FLAD1
entrez
80308
canonical
uniprot
Q8NFF5
canonical
ensembl
ENSG00000160688
resolver
ensp
ENSP00000292180
resolver
ensp
ENSP00000317296
resolver
ensp
ENSP00000357416
resolver
ensp
ENSP00000357417
resolver
genesymbol
FLAD1
resolver
hgnc
HGNC:24671
resolver
uniprot
Q8N5J1
resolver
uniprot
Q8N686
resolver
uniprot
Q8WU93
resolver
uniprot
Q8WUJ4
resolver
uniprot
Q96CR8
resolver
uniprot
Q99764
resolver
uniprot
Q9HBN6
resolver
uniprot_entry
FAD1_HUMAN
resolver
uniprot_sec
Q8N5J1
resolver
uniprot_sec
Q8N686
resolver
uniprot_sec
Q8WU93
resolver
uniprot_sec
Q8WUJ4
resolver
uniprot_sec
Q96CR8
resolver
uniprot_sec
Q99764
resolver
uniprot_sec
Q9HBN6
resolver
activity_regulation
ACTIVITY REGULATION: The reducing agent sodium dithionite stimulates FAD synthase activity (PubMed:21924249). The FAD synthase activity is inhibited by GTP and GDP (PubMed:21951714, PubMed:23443125). The FAD synthase activity is also inhibited by the thiol reagents mersalyl, methylmercury, and mercury chloride; mersalyl also inhibits the reverse pyrophosphorylase activity (PubMed:25135855). FAD diphosphatase activity is stimulated by glutathione and mersalyl (PubMed:26277395, PubMed:31351152). FAD diphosphatase activity is inhibited by ADP and ADP-ribose (PubMed:26277395, PubMed:31351152). {ECO:0000269|PubMed:21924249, ECO:0000269|PubMed:21951714, ECO:0000269|PubMed:23443125, ECO:0000269|PubMed:25135855, ECO:0000269|PubMed:26277395, ECO:0000269|PubMed:31351152}.
uniprot
proteins
amino_acid_sequence
MGWDLGTRLFQRQEQRSRLSRIWLEKTRVFLEGSTRTPALPHCLFWLLQVPSTQDPLFPGYGPQCPVDLAGPPCLRPLFGGLGGYWRALQRGREGRTMTSRASELSPGRSVTAGIIIVGDEILKGHTQDTNTFFLCRTLRSLGVQVCRVSVVPDEVATIAAEVTSFSNRFTHVLTAGGIGPTHDDVTFEAVAQAFGDELKPHPKLEAATKALGGEGWEKLSLVPSSARLHYGTDPCTGQPFRFPLVSVRNVYLFPGIPELLRRVLEGMKGLFQNPAVQFHSKELYVAADEASIAPILAEAQAHFGRRLGLGSYPDWGSNYYQVKLTLDSEEEGPLEECLAYLTARLPQGSLVPYMPNAVEQASEAVYKLAESGSSLGKKVAGALQTIETSLAQYSLTQLCVGFNGGKDCTALLHLFHAAVQRKLPDVPNPLQILYIRSISPFPELEQFLQDTIKRYNLQMLEAEGSMKQALGELQARHPQLEAVLMGTRRTDPYSCSLCPFSPTDPGWPAFMRINPLLDWTYRDIWDFLRQLFVPYCILYDRGYTSLGSRENTVRNPALKCLSPGGHPTYRPAYLLENEEEERNSRT
uniprot
proteins
disease_involvement
DISEASE: Lipid storage myopathy due to flavin adenine dinucleotide synthetase deficiency (LSMFLAD) [MIM:255100]: An autosomal recessive, inborn error of metabolism characterized by variable mitochondrial dysfunction. Clinical features range from severe cardiac and respiratory insufficiency with onset in infancy and resulting in early death, to mild muscle weakness with onset in adulthood. Some patients show significant improvement with riboflavin treatment. Analysis of skeletal muscle show multiple mitochondrial respiratory chain deficiency and a lipid storage myopathy in most patients. {ECO:0000269|PubMed:27259049}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.7.2
uniprot
proteins
ec_number
3.6.1.18
uniprot
proteins
ec_number
3.6.1.22
uniprot
proteins
function
FUNCTION: This enzyme has two activities: FAD diphosphatase activity and FAD synthase activity (PubMed:16643857, PubMed:21924249, PubMed:21951714, PubMed:23443125, PubMed:25135855, PubMed:26277395, PubMed:27259049, PubMed:31351152, PubMed:38688286). FAD diphosphatase acts on FAD and NADH to produce FMN and NMNH(2-), respectively (PubMed:26277395, PubMed:31351152, PubMed:38688286). FAD synthase catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme (PubMed:16643857, PubMed:21924249, PubMed:21951714, PubMed:23443125, PubMed:27259049, PubMed:38688286). In