MET16_CHICK
ID MET16_CHICK Reviewed; 558 AA.
AC Q5ZIA0;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 101.
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=RCJMB04_28o5;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=CB; TISSUE=Bursa of Fabricius;
RX PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6;
RA Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P.,
RA Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P.,
RA Hayashizaki Y., Buerstedde J.-M.;
RT "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene
RT function analysis.";
RL Genome Biol. 6:R6.1-R6.9(2005).
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; AJ720884; CAG32543.1; -; mRNA.
DR RefSeq; NP_001026773.1; NM_001031602.1.
DR AlphaFoldDB; Q5ZIA0; -.
DR SMR; Q5ZIA0; -.
DR STRING; 9031.ENSGALP00000023989; -.
DR PaxDb; Q5ZIA0; -.
DR GeneID; 431184; -.
DR KEGG; gga:431184; -.
DR CTD; 79066; -.
DR VEuPathDB; HostDB:geneid_431184; -.
DR eggNOG; KOG2912; Eukaryota.
DR HOGENOM; CLU_027534_0_0_1; -.
DR InParanoid; Q5ZIA0; -.
DR OrthoDB; 1358504at2759; -.
DR PhylomeDB; Q5ZIA0; -.
DR TreeFam; TF313132; -.
DR PRO; PR:Q5ZIA0; -.
DR Proteomes; UP000000539; 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..558
FT /note="RNA N6-adenosine-methyltransferase METTL16"
FT /id="PRO_0000310769"
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..400
FT /note="VCR 1"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT REGION 407..502
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 511..558
FT /note="VCR 2"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT COMPBIAS 422..472
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 473..502
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 558 AA; 63386 MW; F40CC7B027CC34D0 CRC64;
MALNKSMHAR NRYKDKPPDF AYLAGKYPEF RQHVQTTLAG RVSLNFKDPE AVRALTCTLL
KEDFGLTIDI PLERLIPTVP LRLNYIHWVE DLIGHQDADK RVLRRGIDIG TGASCIYPLL
GSTLNGWYFL ATEVDDMCFN YAKKNVEQNN LSDLIKVVKV PQKTLLMDAL KEESEIIYDF
CMCNPPFFAN QLEAKGVNSR NPRRPPPSSV NTGGITEIMA EGGELEFVKR IIHDSLQLKK
RLRWYSCMLG KKCSLAPLKE ELKIQGVPKV THTEFCQGRT MRWALAWSFY DDVQVPSPPS
KRRKLEKPRK PITFTVLAST VKELSIKAAA MGWDAVEGIA VVRAWIEKIL ADLKVQHKRV
PCGKDEVSLF VTAIENSWVH LRRKKRERVR QLRELPRASD DVLQAMEEEK NSQNSVSNSV
DCEKSKTEDS ETELVAPDED VHLTADDELR EESATKELSE HMEEEETEAK QTEASFNEGS
SSAEQGAQPS EEAGNLTAEK GQSPKETSRC FLFKCLMNVK KEGNDVLVEM HWVEGQNRDL
MNQLCTYLRN QVLRLVAS
