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Information on EC 2.1.1.346 - U6 snRNA m6A methyltransferase
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EC Tree
2.1.1.346 U6 snRNA m6A methyltransferaseIUBMB Comments
This enzyme, found in vertebrates, methylates a specific adenine in a hairpin structure of snRNA. The effects of the binding of the methyltransferase to its substrate is important for the regulation of the activity of an isoform of EC 2.5.1.6, methionine adenosyltransferase, that produces S-adenosyl-L-methionine [1,2]. The enzyme also binds (and maybe methylates) the lncRNAs XIST and MALAT1 as well as a number of pre-mRNAs at specific positions often found in the intronic regions .
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Word Map
- 2.1.1.346
- mettl3
- alkbh5
- methyltransferases
-
writer
-
epitranscriptome
-
n6-adenosine
-
ythdf3
-
erasers
-
igf2bp1
- demethylases
-
malat1
-
rbm15b
The enzyme appears in viruses and cellular organisms
Reaction Schemes
+
adenine in U6 snRNA
=
+
N6-methyladenine in U6 snRNA
Synonyms
mettl16, n6-methyladenosine (m6a) methyltransferase, m6a rna methyltransferase, rna m6a methyltransferase, methyltransferase-like protein 16, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
m6A methyltransferase
METTL16
METTL16
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-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + adenine in U6 snRNA = S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:adenine in U6 snRNA methyltransferase
This enzyme, found in vertebrates, methylates a specific adenine in a hairpin structure of snRNA. The effects of the binding of the methyltransferase to its substrate is important for the regulation of the activity of an isoform of EC 2.5.1.6, methionine adenosyltransferase, that produces S-adenosyl-L-methionine [1,2]. The enzyme also binds (and maybe methylates) the lncRNAs XIST and MALAT1 as well as a number of pre-mRNAs at specific positions often found in the intronic regions [2].
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + adenine in MAT2A hairpin 1
S-adenosyl-L-homocysteine + N6-methyladenine in MAT2A hairpin 1
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-
-
?
S-adenosyl-L-methionine + adenine in U6 lncRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 lncRNA
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-
-
?
S-adenosyl-L-methionine + adenine in U6 ncRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 ncRNA
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-
-
?
S-adenosyl-L-methionine + adenine in U6 pre-mRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 pre-mRNA
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-
-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
S-adenosyl-L-methionine + adenine-43 in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine-43 in U6 snRNA
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-
-
?
additional information
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U6 snRNA lacking the stem-loop near the 5' end is as efficient a substrate as the full-length U6 snRNA. U6 snRNA(41-106) is not methylated efficiently. Deletion of 19 nucleotides of the 3' end stem-loop structure (U6 snRNA(1-88)) reduces the efficiency to 20-45% of the wild-type, and U6 snRNA(1-67) does not serves as substrate at all
-
-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
-
-
-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
the enzyme is responsible for N6-methylation of A43 of the U6 snRNA
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-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
regulation of Mat2a mRNA by Mettl16 is essential for mouse embryonic development
-
-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
the enzyme methylates U6 spliceosomal RNA and interacts with the 3'-terminal RNA triple helix of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1). Full-length METTL16 binds to the MALAT1 RNA triple helix, but monomeric METTL16_291 does not
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-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
generation of a comprehensive atlas of methylome uniquely mediated by methyltransferase. METTL16 indirectly impacts manifold methylation targets beyond its consensus target motif (UACm6AGAGAA)
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-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
when presented with a random pool of RNAs, METTL16 selects for methylation-structured RNAs where the critical adenosine is present in a bulge
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-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
regulation of Mat2a mRNA by Mettl16 is essential for mouse embryonic development
-
-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
when presented with a random pool of RNAs, METTL16 selects for methylation-structured RNAs where the critical adenosine is present in a bulge
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + adenine in MAT2A hairpin 1
S-adenosyl-L-homocysteine + N6-methyladenine in MAT2A hairpin 1
-
-
-
?
S-adenosyl-L-methionine + adenine in U6 lncRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 lncRNA
-
-
-
?
S-adenosyl-L-methionine + adenine in U6 ncRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 ncRNA
-
-
-
?
