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fredag 30 november 2018

Human NUDIX genes


The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes. To a certain extent, their substrate preference redundancies correlate with structural classes, thus linking structure and activity relationships. To elucidate interdependence among the NUDIX hydrolases, we pairwise deplete them generating an epistatic interaction map, evaluate cell cycle perturbations upon knockdown in normal and cancer cells, and analyse their protein and mRNA expression in normal and cancer tissues. Using a novel FUSION algorithm, we integrate all data creating a comprehensive NUDIX enzyme profile map, which will prove fundamental to understanding their biological functionality.

NUDT22(11q13.1) UDP-glucose- and UDP-galactose hydrolase

Ubiquitous expression in duodenum (RPKM 16.3), spleen (RPKM 14.4) and 25 other tissues See more

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NUDT21 (16q13), CFIM, CPSFS , cleavage and polyadenylation specifity factor subunit 5
 The protein encoded by this gene is one subunit of a cleavage factor required for 3' RNA cleavage and polyadenylation processing. The interaction of the protein with the RNA is one of the earliest steps in the assembly of the 3' end processing complex and facilitates the recruitment of other processing factors. This gene encodes the 25kD subunit of the protein complex, which is composed of four polypeptides. [provided by RefSeq, Jul 2008]
Preferred Names
cleavage and polyadenylation specificity factor subunit 5
CPSF 25 kDa subunit
cleavage and polyadenylation specific factor 5, 25 kD subunit
cleavage and polyadenylation specific factor 5, 25 kDa
cleavage and polyadenylation specificity factor 25 kDa subunit
cleavage factor Im complex 25 kDa subunit
nucleoside diphosphate-linked moiety X motif 21
nudix (nucleoside diphosphate linked moiety X)-type motif 21
nudix motif 21
pre-mRNA cleavage factor Im (25kD)
pre-mRNA cleavage factor Im 25 kDa subunit
pre-mRNA cleavage factor Im 68 kDa subunit
pre-mRNA cleavage factor Im, 25kD subunit

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mRNA decapping , Multiplle decapping enzymes exist

Best matches for mRNA decapping:

Grudzien-Nogalska E et al. Wiley Interdiscip Rev RNA. (2017)
Removal of the 5' end cap is a critical determinant controlling mRNA stability and efficient gene expression. Removal of the cap is exquisitely controlled by multiple direct and indirect regulators that influence association with the cap and the catalytic step. A subset of these factors directly stimulate activity of the decapping enzyme, while others influence remodeling of factors bound to mRNA and indirectly stimulate decapping. Furthermore, the components of the general decapping machinery can also be recruited by mRNA-specific regulatory proteins to activate decapping. 

 The Nudix hydrolase, Dcp2, identified as a first decapping enzyme, cleaves capped mRNA and initiates 5'-3' degradation. Extensive studies on Dcp2 led to broad understanding of its activity and the regulation of transcript specific decapping and decay.
 Interestingly, seven additional Nudix proteins possess intrinsic decapping activity in vitro and at least two, Nudt16 and Nudt3, are decapping enzymes that regulate mRNA stability in cells.

Furthermore, a new class of decapping proteins within the DXO family preferentially function on incompletely capped mRNAs. Importantly, it is now evident that each of the characterized decapping enzymes predominantly modulates only a subset of mRNAs, suggesting the existence of multiple decapping enzymes functioning in distinct cellular pathways.
 WIREs RNA 2017, 8:e1379. doi: 10.1002/wrna.1379 For further resources related to this article, please visit the WIREs website.PMID:27425147PMCID:PMC5179306DOI:10.1002/wrna.1379
D'Lima NG et al. Nat Chem Biol. (2017)
Valkov E et al. Curr Opin Struct Biol. (2017)

NUDT20 (5q22.2), DCP2 , mRNA decapping enzyme 2

DCP2 decapping mRNA 2 [ Homo sapiens (human) ]
Gene ID: 167227, updated on 22-Nov-2018
RefSeq status
Homo sapiens
Also known as
The protein encoded by this gene is a key component of an mRNA-decapping complex required for degradation of mRNAs, both in normal mRNA turnover, and in nonsense-mediated mRNA decay (NMD). It removes the 7-methyl guanine cap structure from mRNA, prior to its degradation from the 5' end. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Jun 2011]
Ubiquitous expression in lymph node (RPKM 7.7), placenta (RPKM 6.8) and 24 other tissues See more
Preferred Names
m7GpppN-mRNA hydrolase
DCP2 decapping enzyme homolog
mRNA-decapping enzyme 2
nudix (nucleoside diphosphate linked moiety X)-type motif 20
 Structure, history  
NM_001242377.1NP_001229306.1  m7GpppN-mRNA hydrolase isoform 2

Conserved Domains (2) summary
Dcp2p; mRNA decapping enzyme 2 (Dcp2p), the catalytic subunit, and Dcp1p are the two components of the decapping enzyme complex. Decapping is a key step in both general and nonsense-mediated 5'->3' mRNA-decay pathways. Dcp2p contains an all-alpha helical N-terminal domain and a C-terminal domain which has the Nudix fold. While decapping is not dependent on the N-terminus of Dcp2p, it does affect its efficiency. Dcp1p binds the N-terminal domain of Dcp2p stimulating the decapping activity of Dcp2p. Decapping permits the degradation of the transcript and is a site of numerous control inputs. It is responsible for nonsense-mediated decay as well as AU-rich element (ARE)-mediated decay. In addition, it may also play a role in the levels of mRNA. Enzymes belonging to the Nudix superfamily require a divalent cation, such as Mg2+ or Mn2+, for their activity and are recognized by a highly conserved 23-residue nudix motif
DCP2; Dcp2, box A domain

