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Protein

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

Gene

METTL16

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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, leading to intron retention and preventing MAT2A mRNA splicing (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, leading to stimulate splicing of the MAT2A retained intron, 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). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (PubMed:27872311).2 Publications

Catalytic activityi

S-adenosyl-L-methionine + adenine(43) in U6 snRNA = S-adenosyl-L-homocysteine + N6-methyladenine(43) in U6 snRNA.1 Publication
S-adenosyl-L-methionine + m7G(5')pppAm = S-adenosyl-L-homocysteine + m7G(5')pppm6Am.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

  • 23S rRNA (adenine(1618)-N(6))-methyltransferase activity Source: GO_Central
  • mRNA (2'-O-methyladenosine-N6-)-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 processing Source: UniProtKB-KW
  • posttranscriptional regulation of gene expression Source: UniProtKB
  • regulation of mRNA splicing, via spliceosome Source: UniProtKB
  • RNA splicing Source: UniProtKB-KW
  • rRNA base methylation Source: GO_Central
  • snRNA (adenine-N6)-methylation Source: UniProtKB

Keywordsi

Molecular functionMethyltransferase, RNA-binding, Transferase
Biological processmRNA processing, mRNA splicing
LigandS-adenosyl-L-methionine

Names & Taxonomyi

Protein namesi
Recommended name:
U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase (EC:2.1.1.-1 Publication)
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.

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.

PTM databases

iPTMnetiQ86W50.
PhosphoSitePlusiQ86W50.

Expressioni

Gene expression databases

BgeeiENSG00000127804.
CleanExiHS_METT10D.
ExpressionAtlasiQ86W50. baseline and differential.
GenevisibleiQ86W50. HS.

Organism-specific databases

HPAiHPA020352.
HPA059798.

Interactioni

Protein-protein interaction databases

BioGridi122519. 11 interactors.
STRINGi9606.ENSP00000263092.

Structurei

Secondary structure

1562
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi49 – 64Combined sources16
Helixi79 – 93Combined sources15
Helixi98 – 100Combined sources3
Beta strandi105 – 110Combined sources6
Turni112 – 115Combined sources4
Helixi116 – 125Combined sources10
Beta strandi128 – 134Combined sources7
Helixi136 – 148Combined sources13
Turni152 – 154Combined sources3
Beta strandi155 – 159Combined sources5
Turni167 – 169Combined sources3
Beta strandi178 – 183Combined sources6
Turni215 – 218Combined sources4
Helixi219 – 222Combined sources4
Helixi224 – 238Combined sources15
Helixi239 – 241Combined sources3
Beta strandi245 – 251Combined sources7
Helixi255 – 264Combined sources10
Beta strandi268 – 277Combined sources10
Beta strandi280 – 289Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H00X-ray2.00A/B/C40-291[»]
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 and regulate MAT2A splicing.1 Publication

Sequence similaritiesi

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR017182. METTL16.
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

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

Sequence cautioni

Q86W50: The sequence BAB55094 differs from that shown. Reason: Erroneous termination at position 505. Translated as Lys.Curated
Q86W50: 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

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: September 27, 2017
This is version 108 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. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families
  6. Uncharacterized protein families (UPF)
    List of uncharacterized protein family (UPF) entries