Molecule Information

General Information of the Molecule (ID: Mol00320)

• Name: m7GpppN-mRNA hydrolase (DCP2) ,Homo sapiens
• Synonyms: Nucleoside diphosphate-linked moiety X motif 20; Nudix motif 20; mRNA-decapping enzyme 2; hDpc; NUDT20
• Molecule Type: Protein
• Gene Name: DCP2
• Gene ID: 167227
• Location: chr5:112976702-113022195[+]
• Sequence:
  METKRVEIPGSVLDDLCSRFILHIPSEERDNAIRVCFQIELAHWFYLDFYMQNTPGLPQC
  GIRDFAKAVFSHCPFLLPQGEDVEKVLDEWKEYKMGVPTYGAIILDETLENVLLVQGYLA
  KSGWGFPKGKVNKEEAPHDCAAREVFEETGFDIKDYICKDDYIELRINDQLARLYIIPGI
  PKDTKFNPKTRREIRNIEWFSIEKLPCHRNDMTPKSKLGLAPNKFFMAIPFIRPLRDWLS
  RRFGDSSDSDNGFSSTGSTPAKPTVEKLSRTKFRHSQQLFPDGSPGDQWVKHRQPLQQKP
  YNNHSEMSDLLKGKNQSMRGNGRKQYQDSPNQKKRTNGLQPAKQQNSLMKCEKKLHPRKL
  QDNFETDAVYDLPSSSEDQLLEHAEGQPVACNGHCKFPFSSRAFLSFKFDHNAIMKILDL
• Function: Decapping metalloenzyme that catalyzes the cleavage of the cap structure on mRNAs. Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP. Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. Plays a role in replication-dependent histone mRNA degradation. Has higher activity towards mRNAs that lack a poly(A) tail. Has no activity towards a cap structure lacking an RNA moiety. The presence of a N(6)-methyladenosine methylation at the second transcribed position of mRNAs (N(6),2'-O-dimethyladenosine cap; m6A(m)) provides resistance to DCP2-mediated decapping. Blocks autophagy in nutrient-rich conditions by repressing the expression of ATG-related genes through degradation of their transcripts.
• Uniprot ID: DCP2_HUMAN
• Ensembl ID: ENSG00000172795
• HGNC ID: HGNC:24452

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Methotrexate

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Colon cancer [1]

• Resistant Disease: Colon cancer [ICD-11: 2B90.1]
• Resistant Drug: Methotrexate
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The endogenous overexpression of CDS2, DCP2, HSPC159, MYST3 and SLC4A4 in MTX-resistant HT29 cells. Inhibition of miR-224 with anti-miR224 produced an increase in the mRNA levels of CDS2, HSPC159, MYST3 and SLC4A4. Decreased mRNA levels of SLC4A4, CDS2 and HSPC159 cause an increase in MTX sensitivity in HT29 cells.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Colon cancer [ICD-11: 2B90]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Colon
• The Specified Disease: Colon cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.34E-06; Fold-change: 4.89E-02; Z-score: 2.02E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 5.68E-03; Fold-change: -1.31E-01; Z-score: -3.47E-01

References

• Ref 1: Underexpression of miR-224 in methotrexate resistant human colon cancer cells. Biochem Pharmacol. 2011 Dec 1;82(11):1572-82. doi: 10.1016/j.bcp.2011.08.009. Epub 2011 Aug 16.