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Protein

Histone-lysine N-methyltransferase EHMT1

Gene

Ehmt1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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/TP53.2 Publications

Catalytic activityi

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].1 Publication

Enzyme regulationi

Methyltransferase activity is inhibited by BIX-01294. Efficiently inhibited by compound E72, a BIX-01294 derivative in which the diazepane ring and the benzyl are replaced with a 3-dimethylaminopropyl and a 5-aminopentyl group at sites B and C, respectively (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi1060Zinc 1By similarity1
Metal bindingi1060Zinc 2By similarity1
Metal bindingi1062Zinc 1By similarity1
Metal bindingi1066Zinc 1By similarity1
Metal bindingi1066Zinc 3By similarity1
Metal bindingi1071Zinc 1By similarity1
Metal bindingi1073Zinc 2By similarity1
Metal bindingi1103Zinc 2By similarity1
Metal bindingi1103Zinc 3By similarity1
Metal bindingi1107Zinc 2By similarity1
Metal bindingi1109Zinc 3By similarity1
Metal bindingi1113Zinc 3By similarity1
Binding sitei1153Histone H3K9meBy similarity1
Binding sitei1171S-adenosyl-L-methioninePROSITE-ProRule annotation1
Metal bindingi1201Zinc 4By similarity1
Metal bindingi1254Zinc 4By similarity1
Binding sitei1255S-adenosyl-L-methionine; via amide nitrogenPROSITE-ProRule annotation1
Metal bindingi1256Zinc 4By similarity1
Metal bindingi1261Zinc 4By similarity1

GO - Molecular functioni

GO - Biological processi

  • chromatin organization Source: MGI
  • DNA methylation Source: UniProtKB
  • embryo development Source: UniProtKB
  • histone methylation Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • peptidyl-lysine dimethylation Source: UniProtKB
  • peptidyl-lysine monomethylation Source: UniProtKB
  • response to fungicide Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Transferase

Keywords - Ligandi

Metal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-MMU-3214841. PKMTs methylate histone lysines.
R-MMU-6804760. Regulation of TP53 Activity through Methylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone-lysine N-methyltransferase EHMT1 (EC:2.1.1.-, EC:2.1.1.43)
Alternative name(s):
Euchromatic histone-lysine N-methyltransferase 1
Short name:
Eu-HMTase1
G9a-like protein 1
Short name:
GLP
Short name:
GLP1
Lysine N-methyltransferase 1D
Gene namesi
Name:Ehmt1
Synonyms:Euhmtase1, Glp, Kmt1d
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1924933. Ehmt1.

Subcellular locationi

GO - Cellular componenti

  • chromosome Source: UniProtKB-SubCell
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryos die around E9.5. Levels of H3K9me1 and H3K9me2 are drastically reduced.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1153Y → V in LM7; does not prevent methyltransferase activity; when associated with F-1240. 1 Publication1
Mutagenesisi1198 – 1201Missing in LM3; does not form heterodimer with EHMT2 and is defective in mediating both H3K9me and DNA methylation. 1 Publication4
Mutagenesisi1201C → A in LM4; does not prevent methyltransferase activity. 1 Publication1
Mutagenesisi1240Y → F in LM7; does not prevent methyltransferase activity; when associated with V-1153. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004058441 – 1296Histone-lysine N-methyltransferase EHMT1Add BLAST1296

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki23Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki232Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki430Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei433PhosphoserineBy similarity1
Modified residuei481PhosphoserineBy similarity1
Cross-linki729Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1046PhosphoserineBy similarity1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ5DW34.
PeptideAtlasiQ5DW34.
PRIDEiQ5DW34.

PTM databases

iPTMnetiQ5DW34.
PhosphoSitePlusiQ5DW34.

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

BgeeiENSMUSG00000036893.
ExpressionAtlasiQ5DW34. baseline and differential.
GenevisibleiQ5DW34. MM.

