NUDT3_HUMAN
ID NUDT3_HUMAN Reviewed; 172 AA.
AC O95989; B2R8N4;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Diphosphoinositol polyphosphate phosphohydrolase 1 {ECO:0000305};
DE Short=DIPP-1;
DE EC=3.6.1.52 {ECO:0000269|PubMed:10419486, ECO:0000269|PubMed:10585413, ECO:0000269|PubMed:12370170, ECO:0000269|PubMed:9822604};
DE AltName: Full=Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 1;
DE EC=3.6.1.-;
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 3;
DE Short=Nudix motif 3;
GN Name=NUDT3 {ECO:0000312|HGNC:HGNC:8050}; Synonyms=DIPP, DIPP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, TISSUE SPECIFICITY, AND MUTAGENESIS OF GLU-70.
RC TISSUE=Uterus;
RX PubMed=9822604; DOI=10.1093/emboj/17.22.6599;
RA Safrany S.T., Caffrey J.J., Yang X., Bembenek M.E., Moyer M.B.,
RA Burkhart W.A., Shears S.B.;
RT "A novel context for the 'MutT' module, a guardian of cell integrity, in a
RT diphosphoinositol polyphosphate phosphohydrolase.";
RL EMBO J. 17:6599-6607(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, ENZYME ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10419486; DOI=10.1074/jbc.274.31.21735;
RA Safrany S.T., Ingram S.W., Cartwright J.L., Falck J.R., McLennan A.G.,
RA Barnes L.D., Shears S.B.;
RT "The diadenosine hexaphosphate hydrolases from Schizosaccharomyces pombe
RT and Saccharomyces cerevisiae are homologues of the human diphosphoinositol
RT polyphosphate phosphohydrolase. Overlapping substrate specificities in a
RT MutT-type protein.";
RL J. Biol. Chem. 274:21735-21740(1999).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLY-50; GLY-51; GLY-52;
RP GLU-66; GLY-72; GLY-75; GLY-78; GLY-82; PHE-84 AND HIS-91.
RX PubMed=10585413; DOI=10.1074/jbc.274.50.35434;
RA Yang X., Safrany S.T., Shears S.B.;
RT "Site-directed mutagenesis of diphosphoinositol polyphosphate
RT phosphohydrolase, a dual specificity NUDT enzyme that attacks diadenosine
RT polyphosphates and diphosphoinositol polyphosphates.";
RL J. Biol. Chem. 274:35434-35440(1999).
RN [9]
RP FUNCTION, ENZYME ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12370170; DOI=10.1074/jbc.m209795200;
RA Fisher D.I., Safrany S.T., Strike P., McLennan A.G., Cartwright J.L.;
RT "Nudix hydrolases that degrade dinucleoside and diphosphoinositol
RT polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP)
RT pyrophosphatase activity that generates the glycolytic activator ribose
RT 1,5-bisphosphate.";
RL J. Biol. Chem. 277:47313-47317(2002).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 69-GLU--GLU-70.
RX PubMed=26932476; DOI=10.1261/rna.055699.115;
RA Grudzien-Nogalska E., Jiao X., Song M.G., Hart R.P., Kiledjian M.;
RT "Nudt3 is an mRNA decapping enzyme that modulates cell migration.";
RL RNA 22:773-781(2016).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS;
RP FLUORIDE AND INOSITOL HEXAKISPHOSPHATE, COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=19585659; DOI=10.1002/prot.22489;
RA Thorsell A.G., Persson C., Graslund S., Hammarstrom M., Busam R.D.,
RA Hallberg B.M.;
RT "Crystal structure of human diphosphoinositol phosphatase 1.";
RL Proteins 77:242-246(2009).
