MET16_CAEEL
ID MET16_CAEEL Reviewed; 479 AA.
AC Q09357; Q8I4B2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 11-APR-2003, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase;
DE EC=2.1.1.346 {ECO:0000269|PubMed:33930289};
DE AltName: Full=N6-adenosine-methyltransferase mett-10 {ECO:0000305};
DE EC=2.1.1.348 {ECO:0000269|PubMed:33930289};
GN Name=mett-10 {ECO:0000303|PubMed:19596901, ECO:0000312|WormBase:ZK1128.2a};
GN ORFNames=ZK1128.2 {ECO:0000312|WormBase:ZK1128.2a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 1-MET--THR-260; GLY-110; 240-PHE--ALA-392; GLY-263; 276-GLN--ARG-479 AND
RP GLY-292.
RX PubMed=19596901; DOI=10.1534/genetics.109.105270;
RA Dorsett M., Westlund B., Schedl T.;
RT "METT-10, a putative methyltransferase, inhibits germ cell proliferative
RT fate in Caenorhabditis elegans.";
RL Genetics 183:233-247(2009).
RN [3]
RP FUNCTION, INTERACTION WITH DLC-1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 1-MET--THR-260; GLY-110; 240-PHE--ALA-392; GLY-263; 276-GLN--ARG-479;
RP GLY-292; 361-ALA--ALA-367; ASP-420; ASN-421; SER-423; GLN-424; TYR-426 AND
RP PHE-427.
RX PubMed=19752194; DOI=10.1128/mcb.00815-09;
RA Dorsett M., Schedl T.;
RT "A role for dynein in the inhibition of germ cell proliferative fate.";
RL Mol. Cell. Biol. 29:6128-6139(2009).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=33930289; DOI=10.1016/j.cell.2021.03.062;
RA Mendel M., Delaney K., Pandey R.R., Chen K.M., Wenda J.M., Vaagboe C.B.,
RA Steiner F.A., Homolka D., Pillai R.S.;
RT "Splice site m6A methylation prevents binding of U2AF35 to inhibit RNA
RT splicing.";
RL Cell 0:0-0(2021).
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 splicing of S-adenosylmethionine
CC synthase transcripts (sams-3, sams-4 and sams-5) (PubMed:33930289).
CC Able to N6-methylate a subset of mRNAs containing the 5'UACAGAAAC-3'
CC nonamer sequence (PubMed:33930289). Plays a key role in S-adenosyl-L-
CC methionine homeostasis: under rich-diet conditions, catalyzes N6-
CC methylation of S-adenosylmethionine synthase mRNAs (sams-3, sams-4 and
CC sams-5), directly inhibiting splicing and protein production of S-
CC adenosylmethionine synthase (PubMed:33930289). In addition to mRNAs,
CC also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA)
CC (PubMed:33930289). Required for gamete production, inhibiting germ cell
CC proliferative fate and ensuring germ cell meiotic development
CC (PubMed:19596901, PubMed:19752194). Also promotes progression of the
CC mitotic cell cycle in those germ cells that continue to proliferate
CC (PubMed:19596901, PubMed:19752194). Plays a role in the development of
CC the vulva, somatic gonad and embryo (PubMed:19596901).
CC {ECO:0000269|PubMed:19596901, ECO:0000269|PubMed:19752194,
CC ECO:0000269|PubMed:33930289}.
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:0000269|PubMed:33930289};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55585;
CC Evidence={ECO:0000269|PubMed:33930289};
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:0000269|PubMed:33930289};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52809;
CC Evidence={ECO:0000269|PubMed:33930289};
CC -!- SUBUNIT: Self-associates (PubMed:19752194). Interacts with dlc-1; the
CC interaction is direct, and is required for nuclear localization of
CC mett-10 (PubMed:19752194). {ECO:0000269|PubMed:19752194}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19596901,
CC ECO:0000269|PubMed:19752194}. Note=Accumulates in nuclei as cells enter
CC meiosis (PubMed:19596901, PubMed:19752194). During meiotic prophase,
CC expression is predominantly nuclear, but does not co-localize with DNA
CC (PubMed:19596901). Recruited to the nucleus by dlc-1, a component of
CC the dynein complex (PubMed:19752194). {ECO:0000269|PubMed:19596901,
CC ECO:0000269|PubMed:19752194}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:ZK1128.2a};
CC IsoId=Q09357-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:ZK1128.2b};
CC IsoId=Q09357-2; Sequence=VSP_007120;
CC -!- TISSUE SPECIFICITY: Expressed in the intestine, vulva, and cells of the
CC somatic gonad including distal tip cells, gonadal sheath cells and
CC spermatheca. {ECO:0000269|PubMed:19596901}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. METTL16/RlmF
CC family. {ECO:0000305}.
