NUDT9 (4q22.1) , ADPR-PPase , mitokondriaalinen

Also known as

NUDT10

Summary

The protein encoded by this gene belongs to the Nudix hydrolase family. Nudix boxes are found in a family of diverse enzymes that catalyze the hydrolysis of nucleoside diphosphate derivatives. This enzyme is an ADP-ribose pyrophosphatase that catalyzes the hydrolysis of ADP-ribose to AMP and ribose-5-P. It requires divalent metal ions and an intact Nudix motif for enzymatic activity. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Expression

Ubiquitous expression in kidney (RPKM 6.8), prostate (RPKM 6.3) and 25 other tissues See more

Orthologs mouse all

 

Preferred Names

ADP-ribose pyrophosphatase, mitochondrial

Names

ADP-ribose diphosphatase

ADP-ribose phosphohydrolase

ADP-ribose pyrosphosphatase NUDT9

ADPR-PPase

adenosine diphosphoribose pyrophosphatase

nucleoside diphosphate linked moiety X-type motif 9

nudix (nucleoside diphosphate linked moiety X)-type motif 9

NP_001234940.1

• EC 3.6.1.13

  Structure, History,

NM_001248011.1 → NP_001234940.1  ADP-ribose pyrophosphatase, mitochondrial isoform c precursor

 https://www.ncbi.nlm.nih.gov/protein/NP_001234940.1

Related articles in PubMed

1. Differential expression of NUDT9 at different phases of the menstrual cycle and in different components of normal and neoplastic human endometrium. Chen LY, et al. Taiwan J Obstet Gynecol, 2009 Jun. PMID 19574167.NUDT9 is known to function as a highly specific adenosine diphosphate ribose pyrophosphatase and has been mapped to chromosome 4q22.1. It gives rise to two alternatively spliced messenger RNAs, NUDT9alpha and NUDT9beta, encoding a member of the Nudix hydrolase family. In this study, we purified NUDT9 protein and produced an antibody, which we then used for immunohistochemical studies.Using this anti-NUDT9 antibody, we successfully demonstrated that NUDT9 protein was differentially expressed in endometrial glandular cells at different phases of the menstrual cycle. NUDT9 was also found to be expressed more prominently in the epithelial glandular component than in the stromal component of human endometrial carcinomas.We suggest that NUDT9 may be involved in the regulation of the menstrual cycle and may be related to the proliferation of glandular cells in the human endometrium.
2. The specific, submicromolar-Km ADP-ribose pyrophosphatase purified from human placenta is enzymically indistinguishable from recombinant NUDT9 protein, including a selectivity for Mn2+ as activating cation and increase in Km for ADP-ribose, both elicited by H2O2. Carloto A, et al. Biochim Biophys Acta, 2006 Oct. PMID 16860484
3. The crystal structure and mutational analysis of human NUDT9. Shen BW, et al. J Mol Biol, 2003 Sep 12. PMID 12948489
4. Interaction of C17orf25 with ADP-ribose pyrophosphatase NUDT9 detected via yeast two-hybrid method. Zhang HT, et al. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 2003 Aug. PMID 12897971
5. NUDT9, a member of the Nudix hydrolase family, is an evolutionarily conserved mitochondrial ADP-ribose pyrophosphatase. Perraud AL, et al. J Biol Chem, 2003 Jan 17. PMID 12427752

See all (20) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. NUDT9 may be involved in the regulation of the menstrual cycle and may be related to the proliferation of glandular cells in the human endometrium
2. parallel enzymic characterization of the specific ADP-ribose pyrophosphatase from human placenta and a recombinant NUDT9 protein expressed from a cDNA clone was carried out
3. Data report the crystal structures of NUDT9 in the presence and in the absence of the reaction product ribose 5'-phosphate.
4. analysis of the human NUDT9 gene and its potential alternative transcripts along with detailed studies of the enzymatic properties and cell biological behavior of human NUDT9 protein
5. Hydrolyses ADP-ribose to AMP and ribose-5-phosphate

Submit: New GeneRIF Correction

 

NUDT8 (11q13.2) ( CoAse domain)

https://www.ncbi.nlm.nih.gov/gene/254552
VALIDATED 

Organism

Homo sapiens

Lineage

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo

Expression

Broad expression in kidney (RPKM 5.4), heart (RPKM 4.8) and 25 other tissues See more

Orthologs mouse all

 Structure, History : 
 
