Full text data of NUDT5
NUDT5
[Confidence: low (only semi-automatic identification from reviews)]
ADP-sugar pyrophosphatase; 3.6.1.13 (8-oxo-dGDP phosphatase; 3.6.1.58; Nucleoside diphosphate-linked moiety X motif 5; Nudix motif 5; YSA1H)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
ADP-sugar pyrophosphatase; 3.6.1.13 (8-oxo-dGDP phosphatase; 3.6.1.58; Nucleoside diphosphate-linked moiety X motif 5; Nudix motif 5; YSA1H)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9UKK9
ID NUDT5_HUMAN Reviewed; 219 AA.
AC Q9UKK9; A8K516; Q6IAG0; Q9UH49;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 120.
DE RecName: Full=ADP-sugar pyrophosphatase;
DE EC=3.6.1.13;
DE AltName: Full=8-oxo-dGDP phosphatase;
DE EC=3.6.1.58;
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 5;
DE Short=Nudix motif 5;
DE AltName: Full=YSA1H;
GN Name=NUDT5; ORFNames=HSPC115;
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], AND CHARACTERIZATION.
RX PubMed=10567213; DOI=10.1042/0264-6021:3440331;
RA Gasmi L., Cartwright J.L., McLennan A.G.;
RT "Cloning, expression and characterization of YSA1H, a human adenosine
RT 5'-diphosphosugar pyrophosphatase possessing a MutT motif.";
RL Biochem. J. 344:331-337(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RX PubMed=10722730; DOI=10.1074/jbc.275.12.8844;
RA Yang H., Slupska M.M., Wei Y.-F., Tai J.H., Luther W.M., Xia Y.-R.,
RA Shih D.M., Chiang J.-H., Baikalov C., Fitz-Gibbon S., Phan I.T.,
RA Conrad A., Miller J.H.;
RT "Cloning and characterization of a new member of the Nudix hydrolases
RT from human and mouse.";
RL J. Biol. Chem. 275:8844-8853(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-74, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-210 AND LYS-218, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-10, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-3, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-210 IN COMPLEX WITH AMP;
RP MAGNESIUM IONS AND ADP-RIBOSE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP AND COFACTOR.
RX PubMed=17052728; DOI=10.1016/j.jmb.2006.09.078;
RA Zha M., Zhong C., Peng Y., Hu H., Ding J.;
RT "Crystal structures of human NUDT5 reveal insights into the structural
RT basis of the substrate specificity.";
RL J. Mol. Biol. 364:1021-1033(2006).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-210 IN COMPLEX WITH AMPCPR
RP AND MAGNESIUM IONS, COFACTOR, MUTAGENESIS OF TRP-28; TRP-46; ARG-51;
RP ARG-84; LEU-98; GLU-112; GLU-116 AND GLU-166, AND SUBUNIT.
RX PubMed=18462755; DOI=10.1016/j.jmb.2008.04.006;
RA Zha M., Guo Q., Zhang Y., Yu B., Ou Y., Zhong C., Ding J.;
RT "Molecular mechanism of ADP-ribose hydrolysis by human NUDT5 from
RT structural and kinetic studies.";
RL J. Mol. Biol. 379:568-578(2008).
CC -!- FUNCTION: Hydrolyzes with similar activities ADP-ribose ADP-
CC mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP. Can also hydrolyze
CC other nucleotide sugars with low activity. Does not play a role in
CC U8 snoRNA decapping activity. Binds U8 snoRNA.
CC -!- CATALYTIC ACTIVITY: ADP-D-ribose + H(2)O = AMP + D-ribose 5-
CC phosphate.
CC -!- CATALYTIC ACTIVITY: ADP-sugar + H(2)O = AMP + alpha-D-aldose 5-
CC phosphate.
CC -!- CATALYTIC ACTIVITY: 8-oxo-dGDP + H(2)O = 8-oxo-dGMP + phosphate.
CC -!- COFACTOR: Binds 3 magnesium ions per subunit.
CC -!- SUBUNIT: Homodimer.
CC -!- TISSUE SPECIFICITY: Widely expressed. Most abundant in liver.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family.
