NUD16_HUMAN
ID NUD16_HUMAN Reviewed; 195 AA.
AC Q96DE0; B4E3B4; E9PED4; F5GYJ1; Q96N82;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=U8 snoRNA-decapping enzyme;
DE EC=3.6.1.62 {ECO:0000269|PubMed:15053875, ECO:0000269|PubMed:17567574, ECO:0000269|PubMed:18820299, ECO:0000269|PubMed:21070968, ECO:0000269|PubMed:21337011};
DE AltName: Full=IDP phosphatase;
DE Short=IDPase;
DE EC=3.6.1.64 {ECO:0000269|PubMed:20385596, ECO:0000269|PubMed:26121039};
DE AltName: Full=Inosine diphosphate phosphatase;
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 16;
DE Short=Nudix motif 16;
DE AltName: Full=Nudix hydrolase 16;
DE AltName: Full=U8 snoRNA-binding protein H29K {ECO:0000303|PubMed:17567574};
DE AltName: Full=m7GpppN-mRNA hydrolase;
GN Name=NUDT16;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 21-195 (ISOFORM 1).
RC TISSUE=Kidney, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=16344560; DOI=10.1101/gr.4039406;
RA Kimura K., Wakamatsu A., Suzuki Y., Ota T., Nishikawa T., Yamashita R.,
RA Yamamoto J., Sekine M., Tsuritani K., Wakaguri H., Ishii S., Sugiyama T.,
RA Saito K., Isono Y., Irie R., Kushida N., Yoneyama T., Otsuka R., Kanda K.,
RA Yokoi T., Kondo H., Wagatsuma M., Murakawa K., Ishida S., Ishibashi T.,
RA Takahashi-Fujii A., Tanase T., Nagai K., Kikuchi H., Nakai K., Isogai T.,
RA Sugano S.;
RT "Diversification of transcriptional modulation: large-scale identification
RT and characterization of putative alternative promoters of human genes.";
RL Genome Res. 16:55-65(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Pancreas;
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 [5]
RP FUNCTION AS A DECAPPING ENZYME, AND CATALYTIC ACTIVITY.
RX PubMed=15053875; DOI=10.1016/s1097-2765(04)00127-3;
RA Ghosh T., Peterson B., Tomasevic N., Peculis B.A.;
RT "Xenopus U8 snoRNA binding protein is a conserved nuclear decapping
RT enzyme.";
RL Mol. Cell 13:817-828(2004).
RN [6]
RP FUNCTION AS A DECAPPING ENZYME, SUBUNIT, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=17567574; DOI=10.1074/jbc.m704179200;
RA Peculis B.A., Reynolds K., Cleland M.;
RT "Metal determines efficiency and substrate specificity of the nuclear NUDIX
RT decapping proteins X29 and H29K (Nudt16).";
RL J. Biol. Chem. 282:24792-24805(2007).
RN [7]
RP FUNCTION AS A DECAPPING ENZYME, CATALYTIC ACTIVITY, SUBUNIT, RNA-BINDING,
RP GENE EVOLUTION, AND GENE FAMILY ORGANIZATION.
RX PubMed=18820299; DOI=10.1093/nar/gkn605;
RA Taylor M.J., Peculis B.A.;
RT "Evolutionary conservation supports ancient origin for Nudt16, a nuclear-
RT localized, RNA-binding, RNA-decapping enzyme.";
RL Nucleic Acids Res. 36:6021-6034(2008).
RN [8]
RP FUNCTION AS A DECAPPING ENZYME, CATALYTIC ACTIVITY, AND SUBCELLULAR
RP LOCATION.