NM_001243750.2 → NP_001230679.1  nucleoside diphosphate-linked moiety X motif 8 isoform 1
aminoacids 32..186, CoAse
aminoacids 69..92, Nudix motif   ( k cdpadqdvvh talretreel glavpeehvw gl)
aminoacids 70..91 Nudix box  ( h talretreel glavpeehvw g)
a.a. 70, N-succinyl-lysine (k) 
a.a. 85, metal binding site (e)

ORIGIN      
        1 mlpdclsaeg elrcrrllag atarlrarpa saavlvplcs vrgvpallyt lrssrltgrh
       61 kgdvsfpggk cdpadqdvvh talretreel glavpeehvw gllrpvydpq katvvpvlag
      121 vgpldpqslr pnseevdevf alplahllqt qnqgythfcr gghfrytlpv flhgphrvwg
      181 ltavitefal qllapgtyqp rlagltcsga eglarpkqpl aspcqasstp glnkgl

Related articles in PubMed

1. The mouse Nudt7 gene encodes a peroxisomal nudix hydrolase specific for coenzyme A and its derivatives. Gasmi L, et al. Biochem J, 2001 Jul 1. PMID 11415433, Free PMC Article
2. Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function. Floyd BJ, et al. Mol Cell, 2016 Aug 18. PMID 27499296, Free PMC Article
3. Identification of intrahepatic cholangiocarcinoma related genes by comparison with normal liver tissues using expressed sequence tags. Wang AG, et al. Biochem Biophys Res Commun, 2006 Jul 7. PMID 16712791.  One hundred and thirty-seven genes were identified as being either up- or down-regulated in human ICC cells.
4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. Hendrickson SL, et al. PLoS One, 2010 Sep 21. PMID 20877624, Free PMC Article
5. The BioPlex Network: A Systematic Exploration of the Human Interactome. Huttlin EL, et al. Cell, 2015 Jul 16. PMID 26186194, Free PMC Article

See all (9) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

Observational study of gene-disease association. (HuGE Navigator)

NUDT7 (16q23.1), Peroxisomal CoA diphosphatase (CoAse)

https://www.ncbi.nlm.nih.gov/gene/283927 

 

Summary

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. Alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

Expression

Ubiquitous expression in liver (RPKM 10.5), heart (RPKM 9.9) and 24 other tissues See more

Orthologs

mouse all

 

Preferred Names

peroxisomal coenzyme A diphosphatase NUDT7

Names

nudix (nucleoside diphosphate linked moiety X)-type motif 7

NP_001099133.1   EC 3.6.1.-

 

 Structure,  History 

NP_001099133.1  peroxisomal coenzyme A diphosphatase NUDT7 isoform 1

 

2012:

 Novel genetic loci identified for the pathophysiology of childhood
            obesity in the Hispanic population

 

Conserved Domains (1) summary

cd03426
Location:41 → 201

CoAse; Coenzyme A pyrophosphatase (CoAse), a member of the Nudix hydrolase superfamily, functions to catalyze the elimination of oxidized inactive CoA, which can inhibit CoA-utilizing enzymes. The need of CoAses mainly arises under conditions of oxidative stress. CoAse has a conserved Nudix fold and requires a single divalent cation for catalysis. In addition to a signature Nudix motif G[X5]E[X7]REUXEEXGU, where U is Ile, Leu, or Val, CoAse contains an additional motif upstream called the NuCoA motif (LLTXT(SA)X3RX3GX3FPGG) which is postulated to be involved in CoA recognition. CoA plays a central role in lipid metabolism. It is involved in the initial steps of fatty acid synthesis in the cytosol, in the oxidation of fatty acids and the citric acid cycle in the mitochondria, and in the oxidation of long-chain fatty acids (LCFA) in peroxisomes. CoA has the important role of activating fatty acids for further modification into key biological signalling molecules.

 

Related articles in PubMed

1. The mouse Nudt7 gene encodes a peroxisomal nudix hydrolase specific for coenzyme A and its derivatives. Gasmi L, et al. Biochem J, 2001 Jul 1. PMID 11415433, Free PMC Article
2. Fine mapping and association studies of a high-density lipoprotein cholesterol linkage region on chromosome 16 in French-Canadian subjects. Dastani Z, et al. Eur J Hum Genet, 2010 Mar. PMID 19844255, Free PMC Article
3. A proteome-wide perspective on peroxisome targeting signal 1(PTS1)-Pex5p affinities. Ghosh D, et al. J Am Chem Soc, 2010 Mar 24. PMID 20178365
4. The sequence and analysis of duplication-rich human chromosome 16. Martin J, et al. Nature, 2004 Dec 23. PMID 15616553
5. Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. Comuzzie AG, et al. PLoS One, 2012. PMID 23251661, Free PMC Article

