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O95989 (NUDT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Diphosphoinositol polyphosphate phosphohydrolase 1

Short name=DIPP-1
EC=3.6.1.52
Alternative name(s):
Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 1
EC=3.6.1.-
Nucleoside diphosphate-linked moiety X motif 3
Short name=Nudix motif 3
Gene names
Name:NUDT3
Synonyms:DIPP, DIPP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length172 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. InsP6 (inositol hexakisphophate) is not a substrate. Acts as a negative regulator of the ERK1/2 pathway. Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with Ap6A and Ap5A being the preferred substrates. The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A. Also able to hydrolyze 5-phosphoribose 1-diphosphate. Ref.1

Catalytic activity

Diphospho-myo-inositol polyphosphate + H2O = myo-inositol polyphosphate + phosphate. Ref.1 Ref.7 Ref.9

Cofactor

Binds 3 magnesium ions per subunit. Ref.12

Enzyme regulation

Inhibited by fluoride and InsP6. Ref.12

Subunit structure

Monomer By similarity.

Subcellular location

Cytoplasm Probable.

Tissue specificity

Widely expressed. Expressed at higher level in brain, heart, pancreas and liver. Also expressed in placenta, lung and kidney. Ref.1

Sequence similarities

Belongs to the Nudix hydrolase family. DIPP subfamily.

Contains 1 nudix hydrolase domain.

Biophysicochemical properties

Kinetic parameters:

KM=5.9 µM for Ap6A Ref.1 Ref.7 Ref.9

KM=7.7 µM for Ap5A

KM=38 mM for 5-phosphoribose 1-diphosphate

KM=4.2 nM for PP-InsP5

pH dependence:

Optimum pH is 7-7.5.

Ontologies

Keywords
   Cellular componentCytoplasm
   LigandMagnesium
Metal-binding
   Molecular functionHydrolase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell-cell signaling

Traceable author statement Ref.7. Source: ProtInc

diadenosine polyphosphate catabolic process

Traceable author statement Ref.7. Source: ProtInc

diphosphoinositol polyphosphate catabolic process

Inferred from direct assay Ref.8. Source: UniProtKB

inositol phosphate metabolic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_functiondiphosphoinositol-polyphosphate diphosphatase activity

Inferred from direct assay Ref.8. Source: UniProtKB

inositol diphosphate tetrakisphosphate diphosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 1-diphosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

inositol-1-diphosphate-2,3,4,5,6-pentakisphosphate diphosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

inositol-3,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

inositol-3-diphosphate-1,2,4,5,6-pentakisphosphate diphosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

inositol-5-diphosphate-1,2,3,4,6-pentakisphosphate diphosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

magnesium ion binding

Inferred from direct assay Ref.12. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 172172Diphosphoinositol polyphosphate phosphohydrolase 1
PRO_0000057055

Regions

Domain17 – 142126Nudix hydrolase
Region18 – 203Substrate binding
Region89 – 913Substrate binding
Motif51 – 7222Nudix box

Sites

Active site691Proton acceptor Probable
Metal binding501Magnesium 1; via carbonyl oxygen
Metal binding661Magnesium 2
Metal binding661Magnesium 3
Metal binding701Magnesium 1
Binding site101Substrate
Binding site411Substrate

Amino acid modifications

Modified residue11N-acetylmethionine Ref.11

Experimental info

Mutagenesis501G → A or V: Loss of function. Ref.8
Mutagenesis511G → A: Loss of function. Ref.8
Mutagenesis521G → A or V: Loss of function. Ref.8
Mutagenesis661E → Q: Loss of function. Ref.8
Mutagenesis701E → Q: Loss of function. Ref.1
Mutagenesis721G → A: Loss of function. Ref.8
Mutagenesis751G → A: Loss of function. Ref.8
Mutagenesis781G → A: No effect. Ref.8
Mutagenesis781G → V: Loss of function. Ref.8
Mutagenesis821G → A: Loss of function. Ref.8
Mutagenesis841F → Y: Induces a strong decrease in Ap6A and [PP]-InsP4 hydrolysis, while it only weakly affects PP-InsP5 hydrolysis. Ref.8
Mutagenesis911H → L: Induces a strong decrease in Ap6A and [PP]-InsP4 hydrolysis, while it only weakly affects PP-InsP5 hydrolysis. Ref.8

Secondary structure

....................... 172
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O95989 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: DE823FECF5C6438A

FASTA17219,471
        10         20         30         40         50         60 
MMKLKSNQTR TYDGDGYKKR AACLCFRSES EEEVLLVSSS RHPDRWIVPG GGMEPEEEPS 

        70         80         90        100        110        120 
VAAVREVCEE AGVKGTLGRL VGIFENQERK HRTYVYVLIV TEVLEDWEDS VNIGRKREWF 

