Full text data of NUDT4
NUDT4
(DIPP2, KIAA0487)
[Confidence: low (only semi-automatic identification from reviews)]
Diphosphoinositol polyphosphate phosphohydrolase 2; DIPP-2; 3.6.1.52 (Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 2; 3.6.1.-; Nucleoside diphosphate-linked moiety X motif 4; Nudix motif 4)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Diphosphoinositol polyphosphate phosphohydrolase 2; DIPP-2; 3.6.1.52 (Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 2; 3.6.1.-; Nucleoside diphosphate-linked moiety X motif 4; Nudix motif 4)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9NZJ9
ID NUDT4_HUMAN Reviewed; 180 AA.
AC Q9NZJ9; B7Z916; Q4AEJ6; Q53EZ2; Q68DD7; Q9NPC5; Q9NS30; Q9NZK0;
read moreAC Q9NZK1;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Diphosphoinositol polyphosphate phosphohydrolase 2;
DE Short=DIPP-2;
DE EC=3.6.1.52;
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; Synonyms=DIPP2, KIAA0487; ORFNames=HDCMB47P;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ENZYME
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Cerebellum;
RX PubMed=10777568; DOI=10.1074/jbc.275.17.12730;
RA Caffrey J.J., Safrany S.T., Yang X., Shears S.B.;
RT "Discovery of molecular and catalytic diversity among human
RT diphosphoinositol-polyphosphate phosphohydrolases. The expanding NUDT
RT family.";
RL J. Biol. Chem. 275:12730-12736(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9455484; DOI=10.1093/dnares/4.5.345;
RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D.,
RA Nomura N., Ohara O.;
RT "Characterization of cDNA clones in size-fractionated cDNA libraries
RT from human brain.";
RL DNA Res. 4:345-349(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Zhao Z., Huang X., Li N., Zhu X., Cao X.;
RT "Novel gene identified from dendritic cells.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Trachea;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lymph, and Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=12121577; DOI=10.1186/1472-2091-3-20;
RA Leslie N.R., McLennan A.G., Safrany S.T.;
RT "Cloning and characterisation of hAps1 and hAps2, human diadenosine
RT polyphosphate-metabolising Nudix hydrolases.";
RL BMC Biochem. 3:20-20(2002).
RN [10]
RP ENZYME ACTIVITY.
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
RT ribose 1,5-bisphosphate.";
RL J. Biol. Chem. 277:47313-47317(2002).
RN [11]
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.,
RA Buerckstuemmer T., 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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Cleaves a beta-phosphate from the diphosphate groups in
CC PP-InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 and
CC [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting
CC that it may play a role in signal transduction. Also able to
CC catalyze the hydrolysis of dinucleoside oligophosphate Ap6A, but
CC not Ap5A. The major reaction products are ADP and p4a from Ap6A.
CC Also able to hydrolyze 5-phosphoribose 1-diphosphate. Does not
CC play a role in U8 snoRNA decapping activity. Binds U8 snoRNA.
CC -!- CATALYTIC ACTIVITY: Diphospho-myo-inositol polyphosphate + H(2)O =
CC myo-inositol polyphosphate + phosphate.
CC -!- COFACTOR: Binds 3 magnesium or manganese ions per subunit (By
CC similarity).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.2 nM for PP-InsP5;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Alpha, DIPP2alpha;
CC IsoId=Q9NZJ9-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta, DIPP2beta;
CC IsoId=Q9NZJ9-2; Sequence=VSP_014270;
CC Name=3;
CC IsoId=Q9NZJ9-3; Sequence=VSP_014269, VSP_014270;
CC -!- TISSUE SPECIFICITY: Expressed in heart and, at lower level in
CC skeletal muscle, pancreas and kidney.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. DIPP subfamily.
CC -!- SIMILARITY: Contains 1 nudix hydrolase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF75563.1; Type=Erroneous termination; Positions=181; Note=Translated as stop;
CC Sequence=BAE16985.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AF191649; AAF68855.1; -; mRNA.
