Modomics - A Database of RNA Modifications

Full name:
Synonym:	KIAA1627
GI:	24308265
Orf:
COG:	COG4725
UniProt:	Q9HCE5
Structures:	\| \|
Complex:	METTL3-METTL14
Enzyme type:	methyltransferase
Position of modification - modification:	m:many - m6A

Comments:

METTL14 is a methyltransferase which forms a stable heterodimer with METTL3. The complex mediates m6A deposition on nuclear RNA.

Protein sequence:

MDSRLQEIRERQKLRRQLLAQQLGAESADSIGAVLNSKDEQREIAETRETCRASYDTSAPNAKRKYLDEGETDEDKMEEYKDELEMQQDEENLPYEEEIY
KDSSTFLKGTQSLNPHNDYCQHFVDTGHRPQNFIRDVGLADRFEEYPKLRELIRLKDELIAKSNTPPMYLQADIEAFDIRELTPKFDVILLEPPLEEYYR
ETGITANEKCWTWDDIMKLEIDEIAAPRSFIFLWCGSGEGLDLGRVCLRKWGYRRCEDICWIKTNKNNPGKTKTLDPKAVFQRTKEHCLMGIKGTVKRST
DGDFIHANVDIDLIITEEPEIGNIEKPVEIFHIIEHFCLGRRRLHLFGRDSTIRPGWLTVGPTLTNSNYNAETYASYFSAPNSYLTGCTEEIERLRPKSP
PPKSKSDRGGGAPRGGGRGGTSAGRGRERNRSNFRGERGGFRGGRGGAHRGGFPPR

Enzymatic activities:

Reaction	Substrate	Type	Position
A:m6A	mRNA (m)		many

Diseases connected to this enzyme:

Description	Reaction	Disease Name
METTL3 and METTL14 protein levels are decreased in whole islets from T2D patients. the Insulin/IGF1 -AKT-PDX1 pathway is significantly affected by hypomethylation in T2D	A:m6A	Type 2 Diabetes
Increased P2RX6 mRNA m6A methylation level (induced by METTL14) enhances P2RX6 pre-mRNA splicing, decreases ATP-P2RX6-Ca2+ −p-ERK1/2-MMP9 axis and protects against RCCs migration and invasion.	A:m6A	Renal cell carcinoma
Reduced levels of METTL3/METTL14 may lead to pathogenesis and progression of E/R-positive acute lymphoblastic leukemia and increase relapse rates.	A:m6A	Leukemia
Mutations found in m6A regulatory genes are associated with lower OS and EFS rates in patients with AML ( Acute myeloid Leukemia) and presence of p53 mutations.	A:m6A	Leukemia
"METTL14 is highly expressed in normal hematopoietic stem/progenitor cells (HSPCs) and acute myeloid leukemia (AML) cells carrying t(11q23), t(15;17), or t(8;21), and is down-regulated during myeloid differentiation. Mechanistically, METTL14 exerts its oncogenic role by regulating its mRNA targets (e.g., MYB and MYC) through m6A modification, which in turn leads to enhanced self-renewal/proliferation of LSCs/LICs and blockage of myeloid differentiation"	A:m6A	Leukemia
m6A methylation of pri-miR126 enhances its recogntion by DGCR8 and its subsequent processing to mature miRNA. miR126 plays an important role in tumor metastasis by acting as a tumor suppressor. The downregulation of METTL14 in HCC cells leads to the decreased processing of pri-miR126 thus reducing its tumor-suppressor activity	A:m6A	Hepatocellular carcinoma
Decreased methylation promotes GSCs growth and self-renewal. METTL14 induced methylation protects against GSCs growth and self-renewal	A:m6A	Glioblastoma
Decreased m6A methylation level, by METTL14 downregulation or FTO upregulation, promotes the activation of oncogenic signaling pathways, such as Wnt and PI3K‐Akt and supports GC cell proliferation, migration and invasion.	A:m6A	Gastric cancer
~70% of tumor samples from endometrial cancer patients exhibited decreased m6A levels due to either decreased expression of METTL3 or loss of function mutation in METTL14 (R298P). This generates a reduction in m6A mRNA methylation levels and an enhancement in proliferation and tumorigenicity. Reductions in m6A methylation lead to decreased expression of the negative AKT regulator PHLPP2 and increased expression of the positive AKT regulator mTORC2. Increased AKT activation is one of the main mediators of increased proliferation in cells.	A:m6A	Endometrial cancer
METTL14 is downregulated in CRC tissues and cell lines. It reduces m6A levels in total RNAs and promotes CRC cell growth and metastasis, METTL14 decreases miR-375 expression levels by modulating DGCR8 binding to primary miR-375 (primiR-375) in a m6A-dependent manner.	A:m6A	Colorectal cancer
m6A levels are decreased in immortalized and oncogenically transformed human mammary epithelial cells. The levels of METTL3 are descresed and ALKBH5 are increased. Overexpression of METTL3 and METTL14 and knockdown of ALKBH5 results in increased proliferation and migaration of immortalized cells. m6A levels may be downregulated in immortalized cells. Hypoxia increased m6A levels throgh mechanisms that are independent of METTL3, METTL14 and ALKBH5 expression levels. Increases of m6A levels in hypoxia are regulated by HIF.	A:m6A	Breast cancer
m6A inhibits breast cancer (BC) cell viability, the ability of MDA-MB-231 cells to form colonies and suppressed cell migratory abilities resulting in an overall effect of inhibition of BC growth and metastasis. Reduced expression of m6A is associated with poor prognostic in patient. Functionally, reducing m6A expression by overexpressing METTL14 and/or knockdown of ALKBH5 could inhibit breast cell viability, colony formation and cell migration.	A:m6A	Breast cancer
"m6A levels are reduced in breast cancer samples due to a decrease in m6A methylases expression and an increase in demethylases expression; expression levels of METTL3, METTL14, WTAP and FTO were correlated with poor survival and cancer progression; m6A higher levels suppress cancer cell viability, inhibit MDA-MB-231 colony-formation abilities and cell migratory abilities.Expression levels of writers and readers differes according to the subtype of breast cancer ( luminal A/B vs. triple negative)."	A:m6A	Breast cancer
m6A modification and METTL14 are lowly expressed in bladder cancer. METTL14 and m6A modification participate in the RNA stability of Notch1 mRNA. Notch1 m6A modification inhibits its RNA stability. Notch1 plays an essential role in bladder tumorigenesis and bladder tumor initiating cells self-renewal	A:m6A	Bladder cancer

Publications:

Title	Authors	Journal	Details	PubMed Id	DOI
A METTL3-METTL14 complex mediates mammalian nuclear RNA N-adenosine methylation.	Liu J, Yue Y, Han D, Wang X, Fu Y, Zhang L, Jia G, Yu M, Lu Z, Deng X, Dai Q, Chen W, He C...	Nat Chem Biol	[details]	24316715	-

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