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Information on EC 5.1.99.6 - NAD(P)H-hydrate epimerase and Organism(s) Homo sapiens and UniProt Accession Q8NCW5

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EC Tree
     5 Isomerases
         5.1 Racemases and epimerases
             5.1.99 Acting on other compounds
                5.1.99.6 NAD(P)H-hydrate epimerase
IUBMB Comments
The enzyme can use either (R)-NADH-hydrate or (R)-NADPH-hydrate as a substrate. Its physiological role is to convert the (R) forms to the (S) forms, which could then be restored to active dinucleotides by EC 4.2.1.93, ATP-dependent NAD(P)H-hydrate dehydratase.
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This record set is specific for:
Homo sapiens
UNIPROT: Q8NCW5
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
apoa1bp, nad(p)hx epimerase, ynl200c, nad(p)h-hydrate epimerase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NAD(P)HX epimerase
-
NAD(P)HX epimerase
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(6R)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide 6-epimerase
The enzyme can use either (R)-NADH-hydrate or (R)-NADPH-hydrate as a substrate. Its physiological role is to convert the (R) forms to the (S) forms, which could then be restored to active dinucleotides by EC 4.2.1.93, ATP-dependent NAD(P)H-hydrate dehydratase.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(6R)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide
(6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide
show the reaction diagram
i.e. NADHX
-
-
r
(6R)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate
(6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate
show the reaction diagram
i.e. NADPHX
-
-
r
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(6R)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide
(6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide
show the reaction diagram
i.e. NADHX
-
-
r
(6R)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate
(6S)-6beta-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate
show the reaction diagram
i.e. NADPHX
-
-
r
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.1
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
hydration of NAD(P)H to NAD(P)HX, which inhibits several dehydrogenases, is corrected by an ATP-dependent dehydratase and an epimerase recently identified as the products of the vertebrate Carkd (carbohydrate kinase domain) and Aibp (apolipoprotein AI-binding protein) genes, respectively
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
NNRE_HUMAN
288
0
31675
Swiss-Prot
Mitochondrion (Reliability: 2)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D218V
natural mutation
Lys270del
natural mutation
Q66Stop
natural mutation
Tyr59Stop
natural mutation
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
pathogenic biallelic mutations in NAXE in children from four families lead to (sub-)acute-onset ataxia, cerebellar edema, spinal myelopathy, and skin lesions. Lactate is elevated in cerebrospinal fluid of all affected individuals. Disease onset is during the second year of life and clinical signs as well as episodes of deterioration are triggered by febrile infections. Disease course is rapidly progressive, leading to coma, global brain atrophy, and finally to death in all affected individuals. NAXE levels are undetectable in fibroblasts from affected individuals of two families. These fibroblasts show highly elevated concentrations of the toxic metabolite cyclic-NADHX
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Marbaix, A.Y.; Tyteca, D.; Niehaus, T.D.; Hanson, A.D.; Linster, C.L.; Van Schaftingen, E.
Occurrence and subcellular distribution of the NAD(P)HX repair system in mammals
Biochem. J.
460
49-58
2014
Homo sapiens (Q8NCW5), Mus musculus (Q8K4Z3), Rattus norvegicus (B0BNM1)
Manually annotated by BRENDA team
Kremer, L.S.; Danhauser, K.; Herebian, D.; Petkovic Ramadza, D.; Piekutowska-Abramczuk, D.; Seibt, A.; Mueller-Felber, W.; Haack, T.B.; Ploski, R.; Lohmeier, K.; Schneider, D.; Klee, D.; Rokicki, D.; Mayatepek, E.; Strom, T.M.; Meitinger, T.; Klopstock, T.; Pronicka, E.; Mayr, J.A.; Baric, I.; Distelmaier, F.; Prokisch, H.
NAXE mutations disrupt the cellular NAD(P)HX repair system and cause a lethal neurometabolic disorder of early childhood
Am. J. Hum. Genet.
99
894-902
2016
Homo sapiens (Q8NCW5), Homo sapiens
Manually annotated by BRENDA team