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Protein

U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase

Gene

Mettl16

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

RNA N6-methyltransferase that methylates adenosine residues of a subset of RNAs and plays a key role in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:29262316). 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). 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). 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 (By similarity). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (By similarity).By similarity1 Publication

Caution

Consequences of N6-methylation of MAT2A 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. 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. 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

S-adenosyl-L-methionine + adenine in U6 snRNA = S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA.By similarity
S-adenosyl-L-methionine + a 5-(N7-methyl 5-triphosphoguanosine)-2'-O-methyladenosine-[mRNA] = S-adenosyl-L-homocysteine + a 5-(N7-methyl 5-triphosphoguanosine)-N6,2'-O-dimethyladenosine-[mRNA].1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei82S-adenosyl-L-methionineBy similarity1
Binding sitei110S-adenosyl-L-methionine; via carbonyl oxygenBy similarity1
Binding sitei133S-adenosyl-L-methionineBy similarity1
Binding sitei164S-adenosyl-L-methionineBy similarity1
Binding sitei184S-adenosyl-L-methionineBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionMethyltransferase, RNA-binding, Transferase
LigandS-adenosyl-L-methionine

Names & Taxonomyi

Protein namesi
Recommended name:
U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferaseBy similarity (EC:2.1.1.346By similarity)
Alternative name(s):
Methyltransferase 10 domain-containing protein
Methyltransferase-like protein 16
N6-adenosine-methyltransferase METTL16By similarity (EC:2.1.1.621 Publication)
Gene namesi
Name:Mettl16Imported
Synonyms:Mett10dImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1914743 Mettl16

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003107681 – 553U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferaseAdd BLAST553

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei329PhosphoserineBy similarity1
Modified residuei425PhosphoserineCombined sources1
Modified residuei429PhosphoserineCombined sources1
Modified residuei463PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9CQG2
PaxDbiQ9CQG2
PeptideAtlasiQ9CQG2
PRIDEiQ9CQG2

PTM databases

iPTMnetiQ9CQG2
PhosphoSitePlusiQ9CQG2

Expressioni

Gene expression databases

BgeeiENSMUSG00000010554 Expressed in 242 organ(s), highest expression level in blastocyst
CleanExiMM_METT10D
ExpressionAtlasiQ9CQG2 baseline and differential
GenevisibleiQ9CQG2 MM

Interactioni

Subunit structurei

Interacts with MEPCE. Interacts with LARP7.By similarity

Protein-protein interaction databases

BioGridi212228, 1 interactor
STRINGi10090.ENSMUSP00000114682

Structurei

3D structure databases

ProteinModelPortaliQ9CQG2
SMRiQ9CQG2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni289 – 400VCR 1By similarityAdd BLAST112
Regioni506 – 553VCR 2By similarityAdd BLAST48

Domaini

The VCR (vertebrate conserved) regions bind the first hairpin of MAT2A mRNAs.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2912 Eukaryota
COG3129 LUCA
GeneTreeiENSGT00390000016694
HOVERGENiHBG058052
InParanoidiQ9CQG2
KOiK11393
PhylomeDBiQ9CQG2
TreeFamiTF313132

Family and domain databases

InterProiView protein in InterPro
IPR017182 METTL16/PsiM
IPR010286 rRNA_lsu_MeTfrase_F-like
IPR029063 SAM-dependent_MTases
PANTHERiPTHR13393 PTHR13393, 1 hit
PfamiView protein in Pfam
PF05971 Methyltransf_10, 1 hit
PIRSFiPIRSF037350 Mtase_ZK1128_prd, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This 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 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:553
Mass (Da):62,341
Last modified:June 1, 2001 - v1
Checksum:i9087B88833F3B783
GO
Isoform 2 (identifier: Q9CQG2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     267-296: Missing.