CC -!- SIMILARITY: Contains 1 nudix hydrolase domain.
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DR EMBL; AF155832; AAF06734.1; -; mRNA.
DR EMBL; AF218818; AAF25479.1; -; mRNA.
DR EMBL; AF161464; AAF29079.1; -; mRNA.
DR EMBL; CR457195; CAG33476.1; -; mRNA.
DR EMBL; AK291131; BAF83820.1; -; mRNA.
DR EMBL; CH471072; EAW86322.1; -; Genomic_DNA.
DR EMBL; BC000025; AAH00025.1; -; mRNA.
DR RefSeq; NP_054861.2; NM_014142.2.
DR UniGene; Hs.555956; -.
DR PDB; 2DSB; X-ray; 2.50 A; A/B/C/D=1-219.
DR PDB; 2DSC; X-ray; 2.00 A; A/B=1-210.
DR PDB; 2DSD; X-ray; 2.60 A; A/B=1-210.
DR PDB; 3AC9; X-ray; 2.10 A; A/B=14-208.
DR PDB; 3ACA; X-ray; 2.05 A; A/B=13-208.
DR PDB; 3BM4; X-ray; 2.00 A; A/B=1-210.
DR PDB; 3L85; X-ray; 2.30 A; A/B=14-208.
DR PDBsum; 2DSB; -.
DR PDBsum; 2DSC; -.
DR PDBsum; 2DSD; -.
DR PDBsum; 3AC9; -.
DR PDBsum; 3ACA; -.
DR PDBsum; 3BM4; -.
DR PDBsum; 3L85; -.
DR ProteinModelPortal; Q9UKK9; -.
DR SMR; Q9UKK9; 13-209.
DR IntAct; Q9UKK9; 6.
DR MINT; MINT-1370495; -.
DR STRING; 9606.ENSP00000419628; -.
DR PhosphoSite; Q9UKK9; -.
DR DMDM; 20455192; -.
DR PaxDb; Q9UKK9; -.
DR PRIDE; Q9UKK9; -.
DR DNASU; 11164; -.
DR Ensembl; ENST00000491614; ENSP00000419628; ENSG00000165609.
DR Ensembl; ENST00000537776; ENSP00000445116; ENSG00000165609.
DR GeneID; 11164; -.
DR KEGG; hsa:11164; -.
DR UCSC; uc001ilj.3; human.
DR CTD; 11164; -.
DR GeneCards; GC10M012207; -.
DR HGNC; HGNC:8052; NUDT5.
DR HPA; HPA019827; -.
DR MIM; 609230; gene.
DR neXtProt; NX_Q9UKK9; -.
DR PharmGKB; PA31838; -.
DR eggNOG; COG0494; -.
DR HOGENOM; HOG000174302; -.
DR HOVERGEN; HBG052691; -.
DR KO; K13987; -.
DR OrthoDB; EOG7CVPZW; -.
DR PhylomeDB; Q9UKK9; -.
DR BRENDA; 3.6.1.13; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; Q9UKK9; -.
DR ChiTaRS; NUDT5; human.
DR EvolutionaryTrace; Q9UKK9; -.
DR GeneWiki; NUDT5; -.
DR GenomeRNAi; 11164; -.
DR NextBio; 42475; -.
DR PRO; PR:Q9UKK9; -.
DR ArrayExpress; Q9UKK9; -.
DR Bgee; Q9UKK9; -.
DR CleanEx; HS_NUDT5; -.
DR Genevestigator; Q9UKK9; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0047631; F:ADP-ribose diphosphatase activity; EXP:Reactome.
DR GO; GO:0019144; F:ADP-sugar diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0017110; F:nucleoside-diphosphatase activity; IEA:Ensembl.
DR GO; GO:0030515; F:snoRNA binding; ISS:UniProtKB.
DR GO; GO:0019303; P:D-ribose catabolic process; NAS:UniProtKB.
DR GO; GO:0034656; P:nucleobase-containing small molecule catabolic process; TAS:Reactome.
DR GO; GO:0009117; P:nucleotide metabolic process; NAS:ProtInc.