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 [9]
RP FUNCTION AS AN IDP PHOSPHATASE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=20385596; DOI=10.1093/nar/gkq249;
RA Iyama T., Abolhassani N., Tsuchimoto D., Nonaka M., Nakabeppu Y.;
RT "NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces
RT accumulation of single-strand breaks in nuclear DNA and growth arrest.";
RL Nucleic Acids Res. 38:4834-4843(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP FUNCTION AS A DECAPPING ENZYME, CATALYTIC ACTIVITY, COFACTOR, AND
RP SUBCELLULAR LOCATION.
RX PubMed=21337011; DOI=10.1007/s13238-011-1009-2;
RA Lu G., Zhang J., Li Y., Li Z., Zhang N., Xu X., Wang T., Guan Z., Gao G.F.,
RA Yan J.;
RT "hNUDT16: a universal decapping enzyme for small nucleolar RNA and
RT cytoplasmic mRNA.";
RL Protein Cell 2:64-73(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=18607096; DOI=10.1107/s1744309108016928;
RA Zhang J., Gao F., Zhang Q., Chen Q., Qi J., Yan J.;
RT "Crystallization and crystallographic analysis of human NUDT16.";
RL Acta Crystallogr. F 64:639-640(2008).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) IN COMPLEX WITH IMP AND MAGNESIUM
RP IONS, SUBUNIT, CATALYTIC ACTIVITY, ACTIVITY REGULATION, FUNCTION, AND
RP COFACTOR.
RX PubMed=26121039; DOI=10.1371/journal.pone.0131507;
RA Tresaugues L., Lundbaeck T., Welin M., Flodin S., Nyman T., Silvander C.,
RA Graeslund S., Nordlund P.;
RT "Structural basis for the specificity of human NUDT16 and its regulation by
RT inosine monophosphate.";
RL PLoS ONE 10:E0131507-E0131507(2015).
RN [15] {ECO:0007744|PDB:6X7U, ECO:0007744|PDB:6X7V}
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS,
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND COFACTOR.
RX PubMed=32432673; DOI=10.1093/nar/gkaa402;
RA Sharma S., Grudzien-Nogalska E., Hamilton K., Jiao X., Yang J., Tong L.,
RA Kiledjian M.;
RT "Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs.";
RL Nucleic Acids Res. 48:6788-6798(2020).
CC -!- FUNCTION: RNA-binding and decapping enzyme that catalyzes the cleavage
CC of the cap structure of snoRNAs and mRNAs in a metal-dependent manner.
CC Part of the U8 snoRNP complex that is required for the accumulation of
CC mature 5.8S and 28S rRNA. Has diphosphatase activity and removes m7G
CC and/or m227G caps from U8 snoRNA and leaves a 5'monophosphate on the
CC RNA. Catalyzes also the cleavage of the cap structure on mRNAs. Does
CC not hydrolyze cap analog structures like 7-methylguanosine nucleoside
CC triphosphate (m7GpppG). Also hydrolysis m7G- and m227G U3-capped RNAs
CC but with less efficiencies. Has broad substrate specificity with
CC manganese or cobalt as cofactor and can act on various RNA species.
CC Binds to the U8 snoRNA; metal is not required for RNA-binding. May play
CC a role in the regulation of snoRNAs and mRNAs degradation. Acts also as
CC a phosphatase; hydrolyzes the non-canonical purine nucleotides inosine
CC diphosphate (IDP) and deoxyinosine diphosphate (dITP) as well as
CC guanosine diphosphate (GDP), deoxyguanosine diphosphate (dGDP),
CC xanthine diphosphate (XDP), inosine triphosphate (ITP) and deoxyinosine
CC triphosphate (ITP) to their respective monophosphate derivatives and
CC does not distinguish between the deoxy- and ribose forms
CC (PubMed:20385596, PubMed:26121039). The order of activity with
CC different substrates is IDP > dIDP >> GDP = dGDP > XDP = ITP = dITP
CC (PubMed:20385596). Binds strongly to GTP, ITP and XTP. Participates in
CC the hydrolysis of dIDP/IDP and probably excludes non-canonical purines
CC from RNA and DNA precursor pools, thus preventing their incorporation
CC into RNA and DNA and avoiding chromosomal lesions (PubMed:20385596).