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DR EMBL; Z47357; CAA87421.2; -; Genomic_DNA.
DR EMBL; Z47357; CAD54175.1; -; Genomic_DNA.
DR PIR; T27693; T27693.
DR RefSeq; NP_499247.2; NM_066846.4.
DR RefSeq; NP_871660.1; NM_181931.6. [Q09357-2]
DR AlphaFoldDB; Q09357; -.
DR SMR; Q09357; -.
DR BioGRID; 56058; 7.
DR IntAct; Q09357; 1.
DR STRING; 6239.ZK1128.2a; -.
DR EPD; Q09357; -.
DR PaxDb; Q09357; -.
DR EnsemblMetazoa; ZK1128.2a.1; ZK1128.2a.1; WBGene00014228. [Q09357-1]
DR EnsemblMetazoa; ZK1128.2b.1; ZK1128.2b.1; WBGene00014228. [Q09357-2]
DR GeneID; 191526; -.
DR UCSC; ZK1128.2b; c. elegans. [Q09357-1]
DR CTD; 191526; -.
DR WormBase; ZK1128.2a; CE31860; WBGene00014228; mett-10. [Q09357-1]
DR WormBase; ZK1128.2b; CE31861; WBGene00014228; mett-10. [Q09357-2]
DR eggNOG; KOG2912; Eukaryota.
DR GeneTree; ENSGT00390000016694; -.
DR HOGENOM; CLU_027534_0_0_1; -.
DR InParanoid; Q09357; -.
DR OMA; TEFCQGH; -.
DR OrthoDB; 1358504at2759; -.
DR PhylomeDB; Q09357; -.
DR SignaLink; Q09357; -.
DR PRO; PR:Q09357; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00014228; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
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; IDA:UniProtKB.
DR GO; GO:0120048; F:U6 snRNA (adenine-(43)-N(6))-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007098; P:centrosome cycle; IMP:WormBase.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0048025; P:negative regulation of mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0070475; P:rRNA base methylation; IBA:GO_Central.
DR GO; GO:0040025; P:vulval development; IMP:WormBase.
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 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cell division; Meiosis;
KW Methyltransferase; Mitosis; Nucleus; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..479
FT /note="U6 small nuclear RNA (adenine-(43)-N(6))-
FT methyltransferase"
FT /id="PRO_0000218021"
FT REGION 420..424
FT /note="Involved in dlc-1 binding"
FT /evidence="ECO:0000269|PubMed:19752194"
FT BINDING 82
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 108
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86W50"
FT BINDING 131
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"
FT VAR_SEQ 105..119
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_007120"
FT MUTAGEN 1..260
FT /note="Missing: In ok2204; at 25 degrees Celsius animals
FT are either sterile or maternal-effect lethal, display a
FT protruding vulva phenotype, and germ cells have
FT abnormalities in meiotic development and mitotic
FT progression; when associated with E-292. Enhanced nuclear
FT proliferation defects in germ cells in a weak loss of
FT function dhc-1 (js319) mutant background; when associated
FT with E-292."
FT /evidence="ECO:0000269|PubMed:19596901,
FT ECO:0000269|PubMed:19752194"
FT MUTAGEN 110
FT /note="G->R: In oj32; at 25 degrees Celsius animals are
FT either sterile or maternal-effect lethal and display a
FT protruding vulva phenotype. Enhanced nuclear proliferation
FT defects in germ cells in a weak loss of function dhc-1
FT (js319) mutant background."
FT /evidence="ECO:0000269|PubMed:19596901,
FT ECO:0000269|PubMed:19752194"
FT MUTAGEN 240..392
FT /note="Missing: In tm2697; at 25 degrees Celsius animals
FT are either sterile or maternal-effect lethal and display a
FT protruding vulva phenotype. Enhanced nuclear proliferation
FT defects in germ cells in a weak loss of function dhc-1
FT (js319) mutant background."
FT /evidence="ECO:0000269|PubMed:19596901,
FT ECO:0000269|PubMed:19752194"
FT MUTAGEN 263
FT /note="G->D: In g38; at 25 degrees Celsius animals are
FT either sterile or maternal-effect lethal and display a
FT protruding vulva phenotype. Enhanced nuclear proliferation
FT defects in germ cells in a weak loss of function dhc-1
FT (js319) mutant background."
FT /evidence="ECO:0000269|PubMed:19596901,
FT ECO:0000269|PubMed:19752194"
FT MUTAGEN 276..479
FT /note="Missing: In oz36; at 25 degrees Celsius animals are
FT either sterile or maternal-effect lethal, display a
FT protruding vulva phenotype, a distended intestinal lumen,
FT tumor formation, and germ cells have abnormalities in
FT meiotic development. Enhanced tumor formation in weak loss
FT of function dhc-1 (or195) or dhc-1 (js319) mutant
FT backgrounds. Enhanced nuclear proliferation defects in germ
FT cells in a weak loss of function dhc-1 (js319) mutant
FT background."
FT /evidence="ECO:0000269|PubMed:19596901,
FT ECO:0000269|PubMed:19752194"
FT MUTAGEN 292
FT /note="G->E: In ok2204; at 25 degrees Celsius animals are
FT either sterile or maternal-effect lethal, display a
FT protruding vulva phenotype, and germ cells have
FT abnormalities in meiotic development and mitotic
FT progression; when associated with 1-M--T-260 DEL. Enhanced
FT nuclear proliferation defects in germ cells in a weak loss
FT of function dhc-1 (js319) mutant background; when
FT associated with 1-M--T-260 DEL."
FT /evidence="ECO:0000269|PubMed:19596901,
FT ECO:0000269|PubMed:19752194"
FT MUTAGEN 361..367
FT /note="Missing: Does not block nuclear entry. Blocks
FT nuclear entry, and results in cytoplasmic localization of
FT the mutant mett-10 protein; when associated with A-420; A-
FT 421; A-423 and A-424."
FT /evidence="ECO:0000269|PubMed:19752194"
FT MUTAGEN 420
FT /note="D->A: Abolishes binding to dlc-1. Reduces nuclear
FT accumulation of mett-10; when associated with A-421; A-423
FT and A-424. Blocks nuclear entry, and results in cytoplasmic
FT localization of the mutant mett-10 protein; when associated
FT with 361-A--A-367 DEL; A-421; A-423 and A-424."
FT /evidence="ECO:0000269|PubMed:19752194"
FT MUTAGEN 421
FT /note="N->A: Reduces binding to dlc-1. Abolishes binding to
FT dlc-1, and reduces nuclear accumulation of mett-10; when
FT associated with A-420; A-423 and A-424. Blocks nuclear
FT entry, and results in cytoplasmic localization of the
FT mutant mett-10 protein; when associated with 361-A--A-367
FT DEL; A-420; A-423 and A-424."
FT /evidence="ECO:0000269|PubMed:19752194"
FT MUTAGEN 423
FT /note="S->A: Reduces binding to dlc-1. Abolishes binding to
FT dlc-1, and reduces nuclear accumulation of mett-10; when
FT associated with A-420; A-421 and A-424. Blocks nuclear
FT entry, and results in cytoplasmic localization of the
FT mutant mett-10 protein; when associated with 361-A--A-367
FT DEL; A-420; A-421 and A-424."
FT /evidence="ECO:0000269|PubMed:19752194"
FT MUTAGEN 424
FT /note="Q->A: Reduces binding to dlc-1. Abolishes binding to
FT dlc-1, and reduces nuclear accumulation of mett-10; when
FT associated with A-420; A-421 and A-423. Blocks nuclear
FT entry, and results in cytoplasmic localization of the
FT mutant mett-10 protein; when associated with 361-A--A-367
FT DEL; A-420; A-421 and A-423."
FT /evidence="ECO:0000269|PubMed:19752194"
FT MUTAGEN 426
FT /note="Y->A: Does not affect dlc-1 binding."
FT /evidence="ECO:0000269|PubMed:19752194"
FT MUTAGEN 427
FT /note="F->A: Does not affect dlc-1 binding."
FT /evidence="ECO:0000269|PubMed:19752194"
SQ SEQUENCE 479 AA; 53805 MW; 789AC9237A49BD7F CRC64;
MSQNNEMHPR NPYRNKPPDF KALAVEYPEF RKFCQYVSNG KVTFDFKKDA AVRCLTQTLL
KKDFNLDVEI PPGHLVPRVP QKLNYCLLID DLLKANKLTK NVIGIDIGTG TSCIHALIGA
RQFNWKFIAT DGDEKSVRVA HENVAKNGLS SSICVVHVNP DVKTVLMDVV NTIPDTDYAF
CMCNPPFFEK GNGDDKFCED ISSSTETYSN RVASEFRTAP HSATFASSAE LFVDGGEVAF
VNRIIDDSVL LRDRIKIYTT MIGRKSSLKP LQNRLQRFGD DVKIMISVLN QGKTKRWMLA
WTFSKSVSLT TIDRPISFQC PKPGLTRLMQ EISILNGRLR QEDTLAIVAE FKCVTWTNQR
ARKRAKAILS ESSIKKAKWN FSNVACQVAF GAGDGKDSYT DAGNFVSSES IPTNNLNAWD
NASQAYFPLP NGEVPGPIIR IRIQVFSEDS YDSISFELIS GSKQHLHQLV QYLKNLICR