DR GO; GO:0009191; P:ribonucleoside diphosphate catabolic process; IDA:UniProtKB.
DR Gene3D; 3.90.79.10; -; 1.
DR InterPro; IPR020476; Nudix_hydrolase.
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 PRINTS; PR00502; NUDIXFAMILY.
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; Complete proteome; Hydrolase; Magnesium;
KW Metal-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW RNA-binding.
FT CHAIN 1 219 ADP-sugar pyrophosphatase.
FT /FTId=PRO_0000057048.
FT DOMAIN 57 197 Nudix hydrolase.
FT REGION 46 47 Substrate binding; shared with dimeric
FT partner.
FT MOTIF 97 118 Nudix box.
FT METAL 96 96 Magnesium 1; via carbonyl oxygen.
FT METAL 112 112 Magnesium 2.
FT METAL 112 112 Magnesium 3.
FT METAL 116 116 Magnesium 1.
FT METAL 116 116 Magnesium 3.
FT METAL 166 166 Magnesium 3.
FT BINDING 28 28 Substrate.
FT BINDING 51 51 Substrate; shared with dimeric partner.
FT BINDING 84 84 Substrate.
FT BINDING 98 98 Substrate; via amide nitrogen.
FT BINDING 133 133 Substrate.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 3 3 Phosphoserine.
FT MOD_RES 10 10 Phosphoserine.
FT MOD_RES 74 74 Phosphotyrosine.
FT MOD_RES 210 210 N6-acetyllysine.
FT MOD_RES 218 218 N6-acetyllysine.
FT VARIANT 123 123 I -> T (in dbSNP:rs34863826).
FT /FTId=VAR_034159.
FT MUTAGEN 28 28 W->A: Reduces affinity for substrate
FT about 8-fold. Strongly reduced catalytic
FT activity and strongly reduced affinity
FT for substrate; when associated with A-46.
FT MUTAGEN 46 46 W->A: Reduces affinity for substrate
FT about 6-fold. Strongly reduced catalytic
FT activity and strongly reduced affinity
FT for substrate; when associated with A-28.
FT MUTAGEN 51 51 R->Q: Reduces affinity for substrate
FT about 15-fold and reduces catalytic rate
FT about 17-fold.
FT MUTAGEN 84 84 R->Q: Reduces affinity for substrate
FT about 5-fold and reduces catalytic rate
FT 67-fold.
FT MUTAGEN 98 98 L->A: Reduces affinity for substrate
FT about 6-fold.
FT MUTAGEN 112 112 E->Q: Reduces catalytic rate 6300-fold.
FT MUTAGEN 116 116 E->Q: Reduces catalytic rate 2000-fold.
FT MUTAGEN 166 166 E->Q: Reduces catalytic rate 120-fold.
FT CONFLICT 50 52 KRT -> NVP (in Ref. 2; AAF25479).
FT STRAND 16 25
FT STRAND 27 37
FT STRAND 43 51
FT STRAND 60 69
FT STRAND 76 84
FT HELIX 85 87
FT STRAND 89 93
FT STRAND 96 98
FT HELIX 105 117
FT STRAND 122 126
FT STRAND 130 132
FT TURN 134 136
FT STRAND 140 149
FT HELIX 153 155
FT STRAND 164 166
FT STRAND 169 174
FT HELIX 175 177
FT HELIX 178 189
FT STRAND 192 194
FT HELIX 195 207
FT TURN 211 213
FT HELIX 214 216
SQ SEQUENCE 219 AA; 24328 MW; 6574E0BF1EA2BB26 CRC64;
MESQEPTESS QNGKQYIISE ELISEGKWVK LEKTTYMDPT GKTRTWESVK RTTRKEQTAD
GVAVIPVLQR TLHYECIVLV KQFRPPMGGY CIEFPAGLID DGETPEAAAL RELEEETGYK
GDIAECSPAV CMDPGLSNCT IHIVTVTING DDAENARPKP KPGDGEFVEV ISLPKNDLLQ
RLDALVAEEH LTVDARVYSY ALALKHANAK PFEVPFLKF
//
ID NUDT5_HUMAN Reviewed; 219 AA.