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torsdag 29 november 2018

NUDT19 (19q13.11) , mitchondrial , nucleoside diphosphate-linked moiety X motif 9
Also known as
Ubiquitous expression in adrenal (RPKM 3.2), prostate (RPKM 2.7) and 25 other tissues See more
Preferred Names
nucleoside diphosphate-linked moiety X motif 19
nucleoside diphosphate-linked moiety X motif 19, mitochondrial
nudix (nucleoside diphosphate linked moiety X)-type motif 19
nudix motif 19

Structure, history

 XP_016882295             300 aa            linear   PRI 26-MAR-2018
 nucleoside diphosphate-linked moiety X motif 19 isoform X1 [Homo
ACCESSION   XP_016882295
VERSION     XP_016882295.1
DBLINK      BioProject: PRJNA168
DBSOURCE    REFSEQ: accession XM_017026806.2
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
 MODEL REFSEQ:  This record is predicted by automated computational
            analysis. This record is derived from a genomic sequence
            (NC_000019.10) annotated using gene prediction method: Gnomon,
            supported by EST evidence.
            Also see:
                Documentation of NCBI's Annotation Process
            Annotation Provider         :: NCBI
            Annotation Status           :: Full annotation
            Annotation Name             :: Homo sapiens Annotation Release 109
            Annotation Version          :: 109
            Annotation Pipeline         :: NCBI eukaryotic genome annotation
            Annotation Software Version :: 8.0
            Annotation Method           :: Best-placed RefSeq; Gnomon
            Features Annotated          :: Gene; mRNA; CDS; ncRNA
            COMPLETENESS: full length.
FEATURES             Location/Qualifiers
     source          1..300
                     /organism="Homo sapiens"
     Protein         1..300
                     /product="nucleoside diphosphate-linked moiety X motif 19
                     isoform X1"
     CDS             1..300
        1 mssslrpgps rwrraasivl aagwsrpeta tppsrpppae gfrllllqrs phqgfmpgah
       61 vfsggvldaa drsadwlglf aphhgpprfg lgpapfsrta fpslpdtddh ktdntgtlpe
      121 dvafricavr eafeeagvll lrprtsppgp apgpglalep ppglaswrdr vrqdprhflr
      181 lcahldctpd iwalhnwsaw ltpflrgttr rfdtafflcc lrepppvypd laevvgyqnl
      241 qrsldpadrn scahqcssrn tscprtcnsp rtlligvvvl tnaaaettpa qepatvpgpc

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NUDT18 (8p21.3), 8-oxo-dGDP phosphatase, MTH3
The protein encoded by this gene is a member of the Nudix hydrolase family. Nudix hydrolases eliminate potentially toxic nucleotide metabolites from the cell and regulate the concentrations and availability of many different nucleotide substrates, cofactors, and signaling molecules. This protein contains a Nudix hydrolase domain and hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates. [provided by RefSeq, Sep 2012]
Ubiquitous expression in spleen (RPKM 3.1), lymph node (RPKM 2.8) and 25 other tissues See more
Orthologs mouse all
Preferred Names
8-oxo-dGDP phosphatase NUDT18
2-hydroxy-dADP phosphatase
7,8-dihydro-8-oxoguanine phosphatase
mutT homolog 3
mutT human homolog 3
nucleoside diphosphate-linked moiety X motif 18
nudix (nucleoside diphosphate linked moiety X)-type motif 18
nudix motif 18

 Structure, history


Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine
            and deoxyguanosine diphosphates: comparison with MTH1 and MTH2
GeneRIF: MTH3 is specifically active against 8-oxo-dGDP and hardly
            cleaves 8-oxo-dGTP. Other types of oxidized nucleoside
            diphosphates, 2-hydroxy-dADP and 8-hydroxy-dADP, were also
            hydrolyzed by MTH3.
NM_024815.4NP_079091.3  8-oxo-dGDP phosphatase NUDT18
aminoacids 1..323 
44..166 "NUDIX hydrolase_13"
76..98,  Nudix, motif
76..97  Nudix box

        1 maseglagal asvlagqgss vhscdsapag eppapvrlrk nvcyvvlavf lseqdevlli
       61 qeakrecrgs wylpagrmep getivealqr evkeeaglhc epetllsvee rgpswvrfvf
      121 larptggilk tskeadaesl qaawyprtsl ptplrahdil hlvelaaqyr qqarhplilp
      181 qelpcdlvcq rlvatftsaq tvwvlvgtvg mphlpvtacg ldpmeqrggm kmavlrllqe
      241 cltlhhlvve ikgllglqhl grdhsdgicl nvlvtvafrs pgiqdeppkv rgenfswwkv
      301 meedlqsqll qrlqgssvvp vnr

Related articles in PubMed