CC Exhibits decapping activity towards NAD-capped RNAs and FAD-capped RNAs
CC (PubMed:32432673). Exhibits decapping activity towards dpCoA-capped
CC RNAs in vitro (By similarity). {ECO:0000250|UniProtKB:Q6P3D0,
CC ECO:0000269|PubMed:15053875, ECO:0000269|PubMed:17567574,
CC ECO:0000269|PubMed:18820299, ECO:0000269|PubMed:20385596,
CC ECO:0000269|PubMed:21070968, ECO:0000269|PubMed:21337011,
CC ECO:0000269|PubMed:26121039, ECO:0000269|PubMed:32432673}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside
CC in mRNA + H2O = a 5'-end phospho-ribonucleoside in mRNA + 2 H(+) +
CC N(7)-methyl-GDP; Xref=Rhea:RHEA:67484, Rhea:RHEA-COMP:15692,
CC Rhea:RHEA-COMP:17167, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:63714, ChEBI:CHEBI:138282, ChEBI:CHEBI:156461;
CC EC=3.6.1.62; Evidence={ECO:0000269|PubMed:15053875,
CC ECO:0000269|PubMed:17567574, ECO:0000269|PubMed:18820299,
CC ECO:0000269|PubMed:21070968, ECO:0000269|PubMed:21337011};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67485;
CC Evidence={ECO:0000269|PubMed:15053875, ECO:0000269|PubMed:17567574,
CC ECO:0000269|PubMed:18820299, ECO:0000269|PubMed:21070968,
CC ECO:0000269|PubMed:21337011};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + IDP = H(+) + IMP + phosphate; Xref=Rhea:RHEA:35207,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58053, ChEBI:CHEBI:58280; EC=3.6.1.64;
CC Evidence={ECO:0000269|PubMed:20385596, ECO:0000269|PubMed:26121039};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35208;
CC Evidence={ECO:0000269|PubMed:20385596, ECO:0000269|PubMed:26121039};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dIDP + H2O = dIMP + H(+) + phosphate; Xref=Rhea:RHEA:35211,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61194, ChEBI:CHEBI:62286; EC=3.6.1.64;
CC Evidence={ECO:0000269|PubMed:20385596, ECO:0000269|PubMed:26121039};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35212;
CC Evidence={ECO:0000269|PubMed:20385596, ECO:0000269|PubMed:26121039};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end NAD(+)-phospho-ribonucleoside in mRNA + H2O = a 5'-
CC end phospho-adenosine-phospho-ribonucleoside in mRNA + beta-
CC nicotinamide D-ribonucleotide + 2 H(+); Xref=Rhea:RHEA:60876,
CC Rhea:RHEA-COMP:15698, Rhea:RHEA-COMP:15719, ChEBI:CHEBI:14649,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:144029,
CC ChEBI:CHEBI:144051; Evidence={ECO:0000269|PubMed:32432673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60877;
CC Evidence={ECO:0000269|PubMed:32432673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end FAD-phospho-ribonucleoside in mRNA + H2O = a 5'-end
CC phospho-adenosine-phospho-ribonucleoside in mRNA + FMN + 2 H(+);
CC Xref=Rhea:RHEA:67588, Rhea:RHEA-COMP:15719, Rhea:RHEA-COMP:17275,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:144051, ChEBI:CHEBI:172372;
CC Evidence={ECO:0000269|PubMed:32432673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67589;
CC Evidence={ECO:0000305|PubMed:32432673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end CoA-ribonucleoside in mRNA + H2O = (R)-4'-
CC phosphopantetheine + a 5'-end phospho-adenosine-phospho-
CC ribonucleoside in mRNA + 2 H(+); Xref=Rhea:RHEA:67592, Rhea:RHEA-
CC COMP:15719, Rhea:RHEA-COMP:17276, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:61723, ChEBI:CHEBI:144051,
CC ChEBI:CHEBI:172371; Evidence={ECO:0000250|UniProtKB:Q6P3D0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67593;