DR EMBL; AF191650; AAF68856.1; -; mRNA.
DR EMBL; AF191651; AAF68857.1; -; mRNA.
DR EMBL; AF191652; AAF68858.2; -; mRNA.
DR EMBL; AF191653; AAF68859.1; -; mRNA.
DR EMBL; AB007956; BAE16985.1; ALT_INIT; mRNA.
DR EMBL; AF067803; AAF75563.1; ALT_SEQ; mRNA.
DR EMBL; CR749445; CAH18283.1; -; mRNA.
DR EMBL; BT020109; AAV38912.1; -; mRNA.
DR EMBL; BT020110; AAV38913.1; -; mRNA.
DR EMBL; AK304296; BAH14152.1; -; mRNA.
DR EMBL; AK223497; BAD97217.1; -; mRNA.
DR EMBL; BC012069; AAH12069.1; -; mRNA.
DR EMBL; BC051310; AAH51310.1; -; mRNA.
DR RefSeq; NP_061967.3; NM_019094.4.
DR RefSeq; NP_950241.1; NM_199040.2.
DR RefSeq; XP_005268652.1; XM_005268595.1.
DR UniGene; Hs.506325; -.
DR ProteinModelPortal; Q9NZJ9; -.
DR SMR; Q9NZJ9; 9-146.
DR MINT; MINT-2819936; -.
DR PhosphoSite; Q9NZJ9; -.
DR DMDM; 68565946; -.
DR PRIDE; Q9NZJ9; -.
DR DNASU; 11163; -.
DR Ensembl; ENST00000337179; ENSP00000338352; ENSG00000173598.
DR Ensembl; ENST00000415493; ENSP00000406612; ENSG00000173598.
DR Ensembl; ENST00000547014; ENSP00000448032; ENSG00000173598.
DR Ensembl; ENST00000548662; ENSP00000449724; ENSG00000173598.
DR Ensembl; ENST00000549992; ENSP00000449552; ENSG00000173598.
DR GeneID; 11163; -.
DR KEGG; hsa:11163; -.
DR UCSC; uc001tcm.3; human.
DR CTD; 11163; -.
DR GeneCards; GC12P093771; -.
DR HGNC; HGNC:8051; NUDT4.
DR HPA; HPA017593; -.
DR MIM; 609229; gene.
DR neXtProt; NX_Q9NZJ9; -.
DR PharmGKB; PA31835; -.
DR HOVERGEN; HBG053341; -.
DR InParanoid; Q9NZJ9; -.
DR KO; K07766; -.
DR OMA; IGMFQDD; -.
DR OrthoDB; EOG7T7GVQ; -.
DR BioCyc; MetaCyc:HS10696-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; NUDT4; human.
DR GeneWiki; NUDT4; -.
DR GenomeRNAi; 11163; -.
DR NextBio; 42469; -.
DR PRO; PR:Q9NZJ9; -.
DR ArrayExpress; Q9NZJ9; -.
DR Bgee; Q9NZJ9; -.
DR CleanEx; HS_NUDT4; -.
DR Genevestigator; Q9NZJ9; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0008486; F:diphosphoinositol-polyphosphate diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0052840; F:inositol diphosphate tetrakisphosphate diphosphatase activity; TAS:Reactome.
DR GO; GO:0052846; F:inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 1-diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052847; F:inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052843; F:inositol-1-diphosphate-2,3,4,5,6-pentakisphosphate diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052848; F:inositol-3,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052844; F:inositol-3-diphosphate-1,2,4,5,6-pentakisphosphate diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052845; F:inositol-5-diphosphate-1,2,3,4,6-pentakisphosphate diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030515; F:snoRNA binding; ISS:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; TAS:UniProtKB.
DR GO; GO:0009187; P:cyclic nucleotide metabolic process; TAS:ProtInc.
DR GO; GO:0019935; P:cyclic-nucleotide-mediated signaling; TAS:UniProtKB.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0046907; P:intracellular transport; TAS:UniProtKB.