CC -!- FUNCTION: Cleaves a beta-phosphate from the diphosphate groups in PP-
CC InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4
CC (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a
CC role in signal transduction (PubMed:10419486, PubMed:12370170,
CC PubMed:9822604, PubMed:10585413). InsP6 (inositol hexakisphosphate) is
CC not a substrate (PubMed:9822604). Acts as a negative regulator of the
CC ERK1/2 pathway (By similarity). Also able to catalyze the hydrolysis of
CC dinucleoside oligophosphates, with diadenosine 5',5'''-P1,P6-
CC hexaphosphate (Ap6A) and diadenosine 5',5'''- P1,P5-pentaphosphate
CC (Ap5A) being the preferred substrates (PubMed:12370170). The major
CC reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A
CC (PubMed:12370170). Also able to hydrolyze 5-phosphoribose 1-diphosphate
CC (PubMed:12370170). Acts as a decapping enzyme that modulates the
CC stability of a subset of mRNAs implicated in cell motility
CC (PubMed:26932476). {ECO:0000250|UniProtKB:Q9JI46,
CC ECO:0000269|PubMed:10419486, ECO:0000269|PubMed:10585413,
CC ECO:0000269|PubMed:12370170, ECO:0000269|PubMed:9822604,
CC ECO:0000305|PubMed:26932476}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphospho-myo-inositol polyphosphate + H2O = myo-inositol
CC polyphosphate + phosphate.; EC=3.6.1.52;
CC Evidence={ECO:0000269|PubMed:10419486, ECO:0000269|PubMed:10585413,
CC ECO:0000269|PubMed:12370170, ECO:0000269|PubMed:9822604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate + H2O
CC = 1D-myo-inositol hexakisphosphate + H(+) + phosphate;
CC Xref=Rhea:RHEA:22384, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58130, ChEBI:CHEBI:58628; EC=3.6.1.52;
CC Evidence={ECO:0000269|PubMed:10419486, ECO:0000269|PubMed:10585413,
CC ECO:0000269|PubMed:12370170, ECO:0000269|PubMed:9822604};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3,5-bis(diphospho)-1D-myo-inositol 1,2,4,6-tetrakisphosphate +
CC H2O = 3-diphospho-1D-myo-inositol 1,2,4,5,6-pentakisphosphate + 2
CC H(+) + phosphate; Xref=Rhea:RHEA:56312, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:140372,
CC ChEBI:CHEBI:140374; EC=3.6.1.52;
CC Evidence={ECO:0000269|PubMed:10585413};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:19585659};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000269|PubMed:19585659};
CC -!- ACTIVITY REGULATION: Inhibited by fluoride and InsP6.
CC {ECO:0000269|PubMed:19585659}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.9 uM for Ap6A {ECO:0000269|PubMed:10419486,
CC ECO:0000269|PubMed:12370170, ECO:0000269|PubMed:9822604};
CC KM=7.7 uM for Ap5A {ECO:0000269|PubMed:10419486,
CC ECO:0000269|PubMed:12370170, ECO:0000269|PubMed:9822604};
CC KM=38 mM for 5-phosphoribose 1-diphosphate
CC {ECO:0000269|PubMed:10419486, ECO:0000269|PubMed:12370170,
CC ECO:0000269|PubMed:9822604};
CC KM=4.2 nM for PP-InsP5 {ECO:0000269|PubMed:10419486,
CC ECO:0000269|PubMed:12370170, ECO:0000269|PubMed:9822604};
CC pH dependence:
CC Optimum pH is 7-7.5. {ECO:0000269|PubMed:10419486,
CC ECO:0000269|PubMed:12370170, ECO:0000269|PubMed:9822604};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q566C7}.
CC -!- INTERACTION:
CC O95989; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-713708, EBI-742054;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in
CC brain, heart, pancreas and liver. Also expressed in placenta, lung and
CC kidney. {ECO:0000269|PubMed:9822604}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. DIPP subfamily.
CC {ECO:0000305}.
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DR EMBL; AF062529; AAC83224.1; -; mRNA.
DR EMBL; AF062530; AAC83225.1; -; mRNA.
DR EMBL; BT019984; AAV38787.1; -; mRNA.
DR EMBL; BT019985; AAV38788.1; -; mRNA.
DR EMBL; AK313440; BAG36231.1; -; mRNA.
DR EMBL; Z98036; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355855; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03781.1; -; Genomic_DNA.
DR EMBL; BC007727; AAH07727.1; -; mRNA.