Interactioni

Subunit structurei

Interacts with WIZ. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EHMT1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Interacts with MPHOSPH8 (By similarity). Interacts with CDYL. Interacts with REST only in the presence of CDYL. Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 (By similarity). Heterodimer; heterodimerizes with EHMT2. Interacts (via ANK repeats) with RELA (when monomethylated at 'Lys-310').By similarity2 Publications

GO - Molecular functioni

  • C2H2 zinc finger domain binding Source: UniProtKB
  • p53 binding Source: MGI

Protein-protein interaction databases

BioGridi218847. 7 interactors.
DIPiDIP-49000N.
DIP-59572N.
IntActiQ5DW34. 3 interactors.
STRINGi10090.ENSMUSP00000100002.

Structurei

3D structure databases

ProteinModelPortaliQ5DW34.
SMRiQ5DW34.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati735 – 764ANK 1Add BLAST30
Repeati770 – 799ANK 2Add BLAST30
Repeati803 – 832ANK 3Add BLAST30
Repeati836 – 866ANK 4Add BLAST31
Repeati870 – 899ANK 5Add BLAST30
Repeati903 – 932ANK 6Add BLAST30
Repeati936 – 965ANK 7Add BLAST30
Repeati969 – 1002ANK 8Add BLAST34
Domaini1058 – 1121Pre-SETPROSITE-ProRule annotationAdd BLAST64
Domaini1124 – 1241SETPROSITE-ProRule annotationAdd BLAST118

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni903 – 905Histone H3K9me bindingBy similarity3
Regioni1134 – 1136S-adenosyl-L-methionine bindingBy similarity3
Regioni1160 – 1179Interaction with histone H3By similarityAdd BLAST20
Regioni1198 – 1199S-adenosyl-L-methionine bindingBy similarity2
Regioni1240 – 1243Interaction with histone H3By similarity4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi440 – 447Poly-Arg8
Compositional biasi1290 – 1293Poly-Ala4

Domaini

The ANK repeats specifically recognize and bind H3K9me1 and H3K9me2 (By similarity). They also specifically recognize and bind RELA subunit of NF-kappa-B, when RELA is monomethylated at 'Lys-310'.By similarity1 Publication
The SET domain mediates interaction with WIZ.By similarity
In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.By similarity

Sequence similaritiesi

Belongs to the class V-like SAM-binding methyltransferase superfamily.PROSITE-ProRule annotation
Contains 8 ANK repeats.PROSITE-ProRule annotation
Contains 1 pre-SET domain.PROSITE-ProRule annotation
Contains 1 SET domain.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG1082. Eukaryota.
COG0666. LUCA.
COG2940. LUCA.
GeneTreeiENSGT00780000121845.
HOGENOMiHOG000231216.
HOVERGENiHBG028394.
InParanoidiQ5DW34.
KOiK11420.
OMAiETPLQCS.
OrthoDBiEOG091G00U6.
PhylomeDBiQ5DW34.
TreeFamiTF106443.