DR GO; GO:0046831; P:regulation of RNA export from nucleus; TAS:UniProtKB.
DR Gene3D; 3.90.79.10; -; 1.
DR InterPro; IPR020084; NUDIX_hydrolase_CS.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR InterPro; IPR015797; NUDIX_hydrolase_dom-like.
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; Alternative splicing; Complete proteome; Cytoplasm;
KW Hydrolase; Magnesium; Manganese; Metal-binding; Reference proteome;
KW RNA-binding.
FT CHAIN 1 180 Diphosphoinositol polyphosphate
FT phosphohydrolase 2.
FT /FTId=PRO_0000057058.
FT DOMAIN 18 144 Nudix hydrolase.
FT REGION 18 20 Substrate binding (By similarity).
FT REGION 89 91 Substrate binding (By similarity).
FT MOTIF 51 72 Nudix box.
FT ACT_SITE 69 69 Proton acceptor (By similarity).
FT METAL 50 50 Magnesium 1; via carbonyl oxygen (By
FT similarity).
FT METAL 66 66 Magnesium 2 (By similarity).
FT METAL 66 66 Magnesium 3 (By similarity).
FT METAL 70 70 Magnesium 1 (By similarity).
FT BINDING 10 10 Substrate (By similarity).
FT BINDING 41 41 Substrate (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 1 52 Missing (in isoform 3).
FT /FTId=VSP_014269.
FT VAR_SEQ 85 85 E -> EQ (in isoform 2 and isoform 3).
FT /FTId=VSP_014270.
FT CONFLICT 16 16 G -> D (in Ref. 1; AAF68857).
FT CONFLICT 41 41 R -> Q (in Ref. 7; BAD97217).
FT CONFLICT 73 73 V -> D (in Ref. 3; AAF75563).
FT CONFLICT 164 164 A -> V (in Ref. 1; AAF68857).
FT CONFLICT 177 177 S -> P (in Ref. 1; AAF68858).
SQ SEQUENCE 180 AA; 20306 MW; 86D766F8F5B22D13 CRC64;
MMKFKPNQTR TYDREGFKKR AACLCFRSEQ EDEVLLVSSS RYPDQWIVPG GGMEPEEEPG
GAAVREVYEE AGVKGKLGRL LGIFENQDRK HRTYVYVLTV TEILEDWEDS VNIGRKREWF
KVEDAIKVLQ CHKPVHAEYL EKLKLGCSPA NGNSTVPSLP DNNALFVTAA QTSGLPSSVR
//
ID NUDT4_HUMAN Reviewed; 180 AA.
AC Q9NZJ9; B7Z916; Q4AEJ6; Q53EZ2; Q68DD7; Q9NPC5; Q9NS30; Q9NZK0;
read moreAC Q9NZK1;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Diphosphoinositol polyphosphate phosphohydrolase 2;
DE Short=DIPP-2;
DE EC=3.6.1.52;
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; Synonyms=DIPP2, KIAA0487; ORFNames=HDCMB47P;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ENZYME
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Cerebellum;
RX PubMed=10777568; DOI=10.1074/jbc.275.17.12730;
RA Caffrey J.J., Safrany S.T., Yang X., Shears S.B.;
RT "Discovery of molecular and catalytic diversity among human
RT diphosphoinositol-polyphosphate phosphohydrolases. The expanding NUDT
RT family.";
RL J. Biol. Chem. 275:12730-12736(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9455484; DOI=10.1093/dnares/4.5.345;
RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D.,
RA Nomura N., Ohara O.;
RT "Characterization of cDNA clones in size-fractionated cDNA libraries
RT from human brain.";
RL DNA Res. 4:345-349(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Zhao Z., Huang X., Li N., Zhu X., Cao X.;
RT "Novel gene identified from dendritic cells.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Retina;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Trachea;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lymph, and Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=12121577; DOI=10.1186/1472-2091-3-20;
RA Leslie N.R., McLennan A.G., Safrany S.T.;
RT "Cloning and characterisation of hAps1 and hAps2, human diadenosine
RT polyphosphate-metabolising Nudix hydrolases.";
RL BMC Biochem. 3:20-20(2002).