S-adenosyl-L-methionine + adenine in U6 pre-mRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 pre-mRNA
-
-
-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
S-adenosyl-L-methionine + adenine-43 in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine-43 in U6 snRNA
-
-
-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
-
-
-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
the enzyme is responsible for N6-methylation of A43 of the U6 snRNA
-
-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
regulation of Mat2a mRNA by Mettl16 is essential for mouse embryonic development
-
-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
the enzyme methylates U6 spliceosomal RNA and interacts with the 3'-terminal RNA triple helix of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1). Full-length METTL16 binds to the MALAT1 RNA triple helix, but monomeric METTL16_291 does not
-
-
?
S-adenosyl-L-methionine + adenine in U6 snRNA
S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
regulation of Mat2a mRNA by Mettl16 is essential for mouse embryonic development
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Breast Neoplasms
Expression and Prognostic Characteristics of m6 A RNA Methylation Regulators in Breast Cancer.
Colitis
A New Model of Spontaneous Colitis in Mice Induced by Deletion of an RNA m6A Methyltransferase Component METTL14 in T Cells.
Colonic Neoplasms
Frameshift Mutations in Repeat Sequences of ANK3, HACD4, TCP10L, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8 and METTL16 Genes in Colon Cancers.
Colorectal Neoplasms
Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A-dependent manner.
Colorectal Neoplasms
RNA m6A methyltransferase METTL3 promotes colorectal cancer cell proliferation and invasion by regulating Snail expression.
Colorectal Neoplasms
The differentiation of colorectal cancer is closely relevant to m6A modification.
Lung Neoplasms
N6-methyladenosine (m6A) methyltransferase KIAA1429 accelerates the gefitinib resistance of non-small-cell lung cancer.
Melanoma
ALKBH5-mediated m6A demethylation of FOXM1 mRNA promotes progression of uveal melanoma.
Melanoma
Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma.
Melanoma
RNA m6A methyltransferase METTL3 regulates invasiveness of melanoma cells by matrix metallopeptidase 2.
Mouth Neoplasms
Fat mass and obesity-associated protein regulates tumorigenesis of arecoline-promoted human oral carcinoma.
Neoplasm Metastasis
m6A Methyltransferase 3 Promotes the Proliferation and Migration of Gastric Cancer Cells through the m6A Modification of YAP1.
Neoplasms
ALKBH5-mediated m6A demethylation of FOXM1 mRNA promotes progression of uveal melanoma.
Neoplasms
Fat mass and obesity-associated protein regulates tumorigenesis of arecoline-promoted human oral carcinoma.
Neoplasms
Frameshift Mutations in Repeat Sequences of ANK3, HACD4, TCP10L, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8 and METTL16 Genes in Colon Cancers.
Neoplasms
Identification of m6A methyltransferase-related lncRNA signature for predicting immunotherapy and prognosis in patients with hepatocellular carcinoma.
Neoplasms
METTL16 promotes cell proliferation by up-regulating cyclin D1 expression in gastric cancer.
Neoplasms
Multiple Functions and Mechanisms Underlying the Role of METTL3 in Human Cancers.
Neoplasms
SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma.
Pancreatic Neoplasms
The RNA m6A methyltransferase METTL3 promotes pancreatic cancer cell proliferation and invasion.
Prostatic Neoplasms
RNA m6A Methyltransferase METTL3 Promotes The Growth Of Prostate Cancer By Regulating Hedgehog Pathway.
Pulmonary Disease, Chronic Obstructive
Expression patterns and prognostic value of m6A-related genes in colorectal cancer.
Squamous Cell Carcinoma of Head and Neck
The m6A RNA Modification Quantity and mRNA Expression Level of RNA Methylation-Related Genes in Head and Neck Squamous Cell Carcinoma Cell Lines and Patients.
Stomach Neoplasms
m6A Methyltransferase 3 Promotes the Proliferation and Migration of Gastric Cancer Cells through the m6A Modification of YAP1.
Stomach Neoplasms
METTL16 promotes cell proliferation by up-regulating cyclin D1 expression in gastric cancer.
Stomach Neoplasms
N6-methyladenosine (m6A) methyltransferase WTAP accelerates the Warburg effect of gastric cancer through regulating HK2 stability.