DR CCDS; CCDS4791.1; -.
DR RefSeq; NP_006694.1; NM_006703.3.
DR PDB; 2FVV; X-ray; 1.25 A; A=1-172.
DR PDB; 2Q9P; X-ray; 1.65 A; A=1-172.
DR PDB; 6PCK; X-ray; 1.20 A; A=1-148.
DR PDB; 6PCL; X-ray; 1.30 A; A=1-148.
DR PDB; 6WO7; X-ray; 1.40 A; A=1-148.
DR PDB; 6WO8; X-ray; 1.70 A; A=1-148.
DR PDB; 6WO9; X-ray; 2.00 A; A=1-148.
DR PDB; 6WOA; X-ray; 1.50 A; A=1-148.
DR PDB; 6WOB; X-ray; 1.45 A; A=1-148.
DR PDB; 6WOC; X-ray; 1.35 A; A=1-148.
DR PDB; 6WOD; X-ray; 1.35 A; A=1-148.
DR PDB; 6WOE; X-ray; 1.40 A; A=1-148.
DR PDB; 6WOF; X-ray; 1.60 A; A=1-148.
DR PDB; 6WOG; X-ray; 1.50 A; A=1-148.
DR PDB; 6WOH; X-ray; 1.70 A; A=1-148.
DR PDB; 6WOI; X-ray; 1.50 A; A=1-148.
DR PDBsum; 2FVV; -.
DR PDBsum; 2Q9P; -.
DR PDBsum; 6PCK; -.
DR PDBsum; 6PCL; -.
DR PDBsum; 6WO7; -.
DR PDBsum; 6WO8; -.
DR PDBsum; 6WO9; -.
DR PDBsum; 6WOA; -.
DR PDBsum; 6WOB; -.
DR PDBsum; 6WOC; -.
DR PDBsum; 6WOD; -.
DR PDBsum; 6WOE; -.
DR PDBsum; 6WOF; -.
DR PDBsum; 6WOG; -.
DR PDBsum; 6WOH; -.
DR PDBsum; 6WOI; -.
DR AlphaFoldDB; O95989; -.
DR SMR; O95989; -.
DR BioGRID; 116336; 89.
DR IntAct; O95989; 42.
DR MINT; O95989; -.
DR STRING; 9606.ENSP00000476119; -.
DR ChEMBL; CHEMBL4295689; -.
DR iPTMnet; O95989; -.
DR PhosphoSitePlus; O95989; -.
DR SwissPalm; O95989; -.
DR BioMuta; NUDT3; -.
DR EPD; O95989; -.
DR jPOST; O95989; -.
DR MassIVE; O95989; -.
DR MaxQB; O95989; -.
DR PaxDb; O95989; -.
DR PeptideAtlas; O95989; -.
DR PRIDE; O95989; -.
DR ProteomicsDB; 51165; -.
DR Antibodypedia; 69618; 58 antibodies from 21 providers.
DR DNASU; 11165; -.
DR Ensembl; ENST00000607016.2; ENSP00000476119.1; ENSG00000272325.2.
DR GeneID; 11165; -.
DR KEGG; hsa:11165; -.
DR MANE-Select; ENST00000607016.2; ENSP00000476119.1; NM_006703.4; NP_006694.1.
DR UCSC; uc003ojl.4; human.
DR CTD; 11165; -.
DR DisGeNET; 11165; -.
DR GeneCards; NUDT3; -.
DR HGNC; HGNC:8050; NUDT3.
DR HPA; ENSG00000272325; Low tissue specificity.
DR MIM; 609228; gene.
DR neXtProt; NX_O95989; -.
DR OpenTargets; ENSG00000272325; -.
DR PharmGKB; PA31834; -.
DR VEuPathDB; HostDB:ENSG00000272325; -.
DR eggNOG; KOG2839; Eukaryota.
DR GeneTree; ENSGT00940000157882; -.
DR HOGENOM; CLU_037162_1_0_1; -.
DR InParanoid; O95989; -.
DR OMA; VKVLQYH; -.