AC Q9UKK9; A8K516; Q6IAG0; Q9UH49;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 120.
DE RecName: Full=ADP-sugar pyrophosphatase;
DE EC=3.6.1.13;
DE AltName: Full=8-oxo-dGDP phosphatase;
DE EC=3.6.1.58;
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 5;
DE Short=Nudix motif 5;
DE AltName: Full=YSA1H;
GN Name=NUDT5; ORFNames=HSPC115;
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], AND CHARACTERIZATION.
RX PubMed=10567213; DOI=10.1042/0264-6021:3440331;
RA Gasmi L., Cartwright J.L., McLennan A.G.;
RT "Cloning, expression and characterization of YSA1H, a human adenosine
RT 5'-diphosphosugar pyrophosphatase possessing a MutT motif.";
RL Biochem. J. 344:331-337(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RX PubMed=10722730; DOI=10.1074/jbc.275.12.8844;
RA Yang H., Slupska M.M., Wei Y.-F., Tai J.H., Luther W.M., Xia Y.-R.,
RA Shih D.M., Chiang J.-H., Baikalov C., Fitz-Gibbon S., Phan I.T.,
RA Conrad A., Miller J.H.;
RT "Cloning and characterization of a new member of the Nudix hydrolases
RT from human and mouse.";
RL J. Biol. Chem. 275:8844-8853(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-74, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-210 AND LYS-218, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-10, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
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 [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-3, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-210 IN COMPLEX WITH AMP;
RP MAGNESIUM IONS AND ADP-RIBOSE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT,
RP AND COFACTOR.
RX PubMed=17052728; DOI=10.1016/j.jmb.2006.09.078;
RA Zha M., Zhong C., Peng Y., Hu H., Ding J.;
RT "Crystal structures of human NUDT5 reveal insights into the structural
RT basis of the substrate specificity.";
RL J. Mol. Biol. 364:1021-1033(2006).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-210 IN COMPLEX WITH AMPCPR
RP AND MAGNESIUM IONS, COFACTOR, MUTAGENESIS OF TRP-28; TRP-46; ARG-51;
RP ARG-84; LEU-98; GLU-112; GLU-116 AND GLU-166, AND SUBUNIT.
RX PubMed=18462755; DOI=10.1016/j.jmb.2008.04.006;
RA Zha M., Guo Q., Zhang Y., Yu B., Ou Y., Zhong C., Ding J.;
RT "Molecular mechanism of ADP-ribose hydrolysis by human NUDT5 from
RT structural and kinetic studies.";
RL J. Mol. Biol. 379:568-578(2008).
CC -!- FUNCTION: Hydrolyzes with similar activities ADP-ribose ADP-
CC mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP. Can also hydrolyze
CC other nucleotide sugars with low activity. Does not play a role in
CC U8 snoRNA decapping activity. Binds U8 snoRNA.
CC -!- CATALYTIC ACTIVITY: ADP-D-ribose + H(2)O = AMP + D-ribose 5-
CC phosphate.
CC -!- CATALYTIC ACTIVITY: ADP-sugar + H(2)O = AMP + alpha-D-aldose 5-
CC phosphate.
CC -!- CATALYTIC ACTIVITY: 8-oxo-dGDP + H(2)O = 8-oxo-dGMP + phosphate.
CC -!- COFACTOR: Binds 3 magnesium ions per subunit.
CC -!- SUBUNIT: Homodimer.
CC -!- TISSUE SPECIFICITY: Widely expressed. Most abundant in liver.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family.
CC -!- SIMILARITY: Contains 1 nudix hydrolase domain.
CC -----------------------------------------------------------------------
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DR EMBL; AF155832; AAF06734.1; -; mRNA.
DR EMBL; AF218818; AAF25479.1; -; mRNA.
DR EMBL; AF161464; AAF29079.1; -; mRNA.
DR EMBL; CR457195; CAG33476.1; -; mRNA.
DR EMBL; AK291131; BAF83820.1; -; mRNA.