RN [10]
RP ENZYME ACTIVITY.
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
RT ribose 1,5-bisphosphate.";
RL J. Biol. Chem. 277:47313-47317(2002).
RN [11]
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.,
RA Buerckstuemmer T., 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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Cleaves a beta-phosphate from the diphosphate groups in
CC PP-InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 and
CC [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting
CC that it may play a role in signal transduction. Also able to
CC catalyze the hydrolysis of dinucleoside oligophosphate Ap6A, but
CC not Ap5A. The major reaction products are ADP and p4a from Ap6A.
CC Also able to hydrolyze 5-phosphoribose 1-diphosphate. Does not
CC play a role in U8 snoRNA decapping activity. Binds U8 snoRNA.
CC -!- CATALYTIC ACTIVITY: Diphospho-myo-inositol polyphosphate + H(2)O =
CC myo-inositol polyphosphate + phosphate.
CC -!- COFACTOR: Binds 3 magnesium or manganese ions per subunit (By
CC similarity).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.2 nM for PP-InsP5;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Alpha, DIPP2alpha;
CC IsoId=Q9NZJ9-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta, DIPP2beta;
CC IsoId=Q9NZJ9-2; Sequence=VSP_014270;
CC Name=3;
CC IsoId=Q9NZJ9-3; Sequence=VSP_014269, VSP_014270;
CC -!- TISSUE SPECIFICITY: Expressed in heart and, at lower level in
CC skeletal muscle, pancreas and kidney.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. DIPP subfamily.
CC -!- SIMILARITY: Contains 1 nudix hydrolase domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF75563.1; Type=Erroneous termination; Positions=181; Note=Translated as stop;
CC Sequence=BAE16985.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; AF191649; AAF68855.1; -; mRNA.
DR EMBL; AF191650; AAF68856.1; -; mRNA.
DR EMBL; AF191651; AAF68857.1; -; mRNA.
DR EMBL; AF191652; AAF68858.2; -; mRNA.
DR EMBL; AF191653; AAF68859.1; -; mRNA.
DR EMBL; AB007956; BAE16985.1; ALT_INIT; mRNA.
DR EMBL; AF067803; AAF75563.1; ALT_SEQ; mRNA.
DR EMBL; CR749445; CAH18283.1; -; mRNA.
DR EMBL; BT020109; AAV38912.1; -; mRNA.
DR EMBL; BT020110; AAV38913.1; -; mRNA.
DR EMBL; AK304296; BAH14152.1; -; mRNA.
DR EMBL; AK223497; BAD97217.1; -; mRNA.
DR EMBL; BC012069; AAH12069.1; -; mRNA.
DR EMBL; BC051310; AAH51310.1; -; mRNA.
DR RefSeq; NP_061967.3; NM_019094.4.
DR RefSeq; NP_950241.1; NM_199040.2.
DR RefSeq; XP_005268652.1; XM_005268595.1.
DR UniGene; Hs.506325; -.
DR ProteinModelPortal; Q9NZJ9; -.
DR SMR; Q9NZJ9; 9-146.
DR MINT; MINT-2819936; -.
DR PhosphoSite; Q9NZJ9; -.
DR DMDM; 68565946; -.
DR PRIDE; Q9NZJ9; -.
DR DNASU; 11163; -.
DR Ensembl; ENST00000337179; ENSP00000338352; ENSG00000173598.
DR Ensembl; ENST00000415493; ENSP00000406612; ENSG00000173598.
DR Ensembl; ENST00000547014; ENSP00000448032; ENSG00000173598.
DR Ensembl; ENST00000548662; ENSP00000449724; ENSG00000173598.
DR Ensembl; ENST00000549992; ENSP00000449552; ENSG00000173598.
DR GeneID; 11163; -.
