NUDT4_MOUSE
ID NUDT4_MOUSE Reviewed; 179 AA.
AC Q8R2U6; Q8BXB9; Q9D3T6;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Diphosphoinositol polyphosphate phosphohydrolase 2 {ECO:0000305};
DE Short=DIPP-2;
DE EC=3.6.1.52 {ECO:0000250|UniProtKB:Q9NZJ9};
DE AltName: Full=Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 2;
DE EC=3.6.1.-;
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 4;
DE Short=Nudix motif 4;
GN Name=Nudt4 {ECO:0000312|MGI:MGI:1918457}; Synonyms=Dipp2;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head, and Testis;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, and Spleen;
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).
RN [4]
RP ABSENCE OF FUNCTION AS A DECAPPING ENZYME, AND RNA-BINDING.
RX PubMed=21070968; DOI=10.1016/j.molcel.2010.10.010;
RA Song M.G., Li Y., Kiledjian M.;
RT "Multiple mRNA decapping enzymes in mammalian cells.";
RL Mol. Cell 40:423-432(2010).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 8-145.
RG RIKEN structural genomics initiative (RSGI);
RT "Crystal structure of MS0616.";
RL Submitted (JAN-2007) to the PDB data bank.
CC -!- FUNCTION: Cleaves a beta-phosphate from the diphosphate groups in PP-
CC InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 and [PP]2-InsP4
CC (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a
CC role in signal transduction (By similarity). Can also catalyze the
CC hydrolysis of diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A) but not
CC diadenosine 5',5'''-P1,P5-pentaphosphate (Ap5A) and the major reaction
CC products are ADP and p4a from Ap6A (By similarity). Also able to
CC hydrolyze 5-phosphoribose 1-diphosphate (By similarity). Does not play
CC a role in U8 snoRNA decapping activity (PubMed:16141072). Binds U8
CC snoRNA (PubMed:16141072). {ECO:0000250|UniProtKB:Q9NZJ9,
CC ECO:0000269|PubMed:16141072}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphospho-myo-inositol polyphosphate + H2O = myo-inositol
CC polyphosphate + phosphate.; EC=3.6.1.52;
CC Evidence={ECO:0000250|UniProtKB:Q9NZJ9};
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:0000250|UniProtKB:Q9NZJ9};
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:Q9NZJ9};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q96G61};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q96G61};
CC Note=Binds 3 Mg(2+) or Mn(2+) ions per subunit.
CC {ECO:0000250|UniProtKB:Q96G61};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9NZJ9}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. DIPP subfamily.
CC {ECO:0000305}.
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DR EMBL; AK017075; BAB30582.1; -; mRNA.
DR EMBL; AK048062; BAC33229.1; -; mRNA.
DR EMBL; BC027209; AAH27209.1; -; mRNA.
DR CCDS; CCDS24138.1; -.
DR RefSeq; NP_081998.3; NM_027722.4.
DR PDB; 2DUK; X-ray; 2.62 A; A/B=8-145.
DR PDBsum; 2DUK; -.
DR AlphaFoldDB; Q8R2U6; -.
DR SMR; Q8R2U6; -.
DR BioGRID; 214552; 1.
DR STRING; 10090.ENSMUSP00000020217; -.
DR PhosphoSitePlus; Q8R2U6; -.
DR EPD; Q8R2U6; -.
DR MaxQB; Q8R2U6; -.
DR PaxDb; Q8R2U6; -.
DR PRIDE; Q8R2U6; -.
DR ProteomicsDB; 289949; -.
DR DNASU; 71207; -.
DR Ensembl; ENSMUST00000020217; ENSMUSP00000020217; ENSMUSG00000020029.
DR GeneID; 71207; -.
DR KEGG; mmu:71207; -.
DR UCSC; uc007gwp.2; mouse.
DR CTD; 11163; -.
DR MGI; MGI:1918457; Nudt4.
DR VEuPathDB; HostDB:ENSMUSG00000020029; -.
DR eggNOG; KOG2839; Eukaryota.
DR GeneTree; ENSGT00940000155210; -.
DR HOGENOM; CLU_037162_1_0_1; -.
DR InParanoid; Q8R2U6; -.
DR OMA; NTNPRHN; -.
DR OrthoDB; 1324716at2759; -.
DR PhylomeDB; Q8R2U6; -.
DR TreeFam; TF106349; -.
DR Reactome; R-MMU-1855167; Synthesis of pyrophosphates in the cytosol.
DR BioGRID-ORCS; 71207; 7 hits in 74 CRISPR screens.
DR ChiTaRS; Nudt4; mouse.
DR EvolutionaryTrace; Q8R2U6; -.
DR PRO; PR:Q8R2U6; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8R2U6; protein.
DR Bgee; ENSMUSG00000020029; Expressed in molar tooth and 256 other tissues.
DR ExpressionAtlas; Q8R2U6; baseline and differential.
DR Genevisible; Q8R2U6; 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; IEA:UniProtKB-EC.
DR GO; GO:0052840; F:inositol diphosphate tetrakisphosphate diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030515; F:snoRNA binding; IDA: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:0071543; P:diphosphoinositol polyphosphate metabolic process; IBA:GO_Central.
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; Cytoplasm; Hydrolase; Magnesium; Manganese; Metal-binding;
KW Reference proteome; RNA-binding.
FT CHAIN 1..179
FT /note="Diphosphoinositol polyphosphate phosphohydrolase 2"
FT /id="PRO_0000057059"
FT DOMAIN 17..143
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT MOTIF 50..71
FT /note="Nudix box"
FT ACT_SITE 68
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 9
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 17..19
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 38..40
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 49
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 65
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 65
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 69
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 88..90
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 114
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT BINDING 132
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O95989"
FT CONFLICT 69
FT /note="E -> Q (in Ref. 1; BAC33229)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="A -> C (in Ref. 1; BAB30582)"
FT /evidence="ECO:0000305"
FT STRAND 17..27
FT /evidence="ECO:0007829|PDB:2DUK"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:2DUK"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:2DUK"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:2DUK"
FT HELIX 58..69
FT /evidence="ECO:0007829|PDB:2DUK"
FT STRAND 72..85
FT /evidence="ECO:0007829|PDB:2DUK"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:2DUK"
FT STRAND 90..102
FT /evidence="ECO:0007829|PDB:2DUK"
FT HELIX 109..112
FT /evidence="ECO:0007829|PDB:2DUK"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:2DUK"
FT HELIX 121..129
FT /evidence="ECO:0007829|PDB:2DUK"
FT HELIX 133..139
FT /evidence="ECO:0007829|PDB:2DUK"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:2DUK"
SQ SEQUENCE 179 AA; 20156 MW; 05A78EBBA8256B89 CRC64;
MKFKPNQTRT YDREGFKKRA ACLCFRSEQE DEVLLVSSSR YPDQWIVPGG GMEPEEEPGG
AAVREVYEEA GVKGKLGRLL GIFENQDRKH RTYVYVLTVT EILEDWEDSV NIGRKREWFK
VEDAIKVLQC HKPVHAEYLE KLKLGCSPTN GNSSVPSLPD NNALFVTAAP PSGVPSSIR
