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Protein

ADP-sugar pyrophosphatase

Gene

NUDT5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Enzyme that can either act as an ADP-sugar pyrophosphatase in absence of diphosphate or catalyze the synthesis of ATP in presence of diphosphate (PubMed:27257257). In absence of diphosphate, hydrolyzes with similar activities various modified nucleoside diphosphates such as ADP-ribose, ADP-mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP (PubMed:10567213, PubMed:10722730, PubMed:19699693, PubMed:21389046, PubMed:17052728). Can also hydrolyze other nucleotide sugars with low activity (PubMed:19699693, PubMed:21389046). In presence of diphosphate, mediates the synthesis of ATP in the nucleus by catalyzing the conversion of ADP-ribose to ATP and ribose 5-phosphate. Nuclear ATP synthesis takes place when dephosphorylated at Thr-45 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). Does not play a role in U8 snoRNA decapping activity (By similarity). Binds U8 snoRNA (By similarity).By similarity6 Publications

Catalytic activityi

ATP + D-ribose 5-phosphate = diphosphate + ADP-D-ribose.1 Publication
ADP-D-ribose + H2O = AMP + D-ribose 5-phosphate.2 Publications
8-oxo-dGDP + H2O = 8-oxo-dGMP + phosphate.3 Publications

Cofactori

Mg2+3 PublicationsNote: Binds 3 Mg2+ ions per subunit.3 Publications

Kineticsi

kcat is 0.369 min(-1) for 8-OH-dGDP. kcat is 0.538 min(-1) for 8-OH-dADP. kcat is 0.226 min(-1) for 2-OH-dADP. kcat is 0.209 min(-1) for 5-CHO-dUDP. kcat is 0.929 min(-1) for dGDP. kcat is 0.365 min(-1) for dADP.1 Publication
  1. KM=2.1 µM for 8-oxo-dGDP1 Publication
  2. KM=2.9 µM for 8-oxo-dADP1 Publication
  3. KM=8.8 µM for 2-oxo-dADP1 Publication
  4. KM=4.0 µM for 5-CHO-dUDP1 Publication
  5. KM=7.6 µM for dGDP1 Publication
  6. KM=12.6 µM for dADP1 Publication
  7. KM=3.8 µM for 8-oxo-dGDP (at pH 8.0)1 Publication
  8. KM=3.5 µM for 8-oxo-dGDP (at pH 10.0)1 Publication
  9. KM=1.9 µM for ADP-D-ribose (at pH 8.0)1 Publication
  10. KM=36 µM for 8-oxo-dGTP (at pH 10.0)1 Publication
  11. KM=42.6 µM for ADP-D-ribose (in the presence of diphosphate)1 Publication
  1. Vmax=11 pmol/min/µg enzyme with 8-oxo-dGDP as substrate (at pH 8.0)1 Publication
  2. Vmax=2400 pmol/min/µg enzyme with ADP-D-ribose as substrate (at pH 8.0)1 Publication
  3. Vmax=46 pmol/min/µg enzyme with 8-oxo-dGDP as substrate (at pH 10.0)1 Publication
  4. Vmax=1.7 pmol/min/µg enzyme with 8-oxo-dGTP as substrate (at pH 10.0)1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei28Substrate3 Publications1
Binding sitei51Substrate; shared with dimeric partner3 Publications1
Binding sitei84Substrate3 Publications1
Metal bindingi96Magnesium 1; via carbonyl oxygen3 Publications1
Binding sitei98Substrate; via amide nitrogen1 Publication1
Metal bindingi112Magnesium 23 Publications1
Metal bindingi112Magnesium 33 Publications1
Metal bindingi116Magnesium 13 Publications1
Metal bindingi116Magnesium 33 Publications1
Binding sitei133Substrate1 Publication1
Metal bindingi166Magnesium 33 Publications1

GO - Molecular functioni

  • 8-oxo-dGDP phosphatase activity Source: UniProtKB
  • ADP-ribose diphosphatase activity Source: UniProtKB
  • ADP-sugar diphosphatase activity Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • nucleotidyltransferase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • snoRNA binding Source: UniProtKB

GO - Biological processi

  • ATP generation from poly-ADP-D-ribose Source: UniProtKB
  • chromatin remodeling Source: UniProtKB
  • D-ribose catabolic process Source: UniProtKB
  • nucleobase-containing small molecule catabolic process Source: Reactome
  • nucleotide metabolic process Source: ProtInc
  • ribonucleoside diphosphate catabolic process Source: UniProtKB