DR KEGG; hsa:11163; -.
DR UCSC; uc001tcm.3; human.
DR CTD; 11163; -.
DR GeneCards; GC12P093771; -.
DR HGNC; HGNC:8051; NUDT4.
DR HPA; HPA017593; -.
DR MIM; 609229; gene.
DR neXtProt; NX_Q9NZJ9; -.
DR PharmGKB; PA31835; -.
DR HOVERGEN; HBG053341; -.
DR InParanoid; Q9NZJ9; -.
DR KO; K07766; -.
DR OMA; IGMFQDD; -.
DR OrthoDB; EOG7T7GVQ; -.
DR BioCyc; MetaCyc:HS10696-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; NUDT4; human.
DR GeneWiki; NUDT4; -.
DR GenomeRNAi; 11163; -.
DR NextBio; 42469; -.
DR PRO; PR:Q9NZJ9; -.
DR ArrayExpress; Q9NZJ9; -.
DR Bgee; Q9NZJ9; -.
DR CleanEx; HS_NUDT4; -.
DR Genevestigator; Q9NZJ9; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0008486; F:diphosphoinositol-polyphosphate diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0052840; F:inositol diphosphate tetrakisphosphate diphosphatase activity; TAS:Reactome.
DR GO; GO:0052846; F:inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 1-diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052847; F:inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052843; F:inositol-1-diphosphate-2,3,4,5,6-pentakisphosphate diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052848; F:inositol-3,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052844; F:inositol-3-diphosphate-1,2,4,5,6-pentakisphosphate diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052845; F:inositol-5-diphosphate-1,2,3,4,6-pentakisphosphate diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030515; F:snoRNA binding; ISS:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; TAS:UniProtKB.
DR GO; GO:0009187; P:cyclic nucleotide metabolic process; TAS:ProtInc.
DR GO; GO:0019935; P:cyclic-nucleotide-mediated signaling; TAS:UniProtKB.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0046907; P:intracellular transport; TAS:UniProtKB.
DR GO; GO:0046831; P:regulation of RNA export from nucleus; TAS:UniProtKB.
DR Gene3D; 3.90.79.10; -; 1.
DR InterPro; IPR020084; NUDIX_hydrolase_CS.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR InterPro; IPR015797; NUDIX_hydrolase_dom-like.
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; Alternative splicing; Complete proteome; Cytoplasm;
KW Hydrolase; Magnesium; Manganese; Metal-binding; Reference proteome;
KW RNA-binding.
FT CHAIN 1 180 Diphosphoinositol polyphosphate
FT phosphohydrolase 2.
FT /FTId=PRO_0000057058.
FT DOMAIN 18 144 Nudix hydrolase.
FT REGION 18 20 Substrate binding (By similarity).
FT REGION 89 91 Substrate binding (By similarity).
FT MOTIF 51 72 Nudix box.
FT ACT_SITE 69 69 Proton acceptor (By similarity).
FT METAL 50 50 Magnesium 1; via carbonyl oxygen (By
FT similarity).
FT METAL 66 66 Magnesium 2 (By similarity).
FT METAL 66 66 Magnesium 3 (By similarity).
FT METAL 70 70 Magnesium 1 (By similarity).
FT BINDING 10 10 Substrate (By similarity).
FT BINDING 41 41 Substrate (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 1 52 Missing (in isoform 3).
FT /FTId=VSP_014269.
FT VAR_SEQ 85 85 E -> EQ (in isoform 2 and isoform 3).
FT /FTId=VSP_014270.
FT CONFLICT 16 16 G -> D (in Ref. 1; AAF68857).
FT CONFLICT 41 41 R -> Q (in Ref. 7; BAD97217).
FT CONFLICT 73 73 V -> D (in Ref. 3; AAF75563).
FT CONFLICT 164 164 A -> V (in Ref. 1; AAF68857).
FT CONFLICT 177 177 S -> P (in Ref. 1; AAF68858).