CC Evidence={ECO:0000250|UniProtKB:Q6P3D0};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:17567574, ECO:0000269|PubMed:21337011,
CC ECO:0000269|PubMed:26121039};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:17567574, ECO:0000269|PubMed:21337011,
CC ECO:0000269|PubMed:32432673};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:17567574, ECO:0000269|PubMed:21337011};
CC Note=Binds 3 or 4 divalent metal cations. Acts specifically on U8
CC snoRNA with magnesium as cofactor. Has broad substrate specificity with
CC bound manganese or cobalt (in vitro). {ECO:0000269|PubMed:17567574,
CC ECO:0000269|PubMed:21337011};
CC -!- ACTIVITY REGULATION: The phosphatase activity is inhibited by the
CC product IMP. {ECO:0000269|PubMed:26121039}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.062 uM for IDP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:20385596};
CC KM=0.088 uM for dIDP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:20385596};
CC KM=0.330 uM for GDP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:20385596};
CC KM=0.319 mM for dGDP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:20385596};
CC KM=15.7 mM for XDP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:20385596};
CC KM=22.1 mM for ITP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:20385596};
CC KM=24.1 mM for dITP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:20385596};
CC Note=kcat is 0.931 sec(-1) with IDP. kcat is 0.966 sec(-1) with dIDP.
CC kcat is 0.518 sec(-1) with GDP. kcat is 0.492 sec(-1) with dGDP. kcat
CC is 2.6 sec(-1) with XDP. kcat is 3.06 sec(-1) with ITP. kcat is 3.2
CC sec(-1) with dITP. The catalytic efficiency for IDP is at least 1.3-
CC fold higher than for dIDP, 9.6-fold higher than for GDP and dGDP,
CC 100-fold higher than for XDP, ITP and dITP.
CC {ECO:0000269|PubMed:20385596};
CC pH dependence:
CC Gradually increased from pH 6.5 to 8.5 in its IDP hydrolyzing
CC activity. {ECO:0000269|PubMed:20385596};
CC Temperature dependence:
CC Exhibited a temperature-dependent increase in its IDP hydrolyzing
CC activity up to 60 degrees Celsius. {ECO:0000269|PubMed:20385596};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17567574,
CC ECO:0000269|PubMed:18820299, ECO:0000269|PubMed:26121039,
CC ECO:0000269|PubMed:32432673}.
CC -!- INTERACTION:
CC Q96DE0; Q96DE0: NUDT16; NbExp=2; IntAct=EBI-5464685, EBI-5464685;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20385596,
CC ECO:0000269|PubMed:21337011}. Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q6TEC1}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q6TEC1}. Cytoplasm {ECO:0000269|PubMed:21070968,
CC ECO:0000269|PubMed:21337011}. Note=Localized predominantly in the
CC cytoplasm (PubMed:21070968). Localized in nucleolus, and in a minor
CC proportion in distinct foci in the nucleoplasm (By similarity).
CC {ECO:0000250|UniProtKB:Q6TEC1, ECO:0000269|PubMed:21070968}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q96DE0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96DE0-2; Sequence=VSP_045450, VSP_045451;
CC Name=3;
CC IsoId=Q96DE0-3; Sequence=VSP_045449, VSP_045452;
CC Name=4;
CC IsoId=Q96DE0-4; Sequence=VSP_045451;
CC -!- TISSUE SPECIFICITY: Expressed strongly in lung, kidney, adrenal gland,
CC testis, heart and brain. {ECO:0000269|PubMed:20385596}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. NUDT16 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB71024.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK055827; BAB71024.1; ALT_INIT; mRNA.
DR EMBL; AK304650; BAG65426.1; -; mRNA.
