CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-021543
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Histone-lysine N-methyltransferase EHMT1 
Protein Synonyms/Alias
 Euchromatic histone-lysine N-methyltransferase 1; Eu-HMTase1; G9a-like protein 1; GLP; GLP1; Histone H3-K9 methyltransferase 5; H3-K9-HMTase 5; Lysine N-methyltransferase 1D 
Gene Name
 EHMT1 
Gene Synonyms/Alias
 EUHMTASE1; GLP; KIAA1876; KMT1D 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
153SLPGHAAKTLPGGAGmethylation[1]
209RARKTMPKSVVGLHAubiquitination[2]
219VGLHAASKDPREVREacetylation[3]
239EPKEEINKNISDFGRubiquitination[4, 5]
740KKLRFHPKQLYFSARubiquitination[4, 5]
823NNHLEAVKYLIKAGAubiquitination[6]
827EAVKYLIKAGALVDPubiquitination[2, 3, 4, 5, 6, 7, 8, 9, 10]
890YKHVDLVKLLLSKGSubiquitination[4, 5]
895LVKLLLSKGSDINIRubiquitination[4, 5]
968RDSDVTLKNKEGETPubiquitination[2]
1086SMRCWYDKDGRLLPEubiquitination[6]
Reference
 [1] Mass spectrometry-based identification and characterisation of lysine and arginine methylation in the human proteome.
 Bremang M, Cuomo A, Agresta AM, Stugiewicz M, Spadotto V, Bonaldi T.
 Mol Biosyst. 2013 Jul 30;9(9):2231-47. [PMID: 23748837]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [6] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [8] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [9] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [10] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965] 
Functional Description
 Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non- histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. 
Sequence Annotation
 REPEAT 737 766 ANK 1.
 REPEAT 772 801 ANK 2.
 REPEAT 805 834 ANK 3.
 REPEAT 838 868 ANK 4.
 REPEAT 872 901 ANK 5.
 REPEAT 905 934 ANK 6.
 REPEAT 938 967 ANK 7.
 REPEAT 971 1004 ANK 8.
 DOMAIN 1060 1123 Pre-SET.
 DOMAIN 1126 1243 SET.
 REGION 905 907 Histone H3K9me binding.
 REGION 1136 1138 S-adenosyl-L-methionine binding.
 REGION 1162 1181 Interaction with histone H3.
 REGION 1200 1201 S-adenosyl-L-methionine binding.
 REGION 1242 1245 Interaction with histone H3.
 METAL 1062 1062 Zinc 1.
 METAL 1062 1062 Zinc 2.
 METAL 1064 1064 Zinc 1.
 METAL 1068 1068 Zinc 1.
 METAL 1068 1068 Zinc 3.
 METAL 1073 1073 Zinc 1.
 METAL 1075 1075 Zinc 2.
 METAL 1105 1105 Zinc 2.
 METAL 1105 1105 Zinc 3.
 METAL 1109 1109 Zinc 2.
 METAL 1111 1111 Zinc 3.
 METAL 1115 1115 Zinc 3.
 METAL 1203 1203 Zinc 4.
 METAL 1256 1256 Zinc 4.
 METAL 1258 1258 Zinc 4.
 METAL 1263 1263 Zinc 4.
 BINDING 1155 1155 Histone H3K9me.
 BINDING 1173 1173 S-adenosyl-L-methionine.