DR EMBL; CH471072; EAW86322.1; -; Genomic_DNA.
DR EMBL; BC000025; AAH00025.1; -; mRNA.
DR RefSeq; NP_054861.2; NM_014142.2.
DR UniGene; Hs.555956; -.
DR PDB; 2DSB; X-ray; 2.50 A; A/B/C/D=1-219.
DR PDB; 2DSC; X-ray; 2.00 A; A/B=1-210.
DR PDB; 2DSD; X-ray; 2.60 A; A/B=1-210.
DR PDB; 3AC9; X-ray; 2.10 A; A/B=14-208.
DR PDB; 3ACA; X-ray; 2.05 A; A/B=13-208.
DR PDB; 3BM4; X-ray; 2.00 A; A/B=1-210.
DR PDB; 3L85; X-ray; 2.30 A; A/B=14-208.
DR PDBsum; 2DSB; -.
DR PDBsum; 2DSC; -.
DR PDBsum; 2DSD; -.
DR PDBsum; 3AC9; -.
DR PDBsum; 3ACA; -.
DR PDBsum; 3BM4; -.
DR PDBsum; 3L85; -.
DR ProteinModelPortal; Q9UKK9; -.
DR SMR; Q9UKK9; 13-209.
DR IntAct; Q9UKK9; 6.
DR MINT; MINT-1370495; -.
DR STRING; 9606.ENSP00000419628; -.
DR PhosphoSite; Q9UKK9; -.
DR DMDM; 20455192; -.
DR PaxDb; Q9UKK9; -.
DR PRIDE; Q9UKK9; -.
DR DNASU; 11164; -.
DR Ensembl; ENST00000491614; ENSP00000419628; ENSG00000165609.
DR Ensembl; ENST00000537776; ENSP00000445116; ENSG00000165609.
DR GeneID; 11164; -.
DR KEGG; hsa:11164; -.
DR UCSC; uc001ilj.3; human.
DR CTD; 11164; -.
DR GeneCards; GC10M012207; -.
DR HGNC; HGNC:8052; NUDT5.
DR HPA; HPA019827; -.
DR MIM; 609230; gene.
DR neXtProt; NX_Q9UKK9; -.
DR PharmGKB; PA31838; -.
DR eggNOG; COG0494; -.
DR HOGENOM; HOG000174302; -.
DR HOVERGEN; HBG052691; -.
DR KO; K13987; -.
DR OrthoDB; EOG7CVPZW; -.
DR PhylomeDB; Q9UKK9; -.
DR BRENDA; 3.6.1.13; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; Q9UKK9; -.
DR ChiTaRS; NUDT5; human.
DR EvolutionaryTrace; Q9UKK9; -.
DR GeneWiki; NUDT5; -.
DR GenomeRNAi; 11164; -.
DR NextBio; 42475; -.
DR PRO; PR:Q9UKK9; -.
DR ArrayExpress; Q9UKK9; -.
DR Bgee; Q9UKK9; -.
DR CleanEx; HS_NUDT5; -.
DR Genevestigator; Q9UKK9; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0047631; F:ADP-ribose diphosphatase activity; EXP:Reactome.
DR GO; GO:0019144; F:ADP-sugar diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0017110; F:nucleoside-diphosphatase activity; IEA:Ensembl.
DR GO; GO:0030515; F:snoRNA binding; ISS:UniProtKB.
DR GO; GO:0019303; P:D-ribose catabolic process; NAS:UniProtKB.
DR GO; GO:0034656; P:nucleobase-containing small molecule catabolic process; TAS:Reactome.
DR GO; GO:0009117; P:nucleotide metabolic process; NAS:ProtInc.
DR GO; GO:0009191; P:ribonucleoside diphosphate catabolic process; IDA:UniProtKB.
DR Gene3D; 3.90.79.10; -; 1.
DR InterPro; IPR020476; Nudix_hydrolase.
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 PRINTS; PR00502; NUDIXFAMILY.
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; Complete proteome; Hydrolase; Magnesium;
KW Metal-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW RNA-binding.
