MET16_XENLA
ID MET16_XENLA Reviewed; 547 AA.
AC Q6GR37;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=RNA N6-adenosine-methyltransferase mettl16 {ECO:0000305};
DE AltName: Full=Methyltransferase 10 domain-containing protein;
DE AltName: Full=Methyltransferase-like protein 16;
DE AltName: Full=N6-adenosine-methyltransferase METTL16 {ECO:0000250|UniProtKB:Q86W50};
DE EC=2.1.1.348 {ECO:0000250|UniProtKB:Q86W50};
DE AltName: Full=U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase {ECO:0000250|UniProtKB:Q86W50};
DE EC=2.1.1.346 {ECO:0000250|UniProtKB:Q86W50};
GN Name=mettl16; Synonyms=mett10d;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: RNA N6-methyltransferase that methylates adenosine residues
CC at the N(6) position of a subset of RNAs and is involved in S-adenosyl-
CC L-methionine homeostasis by regulating expression of MAT2A transcripts.
CC Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6
CC snRNAs). In contrast to the METTL3-METTL14 heterodimer, only able to
CC methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3'
CC nonamer sequence and a specific RNA structure. Plays a key role in S-
CC adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A
CC mRNAs, altering splicing of MAT2A transcripts: in presence of S-
CC adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and
CC specifically N6-methylates the first hairpin of MAT2A mRNA, impairing
CC MAT2A splicing and protein expression. In S-adenosyl-L-methionine-
CC limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls
CC due to the lack of a methyl donor, preventing N6-methylation and
CC promoting expression of MAT2A. In addition to mRNAs, also able to
CC mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically
CC N6-methylates adenine in position 43 of U6 snRNAs.
CC {ECO:0000250|UniProtKB:Q86W50}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine in U6 snRNA + S-adenosyl-L-methionine = H(+) + N(6)-
CC methyladenosine in U6 snRNA + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:52808, Rhea:RHEA-COMP:13573, Rhea:RHEA-COMP:13574,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74411, ChEBI:CHEBI:74449; EC=2.1.1.346;
CC Evidence={ECO:0000250|UniProtKB:Q86W50};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an adenosine in mRNA + S-adenosyl-L-methionine = an N(6)-
CC methyladenosine in mRNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:55584, Rhea:RHEA-COMP:12414, Rhea:RHEA-COMP:12417,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74411, ChEBI:CHEBI:74449; EC=2.1.1.348;
CC Evidence={ECO:0000250|UniProtKB:Q86W50};
CC -!- ACTIVITY REGULATION: Methyltransferase activity is autoinhibited by the
CC K-loop region that blocks S-adenosyl-L-methionine-binding. Upon
CC activation, K-loop changes conformation, allowing S-adenosyl-L-
CC methionine-binding and subsequent methyltransferase activity. mRNA N6-
CC adenosine-methyltransferase activity is inhibited by zinc.
CC {ECO:0000250|UniProtKB:Q86W50}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q86W50}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q86W50}.
CC -!- DOMAIN: The VCR (vertebrate conserved) regions bind the first hairpin
CC of MAT2A mRNAs. The VCR regions interact with the internal stem-loop
CC within U6 snRNAs, inducing the conformational rearrangement of the A43-
CC containing region of U6 snRNA, thereby modifying the RNA structure to
CC become suitable for productive catalysis by the methyltransferase
CC region. {ECO:0000250|UniProtKB:Q86W50}.
CC -!- DOMAIN: The K-loop region occludes the S-adenosyl-L-methionine-binding
CC pocket. Upon activation, conformation of the K-loop changes, allowing
CC S-adenosyl-L-methionine-binding. {ECO:0000250|UniProtKB:Q86W50}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. METTL16/RlmF
CC family. {ECO:0000305}.
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DR EMBL; BC071096; AAH71096.1; -; mRNA.
DR RefSeq; NP_001085334.1; NM_001091865.1.
DR AlphaFoldDB; Q6GR37; -.
DR SMR; Q6GR37; -.
DR DNASU; 443759; -.
DR GeneID; 443759; -.
DR KEGG; xla:443759; -.
DR CTD; 443759; -.
DR Xenbase; XB-GENE-952805; mettl16.L.
DR OMA; TEFCQGH; -.
DR OrthoDB; 1358504at2759; -.
DR Proteomes; UP000186698; Chromosome 2L.
DR Bgee; 443759; Expressed in egg cell and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0001734; F:mRNA (N6-adenosine)-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB.
DR GO; GO:0035613; F:RNA stem-loop binding; ISS:UniProtKB.
DR GO; GO:0120048; F:U6 snRNA (adenine-(43)-N(6))-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0030629; F:U6 snRNA 3'-end binding; ISS:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; ISS:UniProtKB.
DR GO; GO:0061157; P:mRNA destabilization; ISS:UniProtKB.
DR GO; GO:0080009; P:mRNA methylation; ISS:UniProtKB.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0006556; P:S-adenosylmethionine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0120049; P:snRNA (adenine-N6)-methylation; ISS:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR017182; METTL16/PsiM.
DR InterPro; IPR010286; METTL16/RlmF.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR13393; PTHR13393; 1.
DR Pfam; PF05971; Methyltransf_10; 1.
DR PIRSF; PIRSF037350; Mtase_ZK1128_prd; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Methyltransferase; Nucleus; Reference proteome; RNA-binding;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..547
FT /note="RNA N6-adenosine-methyltransferase mettl16"
FT /id="PRO_0000310771"
FT REGION 17..20
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 163..167
FT /note="K-loop"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 199..211
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 250..254
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 277..283
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 289..398
FT /note="VCR 1"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 383..473
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 500..547
FT /note="VCR 2"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT COMPBIAS 413..450
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 82
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 110
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 114
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 133
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 164
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 184
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
SQ SEQUENCE 547 AA; 61883 MW; 81D24567AE1D0899 CRC64;
MALNKSMHPR NRYKDKPPDF AYLASKYPEF KQHVNVNLAG RVSLNFKDPC AVRALTCTLL
KEDFGLTIDI PLERLIPTVP LRLNYIHWVE DLINYHDSDK TALRRGIDIG TGASCIYPLL
GATLNGWYFL ATEVDDICYN YAKKNVEQNN LSDLIKVVKV PQKTLLMDAL KEESEIIYDF
CMCNPPFFAN QLEAQGVNSR NPHRSPPSSV NTGGITEIMA EGGELEFVKR IIHDSLKLKK
RLRWYSCMLG KKCSLAPLKE ELRLQGVPKV AHTEFYQGRT MRWALAWSFY EEVIIPNPPK
KRKLEKPRKP MVFTVLESVI KLLTEKLPSG SEVPESITLV ADCIKKILTD LKVQHKIVPC
GRDEESLFLT AVENSWIHIR RKKRDRTRQL RELPRAPNDF LQSNKPDALH KETSDQGQNS
GDPPATKESE SVTQSETCVP HTSSTPESAA PALSEPMEAE NSDSKPDEVC NNDEEQDLGE
DMKQSCGEAS SAPQGSGSPF LFKCVLNVKK ENSDVLVEMH CVEGQNRDLM NQLCTYIRNQ
IYRLATS
