ID MET23_MOUSE Reviewed; 253 AA.
AC A2AA28; Q8R2Z2; Q9D1J5;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 27-MAR-2024, entry version 113.
DE RecName: Full=Histone-arginine methyltransferase METTL23 {ECO:0000305};
DE EC=2.1.1.319 {ECO:0000269|PubMed:28930672};
DE AltName: Full=Methyltransferase-like protein 23 {ECO:0000305};
GN Name=Mettl23 {ECO:0000303|PubMed:28930672, ECO:0000312|MGI:MGI:1921569};
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 22-253.
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE,
RP TISSUE SPECIFICITY, AND INTERACTION WITH TET3 AND STPG4.
RX PubMed=28930672; DOI=10.1016/j.celrep.2017.08.088;
RA Hatanaka Y., Tsusaka T., Shimizu N., Morita K., Suzuki T., Machida S.,
RA Satoh M., Honda A., Hirose M., Kamimura S., Ogonuki N., Nakamura T.,
RA Inoue K., Hosoi Y., Dohmae N., Nakano T., Kurumizaka H., Matsumoto K.,
RA Shinkai Y., Ogura A.;
RT "Histone H3 methylated at arginine 17 is essential for reprogramming the
RT paternal genome in zygotes.";
RL Cell Rep. 20:2756-2765(2017).
CC -!- FUNCTION: Histone methyltransferase that dimethylates histone H3 at
CC 'Arg-17', forming asymmetric dimethylarginine (H3R17me2a), leading to
CC activate transcription via chromatin remodeling (PubMed:28930672).
CC Maternal factor involved in epigenetic chromatin reprogramming of the
CC paternal genome in the zygote: mediates H3R17me2a, promoting histone
CC H3.3 incorporation in the male pronucleus, leading to TET3 recruitment
CC and subsequent DNA demethylation (PubMed:28930672).
CC {ECO:0000269|PubMed:28930672}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arginyl-[protein] + 2 S-adenosyl-L-methionine = 2 H(+) +
CC N(omega),N(omega)-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:48096, Rhea:RHEA-COMP:10532, Rhea:RHEA-
CC COMP:11991, ChEBI:CHEBI:15378, ChEBI:CHEBI:29965, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61897; EC=2.1.1.319;
CC Evidence={ECO:0000269|PubMed:28930672};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48097;
CC Evidence={ECO:0000269|PubMed:28930672};
CC -!- SUBUNIT: Interacts with HSPA5, HSP90B1, TUBULIN, UGGT1 and UGGT2 (By
CC similarity). Interacts with TET3 (PubMed:28930672). Interacts with
CC STPG4 (PubMed:28930672). {ECO:0000250|UniProtKB:Q86XA0,
CC ECO:0000269|PubMed:28930672}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28930672}. Cytoplasm
CC {ECO:0000269|PubMed:28930672}. Note=Localizes in male and female zygote
CC pronucleus and cytoplasm. {ECO:0000269|PubMed:28930672}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:28930672}.
CC -!- DISRUPTION PHENOTYPE: Mice give birth to significantly smaller litter
CC sizes (PubMed:28930672). Moreover, about a third of the homozygous
CC newborn mice die before weaning and only a few survive to adulthood
CC (PubMed:28930672). Strongly reduced 5-hydroxymethylcytosine (5hmC)
CC levels in zygotes (PubMed:28930672). {ECO:0000269|PubMed:28930672}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. METTL23
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH26936.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB22797.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL645542; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026936; AAH26936.1; ALT_INIT; mRNA.
DR EMBL; AK003450; BAB22797.1; ALT_INIT; mRNA.
DR CCDS; CCDS25679.2; -.
DR RefSeq; NP_083141.3; NM_028865.3.
DR AlphaFoldDB; A2AA28; -.
DR SMR; A2AA28; -.
DR STRING; 10090.ENSMUSP00000101978; -.
DR PhosphoSitePlus; A2AA28; -.
DR EPD; A2AA28; -.
DR PaxDb; 10090-ENSMUSP00000101978; -.
DR ProteomicsDB; 252540; -.
DR Antibodypedia; 9811; 12 antibodies from 8 providers.
DR DNASU; 74319; -.
DR Ensembl; ENSMUST00000106370.10; ENSMUSP00000101978.4; ENSMUSG00000090266.11.
DR GeneID; 74319; -.
DR KEGG; mmu:74319; -.
DR UCSC; uc007mml.2; mouse.
DR AGR; MGI:1921569; -.
DR CTD; 124512; -.
DR MGI; MGI:1921569; Mettl23.
DR VEuPathDB; HostDB:ENSMUSG00000090266; -.
DR eggNOG; KOG2793; Eukaryota.
DR GeneTree; ENSGT00510000048008; -.
DR HOGENOM; CLU_082022_1_0_1; -.
DR InParanoid; A2AA28; -.
DR OMA; FYDPEDF; -.
DR OrthoDB; 91554at2759; -.
DR PhylomeDB; A2AA28; -.
DR TreeFam; TF352729; -.
DR BioGRID-ORCS; 74319; 3 hits in 76 CRISPR screens.
DR PRO; PR:A2AA28; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; A2AA28; Protein.
DR Bgee; ENSMUSG00000090266; Expressed in heart left ventricle and 77 other cell types or tissues.
DR ExpressionAtlas; A2AA28; baseline and differential.
DR Genevisible; A2AA28; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0001939; C:female pronucleus; IDA:UniProtKB.
DR GO; GO:0001940; C:male pronucleus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
DR GO; GO:0035642; F:histone H3R17 methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042054; F:histone methyltransferase activity; TAS:Reactome.
DR GO; GO:0035242; F:protein-arginine omega-N asymmetric methyltransferase activity; IEA:RHEA.
DR GO; GO:0050890; P:cognition; ISO:MGI.
DR GO; GO:0044727; P:epigenetic programing of male pronucleus; IMP:UniProtKB.
DR GO; GO:0044725; P:epigenetic programming in the zygotic pronuclei; IMP:UniProtKB.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR InterPro; IPR019410; Methyltransf_16.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR14614; HEPATOCELLULAR CARCINOMA-ASSOCIATED ANTIGEN; 1.
DR PANTHER; PTHR14614:SF130; HISTONE-ARGININE METHYLTRANSFERASE METTL23; 1.
DR Pfam; PF10294; Methyltransf_16; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
PE 1: Evidence at protein level;
KW Chromatin regulator; Cytoplasm; Developmental protein; Methyltransferase;
KW Nucleus; Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..253
FT /note="Histone-arginine methyltransferase METTL23"
FT /id="PRO_0000321521"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 42
FT /note="V -> G (in Ref. 2; AAH26936)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 253 AA; 28289 MW; EEE3B9D8F1CDB4EB CRC64;
MDSVRPRAPW APPPDPASLD SPTCEPGLMA GTQLFRFREE PVPGGNRAVL EVRVPQVLHV
QYGMYVWPCA VVLAQYLWFH RRSLPGKAVL EVGAGVSLPG ILAAKCGAKV ILSDSSEFPH
CLDICRQSCQ MNNLPQVEVV GLTWGHISKD ILSLPPQDII LGSDVFFEPE DFESILATVY
FLMQKNPKVQ FWSTYQVRSA DWSLEGLLYK WDMKCVHIPL ESFDADKEDI AESTLPGRHT
VEMLIISFAK DSF
//
