PYROXD1
entrez
79912
canonical
uniprot
Q8WU10
canonical
ensembl
ENSG00000121350
resolver
ensp
ENSP00000240651
resolver
ensp
ENSP00000438505
resolver
ensp
ENSP00000700845
resolver
ensp
ENSP00000700849
resolver
genesymbol
PYROXD1
resolver
hgnc
HGNC:26162
resolver
uniprot
A6NKI6
resolver
uniprot
B3KWN8
resolver
uniprot
Q9H6P1
resolver
uniprot_entry
PYRD1_HUMAN
resolver
uniprot_sec
A6NKI6
resolver
uniprot_sec
B3KWN8
resolver
uniprot_sec
Q9H6P1
resolver
amino_acid_sequence
MEAARPPPTAGKFVVVGGGIAGVTCAEQLATHFPSEDILLVTASPVIKAVTNFKQISKILEEFDVEEQSSTMLGKRFPNIKVIESGVKQLKSEEHCIVTEDGNQHVYKKLCLCAGAKPKLICEGNPYVLGIRDTDSAQEFQKQLTKAKRIMIIGNGGIALELVYEIEGCEVIWAIKDKAIGNTFFDAGAAEFLTSKLIAEKSEAKIAHKRTRYTTEGRKKEARSKSKADNVGSALGPDWHEGLNLKGTKEFSHKIHLETMCEVKKIYLQDEFRILKKKSFTFPRDHKSVTADTEMWPVYVELTNEKIYGCDFIVSATGVTPNVEPFLHGNSFDLGEDGGLKVDDHMHTSLPDIYAAGDICTTSWQLSPVWQQMRLWTQARQMGWYAAKCMAAASSGDSIDMDFSFELFAHVTKFFNYKVVLLGKYNAQGLGSDHELMLRCTKGREYIKVVMQNGRMMGAVLIGETDLEETFENLILNQMNLSSYGEDLLDPNIDIEDYFD
uniprot
proteins
disease_involvement
DISEASE: Myopathy, myofibrillar, 8 (MFM8) [MIM:617258]: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM8 is an autosomal recessive form, clinically characterized by slowly progressive symmetrical weakness affecting both proximal and distal muscles, with normal to moderately elevated creatine kinase. Mild facial weakness, a high palate, nasal speech, and swallowing difficulties are typical features, mild restrictive lung disease is common, and late-onset cardiac involvement may be present. {ECO:0000269|PubMed:27745833, ECO:0000269|PubMed:33930333}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=A mutation in PYROXD1 is the cause of autosomal recessive limb-girdle muscular dystrophy. The affected individual with a homozygous recessive PYROXD1 mutation showed progressive muscle weakness with an onset at the age of 9 years. Initial symptoms included excessive falling while running, with slowly progressive weakness. Difficulty navigating stairs by the age if 18, and loss of ambulation at the age of 37 years. Neurological examination showed proximal symmetrical muscle weakness and wasting, along with calf muscle pseudohypertrophy. {ECO:0000269|PubMed:30345904}.
uniprot
proteins
ec_number
1.6.99.1
uniprot
proteins
function
FUNCTION: Flavoprotein whose role is to protect RTCB, the catalytic subunit of the tRNA ligase complex (tRNA-LC) involved in tRNA splicing and unfolded protein response, from oxidative inactivation (PubMed:33930333). It directly binds and shields the catalytic center of RTCB, prior to guanylylation, when it is inactive and its active site is vulnerable to oxidation under aerobic conditions. The interaction of PYROXD1 with RTCB is allosterically regulated by NAD(P)H binding and reduction of its FAD cofactor, while reoxidation of PYROXD1 thanks to its NADPH dehydrogenase activity triggers the timed release of RTCB, enabling its subsequent activation. Thereby, this protective mechanism may also function as a molecular timer, regulating RTCB activation through controlled release (PubMed:40069351). {ECO:0000269|PubMed:33930333, ECO:0000269|PubMed:40069351}.
uniprot
proteins
mass_dalton
55793
uniprot
proteins
mutagenesis
MUTAGEN 239; /note="W->A: Changed NADPH dehydrogenase activity and loss of interaction."; /evidence="ECO:0000269|PubMed:40069351"; MUTAGEN 376; /note="W->A: Increased NADPH dehydrogenase activity."; /evidence="ECO:0000269|PubMed:33930333"; MUTAGEN 410; /note="H->A: Loss of NADPH dehydrogenase activity."; /evidence="ECO:0000269|PubMed:33930333"; MUTAGEN 498; /note="Y->A: Decreased interaction with RTCB and decreased ability to preserve RTCB activity in oxidative conditions."; /evidence="ECO:0000269|PubMed:40069351"; MUTAGEN 499; /note="F->A: Decreased interaction with RTCB and decreased ability to preserve RTCB activity in oxidative conditions."; /evidence="ECO:0000269|PubMed:40069351"; MUTAGEN 500; /note="D->A: Decreased interaction with RTCB and decreased ability to preserve RTCB activity in oxidative conditions."; /evidence="ECO:0000269|PubMed:40069351
uniprot
proteins
protein_family
Class-I pyridine nucleotide-disulfide oxidoreductase family
uniprot
proteins
protein_family
PYROXD1 subfamily
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
27745833
uniprot
proteins
pubmed
30345904
uniprot
proteins
pubmed
33930333
uniprot
proteins
pubmed
40069351
uniprot
proteins
sequence_length
500
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27745833}. Cytoplasm, cytosol {ECO:0000269|PubMed:27745833}. Cytoplasm, myofibril, sarcomere {ECO:0000269|PubMed:27745833}.
uniprot
proteins