UniProtKB - Q9CQG2 (MET16_MOUSE)
Protein
RNA N6-adenosine-methyltransferase METTL16
Gene
Mettl16
Organism
Mus musculus (Mouse)
Status
Functioni
RNA N6-methyltransferase that methylates adenosine residues at the N6 position of a subset of RNAs and is involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:29262316, PubMed:30197299). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (By similarity). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure (By similarity). Plays a key role in S-adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A mRNAs, altering splicing and/or stability of MAT2A transcripts: in presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, impairing MAT2A expression (PubMed:29262316, PubMed:30197299). In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:29262316). In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs (By similarity). Also able to bind various lncRNAs, such as 7SK snRNA (7SK RNA) or 7SL RNA (By similarity). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (By similarity) (PubMed:29262316, PubMed:30197299).By similarity2 Publications
Caution
Consequences of N6-methylation of MAT2A transcripts are subject to discussion. According to a report, N6-methylation of MAT2A affects MAT2A mRNA splicing: in presence of S-adenosyl-L-methionine, METTL16 binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, leading to intron retention and preventing MAT2A mRNA splicing (By similarity). In S-adenosyl-L-methionine-limiting conditions, METTL16 binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, leading to stimulate splicing of the MAT2A retained intron, and promoting expression of MAT2A (By similarity). According to a second report, N6-methylation of MAT2A affects MAT2A mRNA stability instead: in presence of S-adenosyl-L-methionine, METTL16 N6-methylates MAT2A mRNA, leading to destabilization and subsequent degradation of MAT2A mRNA (PubMed:29262316). Under low S-adenosyl-L-methionine-limiting condition MAT2A mRNA is not methylated, stabilizing it (PubMed:29262316).By similarity1 Publication
Catalytic activityi
- adenosine in U6 snRNA + S-adenosyl-L-methionine = H+ + N6-methyladenosine in U6 snRNA + S-adenosyl-L-homocysteineBy similarityEC:2.1.1.346By similarity
- adenosine in mRNA + S-adenosyl-L-methionine = H+ + N6-methyladenosine in mRNA + S-adenosyl-L-homocysteine1 PublicationEC:2.1.1.3481 Publication
Activity regulationi
Methyltransferase activity is autoinhibited by the K-loop region that blocks S-adenosyl-L-methionine-binding. Upon activation, K-loop changes conformation, allowing S-adenosyl-L-methionine-binding and subsequent methyltransferase activity.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 82 | S-adenosyl-L-methionineBy similarity | 1 | |
Binding sitei | 110 | S-adenosyl-L-methionine; via carbonyl oxygenBy similarity | 1 | |
Binding sitei | 114 | S-adenosyl-L-methionineBy similarity | 1 | |
Binding sitei | 133 | S-adenosyl-L-methionineBy similarity | 1 | |
Binding sitei | 164 | S-adenosyl-L-methionineBy similarity | 1 | |
Binding sitei | 184 | S-adenosyl-L-methionineBy similarity | 1 |
GO - Molecular functioni
- 23S rRNA (adenine(1618)-N(6))-methyltransferase activity Source: GO_Central
- mRNA (N6-adenosine)-methyltransferase activity Source: UniProtKB
- RNA binding Source: UniProtKB
- RNA stem-loop binding Source: UniProtKB
- U6 snRNA (adenine-(43)-N(6))-methyltransferase activity Source: UniProtKB
- U6 snRNA 3'-end binding Source: UniProtKB
GO - Biological processi
- mRNA catabolic process Source: UniProtKB
- mRNA destabilization Source: UniProtKB
- mRNA methylation Source: UniProtKB
- negative regulation of 3'-UTR-mediated mRNA stabilization Source: MGI
- posttranscriptional regulation of gene expression Source: UniProtKB
- regulation of mRNA splicing, via spliceosome Source: UniProtKB
- RNA methylation Source: UniProtKB
- rRNA base methylation Source: GO_Central
- S-adenosylmethionine biosynthetic process Source: UniProtKB
- snRNA (adenine-N6)-methylation Source: UniProtKB
Keywordsi
Molecular function | Methyltransferase, RNA-binding, Transferase |
Ligand | S-adenosyl-L-methionine |
Names & Taxonomyi
Protein namesi | Recommended name: RNA N6-adenosine-methyltransferase METTL16CuratedAlternative name(s): |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1914743, Mettl16 |
Pathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000310768 | 1 – 553 | RNA N6-adenosine-methyltransferase METTL16Add BLAST | 553 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 329 | PhosphoserineBy similarity | 1 | |
Modified residuei | 425 | PhosphoserineCombined sources | 1 | |
Modified residuei | 429 | PhosphoserineCombined sources | 1 | |
Modified residuei | 463 | PhosphothreonineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9CQG2 |
jPOSTi | Q9CQG2 |
PaxDbi | Q9CQG2 |
PeptideAtlasi | Q9CQG2 |
PRIDEi | Q9CQG2 |
PTM databases
iPTMneti | Q9CQG2 |
PhosphoSitePlusi | Q9CQG2 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000010554, Expressed in blastocyst and 260 other tissues |
ExpressionAtlasi | Q9CQG2, baseline and differential |
Genevisiblei | Q9CQG2, MM |
Interactioni
Subunit structurei
Interacts with MEPCE.
