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Protein

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

Gene

METTL16

Organism
Homo sapiens (Human)
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:28525753). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (PubMed:28525753). 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 (PubMed:28525753). 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:28525753). 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:28525753). 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 (PubMed:28525753, PubMed:29051200). Also able to bind various lncRNAs (PubMed:29051200). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (PubMed:27872311).3 Publications

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 (PubMed:28525753). 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 (PubMed:28525753). 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. Under low S-adenosyl-L-methionine-limiting condition MAT2A mRNA is not methylated, stabilizing it.By similarity1 Publication

Catalytic activityi

S-adenosyl-L-methionine + adenine in U6 snRNA = S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA.2 Publications
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-methionineCombined sources1 Publication1
Binding sitei110S-adenosyl-L-methionine; via carbonyl oxygenCombined sources1 Publication1
Binding sitei133S-adenosyl-L-methionineCombined sources1 Publication1
Binding sitei164S-adenosyl-L-methionineCombined sources1 Publication1
Binding sitei184S-adenosyl-L-methionineCombined sources1 Publication1

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))-methyltransferaseCurated (EC:2.1.1.3462 Publications)
Alternative name(s):
Methyltransferase 10 domain-containing proteinImported
Methyltransferase-like protein 161 Publication
N6-adenosine-methyltransferase METTL16 (EC:2.1.1.621 Publication)
Gene namesi
Name:METTL161 PublicationImported
Synonyms:METT10DImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000127804.12
HGNCiHGNC:28484 METTL16
neXtProtiNX_Q86W50

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi185 – 186PP → AA: Abolishes methyltransferase activity. 1 Publication2
Mutagenesisi187F → G: Abolishes methyltransferase activity. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000127804
PharmGKBiPA142671460

Polymorphism and mutation databases

BioMutaiMETTL16
DMDMi269849619

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003107671 – 562U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferaseAdd BLAST562

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei329PhosphoserineCombined sources1
Modified residuei463PhosphothreonineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ86W50
MaxQBiQ86W50
PaxDbiQ86W50
PeptideAtlasiQ86W50
PRIDEiQ86W50
ProteomicsDBi70116
70117 [Q86W50-2]

PTM databases

iPTMnetiQ86W50
PhosphoSitePlusiQ86W50

Expressioni

Gene expression databases

BgeeiENSG00000127804 Expressed in 216 organ(s), highest expression level in pituitary gland
CleanExiHS_METT10D
ExpressionAtlasiQ86W50 baseline and differential
GenevisibleiQ86W50 HS

Organism-specific databases

HPAiHPA020352
HPA059798

Interactioni

Subunit structurei

Interacts with MEPCE (PubMed:29051200). Interacts with LARP7 (PubMed:29051200).1 Publication

Protein-protein interaction databases

BioGridi122519, 11 interactors
STRINGi9606.ENSP00000263092

Structurei

Secondary structure

1562
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ86W50
SMRiQ86W50
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ86W50

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni289 – 400VCR 11 PublicationAdd BLAST112
Regioni514 – 562VCR 21 PublicationAdd BLAST49

Domaini

The VCR (vertebrate conserved) regions bind the first hairpin of MAT2A mRNAs.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2912 Eukaryota
COG3129 LUCA
GeneTreeiENSGT00390000016694
HOGENOMiHOG000181023
HOVERGENiHBG058052
InParanoidiQ86W50
KOiK11393
OMAiTEFCQGH
OrthoDBiEOG091G07VQ
PhylomeDBiQ86W50
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 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q86W50-1) [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 KQHVQINLNG RVSLNFKDPE
60 70 80 90 100
AVRALTCTLL REDFGLSIDI PLERLIPTVP LRLNYIHWVE DLIGHQDSDK
110 120 130 140 150
STLRRGIDIG TGASCIYPLL GATLNGWYFL ATEVDDMCFN YAKKNVEQNN
160 170 180 190 200
LSDLIKVVKV PQKTLLMDAL KEESEIIYDF CMCNPPFFAN QLEAKGVNSR
210 220 230 240 250
NPRRPPPSSV NTGGITEIMA EGGELEFVKR IIHDSLQLKK RLRWYSCMLG
260 270 280 290 300
KKCSLAPLKE ELRIQGVPKV TYTEFCQGRT MRWALAWSFY DDVTVPSPPS
310 320 330 340 350
KRRKLEKPRK PITFVVLASV MKELSLKASP LRSETAEGIV VVTTWIEKIL
360 370 380 390 400
TDLKVQHKRV PCGKEEVSLF LTAIENSWIH LRRKKRERVR QLREVPRAPE
410 420 430 440 450
DVIQALEEKK PTPKESGNSQ ELARGPQERT PCGPALREGE AAAVEGPCPS
460 470 480 490 500
QESLSQEENP EPTEDERSEE KGGVEVLESC QGSSNGAQDQ EASEQFGSPV
510 520 530 540 550
AERGKRLPGV AGQYLFKCLI NVKKEVDDAL VEMHWVEGQN RDLMNQLCTY
560
IRNQIFRLVA VN
Length:562
Mass (Da):63,621
Last modified:November 24, 2009 - v2
Checksum:i8CF655F19AF572F0
GO
Isoform 2 (identifier: Q86W50-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     214-224: GITEIMAEGGE → DSLEPGRWRLQ
     225-562: Missing.