Family and domain databases

Gene3Di1.25.40.20. 3 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR007728. Pre-SET_dom.
IPR001214. SET_dom.
[Graphical view]
PfamiPF12796. Ank_2. 2 hits.
PF05033. Pre-SET. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 7 hits.
SM00468. PreSET. 1 hit.
SM00317. SET. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS50867. PRE_SET. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q5DW34-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAADAEQAV LAKQETKQDC CMKTELLRED TPMAADEGST EKQEGETPMA
60 70 80 90 100
ADGETNGSCE KSGDPSHLNA PKHTQENTRA SPQEGTNRVS RVAENGVSER
110 120 130 140 150
DTEVGKQNHV TADDFMQTSV IGSNGYFLNK PALQGQPLRT PNILTSSLPG
160 170 180 190 200
HAAKTLPGGA SKCRTLSALP QTPTTAPTVP GEGSADTEDR KPTASGTDVR
210 220 230 240 250
VHRARKTMPK SILGLHAASK DHREVQDHKE PKEDINRNIS ECGRQQLLPT
260 270 280 290 300
FPALHQSLPQ NQCYMATTKS QTACLPFVLA AAVSRKKKRR MGTYSLVPKK
310 320 330 340 350
KTKVLKQRTV IEMFKSITHS TVGAKGEKAL DDSALHVNGE SLEMDSEDED
360 370 380 390 400
SDELEDDEDH GAEQAAAFPT EDSRTSKESM SETDRAAKMD GDSEEEQESP
410 420 430 440 450
DTGEDEDGGD ESDLSSESSI KKKFLKRRGK TDSPWIKPAR KRRRRSRKKP
460 470 480 490 500
SSMLGSEACK SSPGSMEQAA LGDSAGYMEV SLDSLDLRVR GILSSQTENE
510 520 530 540 550
GLASGPDVLG TDGLQEVPLC SCRMETPKSR EISTLANNQC MATESVDHEL
560 570 580 590 600
GRCTNSVVKY ELMRPSNKAP LLVLCEDHRG RMVKHQCCPG CGYFCTAGNF
610 620 630 640 650
MECQPESSIS HRFHKDCASR VNNASYCPHC GEEASKAKEV TIAKADTTST
660 670 680 690 700
VTLAPGQEKS LAAEGRADTT TGSIAGAPED ERSQSTAPQA PECFDPAGPA
710 720 730 740 750
GLVRPTSGLS QGPGKETLES ALIALDSEKP KKLRFHPKQL YFSARQGELQ
760 770 780 790 800
KVLLMLVDGI DPNFKMEHQS KRSPLHAAAE AGHVDICHML VQAGANIDTC
810 820 830 840 850
SEDQRTPLME AAENNHLDAV KYLIKAGAQV DPKDAEGSTC LHLAAKKGHY
860 870 880 890 900
DVVQYLLSNG QMDVNCQDDG GWTPMIWATE YKHVELVKLL LSKGSDINIR
910 920 930 940 950
DNEENICLHW AAFSGCVDIA EILLAAKCDL HAVNIHGDSP LHIAARENRY
960 970 980 990 1000
DCVVLFLSRD SDVTLKNKEG ETPLQCASLS SQVWSALQMS KALRDSAPDK
1010 1020 1030 1040 1050
PVAVEKTVSR DIARGYERIP IPCVNAVDSE LCPTNYKYVS QNCVTSPMNI
1060 1070 1080 1090 1100
DRNITHLQYC VCVDDCSSST CMCGQLSMRC WYDKDGRLLP EFNMAEPPLI
1110 1120 1130 1140 1150
FECNHACSCW RNCRNRVVQN GLRARLQLYR TQDMGWGVRS LQDIPLGTFV
1160 1170 1180 1190 1200
CEYVGELISD SEADVREEDS YLFDLDNKDG EVYCIDARFY GNVSRFINHH
1210 1220 1230 1240 1250
CEPNLVPVRV FMSHQDLRFP RIAFFSTRLI QAGEQLGFDY GERFWDVKGK
1260 1270 1280 1290
LFSCRCGSSK CRHSSAALAQ RQASAAQEPQ ENGLPDTSSA AAADPL
Length:1,296
Mass (Da):141,999
Last modified:March 8, 2011 - v2
Checksum:iB7783B6F38D3C7CB
GO
Isoform 2 (identifier: Q5DW34-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     273-279: Missing.
     455-500: Missing.

Note: No experimental confirmation available.
Show »
Length:1,243
Mass (Da):136,496
Checksum:iAB666EE7F3CE9EC3
GO
Isoform 3 (identifier: Q5DW34-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     550-597: Missing.

Note: No experimental confirmation available.
Show »
Length:1,248
Mass (Da):136,631
Checksum:i6D881B82F181F36E
GO

Sequence cautioni

The sequence CAM22112 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti411E → D in BAD90007 (PubMed:15774718).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_040724273 – 279Missing in isoform 2. 1 Publication7
Alternative sequenceiVSP_040725455 – 500Missing in isoform 2. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_040726550 – 597Missing in isoform 3. 1 PublicationAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB205007 mRNA. Translation: BAD90007.1.
AL732525 Genomic DNA. Translation: CAM22112.1. Different initiation.
AL732525 Genomic DNA. Translation: CAM22113.1.
AL732525 Genomic DNA. Translation: CAM22114.1.
BC056938 mRNA. Translation: AAH56938.1.
BC089302 mRNA. Translation: AAH89302.1.
CCDSiCCDS15740.1. [Q5DW34-1]
CCDS59634.1. [Q5DW34-2]
CCDS59636.1. [Q5DW34-3]
RefSeqiNP_001012536.2. NM_001012518.3. [Q5DW34-1]
NP_001103156.1. NM_001109686.2. [Q5DW34-2]
NP_001103157.1. NM_001109687.2. [Q5DW34-3]
UniGeneiMm.24176.

