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Protein

Diphosphoinositol polyphosphate phosphohydrolase 2

Gene

NUDT4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

Diphospho-myo-inositol polyphosphate + H2O = myo-inositol polyphosphate + phosphate.2 Publications

Cofactori

Mg2+By similarity, Mn2+By similarityNote: Binds 3 Mg2+ or Mn2+ ions per subunit.By similarity

Kineticsi

  1. KM=4.2 nM for PP-InsP51 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei10SubstrateBy similarity1
    Binding sitei41SubstrateBy similarity1
    Metal bindingi50Magnesium 1; via carbonyl oxygenBy similarity1
    Metal bindingi66Magnesium 2By similarity1
    Metal bindingi66Magnesium 3By similarity1
    Active sitei69Proton acceptorBy similarity1
    Metal bindingi70Magnesium 1By similarity1

    GO - Molecular functioni

    GO - Biological processi

    • adenosine 5'-(hexahydrogen pentaphosphate) catabolic process Source: GO_Central
    • calcium-mediated signaling Source: UniProtKB
    • cyclic-nucleotide-mediated signaling Source: UniProtKB
    • cyclic nucleotide metabolic process Source: ProtInc
    • diadenosine hexaphosphate catabolic process Source: GO_Central
    • diadenosine pentaphosphate catabolic process Source: GO_Central
    • diphosphoinositol polyphosphate metabolic process Source: GO_Central
    • inositol phosphate metabolic process Source: Reactome
    • intracellular signal transduction Source: UniProtKB
    • intracellular transport Source: UniProtKB
    • regulation of RNA export from nucleus Source: UniProtKB

    Keywordsi

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

    Enzyme and pathway databases

    BioCyciMetaCyc:HS10696-MONOMER.
    ReactomeiR-HSA-1855167. Synthesis of pyrophosphates in the cytosol.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Diphosphoinositol polyphosphate phosphohydrolase 2 (EC:3.6.1.52)
    Short name:
    DIPP-2
    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 namesi
    Name:NUDT4
    Synonyms:DIPP2, KIAA0487
    ORF Names:HDCMB47P
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 12

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000173598.13.
    HGNCiHGNC:8051. NUDT4.

    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

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    OpenTargetsiENSG00000173598.
    PharmGKBiPA31835.

    Polymorphism and mutation databases

    BioMutaiNUDT4.
    DMDMi68565946.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000570581 – 180Diphosphoinositol polyphosphate phosphohydrolase 2Add BLAST180

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiQ9NZJ9.
    MaxQBiQ9NZJ9.
    PaxDbiQ9NZJ9.
    PeptideAtlasiQ9NZJ9.
    PRIDEiQ9NZJ9.
    TopDownProteomicsiQ9NZJ9-2. [Q9NZJ9-2]

    PTM databases

    iPTMnetiQ9NZJ9.
    PhosphoSitePlusiQ9NZJ9.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    BgeeiENSG00000173598.
    CleanExiHS_NUDT4.
    ExpressionAtlasiQ9NZJ9. baseline and differential.
    GenevisibleiQ9NZJ9. HS.

    Organism-specific databases

    HPAiHPA017593.
    HPA047027.
    HPA057684.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    KEAP1Q141453EBI-4280066,EBI-751001

    Protein-protein interaction databases

    BioGridi116334. 3 interactors.
    IntActiQ9NZJ9. 1 interactor.
    MINTiMINT-2819936.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    5LTUX-ray2.23A/B1-180[»]
    ProteinModelPortaliQ9NZJ9.
    SMRiQ9NZJ9.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini18 – 144Nudix hydrolasePROSITE-ProRule annotationAdd BLAST127

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni18 – 20Substrate bindingBy similarity3
    Regioni89 – 91Substrate bindingBy similarity3

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi51 – 72Nudix boxAdd BLAST22

    Sequence similaritiesi

    Belongs to the Nudix hydrolase family. DIPP subfamily.Curated

    Phylogenomic databases

    eggNOGiENOG410ISY6. Eukaryota.
    ENOG4111I7R. LUCA.
    GeneTreeiENSGT00390000012928.
    HOVERGENiHBG053341.
    InParanoidiQ9NZJ9.
    KOiK07766.
    OMAiASMMKFK.
    PhylomeDBiQ9NZJ9.
    TreeFamiTF106349.

