MET16_DANRE
ID MET16_DANRE Reviewed; 471 AA.
AC Q6DC64;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 93.
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; ORFNames=zgc:100981;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-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; BC078220; AAH78220.1; -; mRNA.
DR RefSeq; NP_001003611.1; NM_001003611.1.
DR AlphaFoldDB; Q6DC64; -.
DR SMR; Q6DC64; -.
DR STRING; 7955.ENSDARP00000072692; -.
DR PaxDb; Q6DC64; -.
DR PRIDE; Q6DC64; -.
DR GeneID; 445217; -.
DR KEGG; dre:445217; -.
DR CTD; 79066; -.
DR ZFIN; ZDB-GENE-040801-130; mettl16.
DR eggNOG; KOG2912; Eukaryota.
DR InParanoid; Q6DC64; -.
DR OrthoDB; 1358504at2759; -.
DR PhylomeDB; Q6DC64; -.
DR PRO; PR:Q6DC64; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0052907; F:23S rRNA (adenine(1618)-N(6))-methyltransferase activity; IBA:GO_Central.
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:0070475; P:rRNA base methylation; IBA:GO_Central.
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..471
FT /note="RNA N6-adenosine-methyltransferase mettl16"
FT /id="PRO_0000310770"
FT REGION 17..20
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 159..163
FT /note="K-loop"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 194..206
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 245..249
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 272..278
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 284..390
FT /note="VCR 1"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 375..412
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 421..470
FT /note="VCR 2"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT COMPBIAS 375..390
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 392..409
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 106
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 129
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 160
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 179
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
SQ SEQUENCE 471 AA; 53621 MW; 13B5A1D75DA7216E CRC64;
MALNKSMHPR NRYKDKPPDF VYLASKYPEF QKHVQTTLTG RVTLNFKDPE AVRALTCTLL
KEDFGLTIEI PLERLIPTVP LRLNYIHWVE DLIGGQGNPQ RGIDIGTGAS CIYPLLGATM
NGWFFLATEV DDICFNYAKK NVEQNHLAEL IKVVKVPQKT LLMDALKEES IVYDFCMCNP
PFFANQLEAK GVNSRNSRRP PPSSINTGGV TEIMAEGGEL EFVKRVIHDS LQLKKRLRWY
SCMLGKKCSL APLKDELRKQ GVAKVTHTEF CQGRTMRWAL AWSFYDDVPV PSPPCKKRKL
EKARKPLTFT VLKATVAELQ AQTPHSSPTE SVSAWLENIL TDLKVLHKRV PGGEVELSLF
LTAVENTWIH SRQKRREQGR HLRELPRAQE PPSEETSVTE QQQQPDIPPE SPANAEALQH
FLFKCLVNVK QEEEKDVLVE MHWVEGQNKD LMNQLCTCLK NALFRQVAKP T