       130        140        150        160        170 
KIEDAIKVLQ YHKPVQASYF ETLRQGYSAN NGTPVVATTY SVSAQSSMSG IR 

« Hide

References

« Hide 'large scale' references
[1]"A novel context for the 'MutT' module, a guardian of cell integrity, in a diphosphoinositol polyphosphate phosphohydrolase."
Safrany S.T., Caffrey J.J., Yang X., Bembenek M.E., Moyer M.B., Burkhart W.A., Shears S.B.
EMBO J. 17:6599-6607(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, MUTAGENESIS OF GLU-70.
Tissue: Uterus.
[2]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Amygdala.
[4]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Uterus.
[7]"The diadenosine hexaphosphate hydrolases from Schizosaccharomyces pombe and Saccharomyces cerevisiae are homologues of the human diphosphoinositol polyphosphate phosphohydrolase. Overlapping substrate specificities in a MutT-type protein."
Safrany S.T., Ingram S.W., Cartwright J.L., Falck J.R., McLennan A.G., Barnes L.D., Shears S.B.
J. Biol. Chem. 274:21735-21740(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[8]"Site-directed mutagenesis of diphosphoinositol polyphosphate phosphohydrolase, a dual specificity NUDT enzyme that attacks diadenosine polyphosphates and diphosphoinositol polyphosphates."
Yang X., Safrany S.T., Shears S.B.
J. Biol. Chem. 274:35434-35440(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLY-50; GLY-51; GLY-52; GLU-66; GLY-72; GLY-75; GLY-78; GLY-82; PHE-84 AND HIS-91.
[9]"Nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate."
Fisher D.I., Safrany S.T., Strike P., McLennan A.G., Cartwright J.L.
J. Biol. Chem. 277:47313-47317(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Crystal structure of human diphosphoinositol phosphatase 1."
Thorsell A.G., Persson C., Graslund S., Hammarstrom M., Busam R.D., Hallberg B.M.
Proteins 77:242-246(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS; FLUORIDE AND INOSITOL HEXAKISPHOSPHATE, COFACTOR, ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF062529 mRNA. Translation: AAC83224.1.
AF062530 mRNA. Translation: AAC83225.1.
BT019984 mRNA. Translation: AAV38787.1.
BT019985 mRNA. Translation: AAV38788.1.
AK313440 mRNA. Translation: BAG36231.1.
Z98036, AL355855 Genomic DNA. Translation: CAI19715.1.
AL355855, Z98036 Genomic DNA. Translation: CAH72222.1.
CH471081 Genomic DNA. Translation: EAX03781.1.
BC007727 mRNA. Translation: AAH07727.1.
CCDSCCDS4791.1.
RefSeqNP_006694.1. NM_006703.3.
UniGeneHs.188882.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2FVVX-ray1.25A1-172[»]
2Q9PX-ray1.65A1-172[»]
ProteinModelPortalO95989.
SMRO95989. Positions 8-142.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116336. 39 interactions.
IntActO95989. 38 interactions.
MINTMINT-1412881.
STRING9606.ENSP00000351650.

PTM databases

PhosphoSiteO95989.

Proteomic databases

MaxQBO95989.
PaxDbO95989.
PeptideAtlasO95989.
PRIDEO95989.

Protocols and materials databases

DNASU11165.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000607016; ENSP00000476119; ENSG00000272325.
GeneID11165.
KEGGhsa:11165.
UCSCuc003ojl.3. human.

Organism-specific databases

CTD11165.
GeneCardsGC06M035232.
HGNCHGNC:8050. NUDT3.
HPAHPA047027.
HPA055953.
MIM609228. gene.
neXtProtNX_O95989.
PharmGKBPA31834.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG250169.
HOGENOMHOG000237336.
HOVERGENHBG053341.
InParanoidO95989.
KOK07766.
OMAFLHIRIT.
OrthoDBEOG7T7GVQ.
PhylomeDBO95989.
TreeFamTF106349.

Enzyme and pathway databases

BioCycMetaCyc:HS03602-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKO95989.

Gene expression databases

BgeeO95989.
CleanExHS_NUDT3.
GenevestigatorO95989.

Family and domain databases

Gene3D3.90.79.10. 1 hit.
InterProIPR020084. NUDIX_hydrolase_CS.
IPR000086. NUDIX_hydrolase_dom.
IPR015797. NUDIX_hydrolase_dom-like.
[Graphical view]
PfamPF00293. NUDIX. 1 hit.
[Graphical view]
SUPFAMSSF55811. SSF55811. 1 hit.
PROSITEPS51462. NUDIX. 1 hit.
PS00893. NUDIX_BOX. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNUDT3. human.
EvolutionaryTraceO95989.
GeneWikiNUDT3.
GenomeRNAi11165.
NextBio42479.
PROO95989.
SOURCESearch...

Entry information

Entry nameNUDT3_HUMAN
AccessionPrimary (citable) accession number: O95989
Secondary accession number(s): B2R8N4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: May 1, 1999
Last modified: July 9, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM