Protein methylation (Homo sapiens)

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Bibliography

1. Biggar KK, Li SS.; ''Non-histone protein methylation as a regulator of cellular signalling and function.''; PubMed Europe PMC Scholia
2. Van Ness BG, Howard JB, Bodley JW.; ''ADP-ribosylation of elongation factor 2 by diphtheria toxin. NMR spectra and proposed structures of ribosyl-diphthamide and its hydrolysis products.''; PubMed Europe PMC Scholia
3. Hamey JJ, Winter DL, Winter DL, Yagoub D, Overall CM, Hart-Smith G, Wilkins MR.; ''Novel N-terminal and Lysine Methyltransferases That Target Translation Elongation Factor 1A in Yeast and Human.''; PubMed Europe PMC Scholia
4. Shimazu T, Barjau J, Sohtome Y, Sodeoka M, Shinkai Y.; ''Selenium-based S-adenosylmethionine analog reveals the mammalian seven-beta-strand methyltransferase METTL10 to be an EF1A1 lysine methyltransferase.''; PubMed Europe PMC Scholia
5. Magnani R, Dirk LM, Trievel RC, Houtz RL.; ''Calmodulin methyltransferase is an evolutionarily conserved enzyme that trimethylates Lys-115 in calmodulin.''; PubMed Europe PMC Scholia
6. Cloutier P, Lavallée-Adam M, Faubert D, Blanchette M, Coulombe B.; ''A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity.''; PubMed Europe PMC Scholia
7. Tang J, Gary JD, Clarke S, Herschman HR.; ''PRMT 3, a type I protein arginine N-methyltransferase that differs from PRMT1 in its oligomerization, subcellular localization, substrate specificity, and regulation.''; PubMed Europe PMC Scholia
8. Davydova E, Ho AY, Malecki J, Moen A, Enserink JM, Jakobsson ME, Loenarz C, Falnes PØ.; ''Identification and characterization of a novel evolutionarily conserved lysine-specific methyltransferase targeting eukaryotic translation elongation factor 2 (eEF2).''; PubMed Europe PMC Scholia
9. Van Ness BG, Howard JB, Bodley JW.; ''ADP-ribosylation of elongation factor 2 by diphtheria toxin. Isolation and properties of the novel ribosyl-amino acid and its hydrolysis products.''; PubMed Europe PMC Scholia
10. Małecki J, Ho AY, Moen A, Dahl HA, Falnes PØ.; ''Human METTL20 is a mitochondrial lysine methyltransferase that targets the β subunit of electron transfer flavoprotein (ETFβ) and modulates its activity.''; PubMed Europe PMC Scholia
11. Sun XJ, Wei J, Wu XY, Hu M, Wang L, Wang HH, Zhang QH, Chen SJ, Huang QH, Chen Z.; ''Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
AdoHcy	Metabolite	CHEBI:16680 (ChEBI)
AdoMet	Metabolite	CHEBI:15414 (ChEBI)
CALM1	Protein	P0DP23 (Uniprot-TrEMBL)
CAMKMT	Protein	Q7Z624 (Uniprot-TrEMBL)
EEF1A1	Protein	P68104 (Uniprot-TrEMBL)
EEF2KMT	Protein	Q96G04 (Uniprot-TrEMBL)
EEF2	Protein	P13639 (Uniprot-TrEMBL)
ETFBKMT	Protein	Q8IXQ9 (Uniprot-TrEMBL)
ETFB	Protein	P38117 (Uniprot-TrEMBL)
HSPA8	Protein	P11142 (Uniprot-TrEMBL)
KIN	Protein	O60870 (Uniprot-TrEMBL)
METTL10	Protein	Q5JPI9 (Uniprot-TrEMBL)
METTL21A	Protein	Q8WXB1 (Uniprot-TrEMBL)
METTL22	Protein	Q9BUU2 (Uniprot-TrEMBL)
Me2aR-RPS2	Protein	P15880 (Uniprot-TrEMBL)