Genome annotation databases

EnsembliENSMUST00000046227; ENSMUSP00000046077; ENSMUSG00000036893. [Q5DW34-3]
ENSMUST00000114432; ENSMUSP00000110075; ENSMUSG00000036893. [Q5DW34-2]
ENSMUST00000147147; ENSMUSP00000119057; ENSMUSG00000036893. [Q5DW34-1]
GeneIDi77683.
KEGGimmu:77683.
UCSCiuc008iph.4. mouse. [Q5DW34-3]
uc008ipi.4. mouse. [Q5DW34-1]
uc012brr.3. mouse. [Q5DW34-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB205007 mRNA. Translation: BAD90007.1.
AL732525 Genomic DNA. Translation: CAM22112.1. Different initiation.
AL732525 Genomic DNA. Translation: CAM22113.1.
AL732525 Genomic DNA. Translation: CAM22114.1.
BC056938 mRNA. Translation: AAH56938.1.
BC089302 mRNA. Translation: AAH89302.1.
CCDSiCCDS15740.1. [Q5DW34-1]
CCDS59634.1. [Q5DW34-2]
CCDS59636.1. [Q5DW34-3]
RefSeqiNP_001012536.2. NM_001012518.3. [Q5DW34-1]
NP_001103156.1. NM_001109686.2. [Q5DW34-2]
NP_001103157.1. NM_001109687.2. [Q5DW34-3]
UniGeneiMm.24176.

3D structure databases

ProteinModelPortaliQ5DW34.
SMRiQ5DW34.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi218847. 7 interactors.
DIPiDIP-49000N.
DIP-59572N.
IntActiQ5DW34. 3 interactors.
STRINGi10090.ENSMUSP00000100002.

PTM databases

iPTMnetiQ5DW34.
PhosphoSitePlusiQ5DW34.

Proteomic databases

PaxDbiQ5DW34.
PeptideAtlasiQ5DW34.
PRIDEiQ5DW34.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000046227; ENSMUSP00000046077; ENSMUSG00000036893. [Q5DW34-3]
ENSMUST00000114432; ENSMUSP00000110075; ENSMUSG00000036893. [Q5DW34-2]
ENSMUST00000147147; ENSMUSP00000119057; ENSMUSG00000036893. [Q5DW34-1]
GeneIDi77683.
KEGGimmu:77683.
UCSCiuc008iph.4. mouse. [Q5DW34-3]
uc008ipi.4. mouse. [Q5DW34-1]
uc012brr.3. mouse. [Q5DW34-2]

Organism-specific databases

CTDi79813.
MGIiMGI:1924933. Ehmt1.

Phylogenomic databases

eggNOGiKOG1082. Eukaryota.
COG0666. LUCA.
COG2940. LUCA.
GeneTreeiENSGT00780000121845.
HOGENOMiHOG000231216.
HOVERGENiHBG028394.
InParanoidiQ5DW34.
KOiK11420.
OMAiETPLQCS.
OrthoDBiEOG091G00U6.
PhylomeDBiQ5DW34.
TreeFamiTF106443.

Enzyme and pathway databases

ReactomeiR-MMU-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-MMU-3214841. PKMTs methylate histone lysines.
R-MMU-6804760. Regulation of TP53 Activity through Methylation.

Miscellaneous databases

ChiTaRSiEhmt1. mouse.
PROiQ5DW34.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000036893.
ExpressionAtlasiQ5DW34. baseline and differential.
GenevisibleiQ5DW34. MM.

Family and domain databases

Gene3Di1.25.40.20. 3 hits.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR007728. Pre-SET_dom.
IPR001214. SET_dom.
[Graphical view]
PfamiPF12796. Ank_2. 2 hits.
PF05033. Pre-SET. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 7 hits.
SM00468. PreSET. 1 hit.
SM00317. SET. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS50867. PRE_SET. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEHMT1_MOUSE
AccessioniPrimary (citable) accession number: Q5DW34
Secondary accession number(s): A2AIS3
, A2AIS4, Q5EBR1, Q6PGM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 8, 2011
Last sequence update: March 8, 2011
Last modified: November 2, 2016
This is version 115 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.