DR EMBL; BP199028; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC010210; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009546; AAH09546.1; -; mRNA.
DR EMBL; BC031215; AAH31215.2; -; mRNA.
DR CCDS; CCDS3070.2; -. [Q96DE0-1]
DR CCDS; CCDS54640.1; -. [Q96DE0-4]
DR CCDS; CCDS54641.1; -. [Q96DE0-3]
DR RefSeq; NP_001165376.1; NM_001171905.1. [Q96DE0-3]
DR RefSeq; NP_001165377.1; NM_001171906.1. [Q96DE0-4]
DR RefSeq; NP_689608.2; NM_152395.2. [Q96DE0-1]
DR PDB; 2XSQ; X-ray; 1.72 A; A=1-195.
DR PDB; 3COU; X-ray; 1.80 A; A=1-195.
DR PDB; 3MGM; X-ray; 1.80 A; A/B=1-195.
DR PDB; 5VY2; X-ray; 2.30 A; A/B=1-195.
DR PDB; 5W6X; X-ray; 2.10 A; A/B=1-195.
DR PDB; 5W6Z; X-ray; 2.61 A; A/B/D/E=1-195.
DR PDB; 5WJI; X-ray; 2.30 A; A/B=1-195.
DR PDB; 6B09; X-ray; 3.20 A; A/B=1-195.
DR PDB; 6CO2; X-ray; 2.49 A; A/B=1-195.
DR PDB; 6X7U; X-ray; 2.70 A; A/C=1-184.
DR PDB; 6X7V; X-ray; 2.30 A; A/B/C/D=1-195.
DR PDBsum; 2XSQ; -.
DR PDBsum; 3COU; -.
DR PDBsum; 3MGM; -.
DR PDBsum; 5VY2; -.
DR PDBsum; 5W6X; -.
DR PDBsum; 5W6Z; -.
DR PDBsum; 5WJI; -.
DR PDBsum; 6B09; -.
DR PDBsum; 6CO2; -.
DR PDBsum; 6X7U; -.
DR PDBsum; 6X7V; -.
DR AlphaFoldDB; Q96DE0; -.
DR SMR; Q96DE0; -.
DR BioGRID; 126295; 24.
DR IntAct; Q96DE0; 3.
DR MINT; Q96DE0; -.
DR STRING; 9606.ENSP00000422375; -.
DR iPTMnet; Q96DE0; -.
DR PhosphoSitePlus; Q96DE0; -.
DR BioMuta; NUDT16; -.
DR DMDM; 68565926; -.
DR EPD; Q96DE0; -.
DR jPOST; Q96DE0; -.
DR MassIVE; Q96DE0; -.
DR MaxQB; Q96DE0; -.
DR PaxDb; Q96DE0; -.
DR PeptideAtlas; Q96DE0; -.
DR PRIDE; Q96DE0; -.
DR ProteomicsDB; 19864; -.
DR ProteomicsDB; 24755; -.
DR ProteomicsDB; 76283; -. [Q96DE0-1]
DR TopDownProteomics; Q96DE0-1; -. [Q96DE0-1]
DR Antibodypedia; 46680; 51 antibodies from 17 providers.
DR DNASU; 131870; -.
DR Ensembl; ENST00000502852.1; ENSP00000422375.1; ENSG00000198585.12. [Q96DE0-4]
DR Ensembl; ENST00000521288.2; ENSP00000429274.2; ENSG00000198585.12. [Q96DE0-1]
DR Ensembl; ENST00000537561.5; ENSP00000440230.1; ENSG00000198585.12. [Q96DE0-3]
DR GeneID; 131870; -.
DR KEGG; hsa:131870; -.
DR MANE-Select; ENST00000521288.2; ENSP00000429274.2; NM_152395.3; NP_689608.2.
DR UCSC; uc003eog.3; human. [Q96DE0-1]
DR CTD; 131870; -.
