Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9NZJ9 (NUDT4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Diphosphoinositol polyphosphate phosphohydrolase 2

Short name=DIPP-2
EC=3.6.1.52
Alternative name(s):
Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 2
EC=3.6.1.-
Nucleoside diphosphate-linked moiety X motif 4
Short name=Nudix motif 4
Gene names
Name:NUDT4
Synonyms:DIPP2, KIAA0487
ORF Names:HDCMB47P
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length180 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), PP-InsP4 and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. Also able to catalyze the hydrolysis of dinucleoside oligophosphate Ap6A, but not Ap5A. The major reaction products are ADP and p4a from Ap6A. Also able to hydrolyze 5-phosphoribose 1-diphosphate. Does not play a role in U8 snoRNA decapping activity. Binds U8 snoRNA. Ref.1

Catalytic activity

Diphospho-myo-inositol polyphosphate + H2O = myo-inositol polyphosphate + phosphate. Ref.1 Ref.10

Cofactor

Binds 3 magnesium or manganese ions per subunit By similarity.

Subcellular location

Cytoplasm Ref.9.

Tissue specificity

Expressed in heart and, at lower level in skeletal muscle, pancreas and kidney. Ref.1

Sequence similarities

Belongs to the Nudix hydrolase family. DIPP subfamily.

Contains 1 nudix hydrolase domain.

Biophysicochemical properties

Kinetic parameters:

KM=4.2 nM for PP-InsP5 Ref.1

Sequence caution

The sequence AAF75563.1 differs from that shown. Reason: Erroneous termination at position 181. Translated as stop.

The sequence BAE16985.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   LigandMagnesium
Manganese
Metal-binding
RNA-binding
   Molecular functionHydrolase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcalcium-mediated signaling

Traceable author statement Ref.1. Source: UniProtKB

cyclic nucleotide metabolic process

Traceable author statement Ref.1. Source: ProtInc

cyclic-nucleotide-mediated signaling

Traceable author statement Ref.1. Source: UniProtKB

inositol phosphate metabolic process

Traceable author statement. Source: Reactome

intracellular signal transduction

Non-traceable author statement Ref.1. Source: UniProtKB

intracellular transport

Traceable author statement Ref.1. Source: UniProtKB

regulation of RNA export from nucleus

Traceable author statement Ref.1. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

intracellular

Traceable author statement Ref.1. Source: UniProtKB

   Molecular_functiondiphosphoinositol-polyphosphate diphosphatase activity

Inferred from direct assay Ref.1. Source: UniProtKB

inositol diphosphate tetrakisphosphate diphosphatase activity

Traceable author statement. Source: Reactome

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

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

snoRNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NZJ9-1)

Also known as: Alpha; DIPP2alpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9NZJ9-2)

Also known as: Beta; DIPP2beta;

The sequence of this isoform differs from the canonical sequence as follows:
     85-85: E → EQ
Isoform 3 (identifier: Q9NZJ9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: Missing.
     85-85: E → EQ

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 180180Diphosphoinositol polyphosphate phosphohydrolase 2
PRO_0000057058

Regions

Domain18 – 144127Nudix hydrolase
Region18 – 203Substrate binding By similarity
Region89 – 913Substrate binding By similarity
Motif51 – 7222Nudix box

Sites

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

Amino acid modifications

Modified residue11N-acetylmethionine Ref.12

Natural variations

Alternative sequence1 – 5252Missing in isoform 3.
VSP_014269
Alternative sequence851E → EQ in isoform 2 and isoform 3.
VSP_014270

Experimental info

Sequence conflict161G → D in AAF68857. Ref.1
Sequence conflict411R → Q in BAD97217. Ref.7
Sequence conflict731V → D in AAF75563. Ref.3
Sequence conflict1641A → V in AAF68857. Ref.1
Sequence conflict1771S → P in AAF68858. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Alpha) (DIPP2alpha) [UniParc].

Last modified July 5, 2005. Version 2.
Checksum: 86D766F8F5B22D13

FASTA18020,306
        10         20         30         40         50         60 
MMKFKPNQTR TYDREGFKKR AACLCFRSEQ EDEVLLVSSS RYPDQWIVPG GGMEPEEEPG 

        70         80         90        100        110        120 
GAAVREVYEE AGVKGKLGRL LGIFENQDRK HRTYVYVLTV TEILEDWEDS VNIGRKREWF 

       130        140        150        160        170        180 
KVEDAIKVLQ CHKPVHAEYL EKLKLGCSPA NGNSTVPSLP DNNALFVTAA QTSGLPSSVR 

« Hide

Isoform 2 (Beta) (DIPP2beta) [UniParc].

