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

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

DCP2 decapping mRNA 2 [ Homo sapiens (human) ]

Gene ID: 167227, updated on 22-Nov-2018

RefSeq status

REVIEWED

Organism

Homo sapiens

Also known as

NUDT20

Summary

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]

Expression

Ubiquitous expression in lymph node (RPKM 7.7), placenta (RPKM 6.8) and 24 other tissues See more

Orthologs

mouse all

Preferred Names

m7GpppN-mRNA hydrolase

Names

DCP2 decapping enzyme homolog

hDpc

mRNA-decapping enzyme 2

nudix (nucleoside diphosphate linked moiety X)-type motif 20

NP_001229306.1

• EC 3.6.1.62

 Structure, history  

NM_001242377.1 → NP_001229306.1  m7GpppN-mRNA hydrolase isoform 2

Conserved Domains (2) summary

cd03672
Location:97 → 246    https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=239644

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

pfam05026
Location:12 → 93

DCP2; Dcp2, box A domain

Related articles in PubMed

1. Competition between Decapping Complex Formation and Ubiquitin-Mediated Proteasomal Degradation Controls Human Dcp2 Decapping Activity. Erickson SL, et al. Mol Cell Biol, 2015 Jun. PMID 25870104, Free PMC Article
2.  A surprising finding from our studies is that the same Dcp2 C-terminal region responsible for the Hedls interaction also actively targets Dcp2 for ubiquitin-mediated proteolysis. This conclusion is supported by the observations that full-length Dcp2 is unstable, ubiquitinated, and stabilized by proteasome inhibitors (Fig. 3 and ​and6).6). In contrast, mutant Dcp2 proteins containing deletions or point mutations within the C terminus show reduced ubiquitination (Fig. 6) and are strongly stabilized (Fig. 5). Therefore, cellular Dcp2 levels are regulated by the Dcp2 C terminus. The specific mechanism by which the Dcp2 C terminus promotes Dcp2 instability remains to be determined. Either it could promote a conformation of the Dcp2 protein that renders it vulnerable to ubiquitination or it could serve as a platform for recruitment of cellular ubiquitin ligases. Consistent with the latter, IP followed by liquid chromatography and tandem mass spectrometry (LC-MS/MS) assays revealed ubiquitin ligases in complex with Dcp2 dependent on the Dcp2 C terminus (see Fig. S5A and B in the supplemental material); however, depletion of these ligases showed only modest effects on Dcp2 stability, suggesting redundancy in the ligases that act on Dcp2 (see Fig. S5C in the supplemental material). Degradation of Dcp2 likely requires regions in addition to the C terminus, as mutation of all lysines within this region failed to stabilize Dcp2 (see Fig. S6A in the supplemental material) and the Dcp2 60 C-terminal amino acids were not sufficient to cause destabilization of a DsRed fusion protein (see Fig. S6B in the supplemental material). An important goal of future studies is to reveal the detailed mechanism of Dcp2 ubiquitination and degradation and the responsible ubiquitin ligases
3. Transcript-specific decapping and regulated stability by the human Dcp2 decapping protein. Li Y, et al. Mol Cell Biol, 2008 Feb. PMID 18039849, Free PMC Article
4. Functional characterization of the mammalian mRNA decapping enzyme hDcp2. Piccirillo C, et al. RNA, 2003 Sep. PMID 12923261, Free PMC Article
5. Visualizing an mRNA destruction line. Grzymski EC. Nat Struct Biol, 2003 Jun. PMID 12768200
6. The hDcp2 protein is a mammalian mRNA decapping enzyme. Wang Z, et al. Proc Natl Acad Sci U S A, 2002 Oct 1. PMID 12218187, Free PMC Article

See all (57) citations in PubMed

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

e all (57) citations in PubMed

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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Human Dcp2 levels and activity are controlled by a competition between decapping complex assembly and Dcp2 degradation.
2. The data indicates that DCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5'-to-3' mRNA degradation by XRN1 in human cells.
3. Data show that Y14 interacts directly with the decapping factor Dcp2 and the 5' cap structure of mRNAs via different but overlapping domains.
4. PNRC2 acts in synergy with Dcp1a to stimulate the decapping activity of Dcp2 by bridging the interaction between Dcp1a and Dcp2.
5. Like Dcp2, Nudt16 also regulates the stability of a subset of mRNAs including a member of the motin family of proteins involved in angiogenesis.
6. These data support the novel notion of the association between Ro52 with hDCP2 protein in cytoplasmic p-bodies, playing a role in mRNA metabolism in response to cellular stimulation.
7. hDcp2 can specifically bind to and can regulate the stability of a subset of mRNAs
8. These data suggest that a human decapping complex containing decapping enzymes hDcp1a and hDcp2 may be recruited to mRNAs containing premature termination codons by the hUpf proteins.
9. Human Dcp2 is a catalytically active mRNA decapping enzyme that localizes to the cytoplasm
10. an mRNA decapping enzyme demonstrated to contain intrinsic decapping activity