ID I3MNF0_ICTTR Unreviewed; 458 AA.
AC I3MNF0;
DT 11-JUL-2012, integrated into UniProtKB/TrEMBL.
DT 22-NOV-2017, sequence version 2.
DT 27-MAR-2024, entry version 56.
DE RecName: Full=N6-adenosine-methyltransferase non-catalytic subunit {ECO:0000256|ARBA:ARBA00026130, ECO:0000256|RuleBase:RU369092};
DE AltName: Full=Methyltransferase-like protein 14 {ECO:0000256|ARBA:ARBA00032942, ECO:0000256|RuleBase:RU369092};
GN Name=METTL14 {ECO:0000313|Ensembl:ENSSTOP00000013175.3};
OS Ictidomys tridecemlineatus (Thirteen-lined ground squirrel) (Spermophilus
OS tridecemlineatus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Sciuromorpha; Sciuridae;
OC Xerinae; Marmotini; Ictidomys.
OX NCBI_TaxID=43179 {ECO:0000313|Ensembl:ENSSTOP00000013175.3, ECO:0000313|Proteomes:UP000005215};
RN [1] {ECO:0000313|Proteomes:UP000005215}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG The Broad Institute Genome Assembly & Analysis Group;
RG Computational R&D Group;
RG and Sequencing Platform;
RA Di Palma F., Alfoldi J., Johnson J., Berlin A., Gnerre S., Jaffe D.,
RA MacCallum I., Young S., Walker B.J., Lindblad-Toh K.;
RT "The Draft Genome of Spermophilus tridecemlineatus.";
RL Submitted (NOV-2011) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSSTOP00000013175.3}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: The METTL3-METTL14 heterodimer forms a N6-methyltransferase
CC complex that methylates adenosine residues at the N(6) position of some
CC mRNAs and regulates the circadian clock, differentiation of embryonic
CC stem cells and cortical neurogenesis. In the heterodimer formed with
CC METTL3, METTL14 constitutes the RNA-binding scaffold that recognizes
CC the substrate rather than the catalytic core. N6-methyladenosine (m6A),
CC which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs,
CC plays a role in mRNA stability and processing. M6A acts as a key
CC regulator of mRNA stability by promoting mRNA destabilization and
CC degradation. In embryonic stem cells (ESCs), m6A methylation of mRNAs
CC encoding key naive pluripotency-promoting transcripts results in
CC transcript destabilization. M6A regulates spermatogonial
CC differentiation and meiosis and is essential for male fertility and
CC spermatogenesis. M6A also regulates cortical neurogenesis: m6A
CC methylation of transcripts related to transcription factors, neural
CC stem cells, the cell cycle and neuronal differentiation during brain
CC development promotes their destabilization and decay, promoting
CC differentiation of radial glial cells. {ECO:0000256|RuleBase:RU369092}.
CC -!- SUBUNIT: Heterodimer; heterodimerizes with METTL3 to form an
CC antiparallel heterodimer that constitutes an active methyltransferase.
CC {ECO:0000256|RuleBase:RU369092}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|RuleBase:RU369092}.
CC -!- SIMILARITY: Belongs to the MT-A70-like family. {ECO:0000256|PROSITE-
CC ProRule:PRU00489, ECO:0000256|RuleBase:RU369092}.
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DR EMBL; AGTP01114083; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AGTP01114084; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AGTP01114085; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AGTP01114086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; I3MNF0; -.
DR SMR; I3MNF0; -.
DR STRING; 43179.ENSSTOP00000013175; -.
DR Ensembl; ENSSTOT00000014708.3; ENSSTOP00000013175.3; ENSSTOG00000014707.3.
DR eggNOG; KOG2097; Eukaryota.
DR GeneTree; ENSGT00550000075003; -.
DR HOGENOM; CLU_046318_1_0_1; -.
DR InParanoid; I3MNF0; -.
DR TreeFam; TF323641; -.
DR Proteomes; UP000005215; Unassembled WGS sequence.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0036396; C:RNA N6-methyladenosine methyltransferase complex; IEA:UniProtKB-UniRule.
DR GO; GO:0001734; F:mRNA (N6-adenosine)-methyltransferase activity; IEA:Ensembl.
DR GO; GO:0003729; F:mRNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0021861; P:forebrain radial glial cell differentiation; IEA:UniProtKB-UniRule.
DR GO; GO:0006402; P:mRNA catabolic process; IEA:Ensembl.
DR GO; GO:0061157; P:mRNA destabilization; IEA:UniProtKB-UniRule.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IEA:Ensembl.
DR GO; GO:1901533; P:negative regulation of hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0045727; P:positive regulation of translation; IEA:Ensembl.
DR GO; GO:0045664; P:regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-UniRule.
DR GO; GO:0019827; P:stem cell population maintenance; IEA:UniProtKB-UniRule.
DR InterPro; IPR045123; METTL14-like.
DR InterPro; IPR007757; MT-A70-like.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR13107; N6-ADENOSINE-METHYLTRANSFERASE NON-CATALYTIC SUBUNIT; 1.
DR PANTHER; PTHR13107:SF0; N6-ADENOSINE-METHYLTRANSFERASE NON-CATALYTIC SUBUNIT; 1.
DR Pfam; PF05063; MT-A70; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR PROSITE; PS51143; MT_A70; 1.
DR PROSITE; PS51592; SAM_MTA70L_2; 1.
PE 3: Inferred from homology;
KW Differentiation {ECO:0000256|RuleBase:RU369092};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|RuleBase:RU369092};
KW Reference proteome {ECO:0000313|Proteomes:UP000005215};
KW RNA-binding {ECO:0000256|RuleBase:RU369092};
KW Spermatogenesis {ECO:0000256|RuleBase:RU369092}.
FT REGION 395..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 426..446
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 458 AA; 52231 MW; 175CD8E014545068 CRC64;
MDSRLQEIRE RQKLRRQGLA ELLSLGAESA DSIGAVLNSK DEQREIAETR ETCRASYDTS
APNAKRKCLD EGETDEDKVE EYKDELEMQQ EEENLPYEEE IYKDSSTFLK GTQSLNPHND
YCQHFVDTGH RPQNFIRDVG LADRFEEYPK LRELIRLKDE LIAKSNTPPM YLQADIEAFD
IRELTPKFDV ILLEPPLEEY YRETGITANE RCWTWDDIMK LEIDEIAAPR SFIFLWCGSG
EGLDLGRVCL RKWGYRRCED ICWIKTNKNN PGKTKTLDPK AVFQRTKEHC LMGIKGTVKR
STDGDFIHAN VDIDLIITEE PEIGNIEKPV EIFHIIEHFC LGRRRLHLFG RDSTIRPGWL
TVGPTLTNSN YNAETYASYF SAPNSYLTGC TEEIERLRPK SPPPKSKSDR GGGAPRGGGR
GGTSAGRGRE RNRSNFRGER GGFRGGRGGA HRGGFPPR
//