FT CHAIN 1 219 ADP-sugar pyrophosphatase.
FT /FTId=PRO_0000057048.
FT DOMAIN 57 197 Nudix hydrolase.
FT REGION 46 47 Substrate binding; shared with dimeric
FT partner.
FT MOTIF 97 118 Nudix box.
FT METAL 96 96 Magnesium 1; via carbonyl oxygen.
FT METAL 112 112 Magnesium 2.
FT METAL 112 112 Magnesium 3.
FT METAL 116 116 Magnesium 1.
FT METAL 116 116 Magnesium 3.
FT METAL 166 166 Magnesium 3.
FT BINDING 28 28 Substrate.
FT BINDING 51 51 Substrate; shared with dimeric partner.
FT BINDING 84 84 Substrate.
FT BINDING 98 98 Substrate; via amide nitrogen.
FT BINDING 133 133 Substrate.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 3 3 Phosphoserine.
FT MOD_RES 10 10 Phosphoserine.
FT MOD_RES 74 74 Phosphotyrosine.
FT MOD_RES 210 210 N6-acetyllysine.
FT MOD_RES 218 218 N6-acetyllysine.
FT VARIANT 123 123 I -> T (in dbSNP:rs34863826).
FT /FTId=VAR_034159.
FT MUTAGEN 28 28 W->A: Reduces affinity for substrate
FT about 8-fold. Strongly reduced catalytic
FT activity and strongly reduced affinity
FT for substrate; when associated with A-46.
FT MUTAGEN 46 46 W->A: Reduces affinity for substrate
FT about 6-fold. Strongly reduced catalytic
FT activity and strongly reduced affinity
FT for substrate; when associated with A-28.
FT MUTAGEN 51 51 R->Q: Reduces affinity for substrate
FT about 15-fold and reduces catalytic rate
FT about 17-fold.
FT MUTAGEN 84 84 R->Q: Reduces affinity for substrate
FT about 5-fold and reduces catalytic rate
FT 67-fold.
FT MUTAGEN 98 98 L->A: Reduces affinity for substrate
FT about 6-fold.
FT MUTAGEN 112 112 E->Q: Reduces catalytic rate 6300-fold.
FT MUTAGEN 116 116 E->Q: Reduces catalytic rate 2000-fold.
FT MUTAGEN 166 166 E->Q: Reduces catalytic rate 120-fold.
FT CONFLICT 50 52 KRT -> NVP (in Ref. 2; AAF25479).
FT STRAND 16 25
FT STRAND 27 37
FT STRAND 43 51
FT STRAND 60 69
FT STRAND 76 84
FT HELIX 85 87
FT STRAND 89 93
FT STRAND 96 98
FT HELIX 105 117
FT STRAND 122 126
FT STRAND 130 132
FT TURN 134 136
FT STRAND 140 149
FT HELIX 153 155
FT STRAND 164 166
FT STRAND 169 174
FT HELIX 175 177
FT HELIX 178 189
FT STRAND 192 194
FT HELIX 195 207
FT TURN 211 213
FT HELIX 214 216
SQ SEQUENCE 219 AA; 24328 MW; 6574E0BF1EA2BB26 CRC64;
MESQEPTESS QNGKQYIISE ELISEGKWVK LEKTTYMDPT GKTRTWESVK RTTRKEQTAD
GVAVIPVLQR TLHYECIVLV KQFRPPMGGY CIEFPAGLID DGETPEAAAL RELEEETGYK
GDIAECSPAV CMDPGLSNCT IHIVTVTING DDAENARPKP KPGDGEFVEV ISLPKNDLLQ
RLDALVAEEH LTVDARVYSY ALALKHANAK PFEVPFLKF
//
MIM
609230
*RECORD*
*FIELD* NO
609230
*FIELD* TI
*609230 NUCLEOSIDE DIPHOSPHATE-LINKED MOIETY X MOTIF 5; NUDT5
;;NUDIX MOTIF 5;;
YSA1, S. CEREVISIAE, HOMOLOG OF; YSA1; YSA1H
read more*FIELD* TX
DESCRIPTION
Nudix hydrolases, such as NUDT5, eliminate toxic nucleotide derivatives
from the cell and regulate the levels of important signaling nucleotides
and their metabolites (McLennan, 1999).