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
the majority of METTL16 protein resides in the cytoplasm. Overexpression of METTL16 can affect both its cellular location as well as its RNA binding preferences
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
METTL16 depletion decreases MAT2A expression, resulting in reduced intracellular S-adenosyl-L-methionine, a key substrate required for RNA methylation. Loss of METTL16 can result in a transcriptome-wide loss of m6A methylation beyond sites directly methylated by METTL16
malfunction
mouse 16-cell embryos lacking Mettl16 display reduced mRNA levels of its methylation target, the S-adenosyl-L-methionine synthetase Mat2a
physiological function
regulation of Mat2a mRNA by Mettl16 is essential for mouse embryonic development
physiological function
regulation of Mat2a mRNA by Mettl16 is essential for mouse embryonic development
physiological function
siRNA knockdown of METTL16 results in expression changes of a few mRNA targets suggesting that METTL16 may play a role in regulating gene expression
Show AA Sequence and Transmembrane Helices (423 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
full-length METTL16 forms a homodimer and METTL16_291 exists as a monomer
monomer
full-length METTL16 forms a homodimer and METTL16_291 exists as a monomer
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging-drop method at 19°C. Crystal structures of the N-terminal methyltransferase domain (residues 1-291) of human METTL16 (METTL16_291): an apo structure at 1.9 A resolution and a post-catalytic S-adenosylhomocysteine bound complex at 2.1 A resolution. The structures revealed a highly conserved Rossmann fold that is characteristic of class I S-adenosylmethionine-dependent methyltransferases and a large, positively charged groove. This groove likely represents the RNA-binding site and it includes structural elements unique to METTL16
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
two constructs (core, 1-291 aa and DELTAN, 40-291 aa) encompassing the methyltransferase domain are expressed in Escherichia coli
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pendleton, K.E.; Chen, B.; Liu, K.; Hunter, O.V.; Xie, Y.; Tu, B.P.; Conrad, N.K.
The U6 snRNA m6A methyltransferase METTL16 regulates SAM synthetase intron retention
Cell
169
824-835.e14
2017
Homo sapiens (Q86W50), Homo sapiens
brenda
Warda, A.S.; Kretschmer, J.; Hackert, P.; Lenz, C.; Urlaub, H.; Hoebartner, C.; Sloan, K.E.; Bohnsack, M.T.
Human METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets pre-mRNAs and various non-coding RNAs
EMBO Rep.
18
2004-2014
2017
Homo sapiens (Q86W50), Homo sapiens
brenda
Shimba, S.; Bokar, J.A.; Rottman, F.; Reddy, R.
Accurate and efficient N-6-adenosine methylation in spliceosomal U6 small nuclear RNA by HeLa cell extract in vitro
Nucleic Acids Res.
23
2421-2426
1995
Homo sapiens (Q86W50)
brenda
Yeon, S.Y.; Jo, Y.S.; Choi, E.J.; Kim, M.S.; Yoo, N.J.; Lee, S.H.
Frameshift mutations in repeat sequences of ANK3, HACD4, TCP10L, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8 and METTL16 genes in colon cancers
Pathol. Oncol. Res.
24
617-622
2018
Homo sapiens (Q86W50)
brenda
Mendel, M.; Chen, K.M.; Homolka, D.; Gos, P.; Pandey, R.R.; McCarthy, A.A.; Pillai, R.S.
Methylation of structured RNA by the m6A writer METTL16 is essential for mouse embryonic development
Mol. Cell
71
986-1000
2018
Homo sapiens (Q86W50), Homo sapiens, Mus musculus (Q9CQG2), Mus musculus
brenda
Koh, C.w.Q.; Goh, Y.T.; Goh, W.S.S.
Atlas of quantitative single-base-resolution N6-methyl-adenine methylomes
Nat. Commun.
10
5636
2019
Homo sapiens (Q86W50)
brenda
Nance, D.J.; Satterwhite, E.R.; Bhaskar, B.; Misra, S.; Carraway, K.R.; Mansfield, K.D.
Characterization of METTL16 as a cytoplasmic RNA binding protein
PLoS One
15
e0227647
2020
Homo sapiens (Q86W50)
brenda
Ruszkowska, A.; Ruszkowski, M.; Dauter, Z.; Brown, J.A.
Structural insights into the RNA methyltransferase domain of METTL16
Sci. Rep.
8
5311
2018
Homo sapiens (Q86W50)
brenda
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Release 2023.1 (January 2023)
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