Me3K115-CALM1	Protein	P0DP23 (Uniprot-TrEMBL)
Me3K135-KIN	Protein	O60870 (Uniprot-TrEMBL)
Me3K200,Me3K203-ETFB	Protein	P38117 (Uniprot-TrEMBL)
Me3K315-VCP	Protein	P55072 (Uniprot-TrEMBL)
Me3K318-EEF1A1	Protein	P68104 (Uniprot-TrEMBL)
Me3K525-EEF2	Protein	P13639 (Uniprot-TrEMBL)
Me3K561-HSPA8	Protein	P11142 (Uniprot-TrEMBL)
Me3K79-EEF1A1	Protein	P68104 (Uniprot-TrEMBL)
N6AMT2	Protein	Q8WVE0 (Uniprot-TrEMBL)
PRMT3	Protein	O60678 (Uniprot-TrEMBL)
RPS2	Protein	P15880 (Uniprot-TrEMBL)
VCPKMT	Protein	Q9H867 (Uniprot-TrEMBL)
VCP	Protein	P55072 (Uniprot-TrEMBL)

Annotated Interactions

Source	Target	Type	Database reference	Comment
	AdoHcy	Arrow	R-HSA-6786205 (Reactome)
	AdoHcy	Arrow	R-HSA-8879123 (Reactome)
	AdoHcy	Arrow	R-HSA-8931858 (Reactome)
	AdoHcy	Arrow	R-HSA-8931974 (Reactome)
	AdoHcy	Arrow	R-HSA-8932221 (Reactome)
	AdoHcy	Arrow	R-HSA-8932243 (Reactome)
	AdoHcy	Arrow	R-HSA-8932275 (Reactome)
	AdoHcy	Arrow	R-HSA-8932276 (Reactome)
	AdoHcy	Arrow	R-HSA-8932413 (Reactome)
AdoMet			R-HSA-6786205 (Reactome)
AdoMet			R-HSA-8879123 (Reactome)
AdoMet			R-HSA-8931858 (Reactome)
AdoMet			R-HSA-8931974 (Reactome)
AdoMet			R-HSA-8932221 (Reactome)
AdoMet			R-HSA-8932243 (Reactome)
AdoMet			R-HSA-8932275 (Reactome)
AdoMet			R-HSA-8932276 (Reactome)
AdoMet			R-HSA-8932413 (Reactome)
CALM1			R-HSA-6786205 (Reactome)
CAMKMT		mim-catalysis	R-HSA-6786205 (Reactome)
EEF1A1			R-HSA-8931974 (Reactome)
EEF1A1			R-HSA-8932413 (Reactome)
EEF2KMT		mim-catalysis	R-HSA-8932243 (Reactome)
EEF2			R-HSA-8932243 (Reactome)
ETFBKMT		mim-catalysis	R-HSA-8931858 (Reactome)
ETFB			R-HSA-8931858 (Reactome)
HSPA8			R-HSA-8932221 (Reactome)
KIN			R-HSA-8932275 (Reactome)
METTL10		mim-catalysis	R-HSA-8932413 (Reactome)
METTL21A		mim-catalysis	R-HSA-8932221 (Reactome)
METTL22		mim-catalysis	R-HSA-8932275 (Reactome)
	Me2aR-RPS2	Arrow	R-HSA-8879123 (Reactome)
	Me3K115-CALM1	Arrow	R-HSA-6786205 (Reactome)
	Me3K135-KIN	Arrow	R-HSA-8932275 (Reactome)
	Me3K200,Me3K203-ETFB	Arrow	R-HSA-8931858 (Reactome)
	Me3K315-VCP	Arrow	R-HSA-8932276 (Reactome)
	Me3K318-EEF1A1	Arrow	R-HSA-8932413 (Reactome)
	Me3K525-EEF2	Arrow	R-HSA-8932243 (Reactome)
	Me3K561-HSPA8	Arrow	R-HSA-8932221 (Reactome)
	Me3K79-EEF1A1	Arrow	R-HSA-8931974 (Reactome)
N6AMT2		mim-catalysis	R-HSA-8931974 (Reactome)
PRMT3		mim-catalysis	R-HSA-8879123 (Reactome)
			R-HSA-6786205 (Reactome)	Calmodulin (CALM1) is a ubiquitous key mediator of Ca2+-dependent signalling and is subject to regulatory post-translational modifications which can affect protein-protein interactions. CALM1 is frequently trimethylated at Lys-115 which can influence changes in growth and development and its activator properties with target enzymes. The cytosolic enzyme calmodulin-lysine N-methyltransferase (CAMKMT) catalyses the transfer of 3 methyl groups from high energy donors S-adenosyl-L-methionine (AdoMet) to lysine residue 115 in CALM1, forming a trimethylated protein (triMe-K115-CALM1) (Magnani et al. 2010).
