METL5_MOUSE
ID METL5_MOUSE Reviewed; 209 AA.
AC Q8K1A0;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=rRNA N6-adenosine-methyltransferase METTL5 {ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:32783360};
DE AltName: Full=Methyltransferase-like protein 5 {ECO:0000305};
GN Name=Mettl5 {ECO:0000303|PubMed:32783360, ECO:0000312|MGI:MGI:1922672};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=31564433; DOI=10.1016/j.ajhg.2019.09.007;
RA Richard E.M., Polla D.L., Assir M.Z., Contreras M., Shahzad M., Khan A.A.,
RA Razzaq A., Akram J., Tarar M.N., Blanpied T.A., Ahmed Z.M., Abou Jamra R.,
RA Wieczorek D., van Bokhoven H., Riazuddin S., Riazuddin S.;
RT "Bi-allelic variants in METTL5 cause autosomal-recessive intellectual
RT disability and microcephaly.";
RL Am. J. Hum. Genet. 105:869-878(2019).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 126-ASN--PHE-129.
RX PubMed=32783360; DOI=10.15252/embr.201949863;
RA Xing M., Liu Q., Mao C., Zeng H., Zhang X., Zhao S., Chen L., Liu M.,
RA Shen B., Guo X., Ma H., Chen H., Zhang J.;
RT "The 18S rRNA m6 A methyltransferase METTL5 promotes mouse embryonic stem
RT cell differentiation.";
RL EMBO Rep. 21:e49863-e49863(2020).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32217665; DOI=10.1101/gad.333369.119;
RA Ignatova V.V., Stolz P., Kaiser S., Gustafsson T.H., Lastres P.R.,
RA Sanz-Moreno A., Cho Y.L., Amarie O.V., Aguilar-Pimentel A.,
RA Klein-Rodewald T., Calzada-Wack J., Becker L., Marschall S., Kraiger M.,
RA Garrett L., Seisenberger C., Hoelter S.M., Borland K., Van De Logt E.,
RA Jansen P.W.T.C., Baltissen M.P., Valenta M., Vermeulen M., Wurst W.,
RA Gailus-Durner V., Fuchs H., de Angelis M.H., Rando O.J., Kellner S.M.,
RA Bultmann S., Schneider R.;
RT "The rRNA m6A methyltransferase METTL5 is involved in pluripotency and
RT developmental programs.";
RL Genes Dev. 34:715-729(2020).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=35033535; DOI=10.1016/j.jbc.2022.101590;
RA Sepich-Poore C., Zheng Z., Schmitt E., Wen K., Zhang Z.S., Cui X.L.,
RA Dai Q., Zhu A.C., Zhang L., Sanchez Castillo A., Tan H., Peng J.,
RA Zhuang X., He C., Nachtergaele S.;
RT "The METTL5-TRMT112 N6-methyladenosine methyltransferase complex regulates
RT mRNA translation via 18S rRNA methylation.";
RL J. Biol. Chem. 298:101590-101590(2022).
CC -!- FUNCTION: Catalytic subunit of a heterodimer with TRMT112, which
CC specifically methylates the 6th position of adenine in position 1832 of
CC 18S rRNA (PubMed:32783360, PubMed:35033535). N6-methylation of
CC adenine(1832) in 18S rRNA resides in the decoding center of 18S rRNA
CC and is required for translation and embryonic stem cells (ESCs)
CC pluripotency and differentiation (PubMed:32783360, PubMed:32217665).
CC {ECO:0000269|PubMed:32217665, ECO:0000269|PubMed:32783360,
CC ECO:0000269|PubMed:35033535}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine(1832) in 18S rRNA + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyladenosine(1832) in 18S rRNA + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:62612, Rhea:RHEA-COMP:16144, Rhea:RHEA-COMP:16145,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74411, ChEBI:CHEBI:74449;
CC Evidence={ECO:0000269|PubMed:32783360};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62613;
CC Evidence={ECO:0000269|PubMed:32783360};
CC -!- ACTIVITY REGULATION: rRNA N6-adenosine-methyltransferase activity is
CC inhibited by zinc. {ECO:0000250|UniProtKB:Q9NRN9}.
CC -!- SUBUNIT: Heterodimer; heterodimerizes with TRMT112.
CC {ECO:0000250|UniProtKB:Q9NRN9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9NRN9}.
CC Presynapse {ECO:0000250|UniProtKB:Q9NRN9}. Postsynapse
CC {ECO:0000250|UniProtKB:Q9NRN9}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in brain.
CC {ECO:0000269|PubMed:31564433}.