Checksum: CB3C131FAD21A4AA
Show »

FASTA18120,434
Isoform 3 [UniParc].

Checksum: 2A8C483085B2D4D3
Show »

FASTA12914,395

References

« Hide 'large scale' references
[1]"Discovery of molecular and catalytic diversity among human diphosphoinositol-polyphosphate phosphohydrolases. The expanding NUDT family."
Caffrey J.J., Safrany S.T., Yang X., Shears S.B.
J. Biol. Chem. 275:12730-12736(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
Tissue: Cerebellum.
[2]"Characterization of cDNA clones in size-fractionated cDNA libraries from human brain."
Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., Nomura N., Ohara O.
DNA Res. 4:345-349(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"Novel gene identified from dendritic cells."
Zhao Z., Huang X., Li N., Zhu X., Cao X.
Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Retina.
[5]"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] (ISOFORMS 1 AND 2).
[6]"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] (ISOFORM 3).
Tissue: Trachea.
[7]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]"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] (ISOFORMS 1 AND 2).
Tissue: Lymph and Placenta.
[9]"Cloning and characterisation of hAps1 and hAps2, human diadenosine polyphosphate-metabolising Nudix hydrolases."
Leslie N.R., McLennan A.G., Safrany S.T.
BMC Biochem. 3:20-20(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"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.
[11]"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].
[12]"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].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF191649 mRNA. Translation: AAF68855.1.
AF191650 mRNA. Translation: AAF68856.1.
AF191651 mRNA. Translation: AAF68857.1.
AF191652 mRNA. Translation: AAF68858.2.
AF191653 mRNA. Translation: AAF68859.1.
AB007956 mRNA. Translation: BAE16985.1. Different initiation.
AF067803 mRNA. Translation: AAF75563.1. Sequence problems.
CR749445 mRNA. Translation: CAH18283.1.
BT020109 mRNA. Translation: AAV38912.1.
BT020110 mRNA. Translation: AAV38913.1.
AK304296 mRNA. Translation: BAH14152.1.
AK223497 mRNA. Translation: BAD97217.1.
BC012069 mRNA. Translation: AAH12069.1.
BC051310 mRNA. Translation: AAH51310.1.
RefSeqNP_061967.3. NM_019094.4.
NP_950241.1. NM_199040.2.
XP_005268652.1. XM_005268595.2.
UniGeneHs.506325.

3D structure databases

ProteinModelPortalQ9NZJ9.
SMRQ9NZJ9. Positions 9-146.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-2819936.

PTM databases

PhosphoSiteQ9NZJ9.

Polymorphism databases

DMDM68565946.

Proteomic databases

PRIDEQ9NZJ9.

Protocols and materials databases

DNASU11163.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000337179; ENSP00000338352; ENSG00000173598. [Q9NZJ9-2]
ENST00000415493; ENSP00000406612; ENSG00000173598. [Q9NZJ9-1]
ENST00000547014; ENSP00000448032; ENSG00000173598. [Q9NZJ9-3]
ENST00000548662; ENSP00000449724; ENSG00000173598.
ENST00000549992; ENSP00000449552; ENSG00000173598.
GeneID11163.
KEGGhsa:11163.
UCSCuc001tcm.3. human. [Q9NZJ9-1]
uc010sup.2. human. [Q9NZJ9-2]
uc010suq.2. human. [Q9NZJ9-3]

Organism-specific databases

CTD11163.
GeneCardsGC12P093771.
HGNCHGNC:8051. NUDT4.
HPAHPA017593.
MIM609229. gene.
neXtProtNX_Q9NZJ9.
PharmGKBPA31835.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

HOVERGENHBG053341.
InParanoidQ9NZJ9.
KOK07766.
OMAIGMFQDD.
OrthoDBEOG7T7GVQ.
PhylomeDBQ9NZJ9.
TreeFamTF106349.

Enzyme and pathway databases

BioCycMetaCyc:HS10696-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ9NZJ9.
BgeeQ9NZJ9.
CleanExHS_NUDT4.
GenevestigatorQ9NZJ9.

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

ChiTaRSNUDT4. human.
GeneWikiNUDT4.
GenomeRNAi11163.
NextBio42469.
PROQ9NZJ9.
SOURCESearch...

Entry information

Entry nameNUDT4_HUMAN
AccessionPrimary (citable) accession number: Q9NZJ9
Secondary accession number(s): B7Z916 expand/collapse secondary AC list , Q4AEJ6, Q53EZ2, Q68DD7, Q9NPC5, Q9NS30, Q9NZK0, Q9NZK1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: April 16, 2014
This is version 121 of the entry and version 2 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

MIM cross-references

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

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM