MET23_HUMAN
ID MET23_HUMAN Reviewed; 190 AA.
AC Q86XA0; H9ZYJ0; K7EK32;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Histone-arginine methyltransferase METTL23 {ECO:0000305};
DE EC=2.1.1.319 {ECO:0000250|UniProtKB:A2AA28};
DE AltName: Full=Methyltransferase-like protein 23 {ECO:0000305};
GN Name=METTL23 {ECO:0000303|PubMed:24501276, ECO:0000312|HGNC:HGNC:26988};
GN Synonyms=C17orf95 {ECO:0000312|HGNC:HGNC:26988};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Baron B.M.;
RT "Isolation of a novel GABPalpha-interacting co-factor, E4TF-1 Binding
RT Methyltransferase (EBM), which encodes a putative methyltransferase.";
RL Submitted (DEC-2011) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [5]
RP INTERACTION WITH HSPA5; HSP90B1; TUBULIN; UGGT1 AND UGGT2, AND SUBCELLULAR
RP LOCATION.
RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210;
RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.;
RT "A newly uncovered group of distantly related lysine methyltransferases
RT preferentially interact with molecular chaperones to regulate their
RT activity.";
RL PLoS Genet. 9:E1003210-E1003210(2013).
RN [6]
RP INVOLVEMENT IN MRT44, AND SUBCELLULAR LOCATION.
RX PubMed=24501276; DOI=10.1093/hmg/ddu054;
RA Reiff R.E., Ali B.R., Baron B., Yu T.W., Ben-Salem S., Coulter M.E.,
RA Schubert C.R., Hill R.S., Akawi N.A., Al-Younes B., Kaya N., Evrony G.D.,
RA Al-Saffar M., Felie J.M., Partlow J.N., Sunu C.M., Schembri-Wismayer P.,
RA Alkuraya F.S., Meyer B.F., Walsh C.A., Al-Gazali L., Mochida G.H.;
RT "METTL23, a transcriptional partner of GABPA, is essential for human
RT cognition.";
RL Hum. Mol. Genet. 23:3456-3466(2014).
RN [7]
RP INVOLVEMENT IN MRT44, AND VARIANT MRT44 133-GLN--LEU-190 DEL.
RX PubMed=24626631; DOI=10.1093/hmg/ddu115;
RA Bernkopf M., Webersinke G., Tongsook C., Koyani C.N., Rafiq M.A., Ayaz M.,
RA Mueller D., Enzinger C., Aslam M., Naeem F., Schmidt K., Gruber K.,
RA Speicher M.R., Malle E., Macheroux P., Ayub M., Vincent J.B.,
RA Windpassinger C., Duba H.C.;
RT "Disruption of the methyltransferase-like 23 gene METTL23 causes mild
RT autosomal recessive intellectual disability.";
RL Hum. Mol. Genet. 23:4015-4023(2014).
RN [8]
RP INVOLVEMENT IN MRT44, AND VARIANT MRT44 THR-150.
RX PubMed=32067349; DOI=10.1002/ajmg.a.61503;
RA Almannai M., Obaid O., Faqeih E., Alasmari A., Samman M.M., Pinz H.,
RA Braddock S.R., Alkuraya F.S.;
RT "Further delineation of METTL23-associated intellectual disability.";
RL Am. J. Med. Genet. A 182:785-791(2020).
RN [9]
RP INVOLVEMENT IN MRT44.
RX PubMed=32439618; DOI=10.1016/j.ejmg.2020.103951;
RA Smaili W., Elalaoui S.C., Zrhidri A., Raymond L., Egea G., Taoudi M.,
RA Mouatassim S.E.L., Sefiani A., Lyahyai J.;
RT "Exome sequencing revealed a novel homozygous METTL23 gene mutation leading
RT to familial mild intellectual disability with dysmorphic features.";
RL Eur. J. Med. Genet. 63:103951-103951(2020).
CC -!- FUNCTION: Histone methyltransferase that dimethylates histone H3 at
CC 'Arg-17', forming asymmetric dimethylarginine (H3R17me2a), leading to
CC activate transcription via chromatin remodeling (By similarity).
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 (By similarity).
CC {ECO:0000250|UniProtKB:A2AA28}.
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:0000250|UniProtKB:A2AA28};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48097;
CC Evidence={ECO:0000250|UniProtKB:A2AA28};
CC -!- SUBUNIT: Interacts with HSPA5, HSP90B1, TUBULIN, UGGT1 and UGGT2
CC (PubMed:23349634). Interacts with TET3 (By similarity). Interacts with
CC STPG4 (By similarity). {ECO:0000250|UniProtKB:A2AA28,
CC ECO:0000269|PubMed:23349634}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24501276}. Cytoplasm
CC {ECO:0000269|PubMed:23349634, ECO:0000269|PubMed:24501276}.
CC Note=Localizes in male and female zygote pronucleus and cytoplasm.
CC {ECO:0000250|UniProtKB:A2AA28}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q86XA0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86XA0-2; Sequence=VSP_055637;
CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 44
CC (MRT44) [MIM:615942]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRT44
CC manifestations include mild to severe cognitive impairment, delayed
CC psychomotor development, seizures in some patients, and dysmorphic
CC features. {ECO:0000269|PubMed:24501276, ECO:0000269|PubMed:24626631,
CC ECO:0000269|PubMed:32067349, ECO:0000269|PubMed:32439618}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. METTL23
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH45819.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; JQ313903; AFH41797.1; -; mRNA.
DR EMBL; AC005837; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89435.1; -; Genomic_DNA.
DR EMBL; CH471099; EAW89437.1; -; Genomic_DNA.
DR EMBL; BC045819; AAH45819.1; ALT_INIT; mRNA.
DR CCDS; CCDS45787.1; -. [Q86XA0-1]
DR CCDS; CCDS59298.1; -. [Q86XA0-2]
DR RefSeq; NP_001073979.3; NM_001080510.4. [Q86XA0-1]
DR RefSeq; NP_001193912.1; NM_001206983.2. [Q86XA0-1]
DR RefSeq; NP_001193913.1; NM_001206984.2. [Q86XA0-1]
DR RefSeq; NP_001193914.1; NM_001206985.2. [Q86XA0-2]
DR RefSeq; NP_001193915.1; NM_001206986.2. [Q86XA0-2]
DR RefSeq; NP_001193916.1; NM_001206987.2. [Q86XA0-2]
DR RefSeq; NP_001289632.1; NM_001302703.1. [Q86XA0-1]
DR RefSeq; NP_001289633.1; NM_001302704.1. [Q86XA0-2]
DR RefSeq; NP_001289634.1; NM_001302705.1.
DR RefSeq; XP_006721737.1; XM_006721674.3.
DR RefSeq; XP_006721743.1; XM_006721680.2.
DR AlphaFoldDB; Q86XA0; -.
DR SMR; Q86XA0; -.
DR BioGRID; 125870; 30.
DR IntAct; Q86XA0; 2.
DR MINT; Q86XA0; -.
DR STRING; 9606.ENSP00000482599; -.
DR iPTMnet; Q86XA0; -.
DR PhosphoSitePlus; Q86XA0; -.
DR BioMuta; METTL23; -.
DR DMDM; 269849695; -.
DR MassIVE; Q86XA0; -.
DR PaxDb; Q86XA0; -.
DR PeptideAtlas; Q86XA0; -.
DR PRIDE; Q86XA0; -.
DR ProteomicsDB; 70258; -. [Q86XA0-1]
DR Antibodypedia; 9811; 9 antibodies from 8 providers.
DR DNASU; 124512; -.
DR Ensembl; ENST00000341249.11; ENSP00000341543.5; ENSG00000181038.14. [Q86XA0-1]
DR Ensembl; ENST00000586752.5; ENSP00000466203.1; ENSG00000181038.14. [Q86XA0-2]
DR Ensembl; ENST00000588822.1; ENSP00000465430.1; ENSG00000181038.14. [Q86XA0-2]
DR Ensembl; ENST00000590964.5; ENSP00000465890.1; ENSG00000181038.14. [Q86XA0-2]
DR Ensembl; ENST00000615984.4; ENSP00000482599.1; ENSG00000181038.14. [Q86XA0-1]
DR GeneID; 124512; -.
