NUDT3_MOUSE
ID NUDT3_MOUSE Reviewed; 168 AA.
AC Q9JI46; B2KF68; Q6PG02; Q8BV71;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Diphosphoinositol polyphosphate phosphohydrolase 1 {ECO:0000305};
DE Short=DIPP-1;
DE Short=muDIPP1;
DE EC=3.6.1.52 {ECO:0000269|PubMed:15212765};
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|MGI:MGI:1928484}; Synonyms=Dipp, Dipp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF GLU-70.
RC TISSUE=Heart;
RX PubMed=15212765; DOI=10.1016/j.cellsig.2004.02.009;
RA Chu C., Alapat D., Wen X., Timo K., Burstein D., Lisanti M., Shears S.,
RA Kohtz D.S.;
RT "Ectopic expression of murine diphosphoinositol polyphosphate
RT phosphohydrolase 1 attenuates signaling through the ERK1/2 pathway.";
RL Cell. Signal. 16:1045-1059(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Mammary tumor;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 81-168.
RC STRAIN=C57BL/6J; TISSUE=Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:15212765). InsP6 (inositol
CC hexakisphosphate) is not a substrate (By similarity). Also able to
CC catalyze the hydrolysis of dinucleoside oligophosphates, with
CC diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A) and diadenosine
CC 5',5'''- P1,P5-pentaphosphate (Ap5A) being the preferred substrates (By
CC similarity). The major reaction products are ADP and p4a from Ap6A and
CC ADP and ATP from Ap5A (By similarity). Also able to hydrolyze
CC 5- phosphoribose 1-diphosphate (By similarity). Acts as a negative
CC regulator of the ERK1/2 pathway (PubMed:15212765). Acts as a decapping
CC enzyme that modulates the stability of a subset of mRNAs implicated in
CC cell motility (By similarity). {ECO:0000250|UniProtKB:O95989,
CC ECO:0000269|PubMed:15212765}.
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:15212765};
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:15212765};
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:0000250|UniProtKB:O95989};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O95989};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:O95989};
CC -!- ACTIVITY REGULATION: Inhibited by fluoride and InsP6.
CC {ECO:0000250|UniProtKB:O95989}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q566C7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Present in heart, lung, liver and spleen (at
CC protein level). Widely expressed. {ECO:0000269|PubMed:15212765}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. DIPP subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH57331.1; Type=Miscellaneous discrepancy; Note=Chimeric at the C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF264064; AAF74761.1; -; mRNA.
DR EMBL; CT027568; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016534; AAH16534.1; -; mRNA.
DR EMBL; BC046805; AAH46805.1; -; mRNA.
DR EMBL; BC057331; AAH57331.1; ALT_SEQ; mRNA.
DR EMBL; AK079658; BAC37717.1; -; mRNA.
DR CCDS; CCDS28566.1; -.
DR RefSeq; NP_062811.1; NM_019837.2.
DR AlphaFoldDB; Q9JI46; -.
DR SMR; Q9JI46; -.
DR BioGRID; 207960; 4.
DR STRING; 10090.ENSMUSP00000025050; -.
DR iPTMnet; Q9JI46; -.
DR PhosphoSitePlus; Q9JI46; -.
DR SwissPalm; Q9JI46; -.
DR EPD; Q9JI46; -.
DR MaxQB; Q9JI46; -.
DR PaxDb; Q9JI46; -.
DR PRIDE; Q9JI46; -.
DR ProteomicsDB; 293813; -.
DR Antibodypedia; 69618; 58 antibodies from 21 providers.
DR DNASU; 56409; -.
DR Ensembl; ENSMUST00000025050; ENSMUSP00000025050; ENSMUSG00000024213.
DR GeneID; 56409; -.
DR KEGG; mmu:56409; -.
DR UCSC; uc008bpg.2; mouse.
DR CTD; 11165; -.
DR MGI; MGI:1928484; Nudt3.
DR VEuPathDB; HostDB:ENSMUSG00000024213; -.
DR eggNOG; KOG2839; Eukaryota.
DR GeneTree; ENSGT00940000157882; -.
DR HOGENOM; CLU_037162_1_0_1; -.
DR InParanoid; Q9JI46; -.
DR OMA; VKVLQYH; -.
DR OrthoDB; 1324716at2759; -.
DR PhylomeDB; Q9JI46; -.
DR TreeFam; TF106349; -.
DR Reactome; R-MMU-1855167; Synthesis of pyrophosphates in the cytosol.
DR BioGRID-ORCS; 56409; 5 hits in 74 CRISPR screens.
DR ChiTaRS; Nudt3; mouse.
DR PRO; PR:Q9JI46; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9JI46; protein.
DR Bgee; ENSMUSG00000024213; Expressed in retinal neural layer and 263 other tissues.
DR ExpressionAtlas; Q9JI46; baseline and differential.
DR Genevisible; Q9JI46; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0000298; F:endopolyphosphatase activity; IBA:GO_Central.
DR GO; GO:0052842; F:inositol diphosphate pentakisphosphate diphosphatase activity; ISO:MGI.
DR GO; GO:0052840; F:inositol diphosphate tetrakisphosphate diphosphatase activity; ISS:UniProtKB.
DR GO; GO:0050072; F:m7G(5')pppN diphosphatase activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:1901911; P:adenosine 5'-(hexahydrogen pentaphosphate) catabolic process; IBA:GO_Central.
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:0071544; P:diphosphoinositol polyphosphate catabolic process; ISS:UniProtKB.
DR GO; GO:0071543; P:diphosphoinositol polyphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0110154; P:RNA decapping; ISS: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 Acetylation; Cytoplasm; Hydrolase; Magnesium; Metal-binding;
KW Reference proteome.
FT CHAIN 1..168
FT /note="Diphosphoinositol polyphosphate phosphohydrolase 1"
FT /id="PRO_0000057056"
FT DOMAIN 17..144
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:0000250"
FT BINDING 10
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 18..20
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 39..41
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 50
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 66
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 66
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 70
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 89..91
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 115
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 133
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT MUTAGEN 70
FT /note="E->Q: Loss of diphosphoinositol polyphosphate
FT phosphohydrolase activity, but retains ability to regulate
FT the ERK1/2 pathway."
FT /evidence="ECO:0000269|PubMed:15212765"
SQ SEQUENCE 168 AA; 19030 MW; E543BE5CBE520910 CRC64;
MMKLKSNQTR TYDGDGYKKR AACLCFRSES EEEVLLVSSS RHPDRWIVPG GGMEPEEEPS
VAAVREVCEE AGVKGTLGRL VGIFENQERK HRTYVYVLIV TEVLEDWEDS VNIGRKREWF
KIEDAIKVLQ CHKPVQASYF ETLRQGYPAN NGTPVVPTTY SSSVSGIR