SQ SEQUENCE 180 AA; 20306 MW; 86D766F8F5B22D13 CRC64;
MMKFKPNQTR TYDREGFKKR AACLCFRSEQ EDEVLLVSSS RYPDQWIVPG GGMEPEEEPG
GAAVREVYEE AGVKGKLGRL LGIFENQDRK HRTYVYVLTV TEILEDWEDS VNIGRKREWF
KVEDAIKVLQ CHKPVHAEYL EKLKLGCSPA NGNSTVPSLP DNNALFVTAA QTSGLPSSVR
//
MIM
609229
*RECORD*
*FIELD* NO
609229
*FIELD* TI
*609229 NUCLEOSIDE DIPHOSPHATE-LINKED MOIETY X MOTIF 4; NUDT4
;;NUDIX MOTIF 4;;
DIPHOSPHOINOSITOL POLYPHOSPHATE PHOSPHOHYDROLASE 2; DIPP2;;
read moreKIAA0487
*FIELD* TX
DESCRIPTION
Members of the DIPP subfamily of Nudix proteins, such as NUDT4,
hydrolyze specific diphosphoinositol polyphosphates and diadenosine
polyphosphates (Caffrey et al., 2000).
CLONING
By searching an EST database for sequences similar to NUDT3 (609228),
followed by PCR of heart and fetal kidney cDNA libraries, Caffrey et al.
(2000) obtained cDNA clones encoding 2 splice variants of NUDT4, which
they designated DIPP2-alpha and DIPP2-beta. The DIPP2 transcripts use
several alternate polyadenylation signals. The 5-prime UTRs have a high
GC content, and the longer 3-prime UTRs contain Alu repeats. DIPP2-alpha
and DIPP2-beta encode proteins of 180 and 181 amino acids, respectively;
an additional CAG codon in the DIPP2-beta transcript results in an
insertion of gln86. Both proteins contain a central Nudix motif,
followed by a gly-rich extension (GxxGxxxxxxG) characteristic of
DIPP-type hydrolases. Northern blot analysis detected transcripts of 1.5
and 1.8 kb in skeletal muscle, kidney, placenta, and pancreas. A 4.2-kb
transcript was detected in heart, skeletal muscle, kidney, and pancreas,
with weaker expression in brain, placenta, lung, and liver.
By PCR analysis, Caffrey and Shears (2001) found that both DIPP2-alpha
and DIPP2-beta were expressed in a human leukemia cell line and in an
adenocarcinoma cell line. They determined that the 2 transcripts result
from alternative splicing at an AGCAG pentamer that offers adjacent,
alternate intronic 3-prime borders.
GENE FUNCTION
Caffrey et al. (2000) determined that purified recombinant DIPP2-alpha
hydrolyzed the beta phosphate from diphosphoinositol pentakisphosphate
(PP-InsP5) and PP-tetrakisphosphate (PP-InsP4). DIPP2-alpha showed high
affinity for PP-InsP5. Recombinant DIPP2-beta was 5-fold less active
against PP-InsP5 and 2.5-fold less active against PP-InsP4 than
DIPP2-alpha. Both enzymes also hydrolyzed diadenosine hexaphosphate.
DIPP2-beta showed activity against diadenosine pentaphosphate, but
DIPP2-alpha did not.
GENE STRUCTURE
Caffrey and Shears (2001) determined that the NUDT4 gene contains 4
exons.
MAPPING
By Southern blot analysis, radiation hybrid analysis, and FISH, Caffrey
and Shears (2001) mapped the NUDT4 gene to chromosome 12q21. They
identified 2 intronless NUDT4 pseudogenes on chromosome 1.
*FIELD* RF
1. Caffrey, J. J.; Safrany, S. T.; Yang, X.; Shears, S. B.: Discovery
of molecular and catalytic diversity among human diphosphoinositol-polyphosphate
phosphohydrolases: an expanding Nudt family. J. Biol. Chem. 275:
12730-12736, 2000.