DR DisGeNET; 131870; -.
DR GeneCards; NUDT16; -.
DR HGNC; HGNC:26442; NUDT16.
DR HPA; ENSG00000198585; Low tissue specificity.
DR MIM; 617381; gene.
DR neXtProt; NX_Q96DE0; -.
DR OpenTargets; ENSG00000198585; -.
DR PharmGKB; PA134955224; -.
DR VEuPathDB; HostDB:ENSG00000198585; -.
DR eggNOG; ENOG502S20E; Eukaryota.
DR GeneTree; ENSGT00390000016224; -.
DR HOGENOM; CLU_110418_1_0_1; -.
DR InParanoid; Q96DE0; -.
DR OMA; HVMLYCD; -.
DR OrthoDB; 1385294at2759; -.
DR PhylomeDB; Q96DE0; -.
DR BioCyc; MetaCyc:MON-17869; -.
DR BRENDA; 3.6.1.62; 2681.
DR BRENDA; 3.6.1.64; 2681.
DR PathwayCommons; Q96DE0; -.
DR Reactome; R-HSA-2393930; Phosphate bond hydrolysis by NUDT proteins.
DR SignaLink; Q96DE0; -.
DR BioGRID-ORCS; 131870; 8 hits in 1081 CRISPR screens.
DR ChiTaRS; NUDT16; human.
DR EvolutionaryTrace; Q96DE0; -.
DR GenomeRNAi; 131870; -.
DR Pharos; Q96DE0; Tbio.
DR PRO; PR:Q96DE0; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q96DE0; protein.
DR Bgee; ENSG00000198585; Expressed in tendon of biceps brachii and 179 other tissues.
DR Genevisible; Q96DE0; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031404; F:chloride ion binding; IDA:UniProtKB.
DR GO; GO:0050897; F:cobalt ion binding; IDA:UniProtKB.
DR GO; GO:0097383; F:dIDP diphosphatase activity; IEA:RHEA.
DR GO; GO:0035870; F:dITP diphosphatase activity; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:1990003; F:inosine-diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:1901641; F:ITP binding; IDA:UniProtKB.
DR GO; GO:0050072; F:m7G(5')pppN diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0008235; F:metalloexopeptidase activity; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0098519; F:nucleotide phosphatase activity, acting on free nucleotides; IDA:UniProtKB.
DR GO; GO:1990174; F:phosphodiesterase decapping endonuclease activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0110153; F:RNA NAD-cap (NMN-forming) hydrolase activity; IEA:RHEA.
DR GO; GO:0030515; F:snoRNA binding; IDA:UniProtKB.
DR GO; GO:1901640; F:XTP binding; IDA:UniProtKB.
DR GO; GO:0006382; P:adenosine to inosine editing; IMP:UniProtKB.
DR GO; GO:0035863; P:dITP catabolic process; ISS:UniProtKB.
DR GO; GO:0046709; P:IDP catabolic process; IDA:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0110155; P:NAD-cap decapping; IDA:UniProtKB.
DR GO; GO:2000233; P:negative regulation of rRNA processing; ISS:UniProtKB.
DR GO; GO:0090068; P:positive regulation of cell cycle process; IMP:UniProtKB.
DR GO; GO:0090502; P:RNA phosphodiester bond hydrolysis, endonucleolytic; IDA:UniProtKB.
DR GO; GO:0016077; P:sno(s)RNA catabolic process; IDA:UniProtKB.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR Pfam; PF00293; NUDIX; 1.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Hydrolase; Magnesium;
KW Manganese; Metal-binding; Nucleotide metabolism; Nucleotide-binding;
KW Nucleus; Reference proteome; RNA-binding.