Note: No experimental confirmation available.
Show »
Length:523
Mass (Da):58,806
Checksum:i8AC25AED3B708AAA
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5SW15Q5SW15_MOUSE
U6 small nuclear RNA (adenine-(43)-...
Mettl16
593Annotation score:
F8WHZ7F8WHZ7_MOUSE
U6 small nuclear RNA (adenine-(43)-...
Mettl16
215Annotation score:
Q5SW13Q5SW13_MOUSE
U6 small nuclear RNA (adenine-(43)-...
Mettl16
33Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti498R → H in BAE26189 (PubMed:16141072).Curated1
Sequence conflicti533R → G in BAB27835 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_029342267 – 296Missing in isoform 2. 1 PublicationAdd BLAST30

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, AL607024 Genomic DNA Translation: CAI24250.1
AL607024, AL604066 Genomic DNA Translation: CAI24379.1
BC049897 mRNA Translation: AAH49897.1
BC054724 mRNA Translation: AAH54724.1
CCDSiCCDS25036.1 [Q9CQG2-1]
RefSeqiNP_080473.1, NM_026197.3 [Q9CQG2-1]
XP_006534061.1, XM_006533998.3 [Q9CQG2-1]
XP_006534062.1, XM_006533999.2 [Q9CQG2-1]
UniGeneiMm.45748

Genome annotation databases

EnsembliENSMUST00000141755; ENSMUSP00000114682; ENSMUSG00000010554 [Q9CQG2-1]
GeneIDi67493
KEGGimmu:67493
UCSCiuc007kch.1 mouse [Q9CQG2-1]
uc011xza.1 mouse [Q9CQG2-2]

Keywords - Coding sequence diversityi

Alternative splicing

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, AL607024 Genomic DNA Translation: CAI24250.1
AL607024, AL604066 Genomic DNA Translation: CAI24379.1
BC049897 mRNA Translation: AAH49897.1
BC054724 mRNA Translation: AAH54724.1
CCDSiCCDS25036.1 [Q9CQG2-1]
RefSeqiNP_080473.1, NM_026197.3 [Q9CQG2-1]
XP_006534061.1, XM_006533998.3 [Q9CQG2-1]
XP_006534062.1, XM_006533999.2 [Q9CQG2-1]
UniGeneiMm.45748

3D structure databases

ProteinModelPortaliQ9CQG2
SMRiQ9CQG2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi212228, 1 interactor
STRINGi10090.ENSMUSP00000114682

PTM databases

iPTMnetiQ9CQG2
PhosphoSitePlusiQ9CQG2

Proteomic databases

EPDiQ9CQG2
PaxDbiQ9CQG2
PeptideAtlasiQ9CQG2
PRIDEiQ9CQG2

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000141755; ENSMUSP00000114682; ENSMUSG00000010554 [Q9CQG2-1]
GeneIDi67493
KEGGimmu:67493
UCSCiuc007kch.1 mouse [Q9CQG2-1]
uc011xza.1 mouse [Q9CQG2-2]

Organism-specific databases

CTDi79066
MGIiMGI:1914743 Mettl16

Phylogenomic databases

eggNOGiKOG2912 Eukaryota
COG3129 LUCA
GeneTreeiENSGT00390000016694
HOVERGENiHBG058052
InParanoidiQ9CQG2
KOiK11393
PhylomeDBiQ9CQG2
TreeFamiTF313132

Miscellaneous databases

PROiPR:Q9CQG2
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000010554 Expressed in 242 organ(s), highest expression level in blastocyst
CleanExiMM_METT10D
ExpressionAtlasiQ9CQG2 baseline and differential
GenevisibleiQ9CQG2 MM

Family and domain databases

InterProiView protein in InterPro
IPR017182 METTL16/PsiM
IPR010286 rRNA_lsu_MeTfrase_F-like
IPR029063 SAM-dependent_MTases
PANTHERiPTHR13393 PTHR13393, 1 hit
PfamiView protein in Pfam
PF05971 Methyltransf_10, 1 hit
PIRSFiPIRSF037350 Mtase_ZK1128_prd, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMET16_MOUSE
AccessioniPrimary (citable) accession number: Q9CQG2
Secondary accession number(s): Q3UMA9, Q9D062
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: June 1, 2001
Last modified: September 12, 2018
This is version 118 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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