UniProtKB - Q8IW45 (NNRD_HUMAN)
ATP-dependent (S)-NAD(P)H-hydrate dehydratase
NAXD
Functioni
Catalyzes the dehydration of the S-form of NAD(P)HX at the expense of ATP, which is converted to ADP. Together with NAD(P)HX epimerase, which catalyzes the epimerization of the S- and R-forms, the enzyme allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration.
UniRule annotation1 PublicationMiscellaneous
Catalytic activityi
Cofactori
Kineticsi
- KM=8.62 µM for (6S)-NADHX1 Publication
- Vmax=8.77 µmol/min/mg enzyme with (6S)-NADHX as substrate1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 153 | NADPHX; via amide nitrogenUniRule annotation | 1 | |
Binding sitei | 275 | NADPHXUniRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 246 – 250 | ATPUniRule annotation | 5 | |
Nucleotide bindingi | 265 – 274 | ATPUniRule annotation | 10 |
GO - Molecular functioni
- ADP-dependent NAD(P)H-hydrate dehydratase activity Source: InterPro
- ATP binding Source: UniProtKB-KW
- ATP-dependent NAD(P)H-hydrate dehydratase activity Source: UniProtKB
GO - Biological processi
- metabolite repair Source: GO_Central
- NAD biosynthesis via nicotinamide riboside salvage pathway Source: Reactome
Keywordsi
Molecular function | Lyase |
Ligand | ATP-binding, NAD, NADP, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 4.2.1.93, 2681 |
PathwayCommonsi | Q8IW45 |
Reactomei | R-HSA-197264, Nicotinamide salvaging |
SignaLinki | Q8IW45 |
Names & Taxonomyi
Protein namesi | Recommended name: ATP-dependent (S)-NAD(P)H-hydrate dehydrataseUniRule annotation (EC:4.2.1.93UniRule annotation1 Publication)Alternative name(s): ATP-dependent NAD(P)HX dehydrataseUniRule annotation Carbohydrate kinase domain-containing proteinUniRule annotation NAD(P)HX dehydrataseImported |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:25576, NAXD |
MIMi | 615910, gene |
neXtProti | NX_Q8IW45 |
VEuPathDBi | HostDB:ENSG00000213995 |
Subcellular locationi
Mitochondrion
- Mitochondrion UniRule annotation
Mitochondrion
- mitochondrial matrix Source: Reactome
Keywords - Cellular componenti
MitochondrionPathology & Biotechi
Involvement in diseasei
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 (PEBEL2)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_082224 | 81 | G → S in PEBEL2; decreased reaction kinetics for ATP-dependent NAD(P)H-hydrate dehydratase activity; decreased affinity for (6S)-NADHX; changed ATP-dependent NAD(P)H-hydrate dehydratase activity; thermostability assays show that activity is lost at temperatures above 30 degrees Celsius. 1 PublicationCorresponds to variant dbSNP:rs1566614549Ensembl. | 1 | |
Natural variantiVAR_082225 | 326 | R → C in PEBEL2; decreased reaction kinetics for ATP-dependent NAD(P)H-hydrate dehydratase activity; decreased affinity for (6S)-NADHX; changed ATP-dependent NAD(P)H-hydrate dehydratase activity; thermostability assays show that activity is lost at temperatures above 30 degrees Celsius. 1 PublicationCorresponds to variant dbSNP:rs767778853Ensembl. | 1 |
Keywords - Diseasei
Disease variant, NeurodegenerationOrganism-specific databases
DisGeNETi | 55739 |
MalaCardsi | NAXD |
MIMi | 618321, phenotype |
OpenTargetsi | ENSG00000213995 |