FT CHAIN 1..195
FT /note="U8 snoRNA-decapping enzyme"
FT /id="PRO_0000057117"
FT DOMAIN 18..173
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT MOTIF 61..82
FT /note="Nudix box"
FT BINDING 24
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:26121039"
FT BINDING 50
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:26121039"
FT BINDING 57
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:26121039"
FT BINDING 59
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:32432673,
FT ECO:0000305|PubMed:26121039, ECO:0007744|PDB:6X7U"
FT BINDING 76
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:26121039"
FT BINDING 76
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6TEC1"
FT BINDING 80
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:32432673,
FT ECO:0000305|PubMed:26121039, ECO:0007744|PDB:6X7U"
FT BINDING 80
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q6TEC1"
FT BINDING 99
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="4"
FT /evidence="ECO:0000269|PubMed:32432673,
FT ECO:0007744|PDB:6X7U, ECO:0007744|PDB:6X7V"
FT BINDING 170
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:26121039"
FT BINDING 173
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="4"
FT /evidence="ECO:0000269|PubMed:32432673,
FT ECO:0007744|PDB:6X7U, ECO:0007744|PDB:6X7V"
FT VAR_SEQ 1..46
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16344560"
FT /id="VSP_045449"
FT VAR_SEQ 1..33
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045450"
FT VAR_SEQ 138..195
FT /note="LGLVRVPLYTLRDGVGGLPTFLENSFIGSAREQLLEALQDLGLLQSGSISGL
FT KIPAHH -> GPAWDSVPFPISSSPKAFSPPRKHPWRKVFAPLTLPSPQLSWWSWDRDH
FT LYSELVLPTWAFCKGLSHPLPGEILSRTHSSMSLCCSLLTV (in isoform 2 and
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045451"
FT VAR_SEQ 174..195
FT /note="ALQDLGLLQSGSISGLKIPAHH -> AALHGPMKTEMRTLVLGREGRTWECF
FT LIGSER (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16344560"
FT /id="VSP_045452"
FT CONFLICT 22
FT /note="A -> V (in Ref. 4; AAH31215)"
FT /evidence="ECO:0000305"
FT STRAND 5..7
FT /evidence="ECO:0007829|PDB:2XSQ"
FT HELIX 9..13
FT /evidence="ECO:0007829|PDB:2XSQ"
FT STRAND 20..35
FT /evidence="ECO:0007829|PDB:2XSQ"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:2XSQ"
FT STRAND 39..50
FT /evidence="ECO:0007829|PDB:2XSQ"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:2XSQ"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:3MGM"
FT HELIX 69..81
FT /evidence="ECO:0007829|PDB:2XSQ"
FT HELIX 83..87
FT /evidence="ECO:0007829|PDB:2XSQ"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:2XSQ"
FT STRAND 95..100
FT /evidence="ECO:0007829|PDB:2XSQ"
FT STRAND 102..114
FT /evidence="ECO:0007829|PDB:2XSQ"
FT HELIX 117..126
FT /evidence="ECO:0007829|PDB:2XSQ"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:2XSQ"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:2XSQ"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:2XSQ"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:6B09"
FT HELIX 155..158
FT /evidence="ECO:0007829|PDB:2XSQ"
FT HELIX 167..177
FT /evidence="ECO:0007829|PDB:2XSQ"
FT TURN 178..181
FT /evidence="ECO:0007829|PDB:2XSQ"
FT CONFLICT Q96DE0-3:128
FT /note="Missing (in Ref. 2; BP199028)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 195 AA; 21273 MW; 4AC7EA679D1D7468 CRC64;
MAGARRLELG EALALGSGWR HACHALLYAP DPGMLFGRIP LRYAILMQMR FDGRLGFPGG
FVDTQDRSLE DGLNRELREE LGEAAAAFRV ERTDYRSSHV GSGPRVVAHF YAKRLTLEEL
LAVEAGATRA KDHGLEVLGL VRVPLYTLRD GVGGLPTFLE NSFIGSAREQ LLEALQDLGL
LQSGSISGLK IPAHH