See all (7) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

Structure, History

GeneRIFs: Gene References Into Functions

Observational study of gene-disease association. (HuGE Navigator)

 

NUDT4 (12q44) , DIPP2, Difosfoinositoii-polyfosfaatti-phosphatase 2

https://www.ncbi.nlm.nih.gov/gene/11163

Also known as

DIPP2; NUDT4B; DIPP-2B; HDCMB47P; DIPP2beta; DIPP2alpha

Summary

The protein encoded by this gene regulates the turnover of diphosphoinositol polyphosphates. The turnover of these high-energy diphosphoinositol polyphosphates represents a molecular switching activity with important regulatory consequences. Molecular switching by diphosphoinositol polyphosphates may contribute to regulating intracellular trafficking. Several alternatively spliced transcript variants have been described, but the full-length nature of some variants has not been determined. Isoforms DIPP2alpha and DIPP2beta are distinguishable from each other solely by DIPP2beta possessing one additional amino acid due to intron boundary skidding in alternate splicing. [provided by RefSeq, Jul 2008]

Expression

Ubiquitous expression in ovary (RPKM 30.0), kidney (RPKM 25.7) and 25 other tissues See more

Orthologs  mouse all

Preferred Names

diphosphoinositol polyphosphate phosphohydrolase 2

Names

DIPP-2

Diphosphoinositol polyphosphate phosphohydrolase NUDT4B

Nucleoside diphosphate-linked moiety X motif 4B

Nudix hydrolase 4B

Nudix motif 4B

diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 2

diphosphoinositol polyphosphate phosphohydrolase type 2

nudix (nucleoside diphosphate linked moiety X)-type motif 4

NP_001287951.1

• EC 3.6.1.52

 Structure, History  

NP_061967.3  diphosphoinositol polyphosphate phosphohydrolase 2 isoform alpha

 2000:

Discovery of molecular and catalytic diversity among human
            diphosphoinositol-polyphosphate phosphohydrolases. An expanding
            Nudt family

Related articles in PubMed

1. Discovery of molecular and catalytic diversity among human diphosphoinositol-polyphosphate phosphohydrolases. An expanding Nudt family. Caffrey JJ, et al. J Biol Chem, 2000 Apr 28. PMID 10777568
2. Cloning and characterisation of hAps1 and hAps2, human diadenosine polyphosphate-metabolising Nudix hydrolases. Leslie NR, et al. BMC Biochem, 2002 Jul 16. PMID 12121577, Free PMC Article
3. Genetic rationale for microheterogeneity of human diphosphoinositol polyphosphate phosphohydrolase type 2. Caffrey JJ, et al. Gene, 2001 May 16. PMID 11376937
4. Nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate. Fisher DI, et al. J Biol Chem, 2002 Dec 6. PMID 12370170
5. Characterization of cDNA clones in size-fractionated cDNA libraries from human brain. Seki N, et al. DNA Res, 1997 Oct 31. PMID 9455484

See all (13) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

This paper demonstrates that KIAA0487 (AB007956) is the 3'-UTR for human diphosphoinositol polyphosphate phosphohydrolase type II

NUDT6 (4q28.1) FGF-AS, FGF2 antisense gene , GFG1

https://www.ncbi.nlm.nih.gov/gene/11162

Also known as

GFG1; GFG-1; ASFGF2; FGF-AS; FGF2AS

Summary

This gene overlaps and lies on the opposite strand from FGF2 gene, and is thought to be the FGF2 antisense gene. The two genes are independently transcribed, and their expression shows an inverse relationship, suggesting that this antisense transcript may regulate FGF2 expression. This gene has also been shown to have hormone-regulatory and antiproliferative actions in the pituitary that are independent of FGF2 expression. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Expression

Ubiquitous expression in fat (RPKM 12.5), kidney (RPKM 8.8) and 23 other tissues See more

Orthologs  mouse all

Preferred Names

nucleoside diphosphate-linked moiety X motif 6

Names

antisense basic fibroblast growth factor

nudix (nucleoside diphosphate linked moiety X)-type motif 6

 

Related articles in PubMed

1. Nanostructured HA crystals up-regulate FGF-2 expression and activity in microvascular endothelium promoting angiogenesis. Pezzatini S, et al. Bone, 2007 Oct. PMID 17681892
2. Alternative splicing of the FGF antisense gene: differential subcellular localization in human tissues and esophageal adenocarcinoma. Zhang SC, et al. J Mol Med (Berl), 2007 Nov. PMID 17569023
3. The endogenous fibroblast growth factor-2 antisense gene product regulates pituitary cell growth and hormone production. Asa SL, et al. Mol Endocrinol, 2001 Apr. PMID 11266510
4. Characterization of the promoter for the human antisense fibroblast growth factor-2 gene; regulation by Ets in Jurkat T cells. Gagnon ML, et al. J Cell Biochem, 1999 Mar 15. PMID 10022609
5. FGF-2 antisense RNA encodes a nuclear protein with MutT-like antimutator activity. Li AW, et al. Mol Cell Endocrinol, 1997 Oct 20. PMID 9406864

See all (26) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsF?

1. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
2. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
3. Observational study of gene-disease association. (HuGE Navigator)
4. Thus, survivin, Smac, and PKC alpha might play important roles in the inhibition of apoptosis by FGF-2 in human small cell lung cancer cells.
5. The aim of this study was to characterize the expression of alternatively spliced FGF-AS transcripts and encoded nudix-motif proteins in normal human tissues and in esophageal adenocarcinoma.
6. hydroxyapatite nanocrystals exposure up-regulated FGF-2 mRNA by 6 fold and increased 18 kDa protein isoform by 40%
7. 18-kDa FGF-2 harbors a C-terminal nonclassical bipartite nuclear localization signal, a portion of which also regulates its nucleolar localization.
8. FGF-2 exhibits antitumor activity in vitro and correlates with expression of FGF receptors expression in medulloblastoma cells

Submit: New GeneRIF Correction

 

 

NUDT5, (10p14) YSA1 ADP-sugar pyrophosphatase

https://www.ncbi.nlm.nih.gov/gene/11164

Also known as

YSA1; YSA1H; YSAH1; hNUDT5

Summary

This gene belongs to the Nudix (nucleoside diphosphate linked moiety X) hydrolase superfamily. The encoded enzyme catalyzes the hydrolysis of modified nucleoside diphosphates, including ADP-ribose (ADPR) and 8-oxoGua-containing 8-oxo-dADP and 8-oxo-dGDP. Protein-bound ADP ribose can be hazardous to the cell because it can modify some amino acid residues, resulting in the inhibition of ATP-activated potassium channels. 8-oxoGua is an oxidized form of guanine that can potentially alter genetic information by pairing with adenine and cytosine in RNA. Presence of 8-oxoGua in RNA results in formation of abnormal proteins due to translational errors. [provided by RefSeq, Aug 2013]

Expression

Ubiquitous expression in liver (RPKM 12.0), skin (RPKM 11.4) and 25 other tissues See more

Orthologs

mouse all

Preferred Names

ADP-sugar pyrophosphatase

Names

8-oxo-dGDP phosphatase

nuclear ATP-synthesis protein NUDIX5

nudix (nucleoside diphosphate linked moiety X)-type motif 5

NP_001308576.1

• EC 2.7.7.96

• EC 3.6.1.13

• EC 3.6.1.58

Related articles in PubMed

1. Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells. Page BDG, et al. Nat Commun, 2018 Jan 17. PMID 29343827, Free PMC Article
2. Lowered Nudix type 5 expression leads to cellular senescence in IMR-90 fibroblast cells. Zhang L, et al. Free Radic Res, 2013 Jul. PMID 23581889
3. [Mechanistic insight into hydrolysis of oxidized nucleotide diphosphates by human NUDT5]. Arimori T, et al. Fukuoka Igaku Zasshi, 2011 Nov. PMID 22351996
4. Lowered nudix type 5 (NUDT5) expression leads to cell cycle retardation in HeLa cells. Zhang LQ, et al. Mol Cell Biochem, 2012 Apr. PMID 22200976
5. Diverse substrate recognition and hydrolysis mechanisms of human NUDT5. Arimori T, et al. Nucleic Acids Res, 2011 Nov 1. PMID 21768126, Free PMC Article

