MT21D_MOUSE
ID MT21D_MOUSE Reviewed; 228 AA.
AC Q8C436; B2RSP0; Q3UML0;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Protein N-lysine methyltransferase METTL21D;
DE EC=2.1.1.- {ECO:0000269|PubMed:26544960};
DE AltName: Full=Methyltransferase-like protein 21D;
DE AltName: Full=VCP lysine methyltransferase;
DE Short=VCP-KMT;
DE AltName: Full=Valosin-containing protein lysine methyltransferase;
GN Name=Vcpkmt; Synonyms=Gm71, Mettl21d;
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] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Hippocampus, and Lung;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY,
RP AND TISSUE SPECIFICITY.
RX PubMed=26544960; DOI=10.1371/journal.pone.0141472;
RA Fusser M., Kernstock S., Aileni V.K., Egge-Jacobsen W., Falnes P.O.,
RA Klungland A.;
RT "Lysine Methylation of the Valosin-Containing Protein (VCP) Is Dispensable
RT for Development and Survival of Mice.";
RL PLoS ONE 10:e0141472-e0141472(2015).
CC -!- FUNCTION: Protein N-lysine methyltransferase that specifically
CC trimethylates 'Lys-315' of VCP/p97; this modification may decrease VCP
CC ATPase activity. {ECO:0000269|PubMed:26544960}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl-[protein] + 3 S-adenosyl-L-methionine = 3 H(+) +
CC N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:54192, Rhea:RHEA-COMP:9752, Rhea:RHEA-
CC COMP:13826, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961;
CC Evidence={ECO:0000269|PubMed:26544960};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54193;
CC Evidence={ECO:0000305|PubMed:26544960};
CC -!- SUBUNIT: Interacts with ALKBH6. Interacts with ASPSCR1 and UBXN6;
CC interaction with ASPSCR1, but not with UBXN6, enhances VCP methylation.
CC {ECO:0000250|UniProtKB:Q9H867}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26544960}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8C436-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C436-2; Sequence=VSP_026588;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:26544960}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are viable, fertile and have no
CC obvious pathological phenotype. {ECO:0000269|PubMed:26544960}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. METTL21
CC family. {ECO:0000305}.
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DR EMBL; AK083148; BAC38784.1; -; mRNA.
DR EMBL; AK144832; BAE26088.1; -; mRNA.
DR EMBL; BC138942; AAI38943.1; -; mRNA.
DR EMBL; BC138943; AAI38944.1; -; mRNA.
DR CCDS; CCDS36464.1; -. [Q8C436-1]
DR RefSeq; NP_001028408.2; NM_001033236.2. [Q8C436-1]
DR AlphaFoldDB; Q8C436; -.
DR SMR; Q8C436; -.
DR BioGRID; 228939; 2.
DR STRING; 10090.ENSMUSP00000055002; -.
DR PhosphoSitePlus; Q8C436; -.
DR EPD; Q8C436; -.
DR MaxQB; Q8C436; -.
DR PaxDb; Q8C436; -.
DR PeptideAtlas; Q8C436; -.
DR PRIDE; Q8C436; -.
DR ProteomicsDB; 290104; -. [Q8C436-1]
DR ProteomicsDB; 290105; -. [Q8C436-2]
DR Antibodypedia; 10369; 23 antibodies from 12 providers.
DR Ensembl; ENSMUST00000058639; ENSMUSP00000055002; ENSMUSG00000049882. [Q8C436-1]
DR GeneID; 207965; -.
DR KEGG; mmu:207965; -.
DR UCSC; uc007nsl.1; mouse. [Q8C436-1]
DR CTD; 79609; -.
DR MGI; MGI:2684917; Vcpkmt.
DR VEuPathDB; HostDB:ENSMUSG00000049882; -.
DR eggNOG; KOG2793; Eukaryota.
DR GeneTree; ENSGT00940000157135; -.
DR HOGENOM; CLU_055721_5_1_1; -.
DR InParanoid; Q8C436; -.
DR OMA; RFMKMAK; -.
DR OrthoDB; 1494909at2759; -.
DR PhylomeDB; Q8C436; -.
DR TreeFam; TF352990; -.
DR Reactome; R-MMU-8876725; Protein methylation.
DR BioGRID-ORCS; 207965; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q8C436; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8C436; protein.
DR Bgee; ENSMUSG00000049882; Expressed in hair follicle and 213 other tissues.
DR ExpressionAtlas; Q8C436; baseline and differential.
DR Genevisible; Q8C436; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0008276; F:protein methyltransferase activity; IMP:UniProtKB.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0032780; P:negative regulation of ATP-dependent activity; ISO:MGI.
DR GO; GO:0018022; P:peptidyl-lysine methylation; ISO:MGI.
DR GO; GO:0018023; P:peptidyl-lysine trimethylation; 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 Acetylation; Alternative splicing; Cytoplasm; Methyltransferase;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT CHAIN 2..228
FT /note="Protein N-lysine methyltransferase METTL21D"
FT /id="PRO_0000089938"
FT BINDING 43
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT BINDING 75..77
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT BINDING 96
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT BINDING 126
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT BINDING 142
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT BINDING 147
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT VAR_SEQ 90..228
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_026588"
SQ SEQUENCE 228 AA; 25535 MW; 56E90DAD2A08F937 CRC64;
MAAAVEPEVE DPLWSFVRVL EKRDGTVLRL QQYGSGGVGC VVWDAAIVLS KYLETPGFSG
DGAHALSRRS VLELGSGTGA VGLMAATLGA DVIVTDLEEL QDLLKMNIDM NKHLVTGSVQ
AKVLKWGEDI EDLMSPDYIL MADCIYYEES LEPLLKTLKD LSGSETCIIC CYEQRTMGKN
PEIEKKYFEL LQLDFDFEEI PLDKHDEEYR SEDIHIVYIR KKKPKPPS