addition to its catalytic activities, the protein also facilitates the delivery of FAD to client apo-flavoproteins (PubMed:25954742). The balance between FAD synthesis and hydrolysis may be regulated by redox-sensing cysteine residues (PubMed:25135855, PubMed:26277395). At a much lower rate, FAD synthase catalyzes the reverse pyrophosphorolytic reaction (PubMed:21951714, PubMed:23443125, PubMed:25135855, PubMed:26277395). FAD synthase can also convert roseoflavin mononucleotide (RoFMN) to roseoflavin adenine dinucleotide (RoFAD); RoFMN is produced by riboflavin kinase when acting on the antibiotic roseoflavin (RoF) (PubMed:21924249). FAD synthase cannot convert 8-demethyl-8-amino-riboflavin mononucleotide (AFMN) to 8-demethyl-8-amino-riboflavin adenine dinucleotide (AFAD); AFMN is produced by riboflavin kinase when acting on the antibiotic 8-demethyl-8-amino-riboflavin (AF) (PubMed:21924249). {ECO:0000269|PubMed:16643857, ECO:0000269|PubMed:21924249, ECO:0000269|PubMed:21951714, ECO:0000269|PubMed:23443125, ECO:0000269|PubMed:25135855, ECO:0000269|PubMed:25954742, ECO:0000269|PubMed:26277395, ECO:0000269|PubMed:27259049, ECO:0000269|PubMed:31351152, ECO:0000269|PubMed:38688286}.
uniprot
proteins
mass_dalton
65266
uniprot
proteins
mutagenesis
MUTAGEN 338; /note="C->A: Decreases FAD synthase turnover number (kcat) and increases its affinity for ATP."; /evidence="ECO:0000269|PubMed:25135855"; MUTAGEN 400; /note="C->A: Decreases FAD synthase turnover number (kcat) and increases its affinity for ATP."; /evidence="ECO:0000269|PubMed:25135855"; MUTAGEN 409; /note="C->A: Decreases FAD synthase turnover number (kcat)."; /evidence="ECO:0000269|PubMed:25135855"; MUTAGEN 496; /note="C->A: Decreases FAD synthase turnover number (kcat) and increases its affinity for ATP."; /evidence="ECO:0000269|PubMed:25135855"; MUTAGEN 537; /note="C->A: Decreases FAD diphosphatase activity. Decreases FAD synthase turnover number (kcat) and increases its affinity for ATP."; /evidence="ECO:0000269|PubMed:25135855, ECO:0000269|PubMed:31351152
uniprot
proteins
pathway_participation
PATHWAY: Cofactor biosynthesis; FAD biosynthesis; FAD from FMN: step 1/1.
uniprot
proteins
post_translational_modification
PTM: May form disulfide bonds. {ECO:0000269|PubMed:25135855}.
uniprot
proteins
protein_family
FAD1 subfamily
uniprot
proteins
protein_family
MoaB/Mog family; PAPS reductase family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15498874
uniprot
proteins
pubmed
16643857
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17049878
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
20060505
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21924249
uniprot
proteins
pubmed
21951714
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23443125
uniprot
proteins
pubmed
23946482
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25135855
uniprot
proteins
pubmed
25954742
uniprot
proteins
pubmed
26277395
uniprot
proteins
pubmed
27259049
uniprot
proteins
pubmed
31351152
uniprot
proteins
pubmed
38688286
uniprot
proteins
pubmed
9110174
uniprot
proteins
sequence_length
587
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25954742}.; SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion matrix {ECO:0000269|PubMed:20060505}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm, cytosol {ECO:0000269|PubMed:20060505, ECO:0000269|PubMed:23946482, ECO:0000269|PubMed:25954742}.
uniprot
proteins