Interacts with LARP7.
By similarityProtein-protein interaction databases
BioGRIDi | 212228, 1 interactor |
STRINGi | 10090.ENSMUSP00000114682 |
Miscellaneous databases
RNActi | Q9CQG2, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 17 – 20 | RNA-bindingBy similarity | 4 | |
Regioni | 163 – 167 | K-loopBy similarity | 5 | |
Regioni | 199 – 211 | RNA-bindingBy similarityAdd BLAST | 13 | |
Regioni | 250 – 254 | RNA-bindingBy similarity | 5 | |
Regioni | 277 – 283 | RNA-bindingBy similarity | 7 | |
Regioni | 289 – 400 | VCR 1By similarityAdd BLAST | 112 | |
Regioni | 506 – 553 | VCR 2By similarityAdd BLAST | 48 |
Domaini
The VCR (vertebrate conserved) regions bind the first hairpin of MAT2A mRNAs. The VCR regions interact with the internal stem-loop within U6 snRNAs, inducing the conformational rearrangement of the A43-containing region of U6 snRNA, thereby modifying the RNA structure to become suitable for productive catalysis by the methyltransferase region.By similarity
The K-loop region occludes the S-adenosyl-L-methionine-binding pocket. Upon activation, conformation of the K-loop changes, allowing S-adenosyl-L-methionine-binding.By similarity
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2912, Eukaryota |
GeneTreei | ENSGT00390000016694 |
HOGENOMi | CLU_027534_0_0_1 |
InParanoidi | Q9CQG2 |
OrthoDBi | 1358504at2759 |
PhylomeDBi | Q9CQG2 |
TreeFami | TF313132 |
Family and domain databases
InterProi | View protein in InterPro IPR017182, METTL16/PsiM IPR010286, METTL16/RlmF IPR029063, SAM-dependent_MTases |
PANTHERi | PTHR13393, PTHR13393, 1 hit |
Pfami | View protein in Pfam PF05971, Methyltransf_10, 1 hit |
PIRSFi | PIRSF037350, Mtase_ZK1128_prd, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9CQG2-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MALSKSMHAR NRYKDKPPDF AYLASKYPDF KQHIQINLNG RVSLNFKDPE
60 70 80 90 100
AVRALTCTLL REDFGLSIDI PLERLIPTVP LRLNYIHWVE DLIGHQDSDK
110 120 130 140 150
TTLRRGIDIG TGASCIYPLL GATLNGWYFL ATEVDDMCFN YAKKNVEQNN
160 170 180 190 200
LSDLIKVVKV PQKTLLMDAL KEESEIVYDF CMCNPPFFAN QLEAKGVNSR
210 220 230 240 250
NSRRPPPSSV NTGGITEIMA EGGELEFVKR IIHDSLQLKK RLRWYSCMLG
260 270 280 290 300
KKCSLAPLKE ELRIQGVPKV TFTEFCQGRT MRWALAWSFY DDVTVPSPPS
310 320 330 340 350
KRRKLEKPRK PITFVVLESV MKELSLKASS LGSETAEGIV VVTTWIEKIL
360 370 380 390 400
TDLKVQHKRI PCGREEVSLF LTAIENSWIH LRRKRRERVR QLREVPRAPE
410 420 430 440 450
DVILALEERK STPKELSSGQ DVAHSPQESA LCGLDVPGGE AAADGGHCLS
460 470 480 490 500
QKLLCQEETP EATEDERDEE RGGMEAMESC KGSSNGAQDG EASEKGDRLD
510 520 530 540 550
GAAGRYLFKC LVNIKKEAGD AVVEMHWVEG QNRDLMNQLC TYVRNQILRL
VAS
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8WHZ7 | F8WHZ7_MOUSE | Methyltransferase 10 domain-contain... | Mettl16 | 215 | Annotation score: | ||
Q5SW15 | Q5SW15_MOUSE | U6 small nuclear RNA (adenine-(43)-... | Mettl16 | 593 | Annotation score: | ||
Q5SW13 | Q5SW13_MOUSE | RNA N6-adenosine-methyltransferase ... | Mettl16 | 33 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 498 | R → H in BAE26189 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 533 | R → G in BAB27835 (PubMed:16141072).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_029342 | 267 – 296 | Missing in isoform 2. 1 PublicationAdd BLAST | 30 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK145022 mRNA Translation: BAE26189.1 AK011780 mRNA Translation: BAB27835.1 AK012739 mRNA Translation: BAB28440.1 AK145662 mRNA Translation: BAE26574.1 AK168798 mRNA Translation: BAE40630.1 AL604066 Genomic DNA No translation available. AL607024 Genomic DNA No translation available. BC049897 mRNA Translation: AAH49897.1 BC054724 mRNA Translation: AAH54724.1 |