CC -!- DISRUPTION PHENOTYPE: Mice were born at non-Mendelian rates and develop
CC morphological, such as craniofacial abnormalities, snout deviation due
CC to altered nasal bone development and incomplete fusion of the frontal
CC bone suture (PubMed:32217665). Mice display reduced body size and
CC evidence of metabolic defects (PubMed:35033535). Mice also show
CC behavioral abnormalities (PubMed:32217665). Deletion in embryonic stem
CC cells (ESCs) results in a decrease in global translation rate,
CC spontaneous loss of pluripotency and compromised differentiation
CC potential (PubMed:32783360, PubMed:32217665). Cells show abolished
CC level of N6-methylation of adenine(1832) in 18S rRNA (PubMed:35033535).
CC {ECO:0000269|PubMed:32217665, ECO:0000269|PubMed:32783360,
CC ECO:0000269|PubMed:35033535}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. PrmA family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH27547.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; BC027547; AAH27547.1; ALT_FRAME; mRNA.
DR CCDS; CCDS16103.2; -.
DR RefSeq; NP_083556.2; NM_029280.4.
DR AlphaFoldDB; Q8K1A0; -.
DR SMR; Q8K1A0; -.
DR STRING; 10090.ENSMUSP00000050907; -.
DR PhosphoSitePlus; Q8K1A0; -.
DR EPD; Q8K1A0; -.
DR MaxQB; Q8K1A0; -.
DR PaxDb; Q8K1A0; -.
DR PeptideAtlas; Q8K1A0; -.
DR PRIDE; Q8K1A0; -.
DR ProteomicsDB; 292298; -.
DR Antibodypedia; 35324; 85 antibodies from 20 providers.
DR Ensembl; ENSMUST00000060447; ENSMUSP00000050907; ENSMUSG00000051730.
DR GeneID; 75422; -.
DR KEGG; mmu:75422; -.
DR UCSC; uc008jyv.3; mouse.
DR CTD; 29081; -.
DR MGI; MGI:1922672; Mettl5.
DR VEuPathDB; HostDB:ENSMUSG00000051730; -.
DR eggNOG; KOG3420; Eukaryota.
DR GeneTree; ENSGT00390000000227; -.
DR HOGENOM; CLU_074702_1_1_1; -.
DR InParanoid; Q8K1A0; -.
DR OMA; DVVYSIH; -.
DR OrthoDB; 1528520at2759; -.
DR PhylomeDB; Q8K1A0; -.
DR TreeFam; TF314953; -.
DR BioGRID-ORCS; 75422; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Mettl5; mouse.
DR PRO; PR:Q8K1A0; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8K1A0; protein.
DR Bgee; ENSMUSG00000051730; Expressed in left lobe of liver and 258 other tissues.
DR ExpressionAtlas; Q8K1A0; baseline and differential.
DR Genevisible; Q8K1A0; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0098794; C:postsynapse; ISS:UniProtKB.
DR GO; GO:0098793; C:presynapse; ISS:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0008988; F:rRNA (adenine-N6-)-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; ISS:UniProtKB.
DR GO; GO:0016740; F:transferase activity; IBA:GO_Central.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
DR GO; GO:0031167; P:rRNA methylation; IDA:UniProtKB.
DR GO; GO:0048863; P:stem cell differentiation; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR002052; DNA_methylase_N6_adenine_CS.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR007848; Small_mtfrase_dom.
DR Pfam; PF05175; MTS; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS00092; N6_MTASE; 1.
PE 1: Evidence at protein level;
KW Cell projection; Methyltransferase; Nucleus; Reference proteome;
KW S-adenosyl-L-methionine; Synapse; Transferase.
FT CHAIN 1..209
FT /note="rRNA N6-adenosine-methyltransferase METTL5"
FT /id="PRO_0000251920"
FT BINDING 28
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9NRN9"
FT BINDING 31
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9NRN9"
FT BINDING 59
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9NRN9"
FT BINDING 62
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9NRN9"
FT BINDING 64
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9NRN9"
FT BINDING 81
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9NRN9"
FT BINDING 108..109
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9NRN9"
FT MUTAGEN 126..129
FT /note="NPPF->APPA: Abolished rRNA N6-adenosine-
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:32783360"
SQ SEQUENCE 209 AA; 23662 MW; 3BA9EB63B7D1CD7B CRC64;
MKKLKLKELE SRLQEVDGFE KPKLLLEQYP TRPHIAACML YTIHNTYDDI ENKAVADLGC
GCGVLSIGAA MLGAGLCVGF DIDEDALEIF NKNVEEFELT NVDMIQCDVY SLSNRMSKLF
DTVIMNPPFG TKNNKGTDMA FLKTALGMAR TAVYSLHKSS TREHIQKKAA EWKVKIEIIA
ELRYDLPALY NFHKKKSVDI EVDLIRFSF