Keywordsi

Molecular functionHydrolase, RNA-binding, Transferase
LigandMagnesium, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS09255-MONOMER
BRENDAi3.6.1.13 2681
3.6.1.58 2681
ReactomeiR-HSA-2393930 Phosphate bond hydrolysis by NUDT proteins
SABIO-RKiQ9UKK9

Names & Taxonomyi

Protein namesi
Recommended name:
ADP-sugar pyrophosphatase (EC:3.6.1.132 Publications)
Alternative name(s):
8-oxo-dGDP phosphatase (EC:3.6.1.583 Publications)
Nuclear ATP-synthesis protein NUDIX51 Publication (EC:2.7.7.961 Publication)
Nucleoside diphosphate-linked moiety X motif 5Curated
Short name:
Nudix motif 5Curated
Short name:
hNUDT51 Publication
YSA1H1 Publication
Gene namesi
Name:NUDT5
Synonyms:NUDIX51 Publication
ORF Names:HSPC1151 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000165609.12
HGNCiHGNC:8052 NUDT5
MIMi609230 gene
neXtProtiNX_Q9UKK9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi28W → A: Reduces affinity for substrate about 8-fold. Strongly reduced catalytic activity and strongly reduced affinity for substrate; when associated with A-46. 1 Publication1
Mutagenesisi45T → A: Impaired phosphorylation; generates ATP in the presence of diphosphate. 1 Publication1
Mutagenesisi45T → D: Phosphomimetic mutant; unable to generate ATP in the presence of diphosphate. 1 Publication1
Mutagenesisi46W → A: Reduces affinity for substrate about 6-fold. Strongly reduced catalytic activity and strongly reduced affinity for substrate; when associated with A-28. 1 Publication1
Mutagenesisi51R → Q: Reduces affinity for substrate about 15-fold and reduces catalytic rate about 17-fold. 1 Publication1
Mutagenesisi84R → Q: Reduces affinity for substrate about 5-fold and reduces catalytic rate 67-fold. 1 Publication1
Mutagenesisi98L → A: Reduces affinity for substrate about 6-fold. 1 Publication1
Mutagenesisi112E → Q: Catalytic inactive mutant for both ADP-sugar pyrophosphatase and nuclear ATP-synthesis activities. Reduces catalytic rate 6300-fold. 2 Publications1
Mutagenesisi116E → Q: Reduces catalytic rate 2000-fold. 1 Publication1
Mutagenesisi166E → Q: Reduces catalytic rate 120-fold. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000165609
PharmGKBiPA31838

Polymorphism and mutation databases

BioMutaiNUDT5

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000570481 – 219ADP-sugar pyrophosphataseAdd BLAST219

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei3PhosphoserineCombined sources1
Modified residuei10PhosphoserineCombined sources1
Cross-linki42Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei45Phosphothreonine1 Publication1
Modified residuei74PhosphotyrosineCombined sources1
Modified residuei210N6-acetyllysineCombined sources1
Modified residuei218N6-acetyllysineCombined sources1

Post-translational modificationi

Phosphorylation at Thr-45 is required for homodimer stability; dephosphorylation results in destabilization of the homodimer. Dephosphorylation at Thr-45 promotes the ATP-synthesis activity.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UKK9
MaxQBiQ9UKK9
PaxDbiQ9UKK9
PeptideAtlasiQ9UKK9
PRIDEiQ9UKK9
ProteomicsDBi84813

PTM databases

iPTMnetiQ9UKK9
PhosphoSitePlusiQ9UKK9

Expressioni

Tissue specificityi

Widely expressed. Most abundant in liver.1 Publication

Inductioni

Overexpressed in cancer patients with a poor outcome.1 Publication

Gene expression databases

BgeeiENSG00000165609
CleanExiHS_NUDT5
ExpressionAtlasiQ9UKK9 baseline and differential
GenevisibleiQ9UKK9 HS

Organism-specific databases

HPAiHPA019827

Interactioni

Subunit structurei

Homodimer (PubMed:27257257, PubMed:17052728, PubMed:18462755, PubMed:21768126). Interacts with PARG (PubMed:27257257).4 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi116335, 27 interactors
IntActiQ9UKK9, 23 interactors
MINTiQ9UKK9
STRINGi9606.ENSP00000419628