CCDSi | CCDS25036.1 [Q9CQG2-1] |
RefSeqi | NP_080473.1, NM_026197.3 [Q9CQG2-1] XP_006534061.1, XM_006533998.3 [Q9CQG2-1] XP_006534062.1, XM_006533999.2 [Q9CQG2-1] |
Genome annotation databases
Ensembli | ENSMUST00000141755; ENSMUSP00000114682; ENSMUSG00000010554 [Q9CQG2-1] |
GeneIDi | 67493 |
KEGGi | mmu:67493 |
UCSCi | uc007kch.1, mouse [Q9CQG2-1] uc011xza.1, mouse [Q9CQG2-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK145022 mRNA Translation: BAE26189.1 AK011780 mRNA Translation: BAB27835.1 AK012739 mRNA Translation: BAB28440.1 AK145662 mRNA Translation: BAE26574.1 AK168798 mRNA Translation: BAE40630.1 AL604066 Genomic DNA No translation available. AL607024 Genomic DNA No translation available. BC049897 mRNA Translation: AAH49897.1 BC054724 mRNA Translation: AAH54724.1 |
CCDSi | CCDS25036.1 [Q9CQG2-1] |
RefSeqi | NP_080473.1, NM_026197.3 [Q9CQG2-1] XP_006534061.1, XM_006533998.3 [Q9CQG2-1] XP_006534062.1, XM_006533999.2 [Q9CQG2-1] |
3D structure databases
SMRi | Q9CQG2 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 212228, 1 interactor |
STRINGi | 10090.ENSMUSP00000114682 |
PTM databases
iPTMneti | Q9CQG2 |
PhosphoSitePlusi | Q9CQG2 |
Proteomic databases
EPDi | Q9CQG2 |
jPOSTi | Q9CQG2 |
PaxDbi | Q9CQG2 |
PeptideAtlasi | Q9CQG2 |
PRIDEi | Q9CQG2 |
Protocols and materials databases
Antibodypediai | 5377, 246 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000141755; ENSMUSP00000114682; ENSMUSG00000010554 [Q9CQG2-1] |
GeneIDi | 67493 |
KEGGi | mmu:67493 |
UCSCi | uc007kch.1, mouse [Q9CQG2-1] uc011xza.1, mouse [Q9CQG2-2] |
Organism-specific databases
CTDi | 79066 |
MGIi | MGI:1914743, Mettl16 |
Phylogenomic databases
eggNOGi | KOG2912, Eukaryota |
GeneTreei | ENSGT00390000016694 |
HOGENOMi | CLU_027534_0_0_1 |
InParanoidi | Q9CQG2 |
OrthoDBi | 1358504at2759 |
PhylomeDBi | Q9CQG2 |
TreeFami | TF313132 |
Miscellaneous databases
BioGRID-ORCSi | 67493, 10 hits in 19 CRISPR screens |
ChiTaRSi | Mettl16, mouse |
PROi | PR:Q9CQG2 |
RNActi | Q9CQG2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000010554, Expressed in blastocyst and 260 other tissues |
ExpressionAtlasi | Q9CQG2, baseline and differential |
Genevisiblei | Q9CQG2, MM |
Family and domain databases
InterProi | View protein in InterPro IPR017182, METTL16/PsiM IPR010286, METTL16/RlmF IPR029063, SAM-dependent_MTases |
PANTHERi | PTHR13393, PTHR13393, 1 hit |
Pfami | View protein in Pfam PF05971, Methyltransf_10, 1 hit |
PIRSFi | PIRSF037350, Mtase_ZK1128_prd, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MET16_MOUSE | |
Accessioni | Q9CQG2Primary (citable) accession number: Q9CQG2 Secondary accession number(s): Q3UMA9, Q9D062 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 13, 2007 |
Last sequence update: | June 1, 2001 | |
Last modified: | December 2, 2020 | |
This is version 131 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families