CLONING
By searching an EST database for sequences similar to S. cerevisiae
Ysa1, Gasmi et al. (1999) identified NUDT5, which they designated YSA1H.
The deduced 219-amino acid protein has a calculated molecular mass of
24.3 kD. NUDT5 contains a central Nudix motif. Northern blot analysis
detected a 1.4-kb transcript in all tissues examined. Minor transcripts
of about 5.0 and 1.1 kb were also detected. RNA dot blot analysis
revealed NUDT5 expression in all tissues examined. Highest levels were
in liver, kidney, pituitary, placenta, and thymus, and lowest levels
were in bone marrow, lymph node, and certain areas of brain. Western
blot analysis detected NUDT5 at an apparent molecular mass of 33 kD in
human nasopharyngeal carcinoma cells, promonocytic cells, and
erythrocytes. Bands of about 66 and 64 kD suggested NUDT5 may form
dimers.
Yang et al. (2000) cloned mouse Nudt5, which encodes a 218-amino acid
protein that shares 81% identity with human NUDT5. Northern blot
analysis detected Nudt5 expression in all adult mouse tissues analyzed,
with highest abundance in liver. RNA dot blot analysis of human tissues
detected abundant NUDT5 expression in liver, pituitary, and placenta, as
well as in HeLa cervical carcinoma cells.
GENE FUNCTION
Gasmi et al. (1999) found that recombinant NUDT5 produced in E. coli was
active against ADP-ribose and ADP-mannose. It showed lower activity
against ADP-glucose and diadenosine diphosphate. cADP-ribose was not a
substrate. Optimal activity was obtained between pH 7.4 and 9.0 in the
presence of Mg(2+) or Mn(2+), and fluoride was inhibitory.
Yang et al. (2000) confirmed that NUDT5 hydrolyzed ADP-ribose and
ADP-mannose in the presence of Mg(2+) or several other divalent cations.
They found that the rate of hydrolysis decreased significantly as the
nucleoside in ADP-sugar changed from adenosine to guanosine or uridine.
Mouse Nudt5 showed slightly different catalytic properties than human
NUDT5.
GENE STRUCTURE
Yang et al. (2000) determined that the NUDT5 gene contains 9 exons and
spans about 18.5 kb. The mouse Nudt5 gene also has 9 exons and spans 13
kb. The introns of the mouse and human genes are in the same positions
within their coding sequences.
MAPPING
By genomic sequence analysis, Gasmi et al. (1999) mapped the NUDT5 gene
to chromosome 10p14-p13. Yang et al. (2000) mapped the mouse Nudt5 gene
to a region of chromosome 2 that shows homology of synteny to human
chromosome 10.
*FIELD* RF
1. Gasmi, L.; Cartwright, J. L.; McLennan, A. G.: Cloning, expression
and characterization of YSA1H, a human adenosine 5-prime-diphosphosugar
pyrophosphatase possessing a MutT motif. Biochem. J. 344: 331-337,
1999.
2. McLennan, A. G.: The MutT family of nucleotide phosphohydrolases
in man and human pathogens. Int. J. Molec. Med. 4: 79-89, 1999.
3. Yang, H.; Slupska, M. M.; Wei, Y.-F.; Tai, J. H.; Luther, W. M.;
Xia, Y.-R.; Shih, D. M.; Chiang, J.-H.; Baikalov, C.; Fitz-Gibbon,
S.; Phan, I. T.; Conrad, A.; Miller, J. H.: Cloning and characterization
of a new member of the Nudix hydrolases from human and mouse. J.
Biol. Chem. 275: 8844-8853, 2000.
