Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

ADP-sugar pyrophosphatase

Gene

NUDT5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Manual assertion based on experiment ini

  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
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Transferase

Keywords - Ligandi

Magnesium, Metal-binding, RNA-binding

Enzyme and pathway databases

BioCyciZFISH:HS09255-MONOMER.
BRENDAi3.6.1.13. 2681.
3.6.1.58. 2681.
ReactomeiR-HSA-2393930. Phosphate bond hydrolysis by NUDT proteins.
SABIO-RKQ9UKK9.

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.-1 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

HGNCiHGNC:8052. NUDT5.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • intracellular Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

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
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, Phosphoprotein

Proteomic databases

EPDiQ9UKK9.
MaxQBiQ9UKK9.
PaxDbiQ9UKK9.
PeptideAtlasiQ9UKK9.
PRIDEiQ9UKK9.

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. 18 interactors.
IntActiQ9UKK9. 10 interactors.
MINTiMINT-1370495.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DSBX-ray2.50A/B/C/D1-219[»]
2DSCX-ray2.00A/B1-210[»]
2DSDX-ray2.60A/B1-210[»]
3AC9X-ray2.10A/B14-208[»]
3ACAX-ray2.05A/B13-208[»]
3BM4X-ray2.00A/B1-210[»]
3L85X-ray2.30A/B14-208[»]
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
Contains 1 nudix hydrolase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3041. Eukaryota.
COG0494. LUCA.
GeneTreeiENSGT00390000006280.
HOGENOMiHOG000174302.
HOVERGENiHBG052691.
InParanoidiQ9UKK9.
KOiK13987.
PhylomeDBiQ9UKK9.
TreeFamiTF106347.

Family and domain databases

Gene3Di3.90.79.10. 1 hit.
InterProiIPR020476. Nudix_hydrolase.
IPR020084. NUDIX_hydrolase_CS.
IPR000086. NUDIX_hydrolase_dom.
IPR015797. NUDIX_hydrolase_dom-like.
[Graphical view]
PfamiPF00293. NUDIX. 1 hit.
[Graphical view]
PRINTSiPR00502. NUDIXFAMILY.
SUPFAMiSSF55811. SSF55811. 1 hit.
PROSITEiPS51462. NUDIX. 1 hit.
PS00893. NUDIX_BOX. 1 hit.
[Graphical view]

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 rs34863826dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DSBX-ray2.50A/B/C/D1-219[»]
2DSCX-ray2.00A/B1-210[»]
2DSDX-ray2.60A/B1-210[»]
3AC9X-ray2.10A/B14-208[»]
3ACAX-ray2.05A/B13-208[»]
3BM4X-ray2.00A/B1-210[»]
3L85X-ray2.30A/B14-208[»]
ProteinModelPortaliQ9UKK9.
SMRiQ9UKK9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116335. 18 interactors.
IntActiQ9UKK9. 10 interactors.
MINTiMINT-1370495.
STRINGi9606.ENSP00000419628.

PTM databases

iPTMnetiQ9UKK9.
PhosphoSitePlusiQ9UKK9.

Polymorphism and mutation databases

BioMutaiNUDT5.

Proteomic databases

EPDiQ9UKK9.
MaxQBiQ9UKK9.
PaxDbiQ9UKK9.
PeptideAtlasiQ9UKK9.
PRIDEiQ9UKK9.

Protocols and materials databases

DNASUi11164.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi11164.
GeneCardsiNUDT5.
HGNCiHGNC:8052. NUDT5.
HPAiHPA019827.
MIMi609230. gene.
neXtProtiNX_Q9UKK9.
OpenTargetsiENSG00000165609.
PharmGKBiPA31838.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3041. Eukaryota.
COG0494. LUCA.
GeneTreeiENSGT00390000006280.
HOGENOMiHOG000174302.
HOVERGENiHBG052691.
InParanoidiQ9UKK9.
KOiK13987.
PhylomeDBiQ9UKK9.
TreeFamiTF106347.

Enzyme and pathway databases

BioCyciZFISH:HS09255-MONOMER.
BRENDAi3.6.1.13. 2681.
3.6.1.58. 2681.
ReactomeiR-HSA-2393930. Phosphate bond hydrolysis by NUDT proteins.
SABIO-RKQ9UKK9.

Miscellaneous databases

ChiTaRSiNUDT5. human.
EvolutionaryTraceiQ9UKK9.
GeneWikiiNUDT5.
GenomeRNAii11164.
PROiQ9UKK9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165609.
CleanExiHS_NUDT5.
ExpressionAtlasiQ9UKK9. baseline and differential.
GenevisibleiQ9UKK9. HS.

Family and domain databases

Gene3Di3.90.79.10. 1 hit.
InterProiIPR020476. Nudix_hydrolase.
IPR020084. NUDIX_hydrolase_CS.
IPR000086. NUDIX_hydrolase_dom.
IPR015797. NUDIX_hydrolase_dom-like.
[Graphical view]
PfamiPF00293. NUDIX. 1 hit.
[Graphical view]
PRINTSiPR00502. NUDIXFAMILY.
SUPFAMiSSF55811. SSF55811. 1 hit.
PROSITEiPS51462. NUDIX. 1 hit.
PS00893. NUDIX_BOX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNUDT5_HUMAN
AccessioniPrimary (citable) accession number: Q9UKK9
Secondary accession number(s): A8K516, Q6IAG0, Q9UH49
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 152 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.