    Family and domain databases

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

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9NZJ9-1) [UniParc]FASTAAdd to basket
    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.

    « Hide

            10         20         30         40         50
    MMKFKPNQTR TYDREGFKKR AACLCFRSEQ EDEVLLVSSS RYPDQWIVPG
    60 70 80 90 100
    GGMEPEEEPG GAAVREVYEE AGVKGKLGRL LGIFENQDRK HRTYVYVLTV
    110 120 130 140 150
    TEILEDWEDS VNIGRKREWF KVEDAIKVLQ CHKPVHAEYL EKLKLGCSPA
    160 170 180
    NGNSTVPSLP DNNALFVTAA QTSGLPSSVR
    Length:180
    Mass (Da):20,306
    Last modified:July 5, 2005 - v2
    Checksum:i86D766F8F5B22D13
    GO
    Isoform 2 (identifier: Q9NZJ9-2) [UniParc]FASTAAdd to basket
    Also known as: Beta, DIPP2beta

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

    Show »
    Length:181
    Mass (Da):20,434
    Checksum:iCB3C131FAD21A4AA
    GO
    Isoform 3 (identifier: Q9NZJ9-3) [UniParc]FASTAAdd to basket

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

    Show »
    Length:129
    Mass (Da):14,395
    Checksum:i2A8C483085B2D4D3
    GO

    Sequence cautioni

    The sequence AAF75563 differs from that shown. Reason: Erroneous termination at position 181. Translated as stop.Curated
    The sequence BAE16985 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti16G → D in AAF68857 (PubMed:10777568).Curated1
    Sequence conflicti41R → Q in BAD97217 (Ref. 7) Curated1
    Sequence conflicti73V → D in AAF75563 (Ref. 3) Curated1
    Sequence conflicti164A → V in AAF68857 (PubMed:10777568).Curated1
    Sequence conflicti177S → P in AAF68858 (PubMed:10777568).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0142691 – 52Missing in isoform 3. 3 PublicationsAdd BLAST52
    Alternative sequenceiVSP_01427085E → EQ in isoform 2 and isoform 3. 6 Publications1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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.
    CCDSiCCDS44952.1. [Q9NZJ9-1]
    CCDS73504.1. [Q9NZJ9-3]
    CCDS9044.1. [Q9NZJ9-2]
    RefSeqiNP_001287951.1. NM_001301022.1. [Q9NZJ9-3]
    NP_001287952.1. NM_001301023.1.
    NP_001287953.1. NM_001301024.1.
    NP_061967.3. NM_019094.5. [Q9NZJ9-1]
    NP_950241.1. NM_199040.3. [Q9NZJ9-2]
    XP_011536096.1. XM_011537794.2. [Q9NZJ9-3]
    XP_011536097.1. XM_011537795.2.
    XP_011536098.1. XM_011537796.2.
    UniGeneiHs.506325.

    Genome annotation databases

    EnsembliENST00000337179; ENSP00000338352; ENSG00000173598. [Q9NZJ9-2]
    ENST00000415493; ENSP00000406612; ENSG00000173598. [Q9NZJ9-1]
    ENST00000547014; ENSP00000448032; ENSG00000173598. [Q9NZJ9-3]
    GeneIDi11163.
    KEGGihsa:11163.
    UCSCiuc001tcm.4. human. [Q9NZJ9-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiNUDT4_HUMAN
    AccessioniPrimary (citable) accession number: Q9NZJ9
    Secondary accession number(s): B7Z916
    , Q4AEJ6, Q53EZ2, Q68DD7, Q9NPC5, Q9NS30, Q9NZK0, Q9NZK1
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2005
    Last sequence update: July 5, 2005
    Last modified: November 22, 2017
    This is version 151 of the entry and version 2 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 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families