Note: No experimental confirmation available.
Show »
Length:224
Mass (Da):25,502
Checksum:i15AB2DF8B5487A54
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L362I3L362_HUMAN
U6 small nuclear RNA (adenine-(43)-...
METTL16
168Annotation score:
I3L3W3I3L3W3_HUMAN
U6 small nuclear RNA (adenine-(43)-...
METTL16
121Annotation score:
K7EKQ8K7EKQ8_HUMAN
U6 small nuclear RNA (adenine-(43)-...
METTL16
101Annotation score:
I3L4V1I3L4V1_HUMAN
U6 small nuclear RNA (adenine-(43)-...
METTL16
148Annotation score:

Sequence cautioni

The sequence BAB55094 differs from that shown. Reason: Erroneous termination at position 505. Translated as Lys.Curated
The sequence CAD89999 differs from that shown. Reason: Frameshift at position 424.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti39N → D in BAB55094 (PubMed:14702039).Curated1
Sequence conflicti214G → A in CAD89999 (PubMed:17974005).Curated1
Sequence conflicti419S → R in BAB55094 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037086479S → N1 PublicationCorresponds to variant dbSNP:rs17834783Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_029340214 – 224GITEIMAEGGE → DSLEPGRWRLQ in isoform 2. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_029341225 – 562Missing in isoform 2. 1 PublicationAdd BLAST338

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK027410 mRNA Translation: BAB55094.1 Sequence problems.
AL832612 mRNA Translation: CAD89999.2 Frameshift.
AC006435 Genomic DNA No translation available.
AC015799 Genomic DNA No translation available.
CH471108 Genomic DNA Translation: EAW90537.1
CH471108 Genomic DNA Translation: EAW90538.1
BC001213 mRNA Translation: AAH01213.1
BC050603 mRNA Translation: AAH50603.1
CCDSiCCDS42232.1 [Q86W50-1]
RefSeqiNP_076991.3, NM_024086.3 [Q86W50-1]
UniGeneiHs.632237

Genome annotation databases

EnsembliENST00000263092; ENSP00000263092; ENSG00000127804 [Q86W50-1]
GeneIDi79066
KEGGihsa:79066
UCSCiuc002fut.4 human [Q86W50-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK027410 mRNA Translation: BAB55094.1 Sequence problems.
AL832612 mRNA Translation: CAD89999.2 Frameshift.
AC006435 Genomic DNA No translation available.
AC015799 Genomic DNA No translation available.
CH471108 Genomic DNA Translation: EAW90537.1
CH471108 Genomic DNA Translation: EAW90538.1
BC001213 mRNA Translation: AAH01213.1
BC050603 mRNA Translation: AAH50603.1
CCDSiCCDS42232.1 [Q86W50-1]
RefSeqiNP_076991.3, NM_024086.3 [Q86W50-1]
UniGeneiHs.632237

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H00X-ray2.00A/B/C40-291[»]
6B91X-ray1.94A1-291[»]
6B92X-ray2.10A1-291[»]
6DU4X-ray1.70A1-310[»]
6DU5X-ray3.01A2-310[»]
6GFKX-ray2.30A/B/C41-291[»]
6GFNX-ray2.86A1-291[»]
6GT5X-ray2.45A/B1-291[»]
ProteinModelPortaliQ86W50
SMRiQ86W50
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122519, 11 interactors
STRINGi9606.ENSP00000263092

PTM databases

iPTMnetiQ86W50
PhosphoSitePlusiQ86W50

Polymorphism and mutation databases

BioMutaiMETTL16
DMDMi269849619

Proteomic databases

EPDiQ86W50
MaxQBiQ86W50
PaxDbiQ86W50
PeptideAtlasiQ86W50
PRIDEiQ86W50
ProteomicsDBi70116
70117 [Q86W50-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263092; ENSP00000263092; ENSG00000127804 [Q86W50-1]
GeneIDi79066
KEGGihsa:79066
UCSCiuc002fut.4 human [Q86W50-1]

Organism-specific databases

CTDi79066
EuPathDBiHostDB:ENSG00000127804.12
GeneCardsiMETTL16
H-InvDBiHIX0013421
HGNCiHGNC:28484 METTL16
HPAiHPA020352
HPA059798
neXtProtiNX_Q86W50
OpenTargetsiENSG00000127804
PharmGKBiPA142671460
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2912 Eukaryota
COG3129 LUCA
GeneTreeiENSGT00390000016694
HOGENOMiHOG000181023
HOVERGENiHBG058052
InParanoidiQ86W50
KOiK11393
OMAiTEFCQGH
OrthoDBiEOG091G07VQ
PhylomeDBiQ86W50
TreeFamiTF313132

Miscellaneous databases

ChiTaRSiMETTL16 human
EvolutionaryTraceiQ86W50
GenomeRNAii79066
PROiPR:Q86W50

Gene expression databases

BgeeiENSG00000127804 Expressed in 216 organ(s), highest expression level in pituitary gland
CleanExiHS_METT10D
ExpressionAtlasiQ86W50 baseline and differential
GenevisibleiQ86W50 HS

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_HUMAN
AccessioniPrimary (citable) accession number: Q86W50
Secondary accession number(s): D3DTI8
, Q86TE5, Q96T16, Q9BVG7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: November 24, 2009
Last modified: November 7, 2018
This is version 116 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. Uncharacterized protein families (UPF)
    List of uncharacterized protein family (UPF) entries
  5. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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