DR PhylomeDB; O95989; -.
DR TreeFam; TF106349; -.
DR BioCyc; MetaCyc:HS03602-MON; -.
DR BRENDA; 3.6.1.17; 2681.
DR BRENDA; 3.6.1.42; 2681.
DR BRENDA; 3.6.1.52; 2681.
DR BRENDA; 3.6.1.60; 2681.
DR PathwayCommons; O95989; -.
DR Reactome; R-HSA-1855167; Synthesis of pyrophosphates in the cytosol.
DR SABIO-RK; O95989; -.
DR SignaLink; O95989; -.
DR SIGNOR; O95989; -.
DR BioGRID-ORCS; 11165; 11 hits in 1059 CRISPR screens.
DR ChiTaRS; NUDT3; human.
DR EvolutionaryTrace; O95989; -.
DR GeneWiki; NUDT3; -.
DR GenomeRNAi; 11165; -.
DR Pharos; O95989; Tbio.
DR PRO; PR:O95989; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O95989; protein.
DR Bgee; ENSG00000272325; Expressed in dorsal motor nucleus of vagus nerve and 211 other tissues.
DR Genevisible; O95989; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0034431; F:bis(5'-adenosyl)-hexaphosphatase activity; IBA:GO_Central.
DR GO; GO:0034432; F:bis(5'-adenosyl)-pentaphosphatase activity; IBA:GO_Central.
DR GO; GO:0008486; F:diphosphoinositol-polyphosphate diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0000298; F:endopolyphosphatase activity; IBA:GO_Central.
DR GO; GO:0052842; F:inositol diphosphate pentakisphosphate diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0052840; F:inositol diphosphate tetrakisphosphate diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0050072; F:m7G(5')pppN diphosphatase activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:1901911; P:adenosine 5'-(hexahydrogen pentaphosphate) catabolic process; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:1901909; P:diadenosine hexaphosphate catabolic process; IBA:GO_Central.
DR GO; GO:1901907; P:diadenosine pentaphosphate catabolic process; IBA:GO_Central.
DR GO; GO:0015961; P:diadenosine polyphosphate catabolic process; TAS:ProtInc.
DR GO; GO:0071544; P:diphosphoinositol polyphosphate catabolic process; IDA:UniProtKB.
DR GO; GO:0071543; P:diphosphoinositol polyphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0110154; P:RNA decapping; IMP:UniProtKB.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR020084; NUDIX_hydrolase_CS.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR Pfam; PF00293; NUDIX; 1.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
DR PROSITE; PS00893; NUDIX_BOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Hydrolase; Magnesium; Metal-binding;
KW Reference proteome.
FT CHAIN 1..172
FT /note="Diphosphoinositol polyphosphate phosphohydrolase 1"
FT /id="PRO_0000057055"
FT DOMAIN 17..142
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT MOTIF 51..72
FT /note="Nudix box"
FT ACT_SITE 69
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 10
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19585659,
FT ECO:0007744|PDB:2FVV, ECO:0007744|PDB:2Q9P"
FT BINDING 18..20
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19585659,
FT ECO:0007744|PDB:2FVV, ECO:0007744|PDB:2Q9P"
FT BINDING 39..41
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19585659,
FT ECO:0007744|PDB:2FVV, ECO:0007744|PDB:2Q9P"
FT BINDING 50
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19585659,
FT ECO:0007744|PDB:2Q9P"
FT BINDING 66
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:19585659,
FT ECO:0007744|PDB:2Q9P"
FT BINDING 66
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:19585659,
FT ECO:0007744|PDB:2Q9P"
FT BINDING 70
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19585659,
FT ECO:0007744|PDB:2Q9P"
FT BINDING 89..91
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19585659,
FT ECO:0007744|PDB:2FVV, ECO:0007744|PDB:2Q9P"
FT BINDING 115
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19585659,
FT ECO:0007744|PDB:2Q9P"
FT BINDING 133
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19585659,
FT ECO:0007744|PDB:2FVV, ECO:0007744|PDB:2Q9P"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MUTAGEN 50
FT /note="G->A,V: Loss of diphosphoinositol polyphosphate
FT phosphohydrolase activity."