Orphaneti | 555402, NAD(P)HX dehydratase deficiency |
PharmGKBi | PA164717652 |
Miscellaneous databases
Pharosi | Q8IW45, Tbio |
Genetic variation databases
BioMutai | NAXD |
DMDMi | 74728128 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000337021 | 1 – 347 | ATP-dependent (S)-NAD(P)H-hydrate dehydrataseAdd BLAST | 347 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 85 | PhosphotyrosineBy similarity | 1 | |
Glycosylationi | 240 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 297 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
EPDi | Q8IW45 |
jPOSTi | Q8IW45 |
MassIVEi | Q8IW45 |
MaxQBi | Q8IW45 |
PaxDbi | Q8IW45 |
PeptideAtlasi | Q8IW45 |
PRIDEi | Q8IW45 |
ProteomicsDBi | 70807 [Q8IW45-1] 70808 [Q8IW45-2] 70809 [Q8IW45-3] 70810 [Q8IW45-4] |
PTM databases
GlyGeni | Q8IW45, 2 sites |
iPTMneti | Q8IW45 |
MetOSitei | Q8IW45 |
PhosphoSitePlusi | Q8IW45 |
Expressioni
Gene expression databases
Bgeei | ENSG00000213995, Expressed in esophagogastric junction muscularis propria and 238 other tissues |
ExpressionAtlasi | Q8IW45, baseline and differential |
Genevisiblei | Q8IW45, HS |
Organism-specific databases
HPAi | ENSG00000213995, Low tissue specificity |
Interactioni
Binary interactionsi
Q8IW45
Protein-protein interaction databases
BioGRIDi | 120857, 63 interactors |
IntActi | Q8IW45, 26 interactors |
MINTi | Q8IW45 |
STRINGi | 9606.ENSP00000311984 |
Miscellaneous databases
RNActi | Q8IW45, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 53 – 344 | YjeF C-terminalUniRule annotationAdd BLAST | 292 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 206 – 212 | NADPHXUniRule annotation | 7 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3974, Eukaryota |
GeneTreei | ENSGT00390000000917 |
HOGENOMi | CLU_030651_0_1_1 |
InParanoidi | Q8IW45 |
OMAi | ITERRYV |
PhylomeDBi | Q8IW45 |
TreeFami | TF300116 |
Family and domain databases
CDDi | cd01171, YXKO-related, 1 hit |
Gene3Di | 3.40.1190.20, 1 hit |
HAMAPi | MF_01965, NADHX_dehydratase, 1 hit |
InterProi | View protein in InterPro IPR000631, CARKD IPR029056, Ribokinase-like |
Pfami | View protein in Pfam PF01256, Carb_kinase, 1 hit |
SUPFAMi | SSF53613, SSF53613, 1 hit |
TIGRFAMsi | TIGR00196, yjeF_cterm, 1 hit |
PROSITEi | View protein in PROSITE PS51383, YJEF_C_3, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MVTRAGAGTA VAGAVVVALL SAALALYGPP LDAVLERAFS LRKAHSIKDM
60 70 80 90 100
ENTLQLVRNI IPPLSSTKHK GQDGRIGVVG GCQEYTGAPY FAAISALKVG
110 120 130 140 150
ADLSHVFCAS AAAPVIKAYS PELIVHPVLD SPNAVHEVEK WLPRLHALVV
160 170 180 190 200
GPGLGRDDAL LRNVQGILEV SKARDIPVVI DADGLWLVAQ QPALIHGYRK
210 220 230 240 250
AVLTPNHVEF SRLYDAVLRG PMDSDDSHGS VLRLSQALGN VTVVQKGERD
260 270 280 290 300
ILSNGQQVLV CSQEGSSRRC GGQGDLLSGS LGVLVHWALL AGPQKTNGSS
310 320 330 340
PLLVAAFGAC SLTRQCNHQA FQKHGRSTTT SDMIAEVGAA FSKLFET
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A7P0T906 | A0A7P0T906_HUMAN | ATP-dependent (S)-NAD(P)H-hydrate d... | NAXD CARKD | 372 | Annotation score: | ||
A0A7P0T9D8 | A0A7P0T9D8_HUMAN | ATP-dependent (S)-NAD(P)H-hydrate d... | NAXD CARKD, FLJ10769, hCG_32552 | 329 | Annotation score: | ||