			R-HSA-8879123 (Reactome)	Protein arginine methyltransferase 3 (PRMT3) is a cytosolic enzyme that catalyzes the formation of omega-mono- or asymmetric dimethylarginine (Tang et al. 1998). It has a unique substrate binding N-terminal C2H2 Zn finger domain and a catalytic C-terminal domain that is homologous to other PRMTs (Zhang et al. 2000). PRMT3 associates with ribosomes in the cytosol, which contain its main in vivo substrate, the small ribosomal subunit Ribosomal protein S2 (RPS2). PRMT3 methylates arginines in the RG-rich N-terminal tail of RPS2 forming asymmetric dimethylarginines (Swiercz et al. 2005). Prmt3–null mice show developmental delay during embryogenesis and have embryos that are markedly smaller than wt , though size at birth is normal suggesting that PRMT3 loss can be compensated for in most cell types but may not be in under conditions that demand extremely fast protein synthesis (Swiercz et al. 2007).
			R-HSA-8931858 (Reactome)	Electron transfer flavoprotein beta subunit lysine methyltransferase (ETFBKMT, METTL20) specifically methylates Lys-200 and Lys-203 of Electron transfer flavoprotein beta (ETFB) ) (Rhein et al 2014, Malecki et al. 2015). ETF shuttles electrons between several FAD-containing dehydrogenases present in the mitochondrial matrix and the membrane-bound ETF:quinone oxidoreductase (Ramsay et al. 1987). ETFB is proposed to contain 'recognition loop' at residues 191–200, responsible for interaction with the dehydrogenases (Toogood et al. 2004). Methylation of ETF impairs its ability to extract electrons from two acyl-CoA dehydrogenases, MCAD and GCDH, suggesting a functional role for ETFBKMT-mediated methylation of ETFB (Malecki et al. 2015).
			R-HSA-8931974 (Reactome)	Eukaryotic elongation factor 1A (EEF1A) is an essential, highly methylated protein that facilitates translational elongation by delivering aminoacyl-tRNAs to ribosomes. EEF1AKMT1 (N6AMT2) trimethylates EEF1A at Lys-79, a high-stoichiometry N-terminal site that is conserved from yeast to humans (Hamey et al. 2016).
			R-HSA-8932221 (Reactome)	Protein N-lysine methyltransferase METTL21A trimethylates lysine-561 of Heat shock cognate 71 kDa protein (HSPA8) and corresponding lysine residues in other Hsp70 isoforms (Jakobsson et al. 2013, Cloutier et al. 2013).
			R-HSA-8932243 (Reactome)	Protein-lysine N-methyltransferase EEF2KMT (EEF2KMT) catalyzes the trimethylation of eukaryotic elongation factor 2 (EEF2) on Lys-525.
			R-HSA-8932275 (Reactome)	METTL22 trimethylates lysine-135 of DNA/RNA-binding protein KIN17 (KIN) (Cloutier et al. 2013)
			R-HSA-8932276 (Reactome)	Protein N-lysine methyltransferase METTL21D (VCPKMT) trimethylates lysine-315 of VCP (Kernstock et al. 2012, Cloutier et al. 2013).
			R-HSA-8932413 (Reactome)	Protein-lysine N-methyltransferase METTL10 trimethylates Elongation factor 1-alpha 1 (EF1A1) at lysine-318 (Shimazu et al. 2014).
RPS2			R-HSA-8879123 (Reactome)
VCPKMT		mim-catalysis	R-HSA-8932276 (Reactome)
VCP			R-HSA-8932276 (Reactome)