2. Caffrey, J. J.; Shears, S. B.: Genetic rationale for microheterogeneity
of human diphosphoinositol polyphosphate phosphohydrolase type 2. Gene 269:
53-60, 2001.
*FIELD* CD
Patricia A. Hartz: 3/2/2005
*FIELD* ED
mgross: 03/02/2005
*RECORD*
*FIELD* NO
609229
*FIELD* TI
*609229 NUCLEOSIDE DIPHOSPHATE-LINKED MOIETY X MOTIF 4; NUDT4
;;NUDIX MOTIF 4;;
DIPHOSPHOINOSITOL POLYPHOSPHATE PHOSPHOHYDROLASE 2; DIPP2;;
read moreKIAA0487
*FIELD* TX
DESCRIPTION
Members of the DIPP subfamily of Nudix proteins, such as NUDT4,
hydrolyze specific diphosphoinositol polyphosphates and diadenosine
polyphosphates (Caffrey et al., 2000).
CLONING
By searching an EST database for sequences similar to NUDT3 (609228),
followed by PCR of heart and fetal kidney cDNA libraries, Caffrey et al.
(2000) obtained cDNA clones encoding 2 splice variants of NUDT4, which
they designated DIPP2-alpha and DIPP2-beta. The DIPP2 transcripts use
several alternate polyadenylation signals. The 5-prime UTRs have a high
GC content, and the longer 3-prime UTRs contain Alu repeats. DIPP2-alpha
and DIPP2-beta encode proteins of 180 and 181 amino acids, respectively;
an additional CAG codon in the DIPP2-beta transcript results in an
insertion of gln86. Both proteins contain a central Nudix motif,
followed by a gly-rich extension (GxxGxxxxxxG) characteristic of
DIPP-type hydrolases. Northern blot analysis detected transcripts of 1.5
and 1.8 kb in skeletal muscle, kidney, placenta, and pancreas. A 4.2-kb
transcript was detected in heart, skeletal muscle, kidney, and pancreas,
with weaker expression in brain, placenta, lung, and liver.
By PCR analysis, Caffrey and Shears (2001) found that both DIPP2-alpha
and DIPP2-beta were expressed in a human leukemia cell line and in an
adenocarcinoma cell line. They determined that the 2 transcripts result
from alternative splicing at an AGCAG pentamer that offers adjacent,
alternate intronic 3-prime borders.
GENE FUNCTION
Caffrey et al. (2000) determined that purified recombinant DIPP2-alpha
hydrolyzed the beta phosphate from diphosphoinositol pentakisphosphate
(PP-InsP5) and PP-tetrakisphosphate (PP-InsP4). DIPP2-alpha showed high
affinity for PP-InsP5. Recombinant DIPP2-beta was 5-fold less active
against PP-InsP5 and 2.5-fold less active against PP-InsP4 than
DIPP2-alpha. Both enzymes also hydrolyzed diadenosine hexaphosphate.
DIPP2-beta showed activity against diadenosine pentaphosphate, but
DIPP2-alpha did not.
GENE STRUCTURE
Caffrey and Shears (2001) determined that the NUDT4 gene contains 4
exons.
MAPPING
By Southern blot analysis, radiation hybrid analysis, and FISH, Caffrey
and Shears (2001) mapped the NUDT4 gene to chromosome 12q21. They
identified 2 intronless NUDT4 pseudogenes on chromosome 1.
*FIELD* RF
1. Caffrey, J. J.; Safrany, S. T.; Yang, X.; Shears, S. B.: Discovery
of molecular and catalytic diversity among human diphosphoinositol-polyphosphate
phosphohydrolases: an expanding Nudt family. J. Biol. Chem. 275:
12730-12736, 2000.
2. Caffrey, J. J.; Shears, S. B.: Genetic rationale for microheterogeneity
of human diphosphoinositol polyphosphate phosphohydrolase type 2. Gene 269:
53-60, 2001.
*FIELD* CD
Patricia A. Hartz: 3/2/2005
*FIELD* ED
mgross: 03/02/2005