CSKMT_HUMAN
ID CSKMT_HUMAN Reviewed; 240 AA.
AC A8MUP2; B7Z4C1;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Citrate synthase-lysine N-methyltransferase CSKMT, mitochondrial {ECO:0000303|PubMed:28887308, ECO:0000305};
DE Short=CS-KMT {ECO:0000303|PubMed:28887308};
DE EC=2.1.1.- {ECO:0000269|PubMed:28887308};
DE AltName: Full=Methyltransferase-like protein 12, mitochondrial {ECO:0000312|HGNC:HGNC:33113};
DE Flags: Precursor;
GN Name=CSKMT {ECO:0000303|PubMed:28887308, ECO:0000312|HGNC:HGNC:33113};
GN Synonyms=METTL12 {ECO:0000312|HGNC:HGNC:33113};
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 [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP SUBCELLULAR LOCATION.
RX PubMed=25023281; DOI=10.1074/jbc.m114.580464;
RA Rhein V.F., Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.;
RT "Human METTL20 methylates lysine residues adjacent to the recognition loop
RT of the electron transfer flavoprotein in mitochondria.";
RL J. Biol. Chem. 289:24640-24651(2014).
RN [5]
RP FUNCTION.
RX PubMed=28391595; DOI=10.1002/1873-3468.12649;
RA Rhein V.F., Carroll J., Ding S., Fearnley I.M., Walker J.E.;
RT "Human METTL12 is a mitochondrial methyltransferase that modifies citrate
RT synthase.";
RL FEBS Lett. 591:1641-1652(2017).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, TRANSIT PEPTIDE CLEAVAGE SITE, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF ASP-107.
RX PubMed=28887308; DOI=10.1074/jbc.m117.808451;
RA Malecki J., Jakobsson M.E., Ho A.Y.Y., Moen A., Rustan A.C., Falnes P.O.;
RT "Uncovering human METTL12 as a mitochondrial methyltransferase that
RT modulates citrate synthase activity through metabolite-sensitive lysine
RT methylation.";
RL J. Biol. Chem. 292:17950-17962(2017).
CC -!- FUNCTION: Protein-lysine methyltransferase that selectively
CC trimethylates citrate synthase (CS) in mitochondria (PubMed:28391595,
CC PubMed:28887308). Seems to conduct trimethylation in a highly
CC distributive manner rather than in a processive manner, and thus
CC introduces a single methyl group per binding event (PubMed:28887308).
CC {ECO:0000269|PubMed:28391595, ECO:0000269|PubMed:28887308}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl-[citrate synthase] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl-[citrate synthase] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:55544, Rhea:RHEA-COMP:14212, Rhea:RHEA-COMP:14213,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929;
CC Evidence={ECO:0000269|PubMed:28887308};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl-[citrate synthase] + S-adenosyl-L-
CC methionine = H(+) + N(6),N(6)-dimethyl-L-lysyl-[citrate synthase] +
CC S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:55548, Rhea:RHEA-
CC COMP:14213, Rhea:RHEA-COMP:14214, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929,
CC ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:28887308};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6),N(6)-dimethyl-L-lysyl-[citrate synthase] + S-adenosyl-L-
CC methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl-[citrate
CC synthase] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:55552,
CC Rhea:RHEA-COMP:14214, Rhea:RHEA-COMP:14215, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961,
CC ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:28887308};
CC -!- ACTIVITY REGULATION: Citrate synthase-lysine methyltransferase activity
CC is inhibited by S-adenosylhomocysteine (AdoHcy) and oxaloacetate (OAA)
CC (PubMed:28887308). {ECO:0000269|PubMed:28887308}.
CC -!- INTERACTION:
CC A8MUP2; Q9NP55: BPIFA1; NbExp=3; IntAct=EBI-12842046, EBI-953896;
CC A8MUP2; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-12842046, EBI-1052037;
CC A8MUP2; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-12842046, EBI-11953846;
CC A8MUP2; Q3LI70: KRTAP19-6; NbExp=3; IntAct=EBI-12842046, EBI-12805508;
CC A8MUP2; O75716: STK16; NbExp=3; IntAct=EBI-12842046, EBI-749295;
CC A8MUP2; Q96M29: TEKT5; NbExp=3; IntAct=EBI-12842046, EBI-10239812;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:25023281,
CC ECO:0000269|PubMed:28887308}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
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DR EMBL; AK297138; BAH12507.1; -; mRNA.