DR KEGG; hsa:124512; -.
DR MANE-Select; ENST00000341249.11; ENSP00000341543.5; NM_001080510.5; NP_001073979.3.
DR UCSC; uc002jsr.4; human. [Q86XA0-1]
DR CTD; 124512; -.
DR DisGeNET; 124512; -.
DR GeneCards; METTL23; -.
DR HGNC; HGNC:26988; METTL23.
DR HPA; ENSG00000181038; Low tissue specificity.
DR MalaCards; METTL23; -.
DR MIM; 615262; gene.
DR MIM; 615942; phenotype.
DR neXtProt; NX_Q86XA0; -.
DR OpenTargets; ENSG00000181038; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA162378566; -.
DR VEuPathDB; HostDB:ENSG00000181038; -.
DR eggNOG; KOG2793; Eukaryota.
DR GeneTree; ENSGT00510000048008; -.
DR InParanoid; Q86XA0; -.
DR OMA; LMQDHTI; -.
DR OrthoDB; 1588190at2759; -.
DR PhylomeDB; Q86XA0; -.
DR TreeFam; TF352729; -.
DR PathwayCommons; Q86XA0; -.
DR SignaLink; Q86XA0; -.
DR BioGRID-ORCS; 124512; 63 hits in 1075 CRISPR screens.
DR ChiTaRS; METTL23; human.
DR GenomeRNAi; 124512; -.
DR Pharos; Q86XA0; Tdark.
DR PRO; PR:Q86XA0; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q86XA0; protein.
DR Bgee; ENSG00000181038; Expressed in kidney epithelium and 196 other tissues.
DR ExpressionAtlas; Q86XA0; baseline and differential.
DR Genevisible; Q86XA0; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0001939; C:female pronucleus; ISS:UniProtKB.
DR GO; GO:0001940; C:male pronucleus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0031072; F:heat shock protein binding; IPI:UniProtKB.
DR GO; GO:0035642; F:histone methyltransferase activity (H3-R17 specific); ISS:UniProtKB.
DR GO; GO:0035242; F:protein-arginine omega-N asymmetric methyltransferase activity; IEA:RHEA.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0044725; P:chromatin reprogramming in the zygote; ISS:UniProtKB.
DR GO; GO:0050890; P:cognition; IMP:UniProtKB.
DR GO; GO:0044727; P:DNA demethylation of male pronucleus; ISS:UniProtKB.
DR GO; GO:0034971; P:histone H3-R17 methylation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR019410; Methyltransf_16.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR14614; PTHR14614; 1.
DR Pfam; PF10294; Methyltransf_16; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromatin regulator; Cytoplasm;
KW Developmental protein; Disease variant; Intellectual disability;
KW Methyltransferase; Nucleus; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..190
FT /note="Histone-arginine methyltransferase METTL23"
FT /id="PRO_0000321520"
FT VAR_SEQ 1..67
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_055637"
FT VARIANT 133..190
FT /note="Missing (in MRT44)"
FT /evidence="ECO:0000269|PubMed:24626631"
FT /id="VAR_085971"
FT VARIANT 141
FT /note="L -> V (in dbSNP:rs12602772)"
FT /id="VAR_039343"
FT VARIANT 150
FT /note="M -> T (in MRT44; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32067349"
FT /id="VAR_085972"
FT CONFLICT 138
FT /note="D -> G (in Ref. 4; AAH45819)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 190 AA; 21469 MW; 7820BDC5E7631700 CRC64;
MYVWPCAVVL AQYLWFHRRS LPGKAILEIG AGVSLPGILA AKCGAEVILS DSSELPHCLE
VCRQSCQMNN LPHLQVVGLT WGHISWDLLA LPPQDIILAS DVFFEPEDFE DILATIYFLM
HKNPKVQLWS TYQVRSADWS LEALLYKWDM KCVHIPLESF DADKEDIAES TLPGRHTVEM
LVISFAKDSL