A0A7P0T9R3 | A0A7P0T9R3_HUMAN | ATP-dependent (S)-NAD(P)H-hydrate d... | NAXD CARKD | 355 | Annotation score: | ||
A0A7P0TAU0 | A0A7P0TAU0_HUMAN | NAD(P)HX dehydratase | NAXD | 111 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 206 | N → D in BAA91797 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 253 | S → P in BAB14863 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_082224 | 81 | G → S in PEBEL2; decreased reaction kinetics for ATP-dependent NAD(P)H-hydrate dehydratase activity; decreased affinity for (6S)-NADHX; changed ATP-dependent NAD(P)H-hydrate dehydratase activity; thermostability assays show that activity is lost at temperatures above 30 degrees Celsius. 1 PublicationCorresponds to variant dbSNP:rs1566614549Ensembl. | 1 | |
Natural variantiVAR_043564 | 140 | K → E. Corresponds to variant dbSNP:rs3742191Ensembl. | 1 | |
Natural variantiVAR_043565 | 149 | V → I. Corresponds to variant dbSNP:rs3742192Ensembl. | 1 | |
Natural variantiVAR_043566 | 152 | P → T. Corresponds to variant dbSNP:rs1044112Ensembl. | 1 | |
Natural variantiVAR_082225 | 326 | R → C in PEBEL2; decreased reaction kinetics for ATP-dependent NAD(P)H-hydrate dehydratase activity; decreased affinity for (6S)-NADHX; changed ATP-dependent NAD(P)H-hydrate dehydratase activity; thermostability assays show that activity is lost at temperatures above 30 degrees Celsius. 1 PublicationCorresponds to variant dbSNP:rs767778853Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_033829 | 1 – 221 | Missing in isoform 3. 1 PublicationAdd BLAST | 221 | |
Alternative sequenceiVSP_042012 | 1 – 129 | MVTRA…VHPVL → MLPDGPGSSLWGNPGLQTS in isoform 4. 1 PublicationAdd BLAST | 129 | |
Alternative sequenceiVSP_033830 | 299 – 347 | SSPLL…KLFET → GISDLKLTIWGPEIETGVKT RAQGSCGPRTTTPTSPHLLL SPSPQVQPSPGGRVWRLLSH QAVQPPSLPEARSLHHHLRH DRRGGGRLQQAL in isoform 2. 1 PublicationAdd BLAST | 49 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK001631 mRNA Translation: BAA91797.1 AK024260 mRNA Translation: BAB14863.1 AK302117 mRNA Translation: BAG63496.1 AL139385 Genomic DNA No translation available. CH471085 Genomic DNA Translation: EAX09121.1 CH471085 Genomic DNA Translation: EAX09125.1 BC041028 mRNA Translation: AAH41028.1 |
CCDSi | CCDS55903.1 [Q8IW45-4] CCDS9513.1 [Q8IW45-2] |
RefSeqi | NP_001229810.1, NM_001242881.1 [Q8IW45-1] NP_001229811.1, NM_001242882.1 NP_001229812.1, NM_001242883.1 [Q8IW45-4] NP_060680.2, NM_018210.3 [Q8IW45-2] |
Genome annotation databases
Ensembli | ENST00000309957; ENSP00000311984; ENSG00000213995 [Q8IW45-2] ENST00000424185; ENSP00000413191; ENSG00000213995 [Q8IW45-4] ENST00000680505; ENSP00000504986; ENSG00000213995 |
GeneIDi | 55739 |
KEGGi | hsa:55739 |
UCSCi | uc001vrc.4, human [Q8IW45-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK001631 mRNA Translation: BAA91797.1 AK024260 mRNA Translation: BAB14863.1 AK302117 mRNA Translation: BAG63496.1 AL139385 Genomic DNA No translation available. CH471085 Genomic DNA Translation: EAX09121.1 CH471085 Genomic DNA Translation: EAX09125.1 BC041028 mRNA Translation: AAH41028.1 |
CCDSi | CCDS55903.1 [Q8IW45-4] CCDS9513.1 [Q8IW45-2] |
RefSeqi | NP_001229810.1, NM_001242881.1 [Q8IW45-1] NP_001229811.1, NM_001242882.1 NP_001229812.1, NM_001242883.1 [Q8IW45-4] NP_060680.2, NM_018210.3 [Q8IW45-2] |