DR EMBL; AP001458; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC147001; AAI47002.1; -; mRNA.
DR EMBL; BC147011; AAI47012.1; -; mRNA.
DR CCDS; CCDS41657.1; -.
DR RefSeq; NP_001036694.1; NM_001043229.1.
DR AlphaFoldDB; A8MUP2; -.
DR SMR; A8MUP2; -.
DR BioGRID; 593305; 7.
DR IntAct; A8MUP2; 6.
DR STRING; 9606.ENSP00000431287; -.
DR BioMuta; METTL12; -.
DR MassIVE; A8MUP2; -.
DR MaxQB; A8MUP2; -.
DR PaxDb; A8MUP2; -.
DR PeptideAtlas; A8MUP2; -.
DR PRIDE; A8MUP2; -.
DR ProteomicsDB; 2121; -.
DR Antibodypedia; 50269; 10 antibodies from 5 providers.
DR DNASU; 751071; -.
DR Ensembl; ENST00000532971.2; ENSP00000431287.1; ENSG00000214756.8.
DR GeneID; 751071; -.
DR KEGG; hsa:751071; -.
DR MANE-Select; ENST00000532971.2; ENSP00000431287.1; NM_001043229.2; NP_001036694.1.
DR UCSC; uc001nug.2; human.
DR CTD; 751071; -.
DR GeneCards; CSKMT; -.
DR HGNC; HGNC:33113; CSKMT.
DR HPA; ENSG00000214756; Not detected.
DR MIM; 617897; gene.
DR neXtProt; NX_A8MUP2; -.
DR OpenTargets; ENSG00000214756; -.
DR PharmGKB; PA164722245; -.
DR VEuPathDB; HostDB:ENSG00000214756; -.
DR eggNOG; KOG2352; Eukaryota.
DR GeneTree; ENSGT00510000049875; -.
DR HOGENOM; CLU_098158_0_0_1; -.
DR InParanoid; A8MUP2; -.
DR OMA; YLIQGCH; -.
DR PhylomeDB; A8MUP2; -.
DR TreeFam; TF354334; -.
DR PathwayCommons; A8MUP2; -.
DR SignaLink; A8MUP2; -.
DR SIGNOR; A8MUP2; -.
DR BioGRID-ORCS; 751071; 11 hits in 1076 CRISPR screens.
DR ChiTaRS; METTL12; human.
DR GenomeRNAi; 751071; -.
DR Pharos; A8MUP2; Tdark.
DR PRO; PR:A8MUP2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; A8MUP2; protein.
DR Bgee; ENSG00000214756; Expressed in colonic epithelium and 97 other tissues.
DR Genevisible; A8MUP2; HS.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016278; F:lysine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0018027; P:peptidyl-lysine dimethylation; IDA:UniProtKB.
DR GO; GO:0018026; P:peptidyl-lysine monomethylation; IDA:UniProtKB.
DR GO; GO:0018023; P:peptidyl-lysine trimethylation; IDA:UniProtKB.
DR GO; GO:0006479; P:protein methylation; IDA:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR041698; Methyltransf_25.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF13649; Methyltransf_25; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Mitochondrion; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; Transit peptide.
FT TRANSIT 1..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:28887308"
FT CHAIN 29..240
FT /note="Citrate synthase-lysine N-methyltransferase CSKMT,
FT mitochondrial"
FT /id="PRO_0000349199"
FT VARIANT 125
FT /note="G -> S (in dbSNP:rs11231181)"
FT /id="VAR_046283"
FT MUTAGEN 107
FT /note="D->A: Inhibits citrate synthase-lysine
FT methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:28887308"
SQ SEQUENCE 240 AA; 25910 MW; BCF0FBD4493D2CE6 CRC64;
MAALRRMLHL PSLMMGTCRP FAGSLADSCL ADRCLWDRLH AQPRLGTVPT FDWFFGYDEV
QGLLLPLLQE AQAASPLRVL DVGCGTSSLC TGLYTKSPHP VDVLGVDFSP VAVAHMNSLL
EGGPGQTPLC PGHPASSLHF MHADAQNLGA VASSGSFQLL LDKGTWDAVA RGGLPRAYQL
LSECLRVLNP QGTLIQFSDE DPDVRLPCLE QGSYGWTVTV QELGPFRGIT YFAYLIQGSH
