forms the minimal tested FAD-hydrolyzing substructure. Reason: PMID:38688286 Results distinguish nucleotide binding by MPTb alone from hydrolysis restored by MPTb plus KH, with an interprotomer active-site arrangement. FAD turnover was assayed with 1 mM CoCl2, 50 mM KCl and 1 micromolar FAD. This establishes biochemical activity; the authors themselves question strong constitutive physiological turnover given low free cobalt. Supporting Evidence: PMID:38688286 the combination of the N-terminal molybdopterin-binding and KH domains is the minimal essential substructure required for the hydrolysis of FAD and other ADP-containing dinucleotides.
GO:0005634 nucleus	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: The rat-to-human nuclear-localization transfer is biologically supported. Reason: The actual donor D4A4P4 is rat Flad1. Its current record carries nuclear IDA annotations to PMID:23946482 and PMID:25954742; the former explicitly reports confocal microscopy and immunoblotting in rat experimental models. Independent human HepG2 staining in PMID:25954742 supports the target location. This is not a claim that each alternative human product is nuclear. Supporting Evidence: PMID:25954742 a novel FADS localisation was found to be the nucleus of mammalian cells
GO:0003919 FMN adenylyltransferase activity	IDA PMID:20060505 Mitochondrial localization of human FAD synthetase isoform 1...	ACCEPT	Summary: Human isoform 1 retains FAD synthase activity. Reason: The PMID:20060505 abstract reports FAD synthesis by recombinant hFADS1 while examining its mitochondrial targeting. The localization study therefore also supports the catalytic annotation; mitochondrial import does not imply a different reaction from cytosolic hFADS2. Supporting Evidence: PMID:20060505 The recombinant hFADS1 produced in Escherichia coli showed apparent K(m) and V(max) values for FMN
GO:0005759 mitochondrial matrix	IDA PMID:20060505 Mitochondrial localization of human FAD synthetase isoform 1...	ACCEPT	Summary: Mitochondrial localization is supported for the longer human isoform. Reason: PMID:20060505 reports import and processing of in-vitro-translated hFADS1 in rat mitochondria and differential localization of human isoforms in BHK-21 and Caco-2 cells. Accept the curated mitochondrial-matrix annotation as a compartment of the core synthase function with this product/assay scope; a core location need not apply to every isoform. The exact first-17-residue transit-peptide boundary is a prediction in the accessible abstract, not an experimentally mapped cleavage site. Supporting Evidence: PMID:20060505 hFADS1, but not hFADS2, localizes in mitochondria
GO:0006747 FAD biosynthetic process	IDA PMID:20060505 Mitochondrial localization of human FAD synthetase isoform 1...	ACCEPT	Summary: The mitochondrial-targeted human isoform catalyzes FAD production. Reason: PMID:20060505 combines human isoform-1 synthase activity with mitochondrial import/localization experiments. FLAD1 therefore performs FAD biosynthesis; neither respiratory-chain deficiencies nor client-enzyme dependence alone are used to establish this process. Supporting Evidence: PMID:20060505 FAD synthetase or ATP:FMN adenylyl transferase (FADS or FMNAT, EC 2.7.7.2) is a key enzyme in the metabolic pathway that converts riboflavin into the redox cofactor FAD.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: Mitochondrial localization is independently supported, with a dataset-specific verification limit. Reason: The root mitochondrion term is an informative location, retained alongside the more specific mitochondrial-matrix annotation under the organelle policy. Independent human hFADS1 import/localization evidence in PMID:20060505 supports a mitochondrial synthase pool and therefore a core location. The original HTP source and term are unchanged. Although the PMID:34800366 body describes mitochondrial proteomics, its exact FLAD1/Q8NFF5 target row was not recovered. The inherited title excerpt is bibliographic provenance and does not establish that hit. Acceptance relies on corroborating localization evidence without claiming an independently verified MitoCoP row or extending the location to every isoform. Supporting Evidence: PMID:20060505 hFADS1, but not hFADS2, localizes in mitochondria
GO:0005829 cytosol	TAS Reactome:R-HSA-196929	ACCEPT	Summary: The Reactome reaction represents a cytosolic FAD-producing FLAD1 pool. Reason: The cached reaction explicitly places FLAD1 in the cytosol, in agreement with human isoform-2 localization and purified-enzyme activity. This supports the cytosolic synthase core while leaving mitochondrial and nuclear pools separately scoped. Supporting Evidence: Reactome:R-HSA-196929 The enzyme responsible , FMN adenylyltransferase (FLAD1 aka FAD synthase), is cytosolic and transfers a phosphate and an adenyl group from ATP to form FAD.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: The 2014 interactome separately records the FLAD1/P15884 association. Reason: Three exact IntAct records match Q8NFF5, P15884 and PMID:25416956 across validated, pooled and array two-hybrid assays. This is a distinct incoming partner context, not a newly proposed GO function. Retain supported generic binding as non-core under the user campaign policy; no transcriptional, adaptor or catalytic function is inferred from the partner identity. Supporting Evidence: file:human/FLAD1/FLAD1-uniprot.txt Q8NFF5; P15884: TCF4; NbExp=3;
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: The 2014 interactome separately records the FLAD1/Q04864 association. Reason: Three exact IntAct records match Q8NFF5, Q04864 and PMID:25416956 across validated, pooled and array two-hybrid assays. This is a distinct incoming partner context, not a newly proposed GO function. Retain supported generic binding as non-core under the user campaign policy; no transcriptional, adaptor or catalytic function is inferred from the partner identity. Supporting Evidence: file:human/FLAD1/FLAD1-uniprot.txt Q8NFF5; Q04864: REL; NbExp=3;
GO:0005634 nucleus	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: The current combined nuclear-location source is supported with species and product limits. Reason: This GO_REF:0000120 context replaces the withdrawn GO_REF:0000044 source assertion, which remains separately retired with its historical review intact. The current source includes rat D4A4P4 and subcellular-location mapping. Actual rat nuclear evidence and independent human HepG2 nuclear staining support localization, without resolving every human splice product. Supporting Evidence: PMID:25954742 a novel FADS localisation was found to be the nucleus of mammalian cells
GO:0005829 cytosol	IEA GO_REF:0000120	ACCEPT	Summary: The current combined source correctly identifies the cytosolic FLAD1 pool. Reason: This separately reviewed GO_REF:0000120 context combines rat D4A4P4, mouse Q8R123 and subcellular-location mapping; the old GO_REF:0000044 assertion remains retired rather than being rewritten. Verified donor identities and direct human isoform-2 localization support cytosol as a location of FAD synthesis. Supporting Evidence: PMID:25954742 Isoform 1 and 2 are located in mitochondria and cytosol, respectively

Gene Description

Existing Annotations Review

Core Functions

Catalyzes hydrolysis of FAD to FMN and AMP through the combined N-terminal MPTb and KH region, with an interprotomer active-site arrangement. This biochemical activity was measured in recombinant human proteins under cobalt-dependent assay conditions.

References

Suggested Questions for Experts

Suggested Experiments

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Notes

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