*FIELD* CD
Patricia A. Hartz: 3/2/2005
*FIELD* ED
mgross: 03/02/2005
*RECORD*
*FIELD* NO
609230
*FIELD* TI
*609230 NUCLEOSIDE DIPHOSPHATE-LINKED MOIETY X MOTIF 5; NUDT5
;;NUDIX MOTIF 5;;
YSA1, S. CEREVISIAE, HOMOLOG OF; YSA1; YSA1H
read more*FIELD* TX
DESCRIPTION
Nudix hydrolases, such as NUDT5, eliminate toxic nucleotide derivatives
from the cell and regulate the levels of important signaling nucleotides
and their metabolites (McLennan, 1999).
CLONING
By searching an EST database for sequences similar to S. cerevisiae
Ysa1, Gasmi et al. (1999) identified NUDT5, which they designated YSA1H.
The deduced 219-amino acid protein has a calculated molecular mass of
24.3 kD. NUDT5 contains a central Nudix motif. Northern blot analysis
detected a 1.4-kb transcript in all tissues examined. Minor transcripts
of about 5.0 and 1.1 kb were also detected. RNA dot blot analysis
revealed NUDT5 expression in all tissues examined. Highest levels were
in liver, kidney, pituitary, placenta, and thymus, and lowest levels
were in bone marrow, lymph node, and certain areas of brain. Western
blot analysis detected NUDT5 at an apparent molecular mass of 33 kD in
human nasopharyngeal carcinoma cells, promonocytic cells, and
erythrocytes. Bands of about 66 and 64 kD suggested NUDT5 may form
dimers.
Yang et al. (2000) cloned mouse Nudt5, which encodes a 218-amino acid
protein that shares 81% identity with human NUDT5. Northern blot
analysis detected Nudt5 expression in all adult mouse tissues analyzed,
with highest abundance in liver. RNA dot blot analysis of human tissues
detected abundant NUDT5 expression in liver, pituitary, and placenta, as
well as in HeLa cervical carcinoma cells.
GENE FUNCTION
Gasmi et al. (1999) found that recombinant NUDT5 produced in E. coli was
active against ADP-ribose and ADP-mannose. It showed lower activity
against ADP-glucose and diadenosine diphosphate. cADP-ribose was not a
substrate. Optimal activity was obtained between pH 7.4 and 9.0 in the
presence of Mg(2+) or Mn(2+), and fluoride was inhibitory.
Yang et al. (2000) confirmed that NUDT5 hydrolyzed ADP-ribose and
ADP-mannose in the presence of Mg(2+) or several other divalent cations.
They found that the rate of hydrolysis decreased significantly as the
nucleoside in ADP-sugar changed from adenosine to guanosine or uridine.
Mouse Nudt5 showed slightly different catalytic properties than human
NUDT5.
GENE STRUCTURE
Yang et al. (2000) determined that the NUDT5 gene contains 9 exons and
spans about 18.5 kb. The mouse Nudt5 gene also has 9 exons and spans 13
kb. The introns of the mouse and human genes are in the same positions
within their coding sequences.
MAPPING
By genomic sequence analysis, Gasmi et al. (1999) mapped the NUDT5 gene
to chromosome 10p14-p13. Yang et al. (2000) mapped the mouse Nudt5 gene
to a region of chromosome 2 that shows homology of synteny to human
chromosome 10.
*FIELD* RF
1. Gasmi, L.; Cartwright, J. L.; McLennan, A. G.: Cloning, expression
and characterization of YSA1H, a human adenosine 5-prime-diphosphosugar
pyrophosphatase possessing a MutT motif. Biochem. J. 344: 331-337,
1999.
2. McLennan, A. G.: The MutT family of nucleotide phosphohydrolases
in man and human pathogens. Int. J. Molec. Med. 4: 79-89, 1999.
3. Yang, H.; Slupska, M. M.; Wei, Y.-F.; Tai, J. H.; Luther, W. M.;
Xia, Y.-R.; Shih, D. M.; Chiang, J.-H.; Baikalov, C.; Fitz-Gibbon,
S.; Phan, I. T.; Conrad, A.; Miller, J. H.: Cloning and characterization
of a new member of the Nudix hydrolases from human and mouse. J.
Biol. Chem. 275: 8844-8853, 2000.
*FIELD* CD
Patricia A. Hartz: 3/2/2005
*FIELD* ED
mgross: 03/02/2005