FT /evidence="ECO:0000269|PubMed:10585413"
FT MUTAGEN 51
FT /note="G->A: Loss of diphosphoinositol polyphosphate
FT phosphohydrolase activity."
FT /evidence="ECO:0000269|PubMed:10585413"
FT MUTAGEN 52
FT /note="G->A,V: Loss of diphosphoinositol polyphosphate
FT phosphohydrolase activity."
FT /evidence="ECO:0000269|PubMed:10585413"
FT MUTAGEN 66
FT /note="E->Q: Loss of diphosphoinositol polyphosphate
FT phosphohydrolase activity."
FT /evidence="ECO:0000269|PubMed:10585413"
FT MUTAGEN 69..70
FT /note="EE->QQ: Loss of mRNA-decapping activity."
FT /evidence="ECO:0000269|PubMed:26932476"
FT MUTAGEN 70
FT /note="E->Q: Loss of diphosphoinositol polyphosphate
FT phosphohydrolase activity."
FT /evidence="ECO:0000269|PubMed:9822604"
FT MUTAGEN 72
FT /note="G->A: Loss of diphosphoinositol polyphosphate
FT phosphohydrolase activity."
FT /evidence="ECO:0000269|PubMed:10585413"
FT MUTAGEN 75
FT /note="G->A: Loss of diphosphoinositol polyphosphate
FT phosphohydrolase activity."
FT /evidence="ECO:0000269|PubMed:10585413"
FT MUTAGEN 78
FT /note="G->A: No effect on diphosphoinositol polyphosphate
FT phosphohydrolase activity."
FT /evidence="ECO:0000269|PubMed:10585413"
FT MUTAGEN 78
FT /note="G->V: Loss of diphosphoinositol polyphosphate
FT phosphohydrolase activity."
FT /evidence="ECO:0000269|PubMed:10585413"
FT MUTAGEN 82
FT /note="G->A: Loss of diphosphoinositol polyphosphate
FT phosphohydrolase activity."
FT /evidence="ECO:0000269|PubMed:10585413"
FT MUTAGEN 84
FT /note="F->Y: Induces a strong decrease in Ap6A and [PP]-
FT InsP4 hydrolysis, while it only weakly affects PP-InsP5
FT hydrolysis."
FT /evidence="ECO:0000269|PubMed:10585413"
FT MUTAGEN 91
FT /note="H->L: Induces a strong decrease in Ap6A and [PP]-
FT InsP4 hydrolysis, while it only weakly affects PP-InsP5
FT hydrolysis."
FT /evidence="ECO:0000269|PubMed:10585413"
FT STRAND 18..28
FT /evidence="ECO:0007829|PDB:6PCK"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:6PCK"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:6PCK"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:6PCK"
FT HELIX 59..71
FT /evidence="ECO:0007829|PDB:6PCK"
FT STRAND 73..86
FT /evidence="ECO:0007829|PDB:6PCK"
FT TURN 87..90
FT /evidence="ECO:0007829|PDB:6PCK"
FT STRAND 91..103
FT /evidence="ECO:0007829|PDB:6PCK"
FT HELIX 108..113
FT /evidence="ECO:0007829|PDB:6PCK"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:6PCK"
FT HELIX 122..129
FT /evidence="ECO:0007829|PDB:6PCK"
FT TURN 130..132
FT /evidence="ECO:0007829|PDB:6PCK"
FT HELIX 134..138
FT /evidence="ECO:0007829|PDB:6PCK"
SQ SEQUENCE 172 AA; 19471 MW; DE823FECF5C6438A CRC64;
MMKLKSNQTR TYDGDGYKKR AACLCFRSES EEEVLLVSSS RHPDRWIVPG GGMEPEEEPS
VAAVREVCEE AGVKGTLGRL VGIFENQERK HRTYVYVLIV TEVLEDWEDS VNIGRKREWF
KIEDAIKVLQ YHKPVQASYF ETLRQGYSAN NGTPVVATTY SVSAQSSMSG IR