Structurei

Secondary structure

1219
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi16 – 25Combined sources10
Beta strandi27 – 37Combined sources11
Beta strandi43 – 51Combined sources9
Beta strandi60 – 69Combined sources10
Beta strandi76 – 84Combined sources9
Helixi85 – 87Combined sources3
Beta strandi89 – 93Combined sources5
Beta strandi96 – 98Combined sources3
Helixi105 – 117Combined sources13
Beta strandi122 – 126Combined sources5
Beta strandi130 – 132Combined sources3
Turni134 – 136Combined sources3
Beta strandi140 – 149Combined sources10
Helixi153 – 155Combined sources3
Beta strandi164 – 166Combined sources3
Beta strandi169 – 174Combined sources6
Helixi175 – 177Combined sources3
Helixi178 – 189Combined sources12
Beta strandi192 – 194Combined sources3
Helixi195 – 207Combined sources13
Turni211 – 213Combined sources3
Helixi214 – 216Combined sources3

3D structure databases

ProteinModelPortaliQ9UKK9
SMRiQ9UKK9
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UKK9

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini57 – 197Nudix hydrolasePROSITE-ProRule annotationAdd BLAST141

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni46 – 47Substrate binding; shared with dimeric partner3 Publications2

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi97 – 118Nudix boxAdd BLAST22

Sequence similaritiesi

Belongs to the Nudix hydrolase family.Curated

Phylogenomic databases

eggNOGiKOG3041 Eukaryota
COG0494 LUCA
GeneTreeiENSGT00390000006280
HOGENOMiHOG000174302
HOVERGENiHBG052691
InParanoidiQ9UKK9
KOiK13987
PhylomeDBiQ9UKK9
TreeFamiTF106347

Family and domain databases

InterProiView protein in InterPro
IPR020476 Nudix_hydrolase
IPR015797 NUDIX_hydrolase-like_dom_sf
IPR020084 NUDIX_hydrolase_CS
IPR000086 NUDIX_hydrolase_dom
PfamiView protein in Pfam
PF00293 NUDIX, 1 hit
PRINTSiPR00502 NUDIXFAMILY
SUPFAMiSSF55811 SSF55811, 1 hit
PROSITEiView protein in PROSITE
PS51462 NUDIX, 1 hit
PS00893 NUDIX_BOX, 1 hit

Sequencei

Sequence statusi: Complete.

Q9UKK9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MESQEPTESS QNGKQYIISE ELISEGKWVK LEKTTYMDPT GKTRTWESVK
60 70 80 90 100
RTTRKEQTAD GVAVIPVLQR TLHYECIVLV KQFRPPMGGY CIEFPAGLID
110 120 130 140 150
DGETPEAAAL RELEEETGYK GDIAECSPAV CMDPGLSNCT IHIVTVTING
160 170 180 190 200
DDAENARPKP KPGDGEFVEV ISLPKNDLLQ RLDALVAEEH LTVDARVYSY
210
ALALKHANAK PFEVPFLKF
Length:219
Mass (Da):24,328
Last modified:May 1, 2000 - v1
Checksum:i6574E0BF1EA2BB26
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti50 – 52KRT → NVP in AAF25479 (PubMed:10722730).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034159123I → T. Corresponds to variant dbSNP:rs34863826Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF155832 mRNA Translation: AAF06734.1
AF218818 mRNA Translation: AAF25479.1
AF161464 mRNA Translation: AAF29079.1
CR457195 mRNA Translation: CAG33476.1
AK291131 mRNA Translation: BAF83820.1
CH471072 Genomic DNA Translation: EAW86322.1
BC000025 mRNA Translation: AAH00025.1
CCDSiCCDS7089.1
RefSeqiNP_054861.2, NM_014142.3
UniGeneiHs.555956
Hs.656304

Genome annotation databases

EnsembliENST00000491614; ENSP00000419628; ENSG00000165609
ENST00000537776; ENSP00000445116; ENSG00000165609
GeneIDi11164
KEGGihsa:11164
UCSCiuc001ilj.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNUDT5_HUMAN
AccessioniPrimary (citable) accession number: Q9UKK9
Secondary accession number(s): A8K516, Q6IAG0, Q9UH49
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: May 1, 2000
Last modified: July 18, 2018
This is version 165 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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