GeneRIFs: Gene References Into Functions

1. Data suggest that targeting nudix hydrolase 5 (NUDT5) may represent a promising new therapeutic approach for breast cancer treatment.
2. In the presence of pyrophosphate, ADP-ribose is used by the pyrophosphatase NUDIX5 to generate nuclear ATP.
3. The NUDT5 protein could play significant roles in the prevention of RNA oxidation and survival in human fibroblast cells.
4. Results suggest that the NUDT5 protein may play significant roles in regulating the G1-S transition in HeLa cells.
5. The human NUDT5, which has an intrinsic activity to cleave ADP sugars to AMP and sugar phosphate, possesses the ability to degrade 8-oxo-dGDP to the monophosphate.
6. The broad substrate specificity of hNUDT5 is achieved by a diversity of not only substrate recognition, but also hydrolysis mechanisms.
7. human MTH1, MTH2, and NUDT5 proteins act as a defense against the mutagenesis induced by oxidized dGTP.
8. NUDT5 protein eliminates various oxidized deoxyribonucleoside diphosphates from the nucleotide pool and prevents their toxic effects.
9. Results report the crystal structure of hNUDT5 in complex with a non-hydrolyzable ADPR analogue, alpha,beta-methyleneadenosine diphosphoribose, and three Mg(2+) ions representing the transition state of the enzyme during catalysis.
10. degrades 8-oxo-dGDP to 8-oxo-dGMP, an unusable form for DNA synthesis, and promotes the cleavage of 8-oxo-dGTP by MTH1 to yield 8-oxo-dGMP also

Submit: New GeneRIF Correction

 

 

NUDT3 (6p21.31), DIPP1, difosfoinositolipolyfosfaattihydrolaasi 1

https://www.ncbi.nlm.nih.gov/gene/11165

Also known as

DIPP; DIPP1; DIPP-1

Summary

NUDT3 belongs to the MutT, or Nudix, protein family. Nudix proteins act as homeostatic checkpoints at important stages in nucleoside phosphate metabolic pathways, guarding against elevated levels of potentially dangerous intermediates, like 8-oxo-dGTP, which promotes AT-to-CG transversions (Safrany et al., 1998 [PubMed 9822604]).[supplied by OMIM, Feb 2011]

Expression

Ubiquitous expression in brain (RPKM 33.6), thyroid (RPKM 19.6) and 25 other tissues See more

Orthologs mouse all

 

 Structure, history

NP_006694.1  diphosphoinositol polyphosphate phosphohydrolase 1

 

 2002:

 Nudix hydrolases that degrade dinucleoside and diphosphoinositol
            polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP)
            pyrophosphatase activity that generates the glycolytic activator
            ribose 1,5-bisphosphate

 1999:

  Site-directed mutagenesis of diphosphoinositol polyphosphate
            phosphohydrolase, a dual specificity NUDT enzyme that attacks
            diadenosine polyphosphates and diphosphoinositol polyphosphates

1998: 

A novel context for the 'MutT' module, a guardian of cell
            integrity, in a DIPP, diphosphoinositol polyphosphate phosphohydrolase

 NUDIX BOX 51-72  ggmepeeeps vaavrevcee ag

ORIGIN      
        1 mmklksnqtr tydgdgykkr aaclcfrses eeevllvsss rhpdrwivpg ggmepeeeps
       61 vaavrevcee agvkgtlgrl vgifenqerk hrtyvyvliv tevledweds vnigrkrewf
      121 kiedaikvlq yhkpvqasyf etlrqgysan ngtpvvatty svsaqssmsg ir
//

Preferred Names

diphosphoinositol polyphosphate phosphohydrolase 1

Names

diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 1

nucleoside diphosphate-linked moiety X motif 3

nudix (nucleoside diphosphate linked moiety X)-type motif 3

nudix motif 3

NP_006694.1

• EC 3.6.1.52

Related articles in PubMed

1. Nudt3 is an mRNA decapping enzyme that modulates cell migration. Grudzien-Nogalska E, et al. RNA, 2016 May. PMID 26932476, Free PMC Article
2. NUDT3 rs206936 is associated with body mass index in obese Japanese women. Kitamoto A, et al. Endocr J, 2013. PMID 23708086
3. Crystal structure of human diphosphoinositol phosphatase 1. Thorsell AG, et al. Proteins, 2009 Oct. PMID 19585659
4. Site-directed mutagenesis of diphosphoinositol polyphosphate phosphohydrolase, a dual specificity NUDT enzyme that attacks diadenosine polyphosphates and diphosphoinositol polyphosphates. Yang X, et al. J Biol Chem, 1999 Dec 10. PMID 10585413
5. The diadenosine hexaphosphate hydrolases from Schizosaccharomyces pombe and Saccharomyces cerevisiae are homologues of the human diphosphoinositol polyphosphate phosphohydrolase. Overlapping substrate specificities in a MutT-type protein. Safrany ST, et al. J Biol Chem, 1999 Jul 30. PMID 10419486

See all (24) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. Nudt3 is an mRNA decapping enzyme that orchestrates expression of a subset of mRNAs to modulate cell migration and further substantiates the existence of multiple decapping enzymes functioning in distinct cellular pathways in mammals
2. results suggest that NUDT3 rs206936 is associated with body mass index in Japanese women

Submit: New GeneRIF Correction