3D structure databases
SMRi | Q8IW45 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 120857, 63 interactors |
IntActi | Q8IW45, 26 interactors |
MINTi | Q8IW45 |
STRINGi | 9606.ENSP00000311984 |
PTM databases
GlyGeni | Q8IW45, 2 sites |
iPTMneti | Q8IW45 |
MetOSitei | Q8IW45 |
PhosphoSitePlusi | Q8IW45 |
Genetic variation databases
BioMutai | NAXD |
DMDMi | 74728128 |
Proteomic databases
EPDi | Q8IW45 |
jPOSTi | Q8IW45 |
MassIVEi | Q8IW45 |
MaxQBi | Q8IW45 |
PaxDbi | Q8IW45 |
PeptideAtlasi | Q8IW45 |
PRIDEi | Q8IW45 |
ProteomicsDBi | 70807 [Q8IW45-1] 70808 [Q8IW45-2] 70809 [Q8IW45-3] 70810 [Q8IW45-4] |
Protocols and materials databases
Antibodypediai | 2137, 63 antibodies from 16 providers |
DNASUi | 55739 |
Genome annotation databases
Ensembli | ENST00000309957; ENSP00000311984; ENSG00000213995 [Q8IW45-2] ENST00000424185; ENSP00000413191; ENSG00000213995 [Q8IW45-4] ENST00000680505; ENSP00000504986; ENSG00000213995 |
GeneIDi | 55739 |
KEGGi | hsa:55739 |
UCSCi | uc001vrc.4, human [Q8IW45-1] |
Organism-specific databases
CTDi | 55739 |
DisGeNETi | 55739 |
GeneCardsi | NAXD |
HGNCi | HGNC:25576, NAXD |
HPAi | ENSG00000213995, Low tissue specificity |
MalaCardsi | NAXD |
MIMi | 615910, gene 618321, phenotype |
neXtProti | NX_Q8IW45 |
OpenTargetsi | ENSG00000213995 |
Orphaneti | 555402, NAD(P)HX dehydratase deficiency |
PharmGKBi | PA164717652 |
VEuPathDBi | HostDB:ENSG00000213995 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3974, Eukaryota |
GeneTreei | ENSGT00390000000917 |
HOGENOMi | CLU_030651_0_1_1 |
InParanoidi | Q8IW45 |
OMAi | ITERRYV |
PhylomeDBi | Q8IW45 |
TreeFami | TF300116 |
Enzyme and pathway databases
BRENDAi | 4.2.1.93, 2681 |
PathwayCommonsi | Q8IW45 |
Reactomei | R-HSA-197264, Nicotinamide salvaging |
SignaLinki | Q8IW45 |
Miscellaneous databases
BioGRID-ORCSi | 55739, 4 hits in 1043 CRISPR screens |
ChiTaRSi | NAXD, human |
GeneWikii | CARKD |
GenomeRNAii | 55739 |
Pharosi | Q8IW45, Tbio |
PROi | PR:Q8IW45 |
RNActi | Q8IW45, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000213995, Expressed in esophagogastric junction muscularis propria and 238 other tissues |
ExpressionAtlasi | Q8IW45, baseline and differential |
Genevisiblei | Q8IW45, HS |
Family and domain databases
CDDi | cd01171, YXKO-related, 1 hit |
Gene3Di | 3.40.1190.20, 1 hit |
HAMAPi | MF_01965, NADHX_dehydratase, 1 hit |
InterProi | View protein in InterPro IPR000631, CARKD IPR029056, Ribokinase-like |
Pfami | View protein in Pfam PF01256, Carb_kinase, 1 hit |
SUPFAMi | SSF53613, SSF53613, 1 hit |
TIGRFAMsi | TIGR00196, yjeF_cterm, 1 hit |
PROSITEi | View protein in PROSITE PS51383, YJEF_C_3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NNRD_HUMAN | |
Accessioni | Q8IW45Primary (citable) accession number: Q8IW45 Secondary accession number(s): B4DXT4 Q9NVF5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 20, 2008 |
Last sequence update: | March 1, 2003 | |
Last modified: | February 23, 2022 | |
This is version 144 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 13
Human chromosome 13: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families