 BINDING 1257 1257 S-adenosyl-L-methionine; via amide  
Keyword
 3D-structure; Alternative splicing; ANK repeat; Chromatin regulator; Chromosome; Complete proteome; Disease mutation; Mental retardation; Metal-binding; Methyltransferase; Nucleus; Polymorphism; Reference proteome; Repeat; S-adenosyl-L-methionine; Transferase; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1298 AA 
Protein Sequence
MAAADAEAVP ARGEPQQDCC VKTELLGEET PMAADEGSAE KQAGEAHMAA DGETNGSCEN 60
SDASSHANAA KHTQDSARVN PQDGTNTLTR IAENGVSERD SEAAKQNHVT ADDFVQTSVI 120
GSNGYILNKP ALQAQPLRTT STLASSLPGH AAKTLPGGAG KGRTPSAFPQ TPAAPPATLG 180
EGSADTEDRK LPAPGADVKV HRARKTMPKS VVGLHAASKD PREVREARDH KEPKEEINKN 240
ISDFGRQQLL PPFPSLHQSL PQNQCYMATT KSQTACLPFV LAAAVSRKKK RRMGTYSLVP 300
KKKTKVLKQR TVIEMFKSIT HSTVGSKGEK DLGASSLHVN GESLEMDSDE DDSEELEEDD 360
GHGAEQAAAF PTEDSRTSKE SMSEADRAQK MDGESEEEQE SVDTGEEEEG GDESDLSSES 420
SIKKKFLKRK GKTDSPWIKP ARKRRRRSRK KPSGALGSES YKSSAGSAEQ TAPGDSTGYM 480
EVSLDSLDLR VKGILSSQAE GLANGPDVLE TDGLQEVPLC SCRMETPKSR EITTLANNQC 540
MATESVDHEL GRCTNSVVKY ELMRPSNKAP LLVLCEDHRG RMVKHQCCPG CGYFCTAGNF 600
MECQPESSIS HRFHKDCASR VNNASYCPHC GEESSKAKEV TIAKADTTST VTPVPGQEKG 660
SALEGRADTT TGSAAGPPLS EDDKLQGAAS HVPEGFDPTG PAGLGRPTPG LSQGPGKETL 720
ESALIALDSE KPKKLRFHPK QLYFSARQGE LQKVLLMLVD GIDPNFKMEH QNKRSPLHAA 780
AEAGHVDICH MLVQAGANID TCSEDQRTPL MEAAENNHLE AVKYLIKAGA LVDPKDAEGS 840
TCLHLAAKKG HYEVVQYLLS NGQMDVNCQD DGGWTPMIWA TEYKHVDLVK LLLSKGSDIN 900
IRDNEENICL HWAAFSGCVD IAEILLAAKC DLHAVNIHGD SPLHIAAREN RYDCVVLFLS 960
RDSDVTLKNK EGETPLQCAS LNSQVWSALQ MSKALQDSAP DRPSPVERIV SRDIARGYER 1020
IPIPCVNAVD SEPCPSNYKY VSQNCVTSPM NIDRNITHLQ YCVCIDDCSS SNCMCGQLSM 1080
RCWYDKDGRL LPEFNMAEPP LIFECNHACS CWRNCRNRVV QNGLRARLQL YRTRDMGWGV 1140
RSLQDIPPGT FVCEYVGELI SDSEADVREE DSYLFDLDNK DGEVYCIDAR FYGNVSRFIN 1200
HHCEPNLVPV RVFMAHQDLR FPRIAFFSTR LIEAGEQLGF DYGERFWDIK GKLFSCRCGS 1260
PKCRHSSAAL AQRQASAAQE AQEDGLPDTS SAAAADPL 1298 
Gene Ontology
 GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; ISS:UniProtKB.
 GO:0046976; F:histone methyltransferase activity (H3-K27 specific); ISS:UniProtKB.
 GO:0046974; F:histone methyltransferase activity (H3-K9 specific); ISS:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0006306; P:DNA methylation; ISS:UniProtKB.
 GO:0009790; P:embryo development; ISS:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; ISS:UniProtKB.
 GO:0018027; P:peptidyl-lysine dimethylation; IDA:UniProtKB.
 GO:0018026; P:peptidyl-lysine monomethylation; ISS:UniProtKB. 
Interpro
 IPR002110; Ankyrin_rpt.
 IPR020683; Ankyrin_rpt-contain_dom.
 IPR007728; Pre-SET_dom.
 IPR003606; Pre-SET_Zn-bd_sub.
 IPR001214; SET_dom. 
Pfam
 PF00023; Ank
 PF12796; Ank_2
 PF05033; Pre-SET
 PF00856; SET 
SMART
 SM00248; ANK
 SM00468; PreSET
 SM00317; SET 
PROSITE
 PS50297; ANK_REP_REGION
 PS50088; ANK_REPEAT
 PS50867; PRE_SET
 PS50280; SET 
PRINTS
 PR01415; ANKYRIN